EUROPEAN
COMMISSION
Strasbourg, 16.12.2025
COM(2025) 1022 final/2
2025/0406 (COD)
Proposal for a
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on establishing a framework of measures for strengthening Union’s biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations
(EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795
and (EU) 2024/1938 (European Biotech Act)
{SWD(2025) 1055 final}
(Text with EEA relevance)
EN EN
EXPLANATORY MEMORANDUM
1. CONTEXT OF THE PROPOSAL
• Reasons for and objectives of the proposal
Biotechnology and biomanufacturing are essential to the EU’s competitiveness, strategic
autonomy and economic security. They are a pillar of the Union’s societal wellbeing in key
areas such as health and food.
This strategic importance is underscored by the sector’s rapid expansion. Over the last decade,
the EU biotechnology industry has grown more than twice as fast as the overall EU
economy and is one of the most economically productive industries. The spillover effect is
also significant, each job in industrial biotechnology generates 3.4 additional jobs in the
broader economy. In 2022, it accounted for EUR 38.1 billion of Union GDP and contributed
to 913 160 jobs, with more than 75% of those jobs (685 000) coming from the health
biotechnology sector 1.
However, the EU lags behind other global regions when it comes to translating its world-
class science and innovation into commercially viable products, and even more so in
manufacturing such products at scale. Despite world-leading biotechnology science, reflected
by a publication record comparable to that of the US and China (Figure 1), the EU faces
structural barriers in clinical development, regulation and manufacturing. As a result, too
often Union start-ups end up investing, growing, employing, creating value and placing their
products on the market abroad rather than in the EU. This is especially true for health
biotechnology, where it is at times challenging for the legislative frameworks to keep pace
with the speed of scientific developments.
Figure 1: Top tier life science publications of the EU compared to the USA and China
1
https://www.europabio.org/wp-content/uploads/2025/03/WifOR_EuropaBio2025.pdf
EN 1 EN
To remain a biotechnology powerhouse, the EU must make the most of its scale. Fragmented
governance and suboptimal coordination across Member States weaken the EU’s ability to
deploy industrial facilities at scale, resulting in underused biomanufacturing potential -
including in strategic areas such as biosimilars, where the EU has strong expertise but
insufficiently exploited capacity. It should also ensure a strong alignment between the
available labour supply and the specialised skills that the biotechnology and biomanufacturing
sectors will require in the future. Current skill shortages across key areas including R&D,
regulatory affairs, AI, and data analytics further hinder Europe’s competitiveness. At the same
time, the widening gender gap and the untapped potential of a diverse workforce represent
missed opportunities for innovation and resilience.
Access to finance for scale-up funding in the EU remains limited compared to other regions.
US biopharma start-ups received around nine times more late-stage funding than EU
biopharma start-ups, with around EUR 219 billion of venture capital focused on health
biotechnology invested in the US compared to EUR 25 billion in the EU between 2015 and
June 2025 (Figure 2). EU public equity markets for biotechnology also remain comparatively
underdeveloped, with stock exchanges still largely fragmented across EU Member States 2.
As a result, many EU scale-ups choose to list abroad: over the last six years, 66 out of 67 EU
biotechnology companies that went public chose to list on non-EU stock exchanges,
illustrating the persistent structural disadvantages faced by EU-based innovators 3.
Figure 2: Health Biotechnology investment in the EU compared to the US and China
Aligned with the objectives of the AI Continent Action Plan and the Apply AI Strategy, the
EU must also tap into the massive potential of AI for biotechnologies, addressing obstacles
like limited testing environments, fragmented data, and exploiting the full potential of AI
across the lifecycle of biotechnology products, in particular for medicines. Further,
2
Joint Research Centre (2024), Exploring the global landscape of biotechnology Innovation: preliminary
insights from patent analysis, https://publications.jrc.ec.europa.eu/repository/handle/JRC137266.
3
From discovery to economic impact: Biotechnology Competitiveness for Europe, Vlaams Instituut voor
Biotechnologie, 2024
EN 2 EN
Regulation (EU) 2024/1689 (AI Act)4, which entered into force in August 2024, lays down a
uniform legal framework in particular for the development, the placing on the market, the
putting into service and the use of AI systems and models in the Union, in accordance with
Union values, to promote the uptake of human centric and trustworthy AI. At the same time,
biotechnology introduces new biosecurity risks as the wider accessibility of these
technologies increases their potential for misuse, posing significant health threats. However,
divergent or absent national rules on screening biotechnology products with significant
potential for misuse, such as the synthetic DNA of dangerous pathogens, raise compliance
costs, fail to offer a level playing field to competitors, and weaken prevention.
Fragmentation and the complexity of the EU regulatory framework are factors that make
the EU less attractive for translating cutting-edge research and innovation into marketable
products. For instance, the global share of commercially sponsored clinical trials in the
European Economic Area has declined from 22% in 2013 to 12% in 2023, while China’s
share of commercial clinical trials rose from 5% to 18% in the same period, with the US share
remaining considerably more stable 5. Importantly, the overall reported decline in small
molecule trials suggests a strategic shift toward the development of biological medicines at
the expense of small molecule programs. The drop in the number of small molecule trials was
the most significant in Phase II trials from 62% in 2015 to 47% in 2024 and in Phase III trials
from 65% to 53% during the same period 6. In particular, the EU is losing ground to other
regions with increasingly agile regulatory and financial systems. Most of these regions issue
decisions on validated clinical trial applications within 60 days, whereas in the EU it takes on
average 113 days for multinational trials.
Highlight: the need to simplify and streamline the Clinical Trials Regulation (CTR)
Clinical trials in the EU are crucial to provide patients with early and equal access to
innovative treatments, uphold scientific excellence, and support the EU’s long-term
competitiveness and prosperity. By attracting investment in research and development
(R&D), creating jobs, and reducing healthcare costs, these trials deliver substantial economic
and societal benefits. They also significantly benefit patients by providing earlier access to
new therapies, including personalised therapies (e.g. for rare diseases and cancers), improving
quality of life, and strengthening the evidence base for clinical guidelines, marketing
authorisation and health technology assessments. The share of clinical trials with biological
medicines seems to be increasing at the expense of low molecule trials. Biological medicines
sales are key drivers of growth. In 2024, the European Union spent €228 Bn on medicines at
list prices, including €95 Bn on biological medicines, which now comprise 41% of total
pharmaceutical spending. Increased clinical trials in the Union for biological medicines could
potentially contribute to more manufacturing in the Union, higher number and earlier
regulatory submission of biological medicines for marketing authorisation applications and a
higher percentage of EU clinical data in marketing authorisation applications. A conducive
environment for clinical trials is essential to speed-up market access for novel medicines,
4
Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying
down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No
167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives
2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (Text with EEA
relevance), OJ L, 2024/1689, 12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj
5
European Federation of Pharmaceutical Industries and Association, Assessing the clinical trial
ecosystem in Europe (2024) assessing-the-clinical-trial-ecosystem-in-europe.pdf
6
Global Trends in R&D 2025 - IQVIA
EN 3 EN
especially against global competition. There are still significant regulatory fragmentations
across Member States that limit the system’s efficiency. Against this background, further
regulatory streamlining and simplification of the authorisation and conduct of clinical trials
are imperative. This is a key point of the Draghi report on the future of European
Competitiveness 7, which highlights the need to address these inefficiencies, stressing the
importance of reducing regulatory delays and administrative burdens. It calls for harmonised
templates, stronger coordination between national ethics committees, and a greater emphasis
on using artificial intelligence (AI) and digital tools to streamline the process. At a time when
global competitors – particularly the US, China, and Japan – are rapidly improving their R&D
incentives and regulatory agility, Europe risks losing its competitive edge in clinical research.
The EU’s position in the global clinical trial landscape has already weakened, and immediate
action is needed to close this gap.
This is why a European Biotech Act was announced by the President of the European
Commission in the 2024 - 2029 Political Guidelines of the Commission 8, with the aim of
creating an enabling environment to make it easier to bring biotechnology products from the
laboratory to the factory and then onto the market, while maintaining the highest safety
standards for the protection of the population and the environment. As previously
acknowledged in the Communication on Biotechnology and Biomanufacturing (March 2024)
and the reports by Enrico Letta 9 (April 2024) and Mario Draghi 10 (September 2024), it is
necessary to address the challenges faced by EU companies, users and consumers to boost the
EU’s technological advancement, competitiveness and economic growth. In its resolution
‘Future of the EU biotechnology and biomanufacturing sector’ 11, the European Parliament
recommended ‘facilitating a fast and efficient uptake of biotechnology and biomanufacturing
through clear regulatory frameworks’. The European Parliament is now preparing an own-
initiative report on ‘Public health aspects of biotechnology and life sciences’ 12. More
recently, EU Member States urged the Commission to unlock the potential of biotechnologies,
by reducing fragmentation and simplifying the EU regulatory framework across policy
areas13.
Given the importance of health biotechnology amongst the other applications of
biotechnology as, it is appropriate that the European Biotech Act focusses on, and sets out
specific measures for, the health dimension of biotechnology. To ensure the effectiveness of
this proposal, its scope of application extends to health biotechnology in a comprehensive
manner and cover health within the wide meaning of Article 168 of the Treaty of the
Functioning of the European Union (TFEU) on the protection of public health. In this regard,
Article 168(1) TFEU emphasises that a high level of human health protection is to be ensured
7
Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,
European Commission, 9 September 2024.
8
European Commission (2024), Political Guidelines for the Next European Commission 2024-2029,
e6cd4328-673c-4e7a-8683-f63ffb2cf648_en
9
Enrico Letta (2024), Much more than a Market. Enrico Letta - Much more than a market (April 2024)
10
Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,
European Commission, 9 September 2024.
11
European Parliament (2025). Future of the EU biotechnology and biomanufacturing sector: leveraging
research, boosting innovation and enhancing competitiveness. Texts adopted - Future of the EU
biotechnology and biomanufacturing sector: leveraging research, boosting innovation and enhancing
competitiveness - Thursday, 10 July 2025
12
European Parliament: 2025/2087(INI)
13
Council of the European Union, A call for action on life sciences for the Union's competitiveness -
Council conclusions (approved on 30 September 2025) (13323/25).
EN 4 EN
when defining and implementing all Union policies and activities. Article 168(4) TFEU
clarifies that this objective is, amongst others, to be pursued through measures setting high
standards of quality and safety for medicinal products and devices for medical use and of
organs and substances of human origin, blood and blood derivatives, measures in the
veterinary and phytosanitary fields which have as their direct objective the protection of
public health. Accordingly, and in line with the One Health approach, this Regulation should
apply to health biotechnology, understood as the application of biotechnology in the human
medical, veterinary, pharmaceutical and phytosanitary areas for the development of
biotechnology products and services. The Regulation should apply to their entire lifecycle,
including the related research, access to funding, development, innovation, testing, validation,
manufacturing, placing on the market and use activities.
The proposal for a European Biotech Act acknowledges the EU’s potential to be a global
leader. The region combines a highly skilled workforce, world-class scientific institutes,
innovative startups and scaleups, advanced infrastructure and large private capital pools that
could be used to support the domestic scale-up of promising companies. The proposal
therefore seeks to address the barriers hindering the development of the EU’s health
biotechnology sector, starting from early-stage research through to later-stage deployment and
scale-up. It introduces facilitation measures in the health biotechnology areas, including a
framework for the recognition of, and support for, health biotechnology strategic projects and
high impact health biotechnology strategic projects, aimed at reducing time-to-market, with
particular attention paid to the needs of small and medium-sized enterprises (SMEs), and
includes future-proofing provisions to anticipate the needs of health biotechnologies. Acting
decisively now will allow the EU to fully harness its fast-moving biotechnology sector,
reinforce strategic autonomy and economic security, and lay the foundations for a competitive
and forward-looking EU biotechnology sector.
With a view to ensure the effectiveness of the substantive provisions put forward in this
proposal, amendments to Union legislation in the areas of health and food and feed safety are
also established for regulatory simplification, that have an impact on innovation and the time
to market for biotechnology products and services, including where such legislation also
applies to products other than biotechnology products. In this regard, without an efficient,
accelerated and streamlined legislative framework for clinical trials in the Union, the other
measures in this Regulation, and in particular the framework for the recognition and support
of health biotechnology strategic projects and high impact biotechnology strategic projects
would be deprived of their effectiveness, as all health biotechnology medicinal products
require state of the art clinical research and a globally competitive regulatory framework for
clinical trials authorisation. Similarly, a timelier risk assessment process for products subject
to pre-market authorisation in accordance with Union food and feed legislation, including for
biotechnology innovations where pre-submission advice of the European Food Safety
Authority for aspects such as study design is paramount, as well as accelerated procedures are
needed for the effectiveness of the substantive facilitation measures put forward in this
proposal.
In a second stage, following this health-focused initiative, the Commission will address in
2026 the wider biotech ecosystem beyond health to ensure a competitive internal market for
all areas of biotechnology.
EN 5 EN
Figure 3: Biotechnology and biomanufacturing sector in Europe, problem tree
• Consistency with existing provisions in the policy area
The European Biotech Act will seek to streamline the relevant EU legislative frameworks to
create an enabling environment for innovation and development in order to accelerate time to
market. With its primary focus on health, the present proposal will amend the Regulation on
clinical trials (CTR)14, the Regulation on advanced therapy medicinal products
(ATMPs)15, the Regulation on standards of quality and safety for substances of human
origin intended for human application (SoHO)16 and the Regulation on veterinary
medicinal products (VMPs) 17. In the field of food safety, the proposed measures are built on
the General Food Law18. The proposal will also amend the legislation on the deliberate
release of genetically modified organisms (GMO)19.
14
Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on
clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC Text with EEA
relevance, OJ L 158, 27.5.2014, pp. 1–76. ELI: http://data.europa.eu/eli/reg/2014/536/oj.
15
Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007
on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No
726/2004 (Text with EEA relevance), OJ L 324, 10.12.2007, pp. 121–137.
ELI: http://data.europa.eu/eli/reg/2007/1394/oj.
16
Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on
standards of quality and safety for substances of human origin intended for human application and
repealing Directives 2002/98/EC and 2004/23/EC (Text with EEA relevance), OJ L, 2024/1938,
17.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1938/oj.
17
Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on
veterinary medicinal products and repealing Directive 2001/82/EC (Text with EEA relevance), OJ L 4,
7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj.
18
Regulation (EC) No 178/2002, of the European Parliament and of the Council of 28 January 2002
laying down the general principles and requirements of food law, establishing the European Food
EN 6 EN
The proposal also considers other existing legislation that is being revised to ensure the
coherence of the overall EU regulatory system, in particular the Regulation on medical
devices (MDR) and the Regulation on in vitro diagnostic medical devices (IVDR) 20, as
well as the proposed simplification measures in food and feed safety legislation (food and
feed simplification package).
The Biotech Act will also exploit synergies with other EU legislation. It will complement the
Critical Medicines Act (CMA) 21 to strengthen EU-based biotechnology research and
manufacturing. The Act is also in line with the pharmaceutical strategy for Europe22 and
complements the ongoing revision of the EU pharmaceutical legislation23 to create the
appropriate conditions for biotechnology from the innovation stage. Moreover, the proposed
measures are complementary to the proposed regulation on plants obtained by certain new
genomic techniques and their use in food and feed.
• Consistency with other Union policies
As one of the flagship initiatives of the Competitiveness Compass24, the proposed Biotech
Act aligns with the EU’s broader innovation and competitiveness agenda, translating the
priorities of the Compass into concrete actions within the strategic sector of biotechnology.
In particular, the Biotech Act is part of the Commission’s life sciences strategy25. It was
presented as a central instrument to strengthen the Union’s biotechnology ecosystem,
streamline regulatory procedural pathways and boost Europe’s competitiveness in life
sciences, recognising biotechnology as a strategically critical and cross-sectoral technology.
Furthermore, the proposed Act is complementary to the other policy initiatives announced in
the Compass. First, it aims to improve access to later-stage capital for biotechnology firms,
Safety Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, pp. 1–24.
ELI: http://data.europa.eu/eli/reg/2002/178/oj.
19
Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the
deliberate release into the environment of genetically modified organisms and repealing Council
Directive 90/220/EEC - Commission Declaration, OJ L 106, 17.4.2001, pp. 1–39.
ELI: http://data.europa.eu/eli/dir/2001/18/oj.
20
Regulations (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical
devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No
1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance),
OJ L 117, 5.5.2017, pp. 1–175. ELI: http://data.europa.eu/eli/reg/2017/745/oj and (EU) 2017/746 of the
European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and
repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance), OJ L
117, 5.5.2017, pp. 176–332. ELI: http://data.europa.eu/eli/reg/2017/746/oj.
21
Critical medicines Act - Public Health - European Commission
22
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Pharmaceutical Strategy for
Europe, COM/2020/761 final.
23
European Commission website, Reform of the EU pharmaceutical legislation
24
European Commission, European Competitiveness Outlook (Competitiveness Compass):
Competitiveness compass - European Commission
25
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Choose Europe for life sciences A
strategy to position the EU as the world’s most attractive place for life sciences by 2030,
COM/2025/525 final.
EN 7 EN
aligning with the start-up and scale-up strategy 26 and complementing the Scaleup Europe
Fund established under that strategy, as well as the Savings and Investments Union 27,
which seeks to mobilise larger pools of private capital, support investment within the EU, and
reduce financing costs for Union businesses.
Second, the provisions on biosecurity also reflect the Compass’s emphasis on talent as a
cornerstone of innovation and on the interdependence between economic strength and
security. In this context, the Act is consistent with the objectives put forward in the Union of
Skills 28 and contributes to EU security by reinforcing safeguards for dual-use
biotechnologies. It also complements the EU Regulation (EU) 2022/2371 on serious cross-
border threats to health 29, helping to ensure a coordinated Union-level response to health
risks that may arise from the misuse of emerging biotechnologies and to the strategic
technologies for Europe platform (STEP) 30 that also target biotechnologies.
Third, the emphasis on the use of AI in the proposed Act also aligns with the Competitiveness
Compass, and echoes the recent Apply AI strategy 31, the AI continent action plan 32, the
European AI Act 33 and the Data Union strategy 34, which stress the need to strengthen
Europe’s innovation capacity, technological competitiveness and secure, data-driven
ecosystems while supporting the biotechnology landscape.
Overall, the Biotech Act is also consistent with the vision for agriculture and food 35., as it
amends the General Food Law to broaden the scope of pre-submission advice provided by the
European Food Safety Authority (EFSA) to study design, and reforms the EFSA Panel system
to speed up risk assessment procedures.
26
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, The EU Startup and Scaleup
Strategy Choose Europe to start and scale, COM/2025/270 final.
27
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Savings and Investments Union A
Strategy to Foster Citizens’ Wealth and Economic Competitiveness in the EU, COM/2025/124 final.
28
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, The Union of Skills, COM/2025/90
final.
29
Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on
serious cross-border threats to health and repealing Decision No 1082/2013/EU (Text with EEA
relevance), OJ L 314, 6.12.2022, pp. 26–63. ELI: http://data.europa.eu/eli/reg/2022/2371/oj.
30
Strategic Technologies for Europe Platform
31
Communication from the Commission to the European Parliament and the Council, Apply AI Strategy,
COM/2025/723 final.
32
https://ec.europa.eu/newsroom/dae/redirection/document/114523
33
Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying
down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No
167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives
2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act), OJ L, 2024/1689,
12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj.
34
Communication from the Commission to the European Parliament and the Council, Data Union
Strategy Unlocking Data for AI, COM(2025) 835 final.
35
Communication from the European Parliament, the Council, the European Economic and Social
Committee and the Committee of the Regions, A Vision for Agriculture and Food Shaping together an
attractive farming and agri-food sector for future generations, COM/2025/75 final
EN 8 EN
Lastly, the proposed Act was informed by the preparation of upcoming and recent initiatives,
such as the future European Innovation Act 36 and the recently adopted bioeconomy
strategy 37, in order to ensure synergies.
Furthermore, climate change has shown the need to also prioritise the resilience of the Union,
including, for instance to focus on sustainable food systems, stronger health prevention and
innovative health solutions. In this context, biotechnology has been identified in the Farm to
Fork Strategy 38, which is a key component of the European Green Deal 39, as a technique
that is safe for consumers and the environment. The proposed Act is also consistent with the
European Commission’s objectives to achieve climate neutrality set out in the EU Climate
Law 40 and the Union’s Strategy on Adaptation to Climate Change 41.
In this context, the proposed European Biotech Act, including through its measures
supporting innovation, will accelerate the placing on the market of biotechnology products
that are adaptable to climate change, that contribute to health and food security through
sustainable biomanufacturing and to the protection of biodiversity. Such biotechnology
products have also the potential to replace products potentially more harmful for the
environment while providing great benefits for consumers and users. Biotechnology and
biomanufacturing will also need to comply with Union legislation in these areas, such as, the
Regulation concerning the Registration, Evaluation, Authorisation and Restriction of
Chemicals (REACH)42 or applying without prejudice to the provisions of Regulation (EU)
2024/1735 regarding sustainable biogas and biomethane technologies and biotechnology
climate and energy solutions43.
This also shows that the proposed Act is in line with the ‘do no significant harm’ principle.
The positive environmental impact of biotechnology and biomanufacturing was also
recognized by stakeholders in their responses to the Public Consultation.
36
European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-
your-say/initiatives/14593-European-Innovation-Act_en
37
European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-
your-say/initiatives/14555-Towards-a-circular-regenerative-and-competitive-bioeconomy_en
38
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, A Farm to Fork Strategy for a fair,
healthy and environmentally-friendly food system, COM/2020/381 final
39
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, The European Green Deal,
COM/2019/640 final.
40
Regulation (EU) 2021/1119 of the European Parliament and of the Council of 30 June 2021 establishing
the framework for achieving climate neutrality and amending Regulations (EC) No 401/2009 and (EU)
2018/1999 (‘European Climate Law’), OJ L 243, 9.7.2021, pp. 1–17. ELI:
http://data.europa.eu/eli/reg/2021/1119/oj.
41
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Forging a climate-resilient Europe
- the new EU Strategy on Adaptation to Climate Change, COM/2021/82 final
42
Consolidated text: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18
December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals
(REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing
Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council
Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and
2000/21/EC (Text with EEA relevance). ELI: http://data.europa.eu/eli/reg/2006/1907/2025-09-01
43
Consolidated text: Regulation (EU) 2024/1735 of the European Parliament and of the Council of 13
June 2024 on establishing a framework of measures for strengthening Europe’s net-zero technology
manufacturing ecosystem and amending Regulation (EU) 2018/1724 (Text with EEA relevance). ELI:
http://data.europa.eu/eli/reg/2024/1735/2025-08-17
EN 9 EN
Finally, the proposed Biotech Act will support digital transformation in line with the
‘digital by default’ principle. One of its specific objectives is to “facilitate the application of
AI into the Union’s biotechnology and health technology manufacturing ecosystems and
frameworks, in line with Regulation (EU) 2024/1689”. The Act is expected, among others, to
support the use of data, digital platforms and analytical methodologies (e.g. reducing the need
for clinical data), in the development of biotechnology and in biomanufacturing.
Digitalisation will also be reinforced in networking cooperation of biotechnology clusters
(e.g. through the promotion of the development of infrastructure and digital platforms, and
AI-enabled technologies). Overall, accelerated digitalisation, in particular through greater data
use and AI integration, aims at contributing to the Union’s technological sovereignty.
Moreover, the proposed European Biotech Act will ensure coherence with relevant digital
policies, such as the Artificial Intelligence Act44, on development and testing of AI enabled
biotechnology solutions, as well as the EU Cybersecurity framework45, on access principles
and security safeguards.
2. LEGAL BASIS, SUBSIDIARITY AND PROPORTIONALITY
• Legal basis
The general objective of this Regulation is threefold: (i) to improve the functioning of the
internal market by establishing a framework to strengthen the competitiveness of the health
biotechnology sector, from research to production, (ii) to create the conditions for the
development and timely placing on the EU market, of biotechnology innovations, products
and services, (iii) while safeguarding high standards for the protection of human health,
animal health, patients and consumers, the environment, ethics, quality, food and feed safety,
and biosecurity.
This general objective translates into the establishment of measures to:
(i) strengthen the biotechnology sector and reinforce the EU’s research, development
and production capabilities, by establishing a framework for the recognition of, and
support measures for, strategic health biotechnology projects and high impact
strategic health biotechnology projects (pillar 1);
(ii) support funding of, investments in, and access to capital for, biotechnology
companies and projects, including through the setting up of an EU health
biotechnology investment pilot to fill the gap in spending on biotechnology
innovation (pillar 2);
(iii) improve the EU manufacturing capacity of, and expertise in biosimilars, including
through international cooperation (pillar 3);
44
Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying
down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No
167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives
2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (Text with EEA
relevance), OJ L, 2024/1689, 12.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1689/oj
45
Regulation (EU) 2019/881 of the European Parliament and of the Council of 17 April 2019 on ENISA
(the European Union Agency for Cybersecurity) and on information and communications technology
cybersecurity certification and repealing Regulation (EU) No 526/2013 (Cybersecurity Act) (Text with
EEA relevance), OJ L 151, 7.6.2019, pp. 15–69. ELI: http://data.europa.eu/eli/reg/2019/881/oj
EN 10 EN
(iv) facilitate the application of AI into the Union’s biotechnology and health technology
manufacturing ecosystems and frameworks, in line with the Regulation (EU)
2024/1689 (pillar 4);
(v) ensure a legislative framework that encourages innovation and takes account of
technological and scientific developments and progress, by establishing provisions
for health biotechnology products (pillar 5);
(vi) prevent the misuse of biotechnologies and strengthen biodefence capabilities (pillar
6).
(vii) enable the effectiveness of the measures under the pillars 1 to 6 through a legislative
framework conducive to the use of biotechnology innovations, by amending Union
legislation in particular on clinical trials, veterinary medicinal products, food and
feed safety and related legislation (pillar 7).
The appropriate legal basis is therefore as follows:
– Article 114 of the Treaty on the Functioning of the European Union (‘TFEU’) which
allows the EU to take measures that increase harmonisation and remove
fragmentation to create a level playing field within, and fully exploit the scale of, the
EU single market, so that the health biotechnology and biomanufacturing sectors can
thrive. In accordance with Article 114(3) TFEU, the proposal seeks to achieve the
objective of a high level of health and safety protection.
– Article 168(4) TFEU, which mandates the Union to contribute to the achievement of
a high level of human health protection through the adoption - in order to meet
common safety concerns - of (i) measures setting high standards of quality and safety
of organs and substances of human origin, blood and blood derivatives; (ii) measures
in the veterinary and phytosanitary fields which have as their direct objective the
protection of public health; and (iii) measures setting high standards of quality and
safety for medicinal products and devices for medical use.
– Article 173(3) TFEU, which allows the Union to decide on specific measures in
support of action taken in the Member States to ensure the conditions necessary for
the competitiveness of the Union’s industry, excluding any harmonisation of the laws
and regulations of the Member States. This article provides a legal basis for the
provisions in this Regulation regarding the EU health biotechnology investment
pilot, establishing the basis for future Union financial support together with
implementing partners, to support the financing of, and investments in, companies
and projects falling within the scope of the European Biotech Act.
• Subsidiarity (for non-exclusive competence)
The objectives of the proposal cannot be achieved by Member States acting alone, as the
issues tackled are of a cross-border nature and are not limited to single Member States or to
several Member States. The proposed actions focus on areas where there is a demonstrable
value added in acting at EU level due to the scale, speed, and scope of the efforts needed.
Furthermore, the market drivers identified are shared across the Member States, affecting the
functioning of the single market and the global competitiveness of EU companies. Access to
finance is scattered across the EU and EU companies lack the capacity to access private
finance at a competitive scale, including at later stages of development. Similarly, European
biotechnology clusters are scattered across the EU, without sufficient continental scale to
compete globally. The development and deployment of AI solutions for biotechnology
EN 11 EN
remains limited, also due to the low level of storage, access and sharing of data relevant for
biotechnology in the EU, including across borders. There is also a clear need across the EU to
attract, reskill and upskill the workforce.
Moreover, while several Member States have taken action to boost innovation in
biotechnology, the above-mentioned bottlenecks persist; improvements are expected to take
considerably more time and without achieving the levels needed to compete at global level.
For example, access to finance would remain scattered at EU level. The growth of clusters in
the EU would also remain limited, without sufficient benefits from cross-border connections.
Lastly, important regulatory barriers faced by European biotechnology companies stem from
EU legislation. Therefore, with a view to enable the effectiveness of the substantive measures
put forward in this proposal, it is proposed to simplify EU legislation in the area of health and
of food and feed safety to make it easier to innovate and place biotechnology products and
services on the Union market and to enhance legal clarity.
• Proportionality
The selected measures under the industrial policy and substantive part of the proposal are
targeted at the specific areas of interventions listed below.
– The provisions on strategic health biotechnology projects and high-impact strategic
health biotechnology projects are proportionate to the aims pursued, including by
recognising the first category of projects at Member State level, and the second
category at EU level on the basis of an assessment at Member State level. Moreover,
the recognition of such projects is based on clear criteria tailored to ensure that
projects that contribute substantially to the Union’s competitiveness, resilience, and
security fall within the enhanced support regime. Moreover, the recognition of such
projects does not restrict Member States’ ability to support additional projects
through other instruments. Member States benefit from flexibility as regards the
authorities that they intend to designate to recognise strategic health biotechnology
projects and assess applications for high-impact strategic health biotechnology
projects. This flexibility also applies to the single points of contact and the provision
of administrative, technical, and financial support, in line with Union law and the
national systems. Accelerated permitting timelines apply only to recognised projects
and are designed to streamline procedures without lowering any environmental,
health or safety standards.
Similarly, measures aimed at supporting networking among health biotechnology clusters are
limited to what is necessary to foster synergies in the internal market, while the EU Health
Biotechnology Support Network is aiming to build on and complement existing national and
EU structures, avoiding any duplication.
– On access to funding, the interventions focus on measures mobilising public funding
and private capital; public funding needs to be in line with State aid rules.
– The proposed interaction modalities with Member States in the context of a
European Health Biotechnology Steering Group allows for priorities to be adjusted,
including by ensuring that the support measures for strategic health biotechnology
project and high-impact strategic health biotechnology projects remain closely
aligned with the Regulation’s general objective.
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The proposed amending provision aimed at reducing the time-to-market of biotechnology
products and services focus on certain sectoral Union legislation where room for
simplification of regulatory and administrative complexities has been identified.
Simplification relates to changes that are necessary with a view to secure the effectiveness of
the substantive provisions put forward in this proposal and will improve the legal clarity,
certainty, and overall efficiency of the concerned EU legislative frameworks.
• Choice of the instrument
The proposal takes the form of a regulation of the European Parliament and of the Council.
A regulation is the most suitable legal instrument for Pillars 1 to 4, given the need for a
uniform application of the new rules, in particular the conditions and procedure for
recognising heath biotechnology strategic projects and high impact health biotechnology
strategic projects, and for their administrative, technical and financial support, and also more
broadly for companies and non-profit organisations active in the relevant biotechnology
sectors across the internal market. This is also the case for Pillar 5, regarding the provisions
on biotechnology health products, given that they aim to ensure a dialogue and more
flexibility across the Union legislative frameworks in the area of health. The choice of a
regulation as a legal instrument is also appropriate for Pillar 6 because only a regulation, with
its directly applicable legal provisions, can provide the necessary degree of uniformity needed
to boost EU biodefence and biosecurity and prevent biotechnology misuse.
In all cases, the choice of the instrument is justified considering that the Pillar 7 establishes
provisions amending several existing Union regulations in the area of health and food and
feed safety.
Lastly, a regulation is appropriate for the provisions regarding on evaluating this Regulation
which do not need to be transposed through national measures and are directly applicable.
3. RESULTS OF EX-POST EVALUATIONS, STAKEHOLDER
CONSULTATIONS AND IMPACT ASSESSMENTS
• Ex-post evaluations/fitness checks of existing legislation
The proposed measures amend several pieces of EU legislation in a targeted manner, without
modifying their objectives, the overall regulatory framework put in place or their functioning.
When relevant, these measures were informed by several studies or ongoing evaluations, such
as the ongoing evaluation of the EFSA. Regarding the Clinical Trials Regulation, an ongoing
study will contribute to the Commission’s report, which will be presented five years after the
application date of the legislation (1 January 2022).
The extensive consultation process and a comprehensive supporting study identifying over
200 regulatory challenges stemming from EU legislation have gathered evidence on the
challenges and problems, the relevant provisions of the legislation, and issues for which there
is no legislation.
EN 13 EN
• Stakeholder consultations
Extensive stakeholder consultations were carried out to prepare for the proposal. A call for
evidence 46, opened for feedback from 14 May to 11 June 2025, gathered 222 valid individual
contributions47 from a wide range of stakeholders: business associations 48 (63), companies
(50), non-governmental organisations (NGOs) (44), academic and research institutions (20),
public authorities in the EU (14), EU citizens (14) and other categories (17) 49.
Figure 4: submissions to the call for evidence
The respondents were largely based in the EU (197 responses from 15 Member States).
Among these, most of the contributions came from Belgium (74), followed by Germany, (29),
France (20), the Netherlands (16), Denmark (12) and Spain (11). 25 contributions were
received from 7 non-EU countries (the United States, Switzerland, the United Kingdom,
Norway, Canada, Australia and Argentina).
With regard to current biotechnology related regulation, various stakeholder groups such as
academic/research institutions, NGOs, representatives of companies (including SMEs), and
public authorities underlined slow and complex regulatory frameworks that lead to long
authorisation/approval processes, thereby hindering innovation and delaying market access.
Representatives from businesses (both associations and large companies) referred to the
unpredictability of some authorisation procedures. Representatives from
academic/research institutions and business associations also expressed concerns regarding
outdated regulatory frameworks, while business associations mentioned in particular the
limited flexibility of the EU regulatory frameworks. In addition, NGOs/others, large
companies and SMEs, business associations and trade unions agreed that divergent national
rules and interpretation/implementation of EU rules create fragmented market entry
46
European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-
your-say/initiatives/14627-Biotech-Act_en
47
Three submissions were received from a single respondent and have been counted as one response. Two
submissions were received from another respondent and have been counted as one response.
48
Three respondents that selected trade unions are analysed together with business associations as
representing the industry.
49
In the analysis, they are grouped together with feedback from NGOs.
EN 14 EN
conditions. Feedback from small companies indicated high regulatory costs as a result of the
regulatory fragmentation, while public authorities also acknowledged high compliance costs.
Lastly, some feedback pointed to inconsistencies between EU legislative frameworks, in
particular the CTR, ATMPs Regulation, MDR/IVDR, REACH Regulation and the General
Data Protection Regulation (GDPR).
Most stakeholders also indicated a shortage of risk-tolerant capital. Stakeholders highlight
fragmented funding schemes, limited early-stage financing, and low EU venture capital
share compared to the US and China. For instance, representatives from academic/research
institutes indicated that the EU’s venture capital accounted for only about 5% of global
venture capital. Representatives of large companies particularly underlined public R&D
under-investment, indicating poor alignment across policies and programmes. Some
contributions from NGOs/others also indicated the risk of dependence on foreign capital,
particularly in health and defense-related biotechnologies.
Stakeholders stressed the fundamental role of education and skills for the biotechnology and
biomanufacturing workforce. Stakeholders expressed concerns about talent drain and global
competition. This is exacerbated by existing regulatory and mobility barriers that hamper
cross-border and cross-sector mobility, as indicated in feedback from academic/research
institutions. In addition, stakeholders underlined the limited entrepreneurial pathways from
academia to company building. Moreover, many stakeholders experienced shortages in the
specialised and interdisciplinary competences needed for the biotechnology and
biomanufacturing workforce. Other limitations mentioned were an insufficient number of
STEM graduates, the lack of funding or low investment in life-long learning (e.g. digital, AI
competencies), and unequal access to upskilling programmes.
Stakeholders across all groups (including academic/research institutions, business
associations/trade unions, large companies, citizens, as well as NGOs/others and public
authorities) stressed the limited manufacturing capabilities in the Union. Some of the
underlying factors mentioned were, among others, the high costs, infrastructure and
investment gaps, limited digitalisation, supply chain vulnerabilities, and the fragmented
regulatory frameworks. SMEs underscored this statement, also pointing to the challenges
related to lack of recognition for quality control technologies.
Furthermore, incubation and acceleration limitations in the EU were mentioned. Many
stakeholder groups, such as academic/research institutions, large companies, NGOs/others
and public authorities, highlighted the need to bridge the gap between research and industry in
Europe’s biotechnology ecosystem. They expressed concerns on the barriers faced in
incubation and acceleration, such as funding gaps in early stages, a fragmented support
landscape, regulatory burdens, hindrances in public-private collaboration and cultural/skill
barriers. Business associations’ and public authorities’ feedback was in line with this
statement, underlining that the EU lacks cohesive pathways to commercialisation. Large
companies specifically pointed out the lack of financial and administrative capacity of SMEs
and start-ups to access EU-level funding or to protect their intellectual property.
Stakeholders overall recognised the pivotal role of AI and data to advance biotechnology. As
part of the challenges faced however, academic/research institutions and large companies
indicated a lack of access to data and secure data sharing, fragmented data ecosystems
including limited data interoperability, unclarity on data governance and insufficient
coordination. Business associations and public authorities also mentioned fragmented
computing power and uneven access to testing infrastructures. Furthermore, SMEs
EN 15 EN
referred to a lack of information and knowledge among companies about AI implementation
and compliance. Feedback from NGOs/others overall echoed these statements, while also
advocating to take into consideration the environmental impact of AI infrastructures. Most
stakeholders additionally pointed out regulatory fragmentation, technical and legal barriers,
innovation barriers, and governance gaps. AI skills shortages were also mentioned by several
stakeholder groups, as well as ethical uncertainties.
Finally, on biosecurity, stakeholders mentioned that while biotechnology and
biomanufacturing offer transformative opportunities across multiple application areas, these
must be governed by policies that balance innovation with safety, equity, and environmental
protection. Various challenges were pointed out by different stakeholder groups in relation to
biosecurity. For instance, academic/research institutions, NGOs and public authorities
mentioned a fragmented biosecurity governance and regulatory complexity as major
issues. Specifically, disjointed EU and national regulations that hinder coherent biosecurity
frameworks were highlighted. Public authorities furthermore indicated limited collaboration
as a key challenge – for instance gaps in cooperation between national authorities and limited
cross-border collaboration. Regarding nucleic acid screening, academic/research institutions,
and NGOs mentioned inconsistent compliance in screening due to current voluntary systems
as a threat to biosecurity. Finally, dual-use risks were mentioned by SMEs and NGOs.
A public consultation 50 was carried out from 4 August to 10 November 2025. A total of 359
contributions were received. No duplicates or campaigns were identified. The contributions
considered for the analysis 51 were submitted by 91 companies/businesses and 61 business
associations, 47 NGOs, 44 academic/research institutions, 54 EU citizens and 9 non-EU
citizens, and 21 public authorities. A further 2 contributions were submitted by 2 trade unions,
2 consumer associations, and 1 by an environmental organisation 52, while 27 additional
respondents identified themselves as ‘Other’.
50
European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-
your-say/initiatives/14627-Biotech-Act/public-consultation_en
51
Four trade unions were analysed under business associations.
52
In the statistics, the 2 trade unions, 2 consumer organisations and the environmental organisation are
reflected with the respondents who identified themselves as ‘other’.
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Figures 5 and 6: submissions to the public consultations and industry submissions per
company size
Concerning the industry sector, most of the contributions came from SMEs (53 in total out
of which 12 medium-, 17 small-, and 24 micro-sized SMEs) and 38 contributions came from
large enterprises. Of the contributing public authorities, 8 had a national remit and 8 had a
regional scope, 2 of them were local authorities and 3 were international organisations.
As part of all contributions received, 16 respondents identified as private investors,
including 13 from the EU and 3 from outside of the EU (Switzerland and the UK). Most of
them identified as company/business. When asked about the type of investment they
provided, 8 stated that they provided ‘Venture capital’, 5 chose ‘Business Angel’, 4 ‘Private
equity’, 3‘Corporate Venture Capital (CVC)’, and 1 ‘Other’.
Lastly, 43 respondents of all contributions received indicated being part of a cluster or of a
cluster organisation. These represented 26 companies/businesses, 15 business associations, 1
NGO and 1 ‘Other’.
There is a strong overall interest from stakeholders to the biotechnology sector and
acknowledgment of its great potential, in line with the EU’s economic, social and
environmental policy goals. More precisely, a strong majority of respondents agreed that
biotechnology and biomanufacturing products could positively impact the EU’s economy and
the society, also recognizing its contribution to the environment 53. Respondents considered
biotechnology and biomanufacturing products that reached the EU market to be safe and
secure 54. However, they did not consider that information to users and consumers 55 on
biotechnology and biomanufacturing products in the EU was sufficiently accessible and
broadly communicated. Moreover, only a minority of respondents were willing to pay a price
premium for such products56.
Answers to the public consultation on the EU regulatory framework were in line with the
focus of the proposed Act. The main regulatory barriers 57 identified by stakeholders
concerned the assessment and obtaining authorisation to market products, followed by
the pre-commercial testing or clinical trials stage, in commercialising products as well as
in the scaling-up production or manufacturing and product development.
Another finding of the public consultation relates to the perception of the EU regulatory
environment compared to that of some countries outside the EU. The EU regulatory
environment is perceived by some stakeholders to have a lower level of predictability58 and
it is also seen as more complex and unclear 59, leading to more compliance costs 60 and
53
Positive economic impact: 90.3% strongly agreed/agreed (324/359); Positive social impact: 89.7%
strongly agreed/agreed (322/359); Positive environmental impact: 80.2% strongly agreed/agreed (288/359)
54
76.3%: 175 strongly agreed, 99 agreed (out of 359).
55
28.1%: 30 strongly agreed, 71 agreed (out of 359).
56
15.6%: 13 strongly agreed, 43 agreed (out of 359).
57
Agreement/strong agreement on these barriers ranged from 63% to 76%.
58
More predictable: 40.8%: 45 strongly disagreed/92 disagreed (out of 336).
59
Less complex and clearer: 64.6%: 99 strongly disagreed/116 disagreed (out of 333).
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slower access to the market 61. Views on whether the EU regulatory environment ensures a
higher level of safety and security were rather mixed 62. Public authorities (57,9%, 11/19),
NGOs (46,5%, 20/43), other stakeholders (48,5%, 15/31) and academic/research institutions
(42,9%, 18/42) had a positive stance.
These findings underscore the urgent need to take action to simplify and streamline the
regulatory environment, making it flexible and innovation-friendly so that biotechnology
products and services can reach the EU market more quickly.
Furthermore, respondents reported low level of access to private investments in the EU, in
particular in accessing to publicly listing, private equity, debt financing, venture capital (VC)
across series B (expansion stage) and C (growth stage) and capital markets/shareholders 63. It
should be noted that stakeholders also expressed low level of accessibility to some public
funding, especially for support for capacity expansion, debt/equity instruments, and
commercialisation support64. Stakeholders indicated less difficulties in accessing strategic
research or sales partnerships/collaborations, angels, venture capital at start-up/early-stage
(series A) and corporate funding 65 and public grants and subsidies 66.
When asked about the factors driving forward investments in a biotechnology company,
there were no major differences in the answers. Some factors scored highly, which are (i)
groundbreaking technology; (ii) regulatory certainty; (iii innovative science; (iv) scientific
evidence; (v) experienced management team; and (vi) sufficient protection of intellectual
property rights 67.
On clusters, the five main barriers faced by EU biotechnology clusters and/or cluster
organisations preventing them from reaching their full potential were identified as: (i)
insufficient financial support; (ii) insufficient public support; (iii) incapacity to reach a critical
mass of stakeholders; (iv) insufficient start-up incubators or business support infrastructure;
and (v) insufficient collaboration among existing clusters68.
Stakeholders identified the main challenges impacting the EU biomanufacturing sector as: (i)
global competition; (ii) length and/or complexity of permitting processes for new facilities;
(iii) difficulty of scaling up from pilot to industrial production; (iv) high energy costs; and
(v) the high cost of raw material and/or of the operations69. A majority of respondents also
agreed that major challenges are also posed by the inconsistent environmental and
sustainability policies, vulnerabilities in the supply chains and other operational costs70.
60
Leads to lower costs for complying with the regulation: 62%: 98 strongly disagreed/109 disagreed (out
of 334).
61
Enables biotechnology and biomanufacturing products to reach the market faster: 65.7%: 126 strongly
disagreed/92 disagreed (out of 332)
62
Ensures a higher level of safety and security: 21.4% disagreed/strongly disagreed. (72/337) 36.8%
agreed/strongly agreed (124/337). 41.8% were neutral or Not applicable/I don’t know (141/337).
63
Agreement/strong agreement that there is easy access to these options ranged from 3.9% to 6.7%.
64
Agreement/strong agreement that there is easy access to these options ranged from 4.2% to 5.6%.
65
Agreement/strong agreement that there is easy access to these options ranged from 11.4% to 21.2%.
66
Agreement/strong agreement that there is easy access was 19.2% (69/359).
67
Agreement/strong agreement on these factors ranged from 72.4% to 79.9%.
68
Agreement/strong agreement on these barriers ranged from 46.2% to 58.5%.
69
Agreement/strong agreement on these challenges ranged from 58.2%% to 66.9%.
70
Agreement/strong agreement on these challenges ranged from 50.1% to 51.5%.
EN 18 EN
The public consultation also confirmed the challenges faced by the EU workforce.
Stakeholders’ views were aligned on three main challenges: (i) the limited financial,
entrepreneurial skills and mindsets; (ii) the insufficient regulatory and quality assurance
expertise; and (iii) the shortage of vocational skills71.
Some stakeholders indicated having difficulties accessing or using data for the development
of biotechnology or biomanufacturing products72. Stakeholders also emphasised that
technological challenges and challenges in the implementation of regulatory frameworks were
the main barriers to both the use of AI in R&D73 and to the deployment of AI-based
biotechnology products74. When asked about the types of support needed for
biotechnology companies, in particular for SMEs, stakeholders stressed (i) skills
development and AI training; (ii) access to annotated datasets; (iii) partnerships with public
research institutions or AI hubs/factories; (iv), dedicated funding instruments; and (v)
regulatory sandboxes for testing biotech-related AI models75.
When it comes to the application of biotechnology in defence and security, the main
challenges identified by stakeholders were: (i) the risks to strategic autonomy in
biomanufacturing (and availability of medical and non-medical countermeasures); (ii)
cybersecurity risks to biotechnology infrastructure and AI tools used in biotechnology; (iii)
vulnerabilities in the resilience of biotechnology supply chains; and (iv) threats related to
biosecurity and biosafety including misuse of biotechnology76. The four main opportunities
that biotechnology for defence and security were creating were: (i) to develop new innovative
medical countermeasures; (ii) to facilitate detecting biological and chemical threats, (iii)
to increase food security; and (iv) to develop materials with new functions and / or
improved characteristics77.
In addition, targeted consultation activities were carried out, as detailed below, including in
the context of an external study announced in the Commission Communication ‘Building the
future with nature: Boosting Biotechnology and Biomanufacturing in the EU’ (Action 1)78.
First, the following consultation activities took place on the analysis of regulatory problems
and challenges faced by the biotechnology sector and on the mapping of applicable EU and
national legislations to biotechnologies:
• survey for public authorities;
• survey for other stakeholders, including industry representatives and patient
organisations;
71
Agreement/strong agreement on these challenges ranged from 51.8% to 58.5%.
72
21.4% replied partially (77/359) and 18.4% replied Yes (66/359) totalling 39.8%. However 44% replied
Not applicable/I don’t know (158/359 answers) and 16.2% replied No (58/359).
73
Technological challenges:61.3%%: 65 strongly agreed/155 agreed (out of 359); challenges in the
implementation of regulatory frameworks: 59.1%: 81 strongly agreed/ 131 agreed (out of 359).
74
Technological challenges:51.5%: 63 strongly agreed/122 agreed (out of 359); challenges in the
implementation of regulatory frameworks: 52.1%: 81 strongly agreed/106 agreed (out of 359).
75
Agreement/strong agreement on the needed types of support ranged from 59.1% to 65.5%
76
Agreement/strong agreement on the four main challenges ranged from 42.3% to 51.5%
77
Agreement/strong agreement on the three main opportunities ranged from 43.7% 48.2%.
78
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Building the future with nature:
Boosting Biotechnology and Biomanufacturing in the EU, COM(2024) 137 final.
EN 19 EN
• interviews with representatives of SMEs and large enterprises, and representatives of
the spin-off, alliance/platform, scale-up and EU association sectors;
• five thematic workshops covering (i) health/pharma; (ii) agriculture/environment;
(iii) food and feed; (iv) bio-based chemicals and plastics; and (v) bio-based materials.
Second, to analyse the impacts of identified policy provisions, evidence was collected on the
impacts of these provisions.
On clinical trials, evidence has been collected (by November 2025) through:
• three workshops organised by the European Commission in June, September, and
November 202579, with representatives of national competent authorities and ethics
committee members from across the EU to exchange views with experts to inform
how policy options would be defined;
• targeted interviews;
• targeted survey to various stakeholder groups:
• a survey targeted to sponsors and clinical research organisations received
48 responses 80.
• another targeted survey collected views from 44 public authorities
representing 25 EU/EEA countries81.
• a survey tailored to patient representatives received 1 response from a
disease-specific patient representing an organisation at national level.
Evidence on the impacts of options on genetically modified microorganisms was collected
through 25 interviews (by November 2025).
Finally, targeted consultation activities were also conducted as part of the supporting study
for the evaluation of EFSA.
• Collection and use of expertise
The major competitiveness gap in biotechnology and the market and regulatory barriers faced
by European companies were identified in the Commission Communication ‘Building the
future with nature: Boosting Biotechnology and Biomanufacturing in the EU’82 and in the
Draghi83 and Letta84 reports.
79
CTAG: Clinical Trials Advisory Group; MedEthics-EU, the Clinical Trials Coordination Group of the
Heads of Medicines Agencies (HMA) was also invited to the workshop. The EMA is an observer to the
CTAG.
80
32 from commercial sponsors, 6 from non-commercial sponsors, 3 from Clinical Rresearch
Organisations (CROs), and 7 from other stakeholders such as non-profits, hospital owners, advocacy
groups, research infrastructures, trade associations and life sciences providers
81
20 responses from ethics committees, 20 from national competent authorities, 3 from ministries or
government bodies, and 1 from a respondent identified as both a ministry and an ethics committee
82
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, Building the future with nature:
Boosting Biotechnology and Biomanufacturing in the EU, COM(2024) 137 final.
83
Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,
European Commission, 9 September 2024.
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In addition, the above-mentioned external study commissioned by the European Commission
(‘Analysis of the Regulatory Framework for Biotechnology and Biomanufacturing in the
EU’) provides an extensive mapping of the main pieces of EU and national legislation that
apply to biotechnology and biomanufacturing products and processes – whether they are
horizontal or sector-specific – and identifies the challenges, their causes and the consequences
for stakeholders. The study also assesses the impacts of policy options related to the EU
regulatory framework.
• Impact assessments
Considering the politically urgent need to address the policy challenges identified, an impact
assessment could not have been delivered in the timeframe available before the proposal’s
adoption. Instead, an analytical staff working document (SWD) will be prepared. The
analytical SWD will explain the proposal and will present the underlying evidence and impact
analysis, including cost-benefit analysis. A large number of provisions of the proposal
concern simplification measures which typically do not offer viable alternatives and do not
modify the objectives of the amended legislation. Nevertheless, the proposed measures are
based on extensive stakeholder consultations, complemented with an analysis of the current
situation to ensure a transparent, proportionate, and evidence-based approach.
• Regulatory fitness and simplification
The proposal lays down measures to strength the EU biotechnology and biomanufacturing
ecosystem and reduce time-to-market for biotechnology products in the EU.
The proposed Act aims to simplify the existing regulatory framework and remove
regulatory burdens hampering the innovation and competitiveness of EU operators. In
particular, the measures seek to clarify and reduce procedural timelines across the full
development cycle (e.g. by alleviating complex and disproportionate requirements) and
provide a flexible regulatory environment for a fast-growing innovative sector (e.g. through
regulatory sandboxes and by enabling an increasing use of data and AI). As such, all actors, in
particular companies, will benefit from a more predictable EU regulatory framework, i.e.
increased legal certainty, reduced procedural timelines, and a flexible and collaborative
regulatory environment. Overall, these measures are expected to enable companies to bring
innovation to the market. SMEs in particular are expected to benefit from these measures
through reduced entry barriers in the field of biotechnology. The supporting measures also
target the needs of SMEs, start-ups and scale-ups.
National and regional authorities will benefit from streamlined, more coherent procedures
and improved coordination, reducing duplication of work, and supporting more consistent
regulatory decisions across the Union.
The proposed measures are targeted amendments that preserve the objectives of the existing
regulations to maintain and safeguard a high level of protection of health and the
environment. Similarly, measures to prevent the misuse of biotechnologies and strengthen
EU biodefence capabilities, including monitoring AI-enabled biological risks, will ensure that
innovation is accompanied by robust safeguards for public health and security.
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letta.pdf
EN 21 EN
Furthermore, EU biotechnology businesses, and in particular those with the potential to be
transformative for the biotechnology ecosystem are expected to have improved access to
capital throughout the different stages of their development and better access to the
infrastructure needed to assess the industrial potential of their innovation, thus contributing to
a thriving biotechnology and biomanufacturing ecosystem in the EU. Strategic biotechnology
projects, which the proposal aims to foster, may also include activities addressing the growing
skills gap in biotechnology and biomanufacturing and are expected to contribute to a
workforce capable of supporting innovation, industrial scale-up and long-term
competitiveness. Investors and financial intermediaries will benefit from a more predictable
pipeline of projects and clearer regulatory certainty, supporting greater availability of risk-
tolerant capital in the EU.
The initiative will foster, in line with the Union policy and legislation on AI, the use of AI
across the biotechnology ecosystem, giving companies – and more particularly SMEs –
more guidance and opportunities to integrate trustworthy, high-quality AI solutions into
research, testing and production processes.
End-users, including patients and citizens will benefit from biotechnology products that
meet their needs. Faster time-to-market and, improved clinical-trial performance are expected
to result in earlier access to safe, effective, high-quality and affordable biotechnology
products, including advanced therapies, diagnostics, biosimilars and innovative
biomanufactured products which will also benefit healthcare systems.
Overall, these targeted measures combined are expected to (i) facilitate the growth of the EU
biotechnology and biomanufacturing industry in the EU; (ii) improve the global
competitiveness and innovation capacity of the EU’s biotechnology companies; and (iii)
increase the EU’s strategic autonomy in critical technological areas.
• Fundamental rights
The Act respects the fundamental rights and principles laid down in the Charter of
Fundamental Rights of the European Union85.
The proposed measures simplifying EU legislation and the new initiatives on EU industrial
policy are expected to contribute to the smooth functioning of the internal market and, in
particular, support the freedom to conduct a business (Article 16 of the Charter). The
measures under this proposal seek to enable innovation, expand the EU’s manufacturing
capacity and clarify procedures for biotechnologies to reach the market. The proposed
measures will also ensure a high level of human health protection and will enhance the right
of access to preventive healthcare and the right to benefit from medical treatment under the
conditions laid down by national laws and practices, as provided in Article 35 of the Charter.
Similarly, the proposal will help ensure a high level of environmental protection and improve
the quality of the environment, in line with Article 37 of the Charter.
4. BUDGETARY IMPLICATIONS
Without prejudice to the outcome of the negotiations on the next Multiannual financial
framework (MFF) proposal, strategic health biotechnology projects and high-impact strategic
85
Charter of Fundamental Rights of the European Union,
ELI: http://data.europa.eu/eli/treaty/char_2012/oj
EN 22 EN
biotechnology projects may be supported by Union programmes, funds and instruments, in
accordance with the objectives set out in the regulations establishing those funds and
programmes. A contribution is expected to come from the “health, biotechnology, agriculture
and bioeconomy” window under the European Competitiveness Fund which, according to the
proposal of the Commission, would receive a total allocation of EUR 20.4 billion over the
MFF 2028-2034. Two agencies, EMA and EFSA are proposed to be reinforced in staff and
financially to conduct tasks related to these projects. The necessary financial resources will be
compensated from applicable programmes under the agencies' headings in the 2028-2034
MFF and where possible by additional income to be generated from third parties. The
Legislative Financial and Digital Statement (LFDS) also presents estimated budgetary impact
under Heading 4 including related human and administrative resources.
5. OTHER ELEMENTS
• Implementation plans and monitoring, evaluation and reporting arrangements
In the short term, implementation will focus on completing the strategic mapping of the
Union’s biotechnology ecosystem within six months of the Regulation’s entry into force, and
on setting up the new governance and support structures, including the EU Health
Biotechnology Support Network, the Foresight Panel for Emerging Health Innovation and the
European Health Biotechnology Steering Group. To support Member States in implementing
the Regulation, to promote a uniform application of the Regulation and to clarify technical or
operational elements where needed, the Commission may issue guidance on specific matters,
including the criteria and procedures for recognising strategic health biotechnology projects
and high-impact health biotechnology strategic projects, and the coordination between the EU
Health Biotechnology Support Network and other relevant networks. Member States will be
required to designate national single points of contact and begin applying the streamlined
regulatory procedures.
Monitoring will rely on the strategic mapping as a continuous evidence base, complemented
by regularly updated information on the list of strategic health biotechnology projects and
high-impact health biotechnology projects.
In the medium term, the strategic mapping of the biotechnology ecosystem will be updated
periodically and used to inform project selection and guide the deployment of Union support.
Five years after the Regulation’s entry into application, and every five years thereafter, the
Commission will evaluate the Regulation’s effectiveness and impact, and report its findings to
the European Parliament, the Council, the European Economic and Social Committee and the
Committee of the Regions.
• Detailed explanation of the specific provisions of the proposal
Chapter I – Subject Matter, Scope and Definitions
This Chapter sets out the subject matter of this proposal, which consists of measures that
articulate its overall objective (i) to improve the functioning of the internal market by
establishing a framework to strengthen the competitiveness of the biotechnology sector, from
research to production, (ii) to create the conditions for the development and timely placing on
the Union market, of biotechnology innovations, products and services, (iii) while
safeguarding high standards for the protection of human health, animal health, patients and
consumers, the environment, ethics, quality, food and feed safety, and biosecurity. This
Chapter also specifies the scope of the proposal, which applies to health biotechnology
EN 23 EN
products and services during their entire lifecycle, including related activities on research,
funding, development, innovation, testing, validation, manufacturing, placing on the market
and use. Lastly, this Chapter establishes definitions for key terms used throughout the
proposal, including ‘biotechnology’, ‘health biotechnology’, ‘biotechnology product’,
‘biotechnology service’ and ‘biomanufacturing’.
Chapter II – Union health biotechnology and biomanufacturing
This Chapter introduces the concepts of health biotechnology strategic projects and high
impact health biotechnology strategic projects and establishes a framework for the recognition
and the support of such projects aimed at strengthening the EU’s industrial biomanufacturing
capacity and value chains. Strategic projects should mobilise and focus action at Union and
Member State level, including on public and private investments and accelerated permitting
and other support measures, to boost Europe's competitiveness and resilience in
biotechnology. To build a strong EU biotechnology ecosystem, provisions are included to
encourage pro-competitive collaboration between projects, networks and clusters. These
measures are to be underpinned by a strategic mapping of the Union’s biotechnology
ecosystem to identify capacities, gaps, dependencies and investment needs, thereby guiding
the prioritisation of strategic and high-impact projects and informing Union policy and
funding decisions. This Chapter also sets up an EU health biotechnology support network of
national and regional antennas to support biotechnology projects and innovators in navigating
regulatory procedural pathways relevant to health biotechnologies and identifying
opportunities for funding, scaling up and networking, leveraging and complementing the
activities of existing national and European networks that support SMEs, start-ups and scale-
ups, and innovators.
Finally, this Chapter establishes the European Health Biotechnology Steering Group,
composed of representatives of Member States and the Commission and its tasks, which
include facilitating communication among Member States, the Commission, and various
stakeholders to ensure biotechnology projects are recognised and implemented effectively.
Chapter III – Access to funding
This Chapter establishes an EU health biotechnology investment pilot in partnership with the
European Investment Bank Group and other implementing partners, which brings together
equity instruments and venture-style debt tailored to biotechnology-specific risk profiles, in
order to mobilise private investment into the sector. Projects contributing to an EU late-stage
Capital Booster Pilot will be recognised by the Commission as high-impact strategic health
biotechnology projects. Companies, projects and initiatives falling within the scope of this
Regulation may be considered for Union and Member State financial support, in line with
applicable State aid rules.
Chapter IV – Extension of the supplementary protection certificate
This chapter introduces an extension of 12 months of the Supplementary Protection
Certificate (SPC) for medicinal products developed by means of biotechnology processes and
for Advanced Therapy Medicinal Products. This provision aims at incentivising the
development of products developed with innovative biotechnology technologies which will
bring a therapeutic advantage to patients. This incentive will also support the clinical
EN 24 EN
development and the manufacturing of these products in the Union, subject to compliance
with applicable competition rules.
Chapter V - Enhancing competitiveness in biosimilars
This Chapter supports EU competitiveness in the field of biosimilars by encouraging the
development of EMA guidelines on facilitating the authorisation of biosimilar medicinal
products. This Chapter also includes measures supporting strategic health biotechnology
projects focused on biosimilar research, development, manufacturing and marketing
authorisation and promotes international cooperation between economic operators and
biotechnology clusters in this area, subject to compliance with applicable competition rules.
Any funding from Member States should be in line with applicable State aid rules.
Chapter VI – Artificial intelligence and data as biotechnology enablers
This Chapter aligns with the AI-first policy introduced in the Apply AI Strategy and
encourages the adoption and integration of AI in actions supporting biotechnology, in order to
foster innovation, efficiency and technological sovereignty in biotechnology and
biomanufacturing. It also provides for guidance to be issued by the EMA on the use of AI
across the medicinal-product lifecycle and creates trusted AI testing environments and data-
quality accelerators as high-impact strategic health biotechnology projects to advance safe AI-
enabled biotechnology.
Chapter VII – Regulatory tools for novel health biotechnology products
This Chapter sets out a flexible, collaborative and anticipatory approach to regulate novel
health biotechnology products by reinforcing and complementing existing mechanisms in
Union law, notably (i) those introduced in the revised Directive 2001/83/EC on the interaction
and combinations between medicinal products and medical devices, and on regulatory
sandboxes; and (ii) the mechanisms provided under the [revised] MDR, IVDR, the revised
Pharmaceutical Regulation and the SoHO Regulation, which allow for the provision of
opinions, recommendations or binding decisions on the regulatory status of products. This
Chapter lays down a Union-wide, cross-framework regulatory status repository, which will
compile relevant opinions, recommendations, decisions and guidance, thus fostering
transparency, consistency and mutual learning across Union and national authorities.
Recognising the need for anticipatory governance, this Chapter also sets up a foresight panel
for emerging health innovation to advice the Commission and conduct structured horizon-
scanning and cross-framework dialogue on forthcoming scientific and technological
developments. Lastly, this Chapter provides for the establishment of a Union level regulatory
sandbox for health biotechnology products at an early stage of development that fall outside
existing health legal frameworks.
Chapter VIII – Biodefence and preventing biotechnology misuse
This Chapter establishes a framework for preventing the misuse of biotechnology products of
concern. It includes provisions for screening, reporting, and tracking suspicious transactions
of biotechnology products of concern, and enforcement mechanisms to ensure compliance.
This Chapter sets out specific conditions for the Commission to recognise high-impact
strategic health biotechnology projects in the form of EU biodefence capability projects, that
may be given particular consideration for funding under Union basic acts, subject to
compliance with applicable State aid rules. Ultimately, the Regulation seeks to promote a high
EN 25 EN
level of protection against biotechnological threats, while fostering innovation and
competitiveness in the biotechnology sector.
Chapter IX – Amendments to Regulations (EC) No 178/2002, (EC) No 1394/2007, (EU)
No 536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938
This Chapter introduces amendments to EU legislative frameworks in the areas of health and
food and feed safety with the aim of simplifying procedures and accelerating time to market
that are necessary to ensure the effectiveness of the substantive provisions established in this
proposal by creating legislative frameworks conducive to innovation. Further, it establishes
amendments to Regulation (EU) 2024/795 (STEP Regulation)86 regarding the status of health
biotechnology strategic projects and of high impact health biotechnology strategic projects
under that Regulation.
Amendments to Regulation (EC) No 178/2002 (General Food Law)
This Regulation proposes amendments to Regulation (EC) No 178/2002 87 laying down the
general principles and requirements of food law, in order to streamline risk assessment
processes. Key changes include (i) broadening pre-submission advice to include scientific
matters, such as study design and testing strategies, while merging it with the renewal-related
advice into a single, unified procedure to simplify application procedures; (ii) shortening the
procedural delay for non-compliance with the study notification requirements at pre-
submission phase from six to three months to reduce time-to-market; (iii) requiring EFSA
staff to chair panels and serve as vice-chairs of the Scientific Committee (without voting
rights) to improve efficiency and coherence across Panels; and (iv) introducing provisions for
regulatory sandboxes, allowing Member States to test innovative technologies under
harmonised conditions that foster innovation while safeguarding consumer health and safety.
Such amendments should contribute, amongst others, to accelerating the risk assessment
process carried out by EFSA for products that are subject to pre-market authorisation in
accordance with Union food and feed law and foster innovation in the sector. As such, those
are necessary amendments with a view to ensure the effectiveness of the substantive measures
put forward in this proposal towards the strengthening of an innovative biotechnology sector
in food and feed safety.
Amendments to Regulation (EC) No 1394/2007 (Advanced Therapy Medicinal Products
Regulation)
To speed up access to advanced investigational therapy medicinal products that consist or
contain GMOs that are complex innovative products, this Regulation proposes special
provisions for facilitating related clinical trials. In this regard, it is proposedto amend
Regulation (EC) No 1394/2007 to provide that when controlling under Regulation (EU) No
536/2014 for risks from the deliberate release into the environment of GMOs, sponsors are to
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establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive
2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,
(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)
2021/241, ELI: http://data.europa.eu/eli/reg/2024/795/oj
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Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying
down the general principles and requirements of food law, establishing the European Food Safety
Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, pp. 1–24. ELI:
http://data.europa.eu/eli/reg/2002/178/oj
EN 26 EN
be exempted from the requirement to submit an environmental risk assessment in respect of
certain clearly delineated categories of advanced investigational therapy medicinal products
that consist or contain GMOs which present no or negligible risks to human health and the
environment. Sponsors of clinical trials are, however, to submit a declaration as part of the
clinical trial application that explains why the advanced investigational therapy medicinal
products concerned fall into one or more of the specific categories of products presenting no
or negligible risks to human health and the environment. The Committee for Medicinal
Products for Human Use (CHMP) referred to in Article [148] of Regulation […] [revised
Regulation No (EC) 726/2004] is to verify this declaration. For the same considerations of a
risk-proportionate approach, this Regulation also proposes that the above-mentioned
categories of advanced investigational therapy medicinal products be exempted from the
GMO related requirements of Regulation (EU) No 536/2014 regarding manufacturing and
import.
Scientific and technological advances are driving forward the development of ATMPs. To
future-proof the ATMP regulatory framework and ensure that it can encompass certain
innovative products that could benefit from the ATMP framework, without them falling under
other EU legal frameworks, the [revised Directive 2001/83/EC] empowers the Commission to
adopt delegated acts to amend the definitions laid down in the ATMP Regulation of a gene
therapy medicinal product and a somatic cell therapy medicinal product, without extending
the scope of these definitions. It should be also possible to amend the definition of a tissue
engineered product in the light of technical and scientific advancements.
Amendments to Regulation (EU) No 536/2014 (Clinical Trials Regulation)
This Chapter, critical to improving Europe’s clinical-trial framework, aims to cut approval
timelines, foster greater collaboration across borders, and improve regulatory efficiency,
without compromising safety, quality, or ethical standards. Simplification and acceleration of
procedures are necessary for ensuring the effectiveness of the enabling substantive measures
put forward in this proposal. Authorisation timelines will be shortened for multinational
clinical trials from 106 days to 75 days, including validation and ethical review. When there is
no request for information to the sponsor, timelines for initial clinical trial authorisations will
be reduced from 75 days to 47 days from submission to decision. Given the growing scientific
and regulatory expertise in ATMPs, the additional 50 days for assessing these products will be
eliminated. The assessment period for substantial modifications will be reduced from 96 days
to 47 days, with options for parallel substantial modifications. If there is no request for
information to sponsor, the timelines for the assessment of substantial modifications will be
reduced from 64 days to 33 days from submission till decision. The reporting Member State’s
role will be strengthened so that it can lead the scientific, ethical, and regulatory assessment
harnessing mutual trust between Member States and reliance on the assessment of the
reporting Member State. Communication between sponsors and Member States will be
improved during assessments. A single, core dossier for investigational products will simplify
clinical trials using the same investigational medicine and help the conduct of registration
trials and the preparation of marketing authorisation applications in Europe. Simplifications
for low-intervention clinical trials will be further supported by introducing a new category of
‘minimal-intervention’ clinical trials. Mandatory EU harmonised templates will enable
harmonisation. A single assessment process will be defined for combined studies involving
the investigation of a medicine together with a medical device or an in-vitro diagnostic. The
legal basis for processing personal data in clinical trials in accordance with Regulation (EU)
2016/679 requirements will be harmonised. Accelerated and simplified procedures will
enable multinational clinical trials to be carried out on in relation to public health
EN 27 EN
emergencies. The uptake of the use of AI systems and digitalisation in clinical trials will be
fostered. Clinical trial sandboxes will be created to test innovative approaches. Annex I to
Regulation (EU) No 536/2014 is also amended to ensure consistency with the amendments to
Regulation (EC) No 1394/2007 proposed in this Regulation, regarding certain categories of
advanced investigational therapy medicinal products containing or consisting of GMOs.
Amendments to Regulation (EU) 2019/6 (Veterinary Medicine Products Regulation)
Biological veterinary medicinal products, derived from living sources, have more complex
lifecycle and variation handling than chemically synthesised medicines. Regulation (EU)
2019/688 introduced variations not requiring assessment to reduce administrative burden,
which will be further optimised in this section without affecting quality, safety, or efficacy.
To cut administrative burden for innovations, this section foresees that the assessment of
human health and environmental impacts of veterinary medicinal products containing
genetically modified organisms should be made solely under the Environmental Risk
Assessment (ERA) pursuant to Regulation (EU) 2019/6, removing the need for assessment
under the Union GMO legislation, while reinforcing obligations under Regulation 2019/6.
The section also clarifies that administering veterinary medicinal products does not place
treated animals or their products under the Union GMO legislation. Also, the Commission is
empowered to adapt technical requirements in Annex II to Regulation 2019/6 to scientific and
technical progress. Veterinary medicinal products developed by means of biotechnology
processes to diagnose, treat or prevent zoonotic diseases are entitled to an extra year of SPC.
Finally, the introduction of regulatory sandboxes for animal health innovation will allow new
technologies, methods, or products to be tested, marketed, or used under proportionate
oversight where no specific EU legislation exists, fostering responsible innovation in
veterinary medicine
Amendments to Regulation (EU) 2024/795 (STEP Regulation)
This provision introduce amendments to Regulation (EU) 2024/795 to establish that health
biotechnology strategic projects, including high-impact health biotechnology strategic
projects recognised in accordance with this Regulation are to be deemed to contribute to the
STEP objectives referred to in Article 2 paragraph 1, point (a)(iii) or point (b) of the STEP
Regulation, as appropriate.
Amendment to Regulation (EU) 2024/1938 (SoHO)
Substances of human origin (SoHO) are a key pillar of biotechnology as they can become
starting materials for innovative medicinal products. This section introduces a regulatory
sandbox in the SoHO framework. It enables access to very innovative but regulatory
challenging therapies and products while generating insights that can inform updates to
regulatory frameworks, ensuring that they remain flexible, adaptive and fit for purpose in the
face of evolving scientific and technological advancements.
Chapter X – Final provisions
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veterinary medicinal products and repealing Directive 2001/82/EC (Text with EEA relevance), OJ L 4,
7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj
EN 28 EN
This Chapter contains provisions on (i) monitoring; (ii) delegation of power; (iii) committee
procedure, (iv) an obligation for the Commission to prepare regular reports to the European
Parliament and to the Council for the evaluation of this Regulation; (v) handling of
confidential information, and entry into force and application.
EN 29 EN
2025/0406 (COD)
Proposal for a
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on establishing a framework of measures for strengthening Union’s biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations
(EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795
and (EU) 2024/1938 (European Biotech Act)
(Text with EEA relevance)
THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,
Having regard to the Treaty on the Functioning of the European Union, and in particular
Articles 114, 168(4) and 173(3) thereof,
Having regard to the proposal from the European Commission,
After transmission of the draft legislative act to the national parliaments,
Having regard to the opinion of the European Economic and Social Committee,
Having regard to the opinion of the Committee of the Regions,
Acting in accordance with the ordinary legislative procedure,
Whereas:
(1) Biotechnology is a strategic technology central for the Union’s competitiveness,
strategic autonomy and innovation leadership. It has applications across several
sectors, with prominence in the health area. In 2021, the Union was the second largest
contributor to the global value of biotechnologies. Between 2008 and 2018, the
biotechnology industry in the Union grew more than twice as fast as the overall
economy, making it one of the fastest growing innovative industries in the Union.
Health biotechnology specifically contributes over 80% to the value of the overall
biotechnology market and it is a key driver of today’s innovative medical industry.
Biological medicines, including biosimilars count for 40% of overall pharmaceutical
sales in the Union.
(2) While recognised globally for its scientific excellence, the Union continues to face
structural challenges in translating cutting-edge research and innovation into large-
scale development, testing, manufacturing and deployment of biotechnology. As a
result, the significant potential of biotechnology applications across several sectors to
contribute to major societal challenges, modernise the Union economy and strengthen
Union strategic autonomy and security remains largely underexploited.
(3) This is due in particular to limited access to risk capital and other sources of funding,
skills shortages within the internal market, slow permitting processes that hinder the
timely deployment of projects and initiatives aiming to bring biotechnology
innovations to the market, as well as fragmented and at times complex regulatory
frameworks.
EN 30 EN
(4) To address this competitiveness gap, this Regulation should aim to improve the
functioning of the internal market by establishing a framework to strengthen the
competitiveness of the health biotechnology sector from research and innovation to
production, to create the conditions for research, development, timely placing on the
Union market and production of health biotechnology innovations, products and
services, including by simplifying and streamlining the Union legislative frameworks,
while safeguarding high standards for the protection of human and animal health,
patients, the environment, ethics, quality, food and feed safety and biosecurity.
(5) Given the importance of health biotechnology amongst the other applications of
biotechnology as referred to in recital (1), it is appropriate that this Regulation
focusses on, and sets out specific measures for, the health dimension of biotechnology.
To ensure the effectiveness of this Regulation, its scope of application should extend
to health biotechnology in a comprehensive manner and cover health within the wide
meaning of Article 168 TFEU on the protection of public health.
(6) Article 168(1) TFEU emphasises that a high level of human health protection is to be
ensured when defining and implementing all Union policies and activities. Article
168(4) TFEU clarifies that this objective is, amongst others, to be pursued through
measures setting high standards of quality and safety for medicinal products and
devices for medical use and of organs and substances of human origin, blood and
blood derivatives, measures in the veterinary and phytosanitary fields which have as
their direct objective the protection of public health.
(7) Accordingly, and in line with the One Health approach, that aims to comprehensively
and sustainably balance and optimise the health of people, animals, and ecosystems1,
this Regulation should apply to health biotechnology, understood as the application of
biotechnology in the human medical, veterinary, pharmaceutical and phytosanitary
areas for the development of biotechnology products and services. This Regulation
should apply to their entire lifecycle, including the related research, access to funding,
development, innovation, testing, validation, manufacturing, placing on the market and
use activities.
(8) With a view to ensuring the effectiveness, consistence and unity of some of the legal
acts that this Regulation should amend to foster the Union’s competitiveness in
biotechnology, this Regulation should in certain cases also apply to products and
activities other than biotechnology products and activities, so as to avoid the creation
of different sets of rules for biotechnology and non-biotechnology products and
activities. This is in particular the case in the area of health for Union legislation
regarding clinical trials, and in the food and feed safety area, for Regulation (EC) No
178/2002 of the European Parliament and of the Council2.
(9) This Regulation should apply without prejudice to the harmonised legal framework for
the development, the placing on the market, the putting into service and the use of
1
European Commission: Group of Chief Scientific Advisors and Directorate-General for Research and
Innovation, One Health governance in the European Union, Publications Office of the European Union,
2024, https://data.europa.eu/doi/10.2777/8697309 .
2
Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying
down the general principles and requirements of food law, establishing the European Food Safety
Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, p. 1.
ELI: http://data.europa.eu/eli/reg/2002/178/oj.
EN 31 EN
artificial intelligence (AI), laid down by Regulation (EU) 2024/16891689 of the
European Parliament and of the Council3.
(10) This Regulation should not affect to the application of the Directive 2010/63/EU of the
European Parliament and of the Council4 on the protection of animals used for
scientific purposes and of Regulation (EC) 2006/1907 of the European Parliament and
of the Council5.
(11) The Union has adopted other initiatives to strengthen the competitiveness of particular
sectors of the Union economy. In this regard, Regulation (EU) 2024/1735 of the
European Parliament and of the Council6 focuses on clean and resource-efficient
technologies which include, in particular, net-zero technologies. That Regulation
establishes a framework to ensure the Union’s access to a secure and sustainable
supply of net-zero technologies listed in Article 4 thereof. Such technologies include
sustainable biogas and biomethane technologies and biotechnology climate and energy
solutions. However, as acknowledged by Regulation (EU) 2024/795 of the European
Parliament and of the Council7, biotechnologies have applications beyond the clean
and resource-efficient technologies. It is therefore appropriate that this Regulation
applies without prejudice to the provisions of Regulation (EU) 2024/1735 regarding
sustainable biogas and biomethane technologies and biotechnology climate and energy
solutions.
(12) Health biotechnology strategic projects should serve as targeted instruments to
mobilise public and private investments through coordinated action among the Union,
the Member States, the industry, the research community and other relevant actors.
They should contribute to the Union’s biotechnology objectives, by strengthening
industrial capacity and value chains, scaling up critical research and technology
infrastructures, accelerating innovation and technology deployment such as New
Approach Methodologies (NAMs), or advanced data and digital platforms.
Accordingly, this Regulation should lay down provisions for the recognition and
support of such projects by the Member States and should establish criteria for such
3
Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying
down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No
167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives
2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (OJ L, 2024/1689,
12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj).
4
Consolidated text: Directive 2010/63/EU of the European Parliament and of the Council of 22
September 2010 on the protection of animals used for scientific purposes (Text with EEA relevance).
ELI: http://data.europa.eu/eli/dir/2010/63/2019-06-26
5
Consolidated text: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18
December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals
(REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing
Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council
Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and
2000/21/EC (Text with EEA relevance). ELI: http://data.europa.eu/eli/reg/2006/1907/2025-09-01.
6
Regulation (EU) 2024/1735 of the European Parliament and of the Council of 13 June 2024 on
establishing a framework of measures for strengthening Europe’s net-zero technology manufacturing
ecosystem and amending Regulation (EU) 2018/1724 (Text with EEA relevance), OJ L 1735 28.6.2024,
p. 1. ELI: http://data.europa.eu/eli/reg/2024/1735/oj.
7
Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024
establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive
2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,
(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)
2021/241 (OJ L, 2024/795, 29.2.2024. ELI: http://data.europa.eu/eli/reg/2024/795/oj).
EN 32 EN
recognition. With a view to facilitate the implementation and ensure a consistent
approach across the Union, the Commission could issue guidance on the application of
those criteria. Recognition of health biotechnology strategic projects would deliver
clear benefits for the most innovative businesses by accelerating permitting, reducing
administrative burden, improving legal certainty and facilitating access to financial
support. It would thus strengthen their capacity to scale biotechnology innovations
faster. For authorities, the framework streamlines coordination, avoids duplication of
assessments, and supports consistent, efficient decision-making.
(13) NAMs applied in biological research, early discovery, preclinical development, and
the regulatory and quality testing of medicinal products and medical technologies,
have the potential to generate scientific and technological data that are comparable to,
or in some cases more informative and generated more rapidly than, those obtained
through current standard methods. The resulting advantage will contribute to
strengthen the innovation ecosystem and enhanced European competitiveness in
biotechnology.
(14) Certain health biotechnology strategic projects have the potential to contribute to the
Union’s objectives in biotechnology in a manner that is systemic and can produce a
multiplier effect. Such projects act as catalysts for cooperation between academia,
industry and public authorities, and can serve as anchors for regional biotechnology
clusters and innovation ecosystems across Member States. Experience in several
Member States has shown that such projects can quickly raise industrial capability,
attract investment and strengthen the Union’s position in global value chains.
Accordingly, such projects should be recognised as high impact health biotechnology
strategic projects by the Commission and could be given particular consideration for
Union funding, priority access to administrative support and fast-tracked procedures at
Member State level. As regards national funding of such projects, Regulation (EU)
2024/7958 provides measures for the support of critical and emerging strategic
technologies and their respective value chains within programmes implemented under
shared management. That Regulation amends the basic acts of several shared-
management funds, namely Regulations (EU) 2021/10569, (EU) 2021/105710 and
(EU) 2021/1058 of the European Parliament and of the Council11 , in order to enable
Member States to steer their national and regional programmes towards investments in
critical technologies, including biotechnologies. Without prejudice to the applicable
rules governing each such funding instrument, and in line with applicable State aid
rules, this approach may therefore be applied to high-impact health biotechnology
strategic projects, which are deemed in accordance with this Regulation as to
contribute to the STEP objectives.
8
Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024
establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive
2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,
(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)
2021/241, ELI: .
9
Regulation (EU) 2021/1056 of the European Parliament and of the Council of 24 June 2021 establishing
the Just Transition Fund (OJ L 231, 30.6.2021, p. 1, ELI: http://data.europa.eu/eli/reg/2021/1056/oj).
10
Regulation (EU) 2021/1057 of the European Parliament and of the Council of 24 June 2021 establishing
the European Social Fund Plus (ESF+) and repealing Regulation (EU) No 1296/2013 (OJ L 231,
30.6.2021, p. 21, ELI: http://data.europa.eu/eli/reg/2021/1057/oj).
11
Regulation (EU) 2021/1058 of the European Parliament and of the Council of 24 June 2021 on the
European Regional Development Fund and on the Cohesion Fund (OJ L 231, 30.6.2021, p. 60, ELI:
http://data.europa.eu/eli/reg/2021/1058/oj).
EN 33 EN
(15) The strategic importance of biotechnology for European competitiveness has already
been established, including through the proposed a European Competitiveness Fund
(ECF) for the Multiannual Financial Framework (MFF) period 2028-2034, which
includes a dedicated ‘Health, Biotech, Agriculture and Bioeconomy’ window. The
Draghi Report on the Future of European Competitiveness12 recommends that the
Union should focus resources on a limited number of world-class centres of excellence
in life sciences and biotechnology. High impact biotechnology health strategic projects
have the potential to contribute to this focus of efforts and be a tool for an impactful
use of resources in the MFF period 2028-2034, to help position the Union among the
leading regions for biotechnology. Examples of categories of such high impact
projects and specific criteria should be established for their recognition by the
Commission. Amongst those categories, high impact health biotechnology strategic
projects in the form of biotechnology development accelerators providing, amongst
others, trusted testing or demonstration facilities replicating real-world
biomanufacturing processes, should play a key role in translating Europe’s scientific
excellence into productive industrial capacity. By pooling advanced equipment and
expertise and offering criteria-based access, including for small and medium-sized
enterprises, start-ups and scale-ups, such projects should reduce duplication of efforts,
lower entry barriers, and foster the specialised skills required for advanced
biomanufacturing. Similarly, high impact health biotechnology strategic projects in the
form of centres of excellence for advanced therapies, including for advanced therapy
medicinal products, should combine research, regulatory science and manufacturing
capabilities, enabling faster, safer and more efficient development of innovative
therapies. When connected to digital and data infrastructures, they should have the
potential to accelerate clinical translation, improve quality control and facilitate patient
access across the Union.
(16) To maximise the Union-wide benefits of investments made in projects or entities
operating infrastructures, facilities and services supported and established or
recognised in accordance with this Regulation, such projects or entities should provide
open, non-discriminatory, transparent and criteria-based access to users from all
Member States, including academic institutions, industrial undertakings, with
particular attention to SMEs, start-ups and scale-ups, and public research bodies.
Access conditions should be proportionate and ensure fair treatment among users,
taking into account the objectives and capacity of each infrastructure, the need to
guarantee equitable opportunities for SMEs, start-ups and scale-ups, and research
actors, and appropriate safeguards to protect security, confidentiality, intellectual
property and economic-security interests.
(17) Effective implementation of objectives pursued in this Regulation relies on good
governance and partnership between all actors at the relevant territorial levels and
socio-economic actors. In particular, biotechnology strategic projects aimed at
targeting talent and skills shortages vital to supporting biotechnology and
biomanufacturing industries and to ensuring a workforce capable to supporting
innovation, industrial scale-up and long-term competitiveness should be designed and
developed with the full involvement of the relevant social partners. Such active
engagement is essential to ensure that social implications are addressed from the outset
and to foster responsible innovation.
12
Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,
European Commission, 9 September 2024.
EN 34 EN
(18) Directive (EU) 2022/2555 of the European Parliament and of the Council13 lays down
obligations for essential and important entities to ensure a high common level of
cybersecurity throughout the Union, including requirements on risk management,
incident reporting and the protection of network and information systems. Therefore,
entities established or supported under this Regulation and falling within the scope of
the Directive (EU) 2022/2555 should comply with the requirements set out in that
Directive.
(19) In order to safeguard the Union’s security, public order and strategic interests, access
to biotechnology infrastructures and datasets of health biotechnology strategic projects
and of high impact health biotechnology strategic projects recognised in accordance
with this Regulation and that receive funding in accordance with Union programmes,
in relation to such infrastructures or datasets, should be governed by the rules
established in those programmes. This addresses risks linked to unlawful technology
transfer, hostile interference or strategic dependency.
(20) To provide an evidence base for future Union action to further strengthen the
biotechnology and biomanufacturing sectors, the Commission should carry out a
strategic mapping of the Union’s biotechnology ecosystem. That mapping should
analyse industrial capacities, infrastructures and facilities relevant to biotechnology
research, development, testing and manufacturing, and assess factors affecting the
Union’s ability to attract and retain investment in biomanufacturing, including access
to public and private risk-tolerant capital across all stages of the innovation cycle, the
development and coordination of biotechnology clusters and biomanufacturing
ecosystems across the Union, and assess challenges and needs in terms of the
workforce.
(21) Recognising the transformative role of data and AI in the area of biotechnology and
biomanufacturing, that mapping should also assess access to data, computing capacity
and digital infrastructure for the health biotechnology sector and identify measures to
foster responsible AI-enabled biotechnology innovation and possible measures to
mitigate related risks, building on analyses done in the context of existing Union
initiatives such as the European Health Data Space14 , the Apply AI Strategy15, the
Data Union Strategy16, the AI Continent Action Plan17 and the European Strategy for
AI in Science18. With a view to ensuring appropriate cooperation with the Member
States and optimising the use of relevant knowledge and expertise available at Union
13
Directive (EU) 2022/2555 of the European Parliament and of the Council of 14 December 2022 on
measures for a high common level of cybersecurity across the Union, amending Regulation (EU) No
910/2014 and Directive (EU) 2018/1972, and repealing Directive (EU) 2016/1148 (NIS 2 Directive), OJ
L 333, 27.12.2022, pp. 80. ELI: http://data.europa.eu/eli/dir/2022/2555/oj.
14
Regulation (EU) 2025/327 of the European Parliament and of the Council of 11 February 2025 on the
European Health Data Space and amending Directive 2011/24/EU and Regulation (EU) 2024/2847 (OJ
L, 2025/327, 5.3.2025, ELI: http://data.europa.eu/eli/reg/2025/327/oj).
15
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions: Apply AI Strategy, COM(2025)723
final of 8 October 2025.
16
Communication from the Commission to the European Parliament and the Council, Data Union
Strategy, Unlocking Data For AI, COM(2025) 835 final, 19 November 2025.
17
https://ec.europa.eu/newsroom/dae/redirection/document/114523
18
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions: European Strategy for Artificial
Intelligence in Science – Harnessing AI for research, innovation and excellence in the Union,
COM(2025)724 final of, 8 October 2025.
EN 35 EN
level, such mapping should be conducted by the Commission in cooperation with
relevant Union agencies and bodies, including, where relevant, the AI Board
established under the Regulation (EU) 2024/1689, and with the European Health
Biotechnology Steering Group (‘the Steering Group’) established in accordance with
this Regulation, to facilitate its implementation, provide advice to the Commission and
to the Member States, and ensure coordinated action in particular with regard to health
biotechnology strategic projects and high impact health biotechnology strategic
projects.
(22) In order to ensure a transparent, coherent and efficient process for the identification of
health biotechnology strategic projects, each Member State should designate a
competent authority responsible for assessing and verifying whether a project fulfils
the conditions set out in this Regulation for its recognition as a health biotechnology
strategic project. The designated authority should carry out the assessment through a
fair, transparent and time-bound process. Where a project is found to fulfil the
conditions for recognition as a biotechnology strategic project, the designated
authority should issue a formal recognition decision.
(23) Considering their systemic and cross-border relevance and the benefits associated with
their status as high impact health biotechnology strategic project, the recognition of
such projects should take place through a two-tier process, involving authorities
designated by the Member States for that purpose and the Commission. Such
authorities should assess and transmit the applications and their assessment to the
Commission in view of the adoption of a Commission decision. This two-tier process
should ensure that such projects are subject to an additional Union-level verification
and benefit from consistent recognition standards across the Union. With a view to
ensure peer review, cooperation with the Member States and coherent implementation
across the Union, in adopting its decision the Commission should take into account the
views of the European Health Biotechnology Steering Group established by this
Regulation.
(24) With a view to enabling the efficient alignment between the Union funding procedures
and the objectives of this Regulation regarding the support to high impact strategic
health biotechnology projects, and to ensure that projects with the highest Union
added value can rapidly benefit from priority support, in addition to the recognition of
such projects through a Commission decision, the Commission could have the
possibility to recognise such projects also in the context of calls for proposals
launched under the relevant Union funding programmes.
(25) To achieve critical mass and ensure that strategic investments deliver wider benefits,
creating positive spill-over effects that reinforce the Union’s competitiveness,
networking and cooperation among health biotechnology strategic projects, high
impact health biotechnology strategic projects, research organisations, industrial
clusters and other relevant actors across borders, should be promoted and facilitated by
the Commission and the Member States, with a view to help pooling national and
Union resources and facilities, promote the development of interoperable
infrastructures and digital platforms and facilitate knowledge transfer. This
cooperation should be in compliance with Union competition law.
(26) Such networking and cooperation should integrate, collaborate with, or build upon,
existing networks emerging from other Union initiatives relevant for biotechnology,
including those operating under the European Cluster Collaboration Platform, the
European Cluster Alliance, networks supported under Horizon Europe, the Smart
EN 36 EN
Specialisation Partnerships, and the European Network of Centres of Excellence for
Advanced Therapy Medicinal Products (ATMPs) announced by the Commission in
the European Strategy for Life Sciences19, the European Reference Networks as
defined in Directive 2011/24/EU of the European Parliament and of the Council20 and
the EU Network of Comprehensive Cancer Centres announced by Europe’s Beating
Cancer Plan21. Such cooperation should aim to reinforce synergies, facilitate access to
regional and Union level funding, and enhance the coordination of biotechnology-
related innovation ecosystems across the Union.
(27) In order to reduce complexity and increase efficiency, transparency and consistency in
the permit-granting process for health biotechnology strategic projects and high impact
health biotechnology strategic projects, there should be a single point of contact at
national level that is responsible for facilitating and coordinating the entire permit-
granting process. The single point of contact should be the interface between the
promoters of health biotechnology strategic projects or of high impact health
biotechnology strategic projects and the relevant permitting authorities. To that end,
Member States should establish or designate one or more authorities as single points
of contact. With a view to ensure streamlined processes, that single point of contact
should be the same as the single point of contact referred to in Regulation (EU) ../..
[Regulation on speeding-up environmental impact assessmentsc - permitting
regulation], responsible for facilitating and coordinating all aspects of the
environmental assessments. It should be for Member States to decide whether a single
point of contact is also an authority that makes permitting decisions. To ensure the
effective implementation of their responsibilities, Member States should provide their
single points of contact, as well as any authority involved in the permit-granting
process with sufficient personnel and resources.
(28) The Union has progressively recognised health biotechnology as a strategic sector
contributing to Union’s overall resilience. Regulation (EU) 2024/795 identifies
biotechnology among the strategic technologies essential for reducing the Union’s
strategic dependencies and strengthening its economic and industrial resilience. The
Commission Communication Commission Communication ‘Building the future with
nature: Boosting Biotechnology and Biomanufacturing in the EU’ further identifies
biotechnology and biomanufacturing as strategic technologies for Europe’s
competitiveness, resilience and autonomy, and furthermore explicitly recognises that
health biotechnology is essential for health-system resilience. In view of this
consistent Union framework confirming biotechnology’s systemic contribution to
resilience, health biotechnology strategic projects and high impact health
biotechnology strategic projects should therefore be deemed to contribute to the
objectives referred to in Article 14 of Regulation […] [Regulation on speeding-up
environmental assessments – permitting regulation].
19
Communication from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions, A strategy for European life
sciences: Choose Europe for life sciences – A strategy to position the EU as the world’s most attractive
place for life sciences by 2030, COM(2025) 525 final of 2 July 2025.
20
Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the
application of patients’ rights in cross-border healthcare, OJ L 88, 4.4.2011, pp. 45–65.
ELI: http://data.europa.eu/eli/dir/2011/24/oj.
21
Communication from the Commission to the European Parliament and the Council, Europe's Beating
Cancer Plan, COM/2021/44 final of 3 February 2021.
EN 37 EN
(29) In light of their contribution to the Union’s competitiveness, resilience and
preparedness, health biotechnology strategic projects recognised by the Member States
in accordance with this Regulation should be considered to be in the public interest.
Similarly, Member States should grant such projects the highest national significance
available under their national law, meaning the strongest designation applicable to
major strategic projects, and should apply the corresponding procedural advantages,
including priority treatment and coordinated and accelerated permit-granting, and
adopt facilitation measures in compliance with Union law.
(30) In view of the potential for cross-border and systemic benefits of high impact health
biotechnology strategic projects, on the basis of its case-by-case assessment, a
permitting authority can conclude that the public interest served by the project
overrides the public interests related to nature and environmental protection and that
consequently the project can be authorised, provided that all relevant conditions set
out in Directives 2000/60/EC22, 2009/147/EC23 or 92/43/EEC24 of the European
Parliament and of the Council, or in Union legislative acts on nature restoration, are
met.
(31) To ensure predictability and administrative efficiency, the overall duration of the
permit-granting process should be limited to ten months from the acknowledgement of
a complete application, for biotechnology health strategic projects, and to eight
months, for high impact health biotechnology strategic projects, given the need to
prioritise the speed of their implementation over any other type of biotechnology
project. In exceptional and duly justified circumstances an extension of up to three
months should be permitted.
(32) Member States whose territories are concerned by health biotechnology strategic
projects or high impact health biotechnology strategic projects should take all
appropriate measures to facilitate their timely and effective development and
deployment. Such measures should include the provision of administrative support,
upon the request of project promoters, as well as, without prejudice to Union
competition law, of public financial and technical support, with a particular attention
paid to SMEs, start-ups and scale-ups.
(33) The Commission should complement the action of the Member States in support of
health biotechnology strategic projects, closely cooperating with them, including
through the European Health Biotechnology Steering Group established by this
Regulation, to ensure synergy and optimal outcomes. In particular, the Commission
should assist project promoters in identifying relevant funding opportunities available
under existing Union funding programmes, including through actions of the EU Health
Biotechnology Support Network established in this Regulation with the purpose of
assisting biotechnology actors in navigating regulatory health biotechnology
procedural pathways and identifying funding, scaling up and networking opportunities
across the Union. Further, to strengthen the Union’s biotechnology innovation
ecosystem, the Commission should also promote measures that enhance access of
22
Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a
framework for Community action in the field of water policy, OJ L 327, 22.12.2000, p. 1. ELI:
http://data.europa.eu/eli/dir/2000/60/oj.
23
Directive 2009/147/EC of the European Parliament and of the Council of 30 November 2009 on the
conservation of wild birds, OJ L 20, 26.1.2010, pp. 7-25. ELI: http://data.europa.eu/eli/dir/2009/147/oj.
24
Council Directive 92/43/EEC of 21 May 1992 on the conservation of natural habitats and of wild fauna
and flora, OJ L 206, 22.7.1992, p. 7. ELI: http://data.europa.eu/eli/dir/1992/43/oj
EN 38 EN
small and medium-sized enterprises, start-ups and scale-ups to research and
technological infrastructures, including those funded through Union programmes.
(34) High impact health biotechnology strategic projects should benefit from financial,
technical and administrative support measures. In addition, in order to ensure that
Union resources for biotechnology are channelled towards the actions that have the
potential to deliver the most benefits at Union level, high impact health biotechnology
strategic projects could be given particular consideration for financial support, in the
context of the preparation, adoption and implementation by the Commission of work
programmes for the relevant Union programmes, funds and instruments.
(35) The scale and nature of the Union support for high impact health biotechnology
strategic projects might require long-term coordination and large-scale public and
private investment. In this context, public-private partnerships play a key role in
pooling expertise, sharing risks and accelerating the uptake of innovation.
Consequently, the Commission could envisage to propose in the future the
establishment of appropriate legal entities to mobilise investments, coordinate research
and innovation activities and support for the industrial deployment of biotechnology
and biomanufacturing capacities across Member States, while ensuring close
alignment with Union policy objectives. Those legal arrangements could take the form
of European Partnerships where the Union together with private and/or public
partners, acting in full compliance with competition rules, commit to jointly
supporting the development and implementation of a programme of activities,
including those related to market, regulatory or policy uptake.
(36) With a view to ensuring that the most favourable provisions apply cross-frameworks,
the provisions of this Regulation regarding the permit granting process, the priority
status of health biotechnology strategic projects and of high impact health
biotechnology strategic projects and the administrative, technical or financial support
for such projects should apply without prejudice to more favourable provisions laid
down in other Union legislation.
(37) Biotechnology undertakings, especially SMEs, start-ups and scale-ups, and non-profits
face challenges in navigating the regulatory processes, financing, scaling up and
networking opportunities in the Union. To address those challenges, the Commission
should manage, coordinate and support an EU Health Biotechnology Support
Network, composed of national and regional antennas, leveraging and complementing
existing structures such as the European Enterprise Network. The Network should
assist developers and project promoters, in particular SMEs, start-ups, and scale-ups,
in navigating more efficiently the legislative framework, health biotechnologies
regulatory pathways and funding opportunities at Union and national level. Moreover,
the EU Health Biotechnology Support Network should provide support for health
biotechnology strategic projects and enhanced assistance for high impact health
biotechnology strategic projects. The Commission should make available to the
Network an AI powered interactive tool to assist developers and project promoters, in
particular SMEs, start-ups, and scale-ups, in navigating more efficiently the regulatory
framework and pathways and funding opportunities at EU and national level.
(38) The European Health Biotechnology Steering Group (‘the Steering Group’) should be
established to provide advice to the Commission and to the Member States with a view
to facilitate the implementation of this Regulation, foster cooperation with the
Commission and among the Member States, and the exchange of best practice. The
EN 39 EN
Steering Group should be composed of representatives from all Member States and the
Commission.
(39) Member States should provide to the Steering Group, on an annual basis, an overview
of the health biotechnology strategic projects and of the high impact health
biotechnology strategic projects that they recognise, as well as of the existing and
emerging cooperation initiatives and networks among such projects. Such overview is
aimed at informing monitoring of progress in the implementation of this Regulation,
supporting coordination and proposals of measures to enhance the Union’s
biotechnology and biomanufacturing ecosystem and facilitate exchange of best
practices. In such overview, Member States should identify progress, obstacles and
best practices.
(40) To ensure effective governance and learning across the Union, the Steering Group
should periodically review systemic challenges in the financing and deployment in
particular for high impact health biotechnology strategic projects and recommend
corrective measures to the Commission and to Member States.
(41) Given the capital-intensive nature of biotechnology and the high probability of non-
commercialisation of individual projects, access to finance is a structural bottleneck
for the sector. To boost the potential of biotechnology to contribute to the Union’s
competitiveness, resilience and the creation and maintenance of quality jobs, sufficient
funding tailored to the sector’s risk profile needs to be mobilised across the financing
life cycle.
(42) To address key challenges in the functioning of Union capital markets, the
Commission is implementing the Savings and Investment Union (SIU) Strategy. The
SIU will reduce market fragmentation, create better investment opportunities for
citizens and help to expand funding options for businesses. In particular, it will seek to
improve access to equity and debt financing for all companies, including startups and
scaleups, strengthen the role of venture capital and institutional investors and better
align Union public funding instruments with SIU objectives. Recent Commission
guidance on legislative programmes25 also clarifies that the biotechnology sector can
be the target of Union, national and regional legislative programmes via reference to
the Competitiveness Compass, supporting favourable prudential treatment of
investments made under such programmes.
(43) The Union’s biotechnology sector faces a persistent financing gap compared with
other leading regions, particularly for the scale-up and industrial deployment stages.
The Union has been acting to address this, including through the flagship InvestEU
programme established by Regulation (EU) 2021/523 of the European Parliament and
of the Council26. InvestEU supports biotechnology investments in a transversal
manner, enabling investment in biotechnology projects and enterprises targeting all
stages of development, including start-up to scale-up stages as well as deployment.
The recent agreement between the Council and the European Parliament on enhancing
the InvestEU programme increases the Union guarantee by EUR 2.9 billion unlocking
nearly EUR 55 billion in additional public and private investments, including
investment into biotechnology. Overall, InvestEU has already mobilized EUR 7.5
25
C(2025) 7231 final
26
Regulation (EU) 2021/523 of the European Parliament and of the Council of 24 March 2021
establishing the InvestEU Programme and amending Regulation (EU) 2015/1017, OJ L 107, 26.3.2021,
pp. 30–89. ELI: http://data.europa.eu/eli/reg/2021/523/oj.
EN 40 EN
billion of biotechnology investments. During the 2026-2027 period, mobilization of at
least EUR 4 billion of additional biotechnology investments is expected. InvestEU
implementing partners play a key role in helping to stimulate investment in
biotechnology projects and enterprises. Both the EIB as well as EIF support
biotechnology – including health biotechnology – via several InvestEU financial
products. HERA Invest further boosts investments in health biotechnology. The
project pipeline is strengthened through InvestEU advisory, supporting initiatives such
as the European Tech Championship Initiative of the European Investment Bank.
(44) Complementing the European Innovation Council support for deep tech and
disruptive innovators in the area of biotechnology, an EU Health Biotechnology
Investment Pilot to mobilise public and private investment and strengthen the Union’s
competitiveness and resilience should be created in partnership with the European
Investment Bank Group (EIBG) or other implementing partners, for implementation in
indirect management, linking equity and guarantee instruments with venture debt
tailored to biotech-specific risk profiles.
(45) The Health Biotechnology Investment Pilot would aim to mobilise a substantial
amount of capital, from the EIBG, Union budget, public national schemes and private
sector investors (including institutional investors), to narrow the sector investment
gap, currently estimated at EUR 40 billion annually, amounting to EUR 400 billion for
the next 10 years, and ensure the sector's long term competitiveness and strategic
autonomy.
(46) The Health Biotechnology Investment Pilot should be tailored to biotechnology risk
profiles and lifecycle needs on the Union market. It should be possible to include
newly created and established instruments, encompassing advisory services, direct and
indirect individual investments, direct and indirect intermediated financing or portfolio
financing. The detailed instruments, eligibility and risk parameters, and indicative
allocations should be specified in the operational design of the Pilot.
(47) The Pilot may receive Union financial support through Union programmes. Pending
the establishment of the Pilot, a scheme, also covering ongoing investment activities,
launched with the support of the EIBG under the current Multiannual Financial
Framework 2021-2027 and supported under the InvestEU programme, will mobilise
up to 10 billion in investments in the biotechnology sector in 2026 and 2027 .
(48) Union public equity markets for biotechnology remain shallow relative to global peers,
which constrains late-stage financing and exit options for European start-ups and
scale-ups. Stock exchanges are still largely fragmented across Member States, with
limited specialised research coverage and dedicated market-making, prompting
European scale-ups to list abroad. To address this bottleneck for a competitive Union
biotechnology sector and complement the SIU strategy, which seeks to promote
integration and increase the depth of Union capital markets, projects contributing to a
Union late-stage capital booster pilot should be recognised by the Commission as
high-impact health biotechnology strategic projects in accordance with the conditions
laid down in this Regulation.
(49) Biotechnology is central for the Union’s sovereignty, strategic autonomy and
innovation leadership. In this regard, the Union is taking action to pursue its policy
objectives in biotechnology, including through the Framework Programme for
Research and Innovation established by Regulation (EU) 2021/695 of the European
EN 41 EN
Parliament and of the Council27 which is supporting the implementation of the Life
Sciences Strategy, and other relevant ‘Choose Europe’ initiatives.
(50) The Commission has proposed a European Competitiveness Fund (ECF)28 for the
MFF period 2028-2034, aiming to increase European competitiveness, notably in
strategic sectors and technologies along the investment journey. It is proposed to be
structured along four policy windows reflecting strategic priorities crucial to Union
competitiveness and resilience. It proposes funding to support the biotechnology
sector through a ‘Health, Biotech, Agriculture and Bioeconomy’ window.
(51) Companies, projects and initiatives falling within the scope of this Regulation could be
given particular consideration for financial support from Union led initiatives,
including those that aim to leverage private capital, and from Union funding
programmes and instruments, as projects in a strategic technology and, where
appropriate, in a strategic deep tech area. Such initiatives, programmes and
instruments include the cohesion policy programmes, the InvestEU programme, the
EIBG’s TechEU programme and the European Tech Champions Initiative, supported
by InvestEU, and launched by the EIBG with several Member States, and the
European Innovation Council established under the Horizon Europe Programme, as
well instruments for the duration of the MFF 2028-2034.
(52) Further, high-impact health biotechnology strategic projects are projects with a high
European added value, including cross-border projects, expected to bring structural
economic transformation, productivity, long-term growth and quality jobs in the
biotechnology sector, and benefiting the Single Market. Considering the necessity to
align Union, public and private spending with Union competitiveness priorities29, such
projects could be given particular consideration for Union financial support including
in the form of blended financing, under Union programmes, funds and financial
instruments.
(53) Regulation (EU) 2024/795 establishes that the development and manufacturing in the
Union of biotechnologies, together with digital technologies and deep tech innovation,
clean and resource-efficient technologies are essential for the purpose of reducing the
Union’s strategic dependencies, and for the green and digital transitions, thus ensuring
the sovereignty and strategic autonomy of the Union and promoting the
competitiveness and sustainability of the Union’s industry. Accordingly, that
Regulation establishes a Strategic Technologies for Europe Platform (STEP) to better
channel and mobilise resources within the existing Union programmes towards critical
investment, including in Union-wide and cross-border projects, that have the aim of
supporting the development or manufacturing of critical and emerging technologies
and their respective value chains, in strategic sectors, including in biotechnology.
27
Regulation (EU) 2021/695 of the European Parliament and of the Council of 28 April 2021 establishing
Horizon Europe – the Framework Programme for Research and Innovation, laying down its rules for
participation and dissemination, and repealing Regulations (EU) No 1290/2013 and (EU) No
1291/2013, OJ L 170, 12.5.2021, pp. 1. ELI: http://data.europa.eu/eli/reg/2021/695/oj.
28
As per Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE
COUNCIL on establishing the European Competitiveness Fund ('ECF’), including the specific
programme for defence research and innovation activities, repealing Regulations (EU) 2021/522, (EU)
2021/694, (EU) 2021/697, (EU) 2021/783, repealing provisions of Regulations (EU) 2021/696, (EU)
2023/588, and amending Regulation (EU) [EDIP].
29
Commission Staff Working Document, Impact Assessment Report on the European Competitiveness
Fund, SWD(2025) 555 final.
EN 42 EN
(54) Union-level funding may be leveraged to facilitate investments in health
biotechnology strategic projects and high impact health biotechnology strategic
projects recognised in accordance with this Regulation. Such projects may benefit
from access to existing Union funding instruments, where they fulfil the criteria
established in those instruments. Authorities in charge of the Union programmes
covered by Regulation (EU) 2024/795 should consider supporting biotechnology
health strategic projects and high impact health biotechnology strategic projects
recognised in accordance with this Regulation. Therefore, Regulation (EU) 2024/795
should be amended to provide that health biotechnology strategic projects and high-
impact health biotechnology strategic projects recognised in accordance with this
Regulation should be deemed to contribute to the STEP objectives of supporting the
development or manufacturing of critical technologies in biotechnologies throughout
the Union, or safeguarding and strengthening their respective value chains and also in
addressing shortages of labour and skills critical to all kinds of quality jobs in support
of that objective, as appropriate.
(55) Member States may provide financial support to biotechnology as a strategic
technology for the Union’s innovation capacity, sovereignty, resilience and leadership,
including in the implementation of the relevant Union programmes. In this regard,
Member States should act in compliance with Union competition law and make use as
appropriate of the relevant frameworks. This includes the criteria for the analysis of
the compatibility with the internal market of State aid to promote the execution of
important projects of common European interest30 (IPCEIs), the guidance on the basis
of a compatibility assessment conducted by the Commission regarding aid to promote
research, development and innovation31, the Commission Regulation (EU) No
651/201432 and the Clean Industrial Deal State Aid Framework33.
(56) Strategic projects in health biotechnology may require blended financing from private,
national and Union sources. National funding should be in full compliance with State
Aid rules. The Commission, including through the European Biotechnology Support
Network, should support project promoters in liaising with potential investors.
Similarly, the European Health Biotechnology Steering Group established by this
Regulation should coordinate financing for biotechnology health strategic projects and
high-impact health biotechnology strategic projects.
(57) Medicinal products developed with innovative biotechnology technologies which will
bring a therapeutic advantage to patients should be incentivised with an extension of
the Supplementary Protection Certificate.
(58) The significant advances in analytical methodologies and biocompatibility assessment
tools enable more precise demonstration of comparability between biosimilar
medicines (‘biosimilars’) and their reference biological medicinal products. Building
30
Communication from the Commission Criteria for the analysis of the compatibility with the internal
market of State aid to promote the execution of important projects of common European interest 2021/C
528/02, C/2021/8481, OJ C 528, 30.12.2021, pp. 10.
31
Communication from the Commission Framework for State aid for research and development and
innovation 2022/C 414/01, C/2022/7388, OJ C 414, 28.10.2022, pp. 1.
32
Commission Regulation (EU) No 651/2014 of 17 June 2014 declaring certain categories of aid
compatible with the internal market in application of Articles 107 and 108 of the Treaty Text with EEA
relevance, OJ L 187, 26.6.2014, pp. 1. ELI: http://data.europa.eu/eli/reg/2014/651/2023-07-01.
33
COMMUNICATION FROM THE COMMISSION – Framework for State Aid measures to support the
Clean Industrial Deal (Clean Industrial Deal State Aid Framework), C/2025/7600, OJ C, C/2025/3602,
4.7.2025.
EN 43 EN
on its ongoing work on a Reflection paper on a tailored clinical approach in biosimilar
development34, the European Medicines Agency35 (‘the Agency’) should develop non-
binding guidance giving consideration to a potential reduction of the clinical data
required for the development and marketing authorisation procedures for biosimilars,
based on robust analytical and other non-clinical evidence.
(59) The manufacturing capacity and expertise for biosimilars in the Union can greatly
contribute to ensure Union competitiveness, strategic autonomy and resilience, both
from a health and sustainability perspective. Therefore, Member States should
recognise, and support projects that fulfil the conditions laid down in this Regulation
for strategic projects for biosimilars manufacturing.
(60) Biosimilars can play an important role in diversifying and strengthening supply chains,
promoting competition and fostering economic growth in the Union and for its global
partners. Accordingly, the promoters of strategic projects for biosimilars and the
companies active in this area should be encouraged to establish or strengthen
cooperation with international biotechnology clusters.
(61) AI can enhance the development, safety, efficiency and scale-up of biotechnology and
biomanufacturing, provided that its use is responsible and aligned with Union
legislation. To pursue this, the Commission and the Member States should promote an
AI-first policy approach as introduced in the Apply AI Strategy when implementing
this Regulation and the exchange of knowledge, standards and best practices relevant
to the responsible application of the AI-First Policy Approach36. The responsible and
effective integration of AI can enhance research, development and regulatory
processes and thereby support the competitiveness of Union innovators in
biotechnology. The Commission and the Member States should therefore encourage
the uptake of such approaches and facilitate the exchange of knowledge, standards and
best practices relevant to their application. That cooperation should remain fully
compliant with Union competition rules.
(62) The rapid expansion and increasing complexity of AI applications throughout the
medicinal-product lifecycle requires structured and coherent guidance to ensure their
safe, effective and trustworthy use. The Agency is developing expertise in this area
through initiatives such as the Good Manufacturing Practice (GMP) Annex 22 –
Artificial Intelligence, Q&A in AI in Pharmacovigilance, the GCP Annex to the
Guideline on computerised systems and electronic data in clinical trials and AI in
Clinical Development. It is therefore appropriate for the Agency to develop non-
binding guidance on the deployment and use of systems based on advanced
technologies, including of AI systems and of general-purpose AI models across
development, manufacturing, clinical trials, and post-authorisation activities for
compliance with applicable Union legislation in the health area. To ensure consistency
34
EMA Reflection paper on a tailored clinical approach in biosimilar development, 17 March 2025, draft
accessible at: https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-
approach-biosimilar-development_en.pdf
35
[Revised REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL laying
down Union procedures for the authorisation and supervision of medicinal products for human use and
establishing rules governing the European Medicines Agency, amending Regulation (EC) No
1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation
(EC) No 141/2000 and Regulation (EC) No 1901/2006]
36
Communication from the Commission to the European Parliament and the Council, Apply AI Strategy,
COM/2025/723 final.
EN 44 EN
across the health and digital domains, when developing or updating such guidance, the
Agency should cooperate with the Commission, including the AI office and should
consult relevant national competent authorities and stakeholders, and relevant expert
coordination groups established under Union legislation in the health and digital areas,
as appropriate.
(63) Moreover, the Agency should develop non-binding guidance on the deployment and
use of AI systems and of general-purpose AI models also in the procedures for the
authorisation of medicinal products, with a view to optimising processes and
increasing efficiency of regulatory activities. Such guidance should be developed and
published in agreement with the Commission, the AI Board and the competent
authorities.
(64) In order to accelerate the development and scale-up of biotechnology innovations that
are enabled, enhanced or significantly supported by AI and advanced computational
methods, the Union requires dedicated testing environments that combine
experimental, computational and data-driven capabilities. Given their essential role for
supporting AI-enabled biotechnology innovations, it is appropriate to establish
requirements in this Regulation for the recognition by the Commission and the support
for high-impact health biotechnology strategic projects in the form of biotechnology
testing environments, under certain conditions.
(65) Such environments could provide the wet-lab, bioprocess, pilot-line and translational
validation capacities necessary for AI-enabled biotechnology development, and should
complement, without duplicating, the functions of regulatory sandboxes established
under Union or national law as well as the testing and experimentation facilities
established in accordance with Regulation (EU) 2024/1689. Where relevant, they
should also leverage health data and the European Health Data Space in accordance
with Union legislation. These infrastructures should support the development of
biotechnology applications where the use of AI has the potential to accelerate
progress, in particular in health-related areas such as advanced therapies, where AI can
improve efficacy and safety — for example through optimised CRISPR site
prediction, tumour antigen identification, sequence engineering, delivery-vehicle
design, or the matching of diverse patient cancer-cell variants with CAR-T cell types.
(66) Having high-quality, interoperable, provenance-verified and well-annotated datasets is
essential for the development, testing and validation of trustworthy and competitive AI
systems and models used in biotechnology applications. For example, datasets
generated in the course of provision of healthcare are usually recorded in a way that
supports their initial purpose, such as diagnosis or treatment. Often, they are
technically not easily usable and fit for training, testing and validation of AI systems,
for example due to the use of different data standards or lacking annotations. Given the
potential of AI systems and models to support research and innovation in
biotechnology applications, it is important to ensure that high-quality data are
available for training, testing and validating AI systems and models used in health
biotechnology applications. To make such data more easily usable for those purposes,
it is appropriate to facilitate the enhancement of the quality of that data. Therefore, this
Regulation should lay down provisions for the recognition by the Commission of high
impact health biotechnology strategic projects in the form of biotechnology data
quality accelerators, to provide assistance to entities that lawfully hold relevant data to
improve data quality, standardize such data and make further improvements.
EN 45 EN
(67) Such biotechnology data quality accelerator projects should complement Union
initiatives such as data labs37 and by addressing the specific data-quality requirements
of biotechnology, ensuring that biological and health datasets are reliable,
interoperable and usable for the development of advanced AI models.
(68) The processing of personal data by the entities that lawfully hold the relevant data and
by the biotechnology data quality accelerators, in the context of biotechnology data
quality accelerators projects, takes place in the public interest. The Commission
should specify in the decision recognising the project as a high impact health
biotechnology strategic project, the specific provisions concerning the processing of
personal data necessary in order to achieve the objectives of the project. Such
provision may in particular include the categories of data, the specific roles of the
parties engaged in the processing, and the entities to which the personal data may be
disclosed. Where biotechnology data quality accelerators are recognised by the
Commission through calls for proposals, the Commission should be empowered to
adopt, by means of an implementing act, specific provisions concerning the processing
of personal data, through a decision prior to the launch of the call and the beneficiaries
of the call should be subject to the obligations laid down in that decision.
(69) Electronic health data referred to in Article 51 of Regulation (EU) 2025/327 of the
European Parliament and of the Council38, enhanced by biotechnology data quality
accelerators should be made available in accordance with that Regulation. The
biotechnology data quality accelerators support the objectives of the European Health
Data Space by contributing to improving the quality of data that is to be made
available under that space.
(70) To enable innovation and competitiveness in biotechnology, it is necessary to ensure
that SMEs, start-ups and scale-ups, and research organisations can access the high
computing capacity and AI resources required for advanced research, development and
biomanufacturing. Those actions may be supported through Union funding
programmes, funds and financial instruments, in accordance with the regulations
governing them. The Commission should ensure effective coordination with other
Union initiatives offering computing capacities to maximise efficiency and avoid
duplication. The Commission, including through the European Biotechnology Support
Network, should provide information and support, in particular to SMEs, start-ups and
scale-ups, for accessing high computing capacity and AI resources relevant to
biotechnology and biomanufacturing activities.
(71) Very innovative health biotechnology products or services vary significantly in the
degree to which they align or can align with existing Union legislative frameworks
and procedures. These products, despite their complexity, should however be
efficiently and adequately assessed within a single regulatory pathway, possibly
through a combination pathway. This is notwithstanding the fact that such health
biotechnology products or services, in the form of preparations, devices, diagnostics,
or other, for human use, exhibit characteristics that challenge the Union legislative
37
Proposed in the Communication from the Commission to the European Parliament, the Council, the
European Economic and Social Committee and the Committee of the Regions, A European Strategy for
Artificial Intelligence in Science – Paving the way for the Resource for AI Science in Europe (RAISE),
COM(2025) 724 final of 8 October 2025.
38
Regulation (EU) 2025/327 of the European Parliament and of the Council of 11 February 2025 on the
European Health Data Space and amending Directive 2011/24/EU and Regulation (EU) 2024/2847, OJ
L, 2025/327, 5.3.2025, ELI: http://data.europa.eu/eli/reg/2025/327/oj .
EN 46 EN
frameworks in the area of health (‘health biotechnology products’), for example
because they are under development and could potentially fall under the scope of an
Union legislative framework but there are questions related to the relevance of other
Union legislative frameworks; and/or because they combine different products,
technologies, processes, or components regulated under different Union legislative
frameworks; and/or because they require targeted adaptations of certain requirements
of the applicable Union legislative frameworks, ideally at an early stage of
development. These characteristics are not mutually exclusive and may overlap.
(72) Developers of such health biotechnology products can consequently face regulatory
uncertainty, potentially delaying or preventing patient access to beneficial
technologies and creating barriers to innovation and access to finance, hampering
competitiveness. To offer developers efficient and predictable regulatory procedural
pathways, the Union legislative frameworks in the health area should be equipped with
the right tools and should integrate consultative and collaborative approaches, to be
able to assess these health biotechnology products efficiently and timely. In addition,
developers of health biotechnology products should be supported in navigating
regulatory procedural pathways for their products in the best possible way. This
Regulation should therefore provide for measures and facilitators to ensure efficient
pathways to developers with reduced time-to-market, while safeguarding all existing
provisions to protect public health.
(73) At the same time, the Union has the strong experience and expertise to handle
regulatory complexity, and important measures to deal with health biotechnology
products have already been proposed. Directive 2001/83/EC of the European
Parliament and of the Council39 clarifies which legislative frameworks apply to
combinations of medicinal products and other products and establishes a single
authorisation pathway for them. In addition, existing Union legislative frameworks in
the area of health such as [revised Regulation (EU) 2017/745 of the European
Parliament and of the Council, [revised Regulation (EU) 2017/746], [revised
Regulation No (EC) 726/2004], Regulation (EU) 2024/1938 of the European
Parliament and of the Council40 contain specific mechanisms to manage the
determination of the regulatory status of products that do not fall clearly within a
Union legislative framework in the area of health. These mechanisms include the
possibility of requesting a recommendation or opinion from the respective advisory
bodies or the Agency, as applicable, at Union level, and eventually the possibility for
binding decisions of the Commission on the regulatory status. These mechanisms
should ensure predictability and conclusive opinions for products of which the status is
being debated, avoiding cases where it remains unclear which framework applies, and
the assessment of the product is consequently halted or delayed.
(74) Developers of health biotechnology products, in particular SMEs, start-ups and scale-
ups, often lack the regulatory expertise and capacity needed to identify, anticipate and
plan their entry into the appropriate regulatory procedural pathways. In order to
39
Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the
Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67, ELI:
http://data.europa.eu/eli/dir/2001/83/oj.
40
Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on
standards of quality and safety for substances of human origin intended for human application and
repealing Directives 2002/98/EC and 2004/23/EC (OJ L, 2024/1938, 17.07.2024, ELI:
http://data.europa.eu/eli/reg/2024/1938/oj).
EN 47 EN
address this challenge, the EU Health Biotechnology Support Network, acting as a
service provider, should provide preliminary support to such developers by facilitating
information on, and access to, applicable legislative frameworks, and should point to
relevant opinions, recommendations, guidance and decisions.
(75) To allow developers to anticipate and navigate procedures to determine the regulatory
status, a Union-wide and cross-framework Regulatory Status Repository should be
established. That Repository should compile relevant opinions, recommendations,
decisions and guidance developed under the mechanisms established in the Union
legislative frameworks in the area of health with a view to determine the regulatory
status of a product. That Repository should also include the recommendations on the
classifications of products as advanced therapy medicinal products (ATMPs) issued by
the Committee for Advanced Therapies, established in accordance with Regulation
(EC) No 1394/2007 of the European Parliament and of the Council 41 prior to the date
of application of Regulation (EC) No 726/2004. Such repository should be accessible
for developers and authorities to enable them to understand how similar health
biotechnology products are evaluated in terms of status, and what considerations are
put forward. This will guide developers and authorities, to improve efficiency, foster
transparency, and ensure consistency and mutual learning across Union and national
authorities. This Regulatory Status Repository should not include opinions,
recommendations, decisions and guidance on the regulatory status of AI systems and
models within the scope of the Regulation (EU) 2024/1689.
(76) Existing mechanisms for addressing health biotechnology products, including those
for determining their regulatory status as described above, provide for consultation
among various advisory bodies and the Agency. However, such procedures are
typically focused on individual products on a case-by-case basis. There is, therefore, a
need for more systematic coordination across Union legislative frameworks to better
identify and prepare for emerging innovations driving the development of health
biotechnology products that may challenge existing Union legislative frameworks in
the area of health. With an expected increase in health biotechnology products entering
the regulatory system, there is a growing need for horizontal foresight anticipating
technological developments through structured horizon-scanning activities which will
enable the regulators to adopt regulatory approaches proactively, rather than reactively
addressing each new difficult case.
(77) To that end, this Regulation should establish a Foresight Panel for Emerging Health
Innovation to complement existing mechanisms by providing a platform for horizontal
coordination and forward-looking analysis. The Panel should conduct horizon
scanning to identify emerging technologies at an early stage and discuss cross-cutting
regulatory issues, thereby informing and anticipating discussions on health
biotechnology products that may subsequently arise within individual frameworks. It
should provide expertise on emerging science and technology in the field of health
underpinning the development of health biotechnology products to the Commission,
the Agency and to relevant Union-level advisory bodies and competent authorities and
other entities in the Member States in the area of health.
41
Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007
on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No
726/2004, OJ L 324, 10.12.2007, p. 121. ELI: http://data.europa.eu/eli/reg/2007/1394/oj.
EN 48 EN
(78) This Panel should complement, without replacing, existing classification
mechanisms established under the respective Union legislative frameworks, which
remain exclusively competent to provide opinions, recommendations or binding
determinations on the regulatory status of specific products. Member States, as
authorities primarily responsible for decisions on regulatory status, should be closely
involved in the Panel’s work, sharing practical expertise and experience to inform
cross-framework dialogue, support harmonisation efforts, and designate experts that
bring the Member State perspective.
(79) Health biotechnology products increasingly challenge Union legislation in the area of
health and necessitate further flexibility of that legislation, in
particular regarding health biotechnology products that could be candidates for
regulatory sandboxes under such frameworks. The development and implementation
of those sandboxes can clearly benefit from effective consultation across the
authorities responsible for regulatory sandboxes falling within the scope of Union
legislative acts other than this Regulation. By facilitating the exchange of information
and experiences between sandboxes, including on regulatory approaches,
technological challenges, and emerging scientific understanding, the Union can
develop more coherent and responsive regulatory responses to health biotechnology
products. The activities of sandboxes should be carried out in full compliance of
antitrust information exchanges provisions under Union competition law. The
Foresight Panel for Emerging Health Innovation could play a role in promoting such
coherence and knowledge sharing.
(80) The Commission should be able to establish regulatory sandboxes for health
biotechnology products which are at a very early stage of development and do not fall
within the scope of existing Union legislative acts in the area of health, thus not being
in a position to benefit from the regulatory sandboxes established in accordance with
those other acts. Those sandboxes should provide a controlled environment in which
to explore and assess innovative technologies. The sandboxes should operate
according to a specific sandbox plan that specifies the duration of the sandbox, risk
mitigation measures and supervision arrangements. For the development and
implementation of the sandbox plan for such products, the Commission may consult
advisory bodies and Agencies established under the Union legislative acts in the area
of health for example to determine which requirements or rules laid down in those acts
could, or could not, be applied to the products concerned. The outcome of the sandbox
would be a recommendation by the Commission on an existing appropriate regulatory
procedural pathway for authorising the product in question. The lessons learned from
those sandboxes should lead to reflections on possible regulatory actions to be taken at
Union level for the products or categories of products concerned. Accordingly, this
approach would provide a flexible Union response to emerging innovations while
building an evidence base for potential future legislative developments.
(81) Biotechnologies are critical for the Union’s defence and security. Closer coordination
between civil and defence research, development and manufacturing can accelerate
safe innovation and reduce fragmentation. Therefore, this Regulation should make
provisions for the recognition by the Commission and support of projects contributing
to an EU Biothreat Radar as high impact health biotechnology strategic projects,
subject to conditions established in this Regulation.
(82) Furthermore, this Regulation should make provisions for the recognition by the
Commission and support of high impact biodefence capability projects, as part of the
category of high impact health biotechnology strategic projects, subject to conditions
EN 49 EN
laid down in this Regulation. Such projects should make a significant contribution to
objectives such as the prevention or mitigation of the misuse of biotechnologies. As
such, those projects should benefit from priority status in administrative procedures in
accordance with this Regulation and could be given particular consideration for
support under national and Union funding programmes and instruments, including
from those budgets allocated to defence.
(83) Without prejudice to Member States’ competences and in accordance with the Union
funding programmes and instruments, biotechnology activities relevant to defence,
security, safety, preparedness, and resilience, including dual-use technologies could
be given particular consideration, where appropriate, for support under the European
Defence Fund, the Union Research Framework Programmes and other Union funding
instruments.
(84) Moreover, where national authorities so decide, expenditure on such dual-use
infrastructures and related biodefence activities may be counted toward relevant
defence spending targets.
(85) The biotechnology landscape is evolving at an unprecedented speed, driven by
advances in synthetic biology and genome editing, which, coupled with AI, make
biotechnology stand at the forefront of innovation, offering unprecedented
opportunities for advancing health and protecting against biological threats. These
advances also make biotechnological misuse faster, cheaper, and more accessible.
Biotechnologies can pose serious and distinctive risks that call for continuous
assessment and anticipatory safeguards. Therefore, a limited set of biotechnology
products with significant potential for misuse (‘biotechnology products of concern’)
require a specific framework to prevent and protect against their misuse.
(86) Union and international rules address certain aspects related to biological threats,
biological incidents or biological risks, in particular in relation to serious cross-border
threats to health42, the control of exports, brokering, technical assistance, transit and
transfer of dual-use items43, resilience in biosafety and biosecurity through the
Biological and Toxin Weapons Convention (BTWC)44, the Chemical Weapons
Convention (CWC), the contained use of genetically modified micro-organisms45,
workers’ protection from risks related to exposure to biological agents at work 46, in
relation to AI systems and models through Regulation (EU) 2024/1689. However, the
42
Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on
serious cross-border threats to health and repealing Decision No 1082/2013/, p. 26.
ELI: http://data.europa.eu/eli/reg/2022/2371/oj.
43
Regulation (EU) 2021/821 of the European Parliament and of the Council of 20 May 2021 setting up a
Union regime for the control of exports, brokering, technical assistance, transit and transfer of dual-use
items , OJ L 206, 11.6.2021, pp. 1. ELI: http://data.europa.eu/eli/reg/2021/821/oj.
44
Council Decision (CFSP) 2023/2636 of 20 November 2023 amending Decision (CFSP) 2021/2072 in
support of building resilience in biosafety and biosecurity through the Biological and Toxin Weapons
Convention, no longer in force. OJ L, 2023/2636, 22.11.2023, ELI:
http://data.europa.eu/eli/dec/2023/2636/oj
45
Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained
use of genetically modified micro-organisms (Recast) (Text with EEA relevance), OJ L 125, 21.5.2009,
p. 75. ELI: http://data.europa.eu/eli/dir/2009/41/oj.
46
Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the
protection of workers from risks related to exposure to biological agents at work (seventh individual
directive within the meaning of Article 16(1) of Directive 89/391/EEC), OJ L 262, 17.10.2000, p. 21.
ELI: http://data.europa.eu/eli/dir/2000/54/oj.
EN 50 EN
approach remains fragmented and does not sufficiently address all aspects related to
the misuse related to biotechnologies. A consistent and high level of protection
throughout the Union should therefore be ensured in order to guarantee biotechnology
remains trustworthy and provides legal certainty for economic operators in the
biotechnology sector.
(87) There are divergent requirements in Member States for screening, verification,
reporting and tracking of suspicious transactions for biotechnology products of
concern, which includes benchtop equipment and sequences of concern. This lack of
harmonisation creates additional costs for economic operators, especially for those
with strong security systems in place, and might distort competition within the internal
market as well as potentially create barriers to trade and innovation.
(88) A Union framework for strengthening monitoring of the potential misuse of
biotechnology products of concern is therefore needed and requested by industry
actors, including SMEs, to safeguard the free movement of goods and ensure a level
playing field in the internal market. This framework needs to take into account recent
international developments and good practices in other jurisdictions and relevant
industry consortia and standard-setting fora, including to promote interoperability for
Union operators active globally and providing for a level playing field in the internal
market.
(89) To ensure that oversight remains proportionate and appropriately calibrated to the
risks, and in line with existing Union harmonisation legislation, the complementary
harmonisation measures established in this Regulation to prevent misuse should only
apply to a limited subset of biotechnology products of concern which pose the highest
risk of misuse, and whose misuse has the highest consequences, such as certain
sequences of concern or benchtop nucleic synthesis equipment able to create such
sequences of concern. For the purposes of legal clarity and certainty, such products
should be listed in Annex I to this Regulation. As biotechnology will continue to
rapidly evolve, the Union framework should remain flexible and capable of
responding to emerging biotechnology products, materials, and scientific evidence
regarding potential risks. Therefore, the Commission should be empowered to adopt
delegated acts to amend Annex I to respond swiftly to scientific and security
developments and in consultation with relevant experts including the Advisory Group
on Biosecurity established under this Regulation, while following the existing
international and other relevant regulatory frameworks
(90) The Union framework should be comprehensive to apply to the making available to,
introduction, or use of, biotechnology products of concern, by any natural or legal
person in the Union as well as to the making available to any natural or legal person
outside the Union.
(91) To reduce risks at the point of sale within the Union, economic operators should verify
the legitimate need and peaceful purposes of prospective customers before making
available the biotechnology products of concern included in Annex I to this
Regulation.
(92) Apart from economic operators, other natural and legal persons that are not economic
operators, including researchers, laboratories, universities, or research institutes, may
also make available and use biotechnology products of concern. Such persons should
be subject to the same screening obligations as economic operators, while preserving
freedom of research and academic freedom in accordance with Article 13 of the
Charter of Fundamental Rights of the European Union and Article 179 of the Treaty
EN 51 EN
on the Functioning of the European Union, except where knowledge and material are
shared with persons employed within the same legal entity. Biotechnology products of
concern should not be made available to members of the general public.
(93) Benchtop nucleic acid synthesis equipment poses a particular challenge to the
verification of legitimate need and the tracking and monitoring of sequences of
concern. Such equipment should therefore contain an automatic mechanism to screen
for sequences of concern.
(94) This Regulation should lay down provisions requiring economic operators to report
suspicious transactions throughout the supply chain, regardless of whether the
prospective customer is a member of the general public or an economic operator,
private or public, and should apply in relation to biotechnology products that are
considered of concern provided the risk or threat they may pose, which includes
certain sequences of concern and biotechnology products. Reporting and recording for
three years the suspicious transactions would allow other operators to be aware of the
risks of the concerned product, while avoiding duplicate reporting, and allowing
authorities to monitor and assess the risks and verify compliance with the obligations
laid down in this Regulation.
(95) Suspicious transactions should be detected and reported rapidly through harmonised
procedures, with Member States designating national contact points that provide clear
reporting channels, as well as record data and ensure compliance, with a view to
contributing to safeguarding national and Union’s safety.
(96) Where a biotechnology product of concern falls also under categories regulated under
other Union legislation, to avoid duplication of reporting, where a suspicious
transaction of that biotechnology product of concern has already been reported under
one legal framework, it should not be reported again.
(97) Licensed biotechnology products containing nucleic acid sequences, including
authorised medicinal products for human and veterinary use, should not be subject to
verification of legitimate need, as they have undergone regulatory assessment and do
not constitute independent biological threats. However, the stand-alone nucleic acid
sequences in synthetic form should fall within the scope of legitimate-need screening,
as they may be misused and be relevant to biosecurity oversight.
(98) Certain tools with a potential to be misused without further modification and to cause
serious harm to public health and safety, agricultural crops and other plants, to
animals, the environment, material or government security (dual-use research of
concern - ‘DURC’) are increasingly affordable and accessible, also through progress
in AI capabilities, which elevates the risk of misuse by actors lacking appropriate
competence, oversight, legitimate or peaceful intent. A proportionate and risk-based
framework is therefore necessary to minimise opportunities for misuse of DURC,
including on AI models in biological applications, while preserving legitimate
research and innovation.
(99) Supervision by the public authorities is needed to ensure that research, innovation and
commercial operations are conducted responsibly and securely. This in turn can build
public trust in biotechnology. Effective supervision requires adequately resourced and
trained national inspection authorities with adequate investigative powers,
complemented by risk-based audits to verify the effectiveness of the screening
obligations laid down in this Regulation, as well as training and awareness-raising for
the staff of the designated inspection authorities and stakeholders, and regular
EN 52 EN
exchanges among inspection authorities and economic operators, including operators
involved in online marketplaces. Moreover, Member States should lay down rules on
penalties applicable to infringemens of the provisions laid down in this Regulation
regarding the prevention of biotechnology misuse. Such penalties should be effective,
proportionate and dissuasive.
(100) The Commission should monitor Member States in the enforcement of this legislation,
including by requesting information and records to check the screening and suspicious
transaction reporting frameworks of economic operators.
(101) Considering the evolving biosecurity landscape and the misuse risks of biotechnology
products of concern, this Regulation should establish an Advisory Group on
Biosecurity (‘the Advisory Group’) to monitor the landscape of biological risks and
alert the Commission when it identifies new biotechnology products of concern. The
Advisory Group should complement the work of existing expert groups in health
security. It should be composed of globally leading independent scientists. Its
members should be selected and operate in accordance with the Commission Decision
of 30 May 2016 establishing horizontal rules on the creation and operation of
Commission expert groups. The members of the Advisory Group should be appointed
by the Commission based on up-to-date scientific or technical expertise in the area of
biosecurity, biodefence and AI.
(102) AI offers significant potential to enhance the Union’s competitiveness and innovation
capacity, including in the area of biotechnology. This potential should be realised in a
safe and responsible manner. In this regard, Regulation (EU) 2024/1689 lays down
harmonised rules for placing on the market putting into service and use of AI systems
and models in the Union, prohibitions of certain AI practices, harmonised
transparency rules for certain AI systems, rules on market monitoring, market
surveillance, governance and enforcement as well as measures to support innovation.
AI systems and general-purpose AI models can lower the barrier for actors to misuse
biotechnology. The provisions of Regulation (EU) 2024/1689 governing AI systems
and general-purpose AI models aim to mitigate this. Further, AI models, as described
in Regulation (EU) 2024/1689, used in biological applications, that are not covered by
Regulation (EU) 2024/1689 (‘AI models in biological applications’) can also pose
risks, including different types of systemic biological risks.
(103) AI models in biological applications encompass both specialised tools and more
general models trained on large datasets of biological sequences that can be adapted
for a variety of downstream tasks. Such models in biological applications can aid in
the development of novel, more dangerous biological threats, increasing the ceiling of
harm of biotechnology misuse. Capabilities of such AI models in biological
applications therefore need to be monitored, investigating and assessing risks to
identify any models posing biological systemic risks and ensuring necessary risk
mitigation measures are taken. In addition, systemic resilience would need to improve
to prevent, detect and respond to any misuse incidents.
(104) The Advisory Group should therefore monitor the capabilities of AI models in
biological applications, working closely with scientists and companies developing
such models and should be tasked to issue a qualified alert to the Commission if it
identifies that an AI model in biological applications not covered by Regulation (EU)
2024/1689 poses biological systemic risk. The Advisory Group should inform the
Scientific Panel of independent experts established under Article 68 of Regulation
(EU) 2024/1689, if it has reasonable grounds to suspect that an AI model covered by
EN 53 EN
that Regulation poses biological systemic risks. That panel could in turn issue a
qualified alert to the AI Office in accordance with Regulation (EU) 2024/1689.
Considering that the AI Office established by Commission Decision C(2024) 39047
has as its mission to develop Union expertise and capabilities in the field of AI and to
contribute to the implementation of Union law on AI, that office should participate in
the establishment of the Advisory Group.
(105) The European Health Biotechnology Steering Group established by this Regulation
should also ensure proper coordination and information exchanges among Member
States on the enforcement of the biosecurity provisions in this Regulation, consulting
the Advisory Group, other relevant existing bodies and external experts where
appropriate.
(106) This Regulation should establish a framework of measures, in particular for health
biotechnology strategic projects and high impact health biotechnology strategic
projects, to ensure the growth of the health biotechnology sector. This Regulation and,
in particular, the measures in Chapters II to VIII, should serve the aim of creating and
reinforcing favourable conditions for health biotechnology, from research and
development to the timely placing on the Union market and production of
biotechnology innovations and products. The pathway to placing on the the market of
health biotechnology innovations and products are governed by important and
comprehensive sets of regulatory rules and procedures. Reviewing and streamlining
these rules and procedures is an inherent part to achieve the aim of facilitating and
accelerating the development, placing on the market and production of health
biotechnology innovations and products. The practical effectiveness of the measures of
this Regulation, in particular those in Chapters II to VIII, depends to a large extent on
a review and streamlining of certain rules and procedures applicable to health
biotechnology innovations and products so as to facilitate timely access to the market.
As set out in recitals [5 to 7], health biotechnology must be understood broadly and
encompasses also the veterinary and phytosanitary fields which have as their direct
objective the protection of public health.
(107) For instance, a timelier and facilitated risk assessment process for products subject to
pre-market authorisation in accordance with Union food law, accelerated procedures
and measures facilitating innovation, such as measures on regulatory sandboxes are
needed for the efficiency of the facilitation measures laid down in this Regulation.
(108) Regulation (EC) No 178/2002 lays down the general principles and requirements of
food law, so as to form a common basis for measures governing food law at both
Union and national level. For the purposes of risk assessment at Union level, it
establishes the European Food Safety Authority (‘the Authority’), as the responsible
Union risk assessment body in matters primarily relating to food and feed safety.
(109) Considering the increasing prevalence of diet-related health issues, it is essential to
expand the Authority’s mandate to encompass all aspects of nutrition and to enable it
to provide advice concerning the nutritional properties of food products and practices,
including those derived from advanced biotechnological processes.
(110) It has been observed that a significant number of application and notification dossiers
submitted to the Authority are either incomplete or do not meet the applicable
47
Commission Decision of 24.1.2024 establishing the European Artificial Intelligence Office C(2024)
390.
EN 54 EN
regulatory and scientific specifications requirements to enable the best quality
scientific assessment by the Authority, resulting in the need for requests for additional
information during the risk assessment process and, consequently, leading to
sometimes significant delays. This is also the case where biotechnology innovations
and products are concerned, as such products would benefit strongly from pre-
submission scientific advice on study design and testing strategies. Applicants or
notifiers of such products, in particular small and medium-sized enterprises do not
always have a clear understanding of the applicable regulatory and scientific
requirements when compiling application dossiers, in particular as regards the types
and details of studies to conduct. It is thus appropriate to enlarge the scope of the
general pre-submission advice provided by the Authority at the request of a potential
applicant or notifier to encompass non-committal advice on regulatory aspects
including applicable rules and guidance documents, as well as scientific advice on
study design and testing strategies. This advice should be provided by the staff and
experts of the Authority to ensure the most updated scientific advice. Given the
broadening of the scope of the general pre-submission advice which is already
available for both new and renewals of approvals/authorisations, it is no longer
necessary to provide for a specific pre-submission advice for renewals.
(111) Practice has shown that the existing procedural consequences in the event of non-
compliance with the notification requirement of commissioned studies at pre-
submission phase appear to be too severe, particularly for small and medium-sized
enterprises, and could impede competitiveness and innovation in the food chain. It is
therefore necessary to shorten the existing procedural consequence in the event of non-
compliance from six months to three months following the re-submission of the
relevant application or notification.
(112) In order to strengthen the coherence of risk assessments carried out by different
Scientific Panels within the Authority, foster stronger synergies and promote greater
harmonisation across guidance documents and scientific opinions, for the benefit of
applicants while enhancing the effectiveness and efficiency of the Authority’s risk
assessment processes, it is appropriate that the staff of the Authority chairs the
Scientific Committee and the Scientific Panels, without voting rights. The Scientific
Committee should continue to be composed by experts.
(113) The food and feed sector is experiencing rapid technological advancements, including
biotechnology, AI, smart farming techniques, development of new approach
methodologies, that could contribute to reduction of animal testing and circular
economy practices promoting resource efficiency and waste reduction. It is therefore
appropriate to provide Member States with the possibility of setting up regulatory
sandboxes that can provide an environment for the testing of those innovations in a
controlled manner, incentivising research and development, whilst allowing for
adaptive regulatory practices that can be modified based on feedback and results from
live trials. Regulation (EC) No 178/2002 should therefore be amended accordingly.
(114) Given the diversity of sectors covered by Union food law, and the fact that Member
States have diverse food systems, cultural preferences, local market conditions, and
research and risk assessment bodies, regulatory sandboxes should be established a
national level in order to ensure the necessary flexibility to allow for experimentation
specifically tailored to address local needs, preferences, and consumer behaviours. For
the same reasons, and in order to support innovation along the whole food chain,
regulatory sandboxes should be allowed also at retail level and, thus, making available
products under the regulatory sandboxes to food business operators or consumers
EN 55 EN
should not be considered as placing on the market. However, in order to ensure that
the establishment of regulatory sandboxes does not jeopardise food safety or
consumers’ information and that they are established and function in such a way as to
enable the collection of sound and useful information to inform future regulatory
changes, rules should be laid down concerning the objectives pursued within
regulatory sandboxes, the modalities for their adoption, amendment and revocation,
the control of the activities carried out under the regulatory sandbox, monitoring and
reporting as well as rules ensuring the protection of human and animal health and of
the environment.
(115) Regulatory sandboxes should not be allowed for some products. Experience has shown
that certain types of novel foods trigger ethical or cultural concerns among various
consumer segments regarding their acceptability. Since those aspects are best
addressed within the applicable rigorous regulatory framework established by
Regulation (EU) 2015/2283 of the European Parliament and of the Council48, it is
appropriate to exclude novel foods from the scope of regulatory sandboxes. For GMOs
legal pathways exist to allow testing of innovations, such as under Part B of Directive
2001/18/EC on the deliberate release of genetically modified organisms (GMOs) for
purposes other than placing on the market, and there should not be a duplication of
paths in order to maintain legal certainty. For this reason, regulatory sandboxes should
be restricted to products containing or consisting of GMOs subject to authorisation
under Part C of Directive 2001/18/EC. As regards innovations concerning novel
plastic recycling technologies for plastics intended to come into contact with food,
chapter IV of Commission Regulation (EU) 2022/161649 already establishes a
framework that is meant to encourage the development of such novel technologies
without prior authorisation. To ensure uniform rules on the development of novel
recycling technologies that safeguard the health of the consumers, it is appropriate to
exclude the development of recycling technologies from the possible use of regulatory
sandboxes and rely instead on the procedure established in chapter IV of Regulation
(EU) 2022/1616.
(116) To ensure uniform conditions and principles for the setting up, operation and
supervision of Regulatory sandboxes, implementing powers should be conferred on
the Commission in the context of Regulation (EC) No 178/2002. Those implementing
powers should be exercised in accordance with Regulation (EU) 182/2011 of the
European Parliament and of the Council50. In case of emergencies, the Commission
may provisionally adopt an measures in accordance with an urgency procedure
requesting the suspension of the regulatory sandbox concerned.
48
Regulation (EU) 2015/2283 of the European Parliament and of the Council of 25 November 2015 on
novel foods, amending Regulation (EU) No 1169/2011 of the European Parliament and of the Council
and repealing Regulation (EC) No 258/97 of the European Parliament and of the Council and
Commission Regulation (EC) No 1852/2001 (OJ L 327, 11.12.2015, p. 1, ELI:
http://data.europa.eu/eli/reg/2015/2283/oj).
49
Commission Regulation (EU) 2022/1616 of 15 September 2022 on recycled plastic materials and
articles intended to come into contact with foods, and repealing Regulation (EC) No 282/2008 (OJ L
243, 20.9.2022, p. 3, ELI: http://data.europa.eu/eli/reg/2022/1616/oj).
50
Regulation (EU) No 182/2011 of the European Parliament and of the Council of 16 February 2011
laying down the rules and general principles concerning mechanisms for control by Member States of
the Commission’s exercise of implementing powers (OJ L 55, 28.2.2011, p. 13, ELI:
http://data.europa.eu/eli/reg/2011/182/oj).
EN 56 EN
(117) Considering the additional financial burden established on the Authority with the
expansion of its mandate following the amendments set out in this Regulation, the
possibility of establishing fees in order to fully or partially fund EFSA’s new tasks
could be considered.
(118) Clinical trials with advanced investigational therapy medicinal products (ATMPs),
including those consisting or containing genetically modified organisms (GMOs)
within the meaning of Article 2 of Directive 2001/18/EC of the European Parliament
and of the Council51, can provide early access to transformative treatments for patients
with rare or otherwise untreatable conditions and are important to prepare for the
marketing authorisation of the medicinal products for such treatments. The nature and
design of certain advanced investigational therapy medicinal products is such that the
risks to human health and the environment resulting from a deliberate release of a
GMO into the environment are, in practice, either excluded or negligible. For example,
in viral vectors, which are genetically modified viruses used to deliver genetic material
into cells, the wild-type virus genome is largely removed resulting in replication-
defective recombined particles. As these particles cannot reproduce themselves, they
present at most a negligible risk to human health and the environment.
(119) Consequently, when controlling under Regulation (EU) No 536/2014 for risks from
the deliberate release into the environment of GMOs, a risk-proportionate approach
should be applied and Regulation (EC) No 1394/2007 should be amended with respect
to certain, clearly delineated categories of advanced investigational therapy medicinal
products that consist or contain GMOs, which present no or negligible risks to human
health and the environment. Whilst it is appropriate to exempt such clearly delineated
categories of advanced investigational therapy medicinal products from the
requirement to submit an environmental risk assessment, sponsors of clinical trials
should, however, submit a declaration as part of the clinical trial application that
explains why the advanced investigational therapy medicinal products concerned falls
into one or more of the specific categories of products presenting no or negligible risks
to human health and the environment. The Committee for Medicinal Products for
Human Use (CHMP) referred to in Article [148] of Regulation […] [revised
Regulation No (EC) 726/2004] should verify this declaration. For the same
considerations of a risk-proportionate approach, the above-mentioned categories of
advanced investigational therapy medicinal products should also be exempted from the
requirements of Regulation (EU) No 536/2014 regarding manufacturing and import.
Annex I to the Regulation (EU) No 536/2014 should also be amended to ensure
consistency with the aforementioned amendments to the Regulation (EC) No
1394/2007.
(120) Scientific and technological advances are driving the development of advance therapy
medicinal products (ATMPs). To future proof the ATMPs legislative framework, the
power to adopt delegated acts should be delegated to the Commission to amend
Regulation (EC) No 1394/2007, by clarifying the definition, without extending its
scope, of what constitutes a tissue engineered product, in light of technical and
scientific advancements in the field of ATMPs. To that effect, the Commission should
carry out appropriate consultations of the Agency and of the Substances of Human
Origin Coordination Board (‘the SCB’).
51
Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the
deliberate release into the environment of genetically modified organisms and repealing Council
Directive 90/220/EEC, OJ L 106, 17.4.2001, p. 1, ELI: http://data.europa.eu/eli/dir/2001/18/oj .
EN 57 EN
(121) The measures established in this Regulation, including regarding health biotechnology
strategic projects and high impact health biotechnology strategic projects, access to
funding, biosimilars and the application of artificial intelligence in the health
biotechnology sector aim to strengthen the health biotechnology sector. Those
measures aim to foster research, development, testing, and preparing for market entry
of health biotechnology products and services. This is the case for the centres of
excellence for advanced therapies, the overall aim of which is to accelerate the placing
on the market of advanced therapies, accelerate clinical translation, improve quality
control and facilitate patient access across the Union. Similarly, the biotechnology
development accelerators aim to provide trusted testing or demonstration facilities for
process testing, validation, and small batch manufacturing, including for the initial
phases of clinical trials. Similarly, time to market for biotechnology products is one
key factor that impacts investments in the sector and accordingly access to funding for
developers and start-ups in the biotechnology sector. Many of the products subject to
those measures are expected to be biological medicinal products (‘biologicals’), for
which clinical research and trials are an essential step on their way to the market.
Therefore, the measures established in this Regulation, in particular on biotechnology
health strategic projects and high impact health biotechnology strategic projects, are
intrinsically intertwined with, and depend on, the strengthening of clinical research in
Europe. This is because all biotechnology products expected to be developed or
supported through the health biotechnology strategic projects and high impact health
biotechnology strategic projects are depending to a very large extent on an efficient
and vibrant ecosystem of clinical research in the Union.
(122) Amending Regulation (EU) No 536/2014 of the European Parliament and of the
Council52 to bring simplification and shorten the time for biotechnology innovations to
reach the Union market is crucial to streamline and accelerate clinical trials processes
in the Union and to make the legislative framework competitive globally so as to
attract more clinical research to the Union. Without an efficient, accelerated and
streamlined legislative framework for clinical trials authorisation in the Union, the
other measures in this Regulation, and in particular the framework for the recognition
and support of health biotechnology strategic projects and high impact health
biotechnology strategic projects would be deprived of their effectiveness, as all health
biotechnology medicinal products require state of the art clinical research and a
globally competitive regulatory framework for clinical trials authorisation.
(123) The clinical trials offer early access to the most innovative therapies, contribute to a
sustainable healthcare system, maintain scientific excellence and specialised skills and
they also support prosperity in the Union. Enabling the development of innovative
biological medicines through clinical trials is particularly important, since those
medicines often provide life-saving therapeutic options, including in cancer care or
against rare genetic conditions, and, due to their complexity, they are often more
difficult and expensive to develop. Increased clinical trials in the Union for biological
medicines could potentially contribute to more manufacturing in the Union, higher
number and earlier regulatory submission of biological medicines for marketing
authorisation applications and higher percentage of EU clinical data in marketing
authorisation applications. In relation to this, biological medicines sales are key
52
Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on
clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158,
27.5.2014, p. 1, ELI: http://data.europa.eu/eli/reg/2014/536/oj).
EN 58 EN
drivers of growth. In 2024, the European Union spent €228 billion on medicines at list
prices, including €95 billion on biological medicines, which now comprise 41% of
total pharmaceutical spending. Spending on biological medicines continues to outpace
that of small molecules (~5%) by 3x and the total prescription market, at a rate of
14.7% in the most recent period53. In this context, simplifying Regulation (EU) No
536/2014 and accelerating multinational clinical trials appears necessary with a view
to accelerate time to market of heath biotechnology innovations and thus secure the
effectiveness of the substantive provisions laid down in this Regulation.
(124) At the same time, Regulation (EU) No 536/2014 applies to all clinical trials
irrespective of the type of investigational medicinal product, whether it be biological
or chemical molecules. However, the amendments to Regulation (EU) No 536/2014
through this Regulation, for streamlining and simplifying that Regulation, are
particularly relevant for biologicals. This is because the development of biologicals
relies heavily on multinational clinical trials to be able to recruit the necessary number
of patients.
(125) Moreover, the limitation of the scope of the envisaged amendments to biologicals
would be against the core principle of Regulation (EU) No 536/2014 to create a
harmonised EU-level system for clinical trials authorisations. It would create two
authorisation pathways for chemical medicines and biologicals and it would not be
appropriate to distinguish these procedurally, considering the coordinated assessment
procedure established in Regulation (EU) No 536/2014 and the single EU Portal and
database as IT system provided for in that Regulation for the electronic submissions
and assessment of all applications. In addition, providing for different timelines for
biological and chemical medicines could create uncertainty for developers and could
be perceived as creating double standards for clinical research on medicines, where the
biotechnology products, often more complex, would benefit from shorter and more
streamlined timelines. Such fragmented approach could potentially also increase the
burden on regulators and could lead to different national interpretations regarding the
implementation of the respective authorisation procedures. This in turn would risk
putting multinational clinical trials at disadvantage with more associated negative
effects for biological development. Further, such an approach could have a particularly
negative impact on combination trials testing combination medicinal products, where
biological and chemical active substances are combined within a single
pharmaceutical form, to treat debilitating medical conditions for example but not
limited to breast, lung, colorectal cancers or autoimmune diseases, as well as on trials
comparing a biological and a chemical medicinal products or on trials using a
chemical medicine as a standard of care treatment in the control arm . Consequently,
the amendments to Regulation (EU) No 536/2014 should apply to both biologicals and
chemicals.
(126) The Union has unique advantages as a place for multinational clinical trials due to its
large population, rich genetic diversity, scientific excellence and robust research
infrastructures, and high ethical, quality and safety standards. To fully leverage these
strengths and considering the key and increasing role of research and clinical trials for
a thriving health biotechnology sector, it is necessary to amend the Regulation (EU)
No 536/2014 to further streamline and speed up the authorisation processes especially
for multinational clinical trials.
53
See figure 2, EU spending growth at list price levels by segment and leading therapy area, in Annex to
this document.
EN 59 EN
(127) To accelerate and streamline the approval processes in multinational clinical trials it is
necessary to give a stronger leading role to the reporting Member State and further
strengthen the principles of mutual trust and reliance. The assessment by the reporting
Member State, including of the ethical aspects of the trial, should serve as a reference
for the other Member States concerned. Member States concerned should complement
the assessment by the reporting Member State only when necessary, and be entitled to
raise considerations from ethical, relevant national law or national standard of care
perspectives. Strengthening reliance on the reporting Member State’s assessment
would reduce duplication of work and allow Member States and sponsors to allocate
resources more effectively, while ensuring high level of protection of subjects and the
robustness of data.
(128) Defined timelines in the context of clinical trials approval are necessary to guarantee
speed and enhance predictability of the authorisation process, especially for
multinational clinical trials. Defined maximum timelines should allow the Member
State authorities with efficient planning to reduce periods of inactivity and thus
regulatory delays between the assessment phases and enable short procedure for
clinical trial approval overall. Stronger reliance on the reporting Member State would
also result in efficiency gains, improve resource allocation and would enable the
shortening of the consecutive assessment steps without compromising the quality of
the assessments. It would benefit the sponsors as well, as it will result in a quicker start
of a clinical trial, as well as in increased transparency and predictability for more
effective planning. To reduce regulatory bottlenecks by allowing coordinated
interaction between Part I and Part II assessments in multinational clinical trials, their
respective assessment timelines should be aligned.
(129) Recognising the importance of advanced therapeutic medicinal products (ATMPs) as
drivers of innovation in biotechnology and regenerative medicine, it is appropriate to
introduce a series of regulatory provisions to simplify and shorten the timelines for
authorisation of clinical trials in the Union. In particular, to accelerate the conduct of
clinical trials investigating the ATMPs, the authorisation procedure should be
shortened by removing the additional 50 days of assessment period which is currently
applicable
(130) Furthermore, to leverage the mutual trust and foster the high ethical standards, the
ethics committees should be involved in the assessment of ethical aspects of Part I of
the application dossier. This ethical perspective should be integrated in the assessment
report by the reporting Member State. Member States concerned should be able to
raise, where relevant, consolidated considerations integrating inputs from their
responsible ethics committees. The mandatory integration of ethical review in Part I
assessment by the reporting Member State would ensure that the ethical review is
conducted in a more harmonised and transparent manner. Such integration should also
result in fewer and more consistent considerations and therefore support overall
robustness of the evaluation with decreased burden for sponsors and national
regulatory bodies.
(131) It is appropriate that an enhanced EU portal provides technical means for a clear and
timely communication between the involved Member States and the sponsor during
the assessment, when requests for information are issued.
(132) To increase further the efficiency and speed of Part I assessments in multinational
clinical trials, when translations of Part I documents are required by national law,
these should be assessed with the Part II. Considerations regarding the accuracy of
EN 60 EN
these translations will be raised by the Member States concerned with the sponsor in
the Part II assessment process. Moving the assessment of translation quality into Part
II of the application will allow the reporting Member State to focus on the technical
and scientific assessment of the trial, while Member States concerned would retain
their ability to verify the linguistic accuracy and suitability for their territories.
(133) To ensure that the sponsor of clinical trials can adapt them dynamically through their
life cycle to changed circumstances or to consider the scientific developments and
ensure smooth conduct of the clinical trial, a submission of parallel substantial
modification should be allowed. Such submissions should be allowed when the
substantial modification, despite an ongoing approval of another one, concerns distinct
and independent aspects of the dossier. Allowing parallel substantial modifications
would support increased flexibility and responsiveness of the regulatory system. It
would facilitate updates related to subjects' safety and enable timely response to
emerging scientific knowledge or allow operational adaptations to improve patients
access and trial efficiency.
(134) To further support the efficiency and consistency of clinical trial submissions across
the Member States, it is appropriate to develop and oblige the use of harmonised
templates for the submission of Part II documents of clinical trial applications. The use
of harmonised templates is expected to simplify the application and assessment
processes reducing administrative burden both for sponsors and Member States.
Harmonised templates may be updated in the light of technical and scientific
evolution. Member States concerned may choose to rely also on the assessment of the
reporting Member State of common aspects and elements in Part II application further
streamlining initial authorisation and for additional efficiency gains.
(135) Innovative and personalised therapies often combine the use of medicinal products
with medical devices, including in vitro diagnostic medical devices. During the
development of such therapies, clinical trials of one or more medicinal products may
need to be combined with clinical investigation of one or more medical devices or
performance studies of one or more in-vitro diagnostic medical devices. The
authorisation and conduct of such combined studies are complex due to the application
of requirements of two or three Union legislative frameworks in the area of health and
the fact that these are typically conducted across several Member States. In order to
support innovation and make efficient use of sponsors’ and Member States’ resources,
it is necessary to put in place a dedicated pathway for the authorisation and conduct of
such combined studies, involving coordinated assessment across Member States.
(136) The experience gained during the Covid-19 pandemic has shown the need for the
Union to swiftly take up measures to strengthen the development and access to crisis-
relevant medicines, including to accelerate, simplify, and streamline the authorisation
of multinational clinical trials relevant to prevent, treat or diagnose the disease caused
by an emerging serious cross-border threat to health. Regulatory flexibility, including
an accelerated authorisation procedure for clinical trials, is necessary to address and
possibly contain an emerging health threat in a timely, efficient and coordinated
manner. Therefore, it is appropriate to allow for an accelerated procedure for the
authorisation of multinational clinical trials in situations where a public health
emergency at Union level has been recognised in accordance with Article 23(1) of
EN 61 EN
Regulation (EU) 2022/2371 of the European Parliament and of the Council54, or in
situations of an emerging serious cross-border threat to health that is likely to lead to
the recognition of a public health emergency at Union level. This should also
complement measures from the Regulation (EU) 2022/2372 of the Council55 on a
framework of measures for ensuring the supply of crisis-relevant medical
countermeasures in the event of a public health emergency at Union level.
(137) Based on the experiences gained from the application of Regulation (EU) No
536/2014, it is appropriate to further tailor the requirements for the authorisation and
oversight of clinical trials according to the risks they pose to the subjects. In this
context, the risk categorisation scheme should be further refined by differentiating
between minimal-intervention clinical trials that present post-marketing authorisation
trials and low-intervention clinical trials that use authorised medicinal products with
proven scientific evidence on the efficacy and safety but are used outside their initial
marketing authorisation.
(138) Clinical trials that meet the criteria for minimal-intervention clinical trials should only
require an ethical review before the clinical trial can begin. An enhanced application
of a risk-proportionate approach will contribute to fostering a regulatory framework
that is conducive to research and innovation. Sponsors, particularly non-commercial
ones who conduct the majority of minimal-intervention and low-intervention clinical
trials in the Union, will greatly benefit from simplified and risk-proportionate
regulatory requirements through a reduced administrative burden, while not
compromising subjects’ safety, well-being, and rights. A reinforced application of a
risk-proportionate regulatory framework further allows Member States to concentrate
on their assessment on clinicals trials associated with greater risk to the subjects.
(139) To ensure that clinical trials accurately represent the target population in all its
diversity, and to enhance the treatments available for vulnerable populations,
medicinal products which are likely to offer significant clinical benefit should be fully
and appropriately studied for their effects in these specific groups, including as regards
requirements related to their specific characteristics and the protection of the health
and well-being of subjects belonging to these groups. The protection of vulnerable
populations, in this context, such as incapacitated subjects, minors and pregnant or
breastfeeding women, requires a proper consideration of the risks of exclusion against
risks of inclusion in clinical trials. This is in accordance with the 2024 version of the
World Medical Association's Declaration of Helsinki.
(140) Electronic health data accessed under Chapter IV of Regulation (EU) 2025/327 can
offer valuable insights for clinical trials, particularly regarding the protocol or the
investigational medicinal products dossier design. Therefore, sponsors should be able
to utilize this data when applying for clinical trial authorisation or modifications.
Additionally, competent authorities should consider this data during the assessment of
such applications.
54
Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on
serious cross-border threats to health and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022,
ELI: http://data.europa.eu/eli/reg/2022/2371/oj)
55
Council Regulation (EU) 2022/2372 of 24 October 2022 on a framework of measures for ensuring the
supply of crisis-relevant medical countermeasures in the event of a public health emergency at Union
level.
EN 62 EN
(141) The development of a medicinal product may require various clinical trials until robust
data regarding its safety and efficacy are available to support the submission of a
marketing authorisation application. The knowledge of the products is built gradually
during this development. Using the same dossier for an investigational medicinal
product in different clinical trials helps to ensure the collection of consistent and
complete information, streamlines product development, supports efficient assessment,
management and oversight, and can speed up the time to the market. For this reason, a
sponsor should be able to request the establishment of an investigational medicinal
product core dossier and rely on this dossier by referencing it in all clinical trials
related to the investigational product concerned. In order to keep the core dossier
updated, sponsors should be able to request its modification. One of the Member
States concerned by the trials with investigational medicinal product should assume
the role of core dossier depositary Member State and take responsibility for verifying
completeness and suitability of the core dossier and managing the requests for its
updates. Member States concerned in the core dossier should rely on the assessment
by the depositary Member State. The depositary Member State may consult the
Member States concerned as appropriate.
(142) In the development of biosimilar medicinal products, the rapid evolution of analytical
and functional characterisation methods for complex biological and biotechnological
active substances calls for tailored clinical approach in biosimilar development with
reduced need for confirmatory comparative clinical efficacy trials. Submission of a
simplified investigational medicinal product dossier (IMPD) for biosimilar medicines
to replace, as appropriate quality and quality control data, with a reference to the
relevant additional quality substance master file or corresponding certificates would
complement the shift in more risk proportionate clinical data requirements. This dual
simplification and streamlining should focus on the regulatory scrutiny of key
comparability data rather than require duplicative submission and assessment of the
full IMPD quality dossier. Combining streamlined and robust quality data assessment
with targeted clinical data generation should support an integrated and efficient
development pathway for biosimilars with reduced administrative burden and
development costs for biosimilar manufacturers, in particular in the Union.
Accelerated access to biosimilar medicines to the market should support patients'
access to more affordable biological therapies.
(143) To further optimise the use of resources for both the sponsors and Member States, the
possibility to refer, in a clinical trial application, to an active substance master file or a
corresponding certificate, or a certificate confirming that the quality of the substance is
suitably controlled by the relevant monograph of the European Pharmacopeia, or a
certified platform technology master file should be available as appropriate for any
investigational medicinal product, including for ATMPs. In these cases, the simplified
IMPD must contain all relevant data to the active substance or its manufacturing,
which is not covered in the referenced master file or certificate.
(144) To address the increased significance of delivery of investigational medicinal products
and auxiliary medicinal products to subjects, Regulation (EU) No 536/2014 should be
amended to provide a framework for the controlled transport within a Member State,
where the clinical trials have been authorised, of such products directly to subjects'
residences or through a dispensing pharmacy or by an authorised person, under the
investigator's oversight. This ensures responsible and transparent delivery practices
and adapts to the real word necessities, as demonstrated during the COVID 19
EN 63 EN
pandemic. Distribution through a dispensing pharmacy or by an authorised person
could be considered in particular in cluster trials.
(145) To enhance regulatory efficiency, to ensure consistency in the implementation of
Regulation (EU) No 536/2014 across the Union, and to facilitate predictability of
requirements for the developers of medicinal products, it is necessary to provide a
framework for the harmonisation of national requirements regarding the distribution of
investigational and auxiliary medicinal products, notably for decentralised and
multinational clinical trials. To achieve such harmonisation, the inspection working
groups, which provide input and recommendations on all matters relating, directly or
indirectly, to good clinical practice, good manufacturing practice, and good
distribution practice should draw up guidelines, in collaboration with the Commission,
and revise them as necessary to reflect technical and scientific progress in the field of
clinical trials. In consideration of the specialised knowledge and experience of its
members, who represent the Member States, the inspection working groups are
particularly well-suited to facilitate the coordination of national requirements,
eliminate unnecessary administrative obstacles, and promote a more efficient and
harmonised approach to the conduct of clinical trials within the Union.
(146) To facilitate the implementation of Regulation (EU) No 536/2014, while at the same
time preserving the protection of quality of investigational medicinal products and
ensuring greater predictability for sponsors, it is also appropriate to provide the
general principles on how to ensure quality in the processes not subject to a
manufacturing and import authorisation, such as re-packaging and re-labelling.
(147) Verification of compliance with the legal requirements of manufacturing of
investigational medicinal products by relevant entities through a system of
supervision, is of fundamental importance to ensure that the objectives of this
Regulation are effectively achieved. The provisions of Directive (EU) …/… [reference
to be added after adoption cf. COM(2023) 192 final] regarding the supervision system
and the cooperation on inspections, and provisions of [Regulation (EU) …/… of the
European Parliament and the Council [reference to be added after adoption cf.
COM(2023) 193 final] regarding the cooperation between national competent
authorities and the Agency for inspections in third countries should apply to the
supervisions of manufacturing of investigational medicinal products.
(148) Verification of compliance with the provisions of Regulation (EU) No 536/2014,
including for verification of compliance with good clinical practices, through a system
of supervision, is of fundamental importance to ensure that the objectives of this
Regulation are effectively achieved. Therefore, the competent authorities of the
Member States should have the power to perform on site or remote inspections,
including unannounced inspections, where necessary. Where needed, the competent
authority of a Member State should also be able to request support from another
Member State or the Agency to carry out a joint inspection, or to request a Member
State or the Agency to carry out the inspection on their behalf.
(149) The disruptive and innovative approaches to clinical trials may require adaptations to
the rules governing clinical trial approvals and conduct. To harness the benefits of this
innovation while providing necessary safeguards, it is essential to create a safe space
for testing new regulatory approaches and technologies. This includes, where
appropriate, the use of AI in trial design, data collection, analysis, and participant
interaction. For that reason, it is necessary to provide for a possibility of setting up a
controlled experimental environment in the form of a regulatory sandbox, allowing
EN 64 EN
regulators to test new methods for authorising and conducting clinical trials, for
example, when some requirements of the dossier cannot be fully complied with, while
ensuring strong safeguards for participant protection and data robustness. Insights
gained from sandbox activities should inform future guidance and, where appropriate,
legislative amendments.
(150) The processing of personal data under Regulation (EU) No 536/2014 should comply
with the requirements for the protection of personal data, including genetic data and
data concerning health, laid down in Regulations (EU) 2016/67956 and (EU)
2018/172557 of the European Parliament and of the Council. It is appropriate to clarify
that the basis for the processing of personal data in the context of clinical trials is laid
down in Regulation (EU)No 536/2014, pursuant to Article 6(1), point (c), of
Regulation (EU) 2016/679. The Agency should have access to personal data necessary
to perform its tasks in the public interest or complying with legal obligations in
accordance with Articles 40, 80 and 81 of Regulation (EU) No 536/2014. The
Commission should have access to personal data necessary for it to perform its task in
accordance with Articles 78, 79, 80, 81, of Regulation (EU) No 536/2014.
(151) In particular, Regulation (EU) No 536/2014 should be amended torequire the
processing of personal data by the sponsors and investigators where this is necessary
to comply with the legal obligations imposed on them to ensure the safety and efficacy
of medicinal products, when they request authorisation for and conduct clinical trials.
This includes obligations to perform research activities in accordance with an
authorised protocol, to perform safety reporting, and to perform archiving in
accordance with Regulation (EU) No 536/2014. The relevant information to be
collected according to the authorised protocol will contain personal data of the
subjects, including genetic data or data concerning health. The processing of such
special categories of personal data in the context of clinical trials takes place for
reasons of public interest in the area of public health, in particular for ensuring high
standards of medicinal products in compliance with Article 9(2), point (i), of
Regulation (EU) 2016/679. Additionally, personal data may encompass identification
details, such as sex and age, social insurance numbers and contact information.
Moreover, sponsors may collect and process other data necessary for implementing the
authorised protocol, such as the personal data of investigators. The categories of
personal data to be collected and processed in the context of a specific clinical trial
should be specified in the authorised protocol. Regulation (EU) No 536/2014 should
be amended to establish specific safeguards for the processing of personal data,
including genetic data or data concerning health, in compliance with Article 9(2),
points (i) and (j), of Regulation (EU) 2016/679. For instance, it should require
informed consent to participate in the clinical trial, as well as to maintain
confidentiality of records and personal data of participants. The protocol should
specify further appropriate safeguards such as specific technical and organisational
56
Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the
protection of natural persons with regard to the processing of personal data and on the free movement of
such data, and repealing Directive 95/46/EC (General Data Protection Regulation) (OJ L 119, 4.5.2016,
p. 1, ELI: http://data.europa.eu/eli/reg/2016/679/oj).
57
Regulation (EU) 2018/1725 of the European Parliament and of the Council of 23 October 2018 on the
protection of natural persons with regard to the processing of personal data by the Union institutions,
bodies, offices and agencies and on the free movement of such data, and repealing Regulation (EC) No
45/2001 and Decision No 1247/2002/EC (OJ L 295, 21.11.2018, p. 39, ELI:
http://data.europa.eu/eli/reg/2018/1725/oj).
EN 65 EN
measures that should be employed, including pseudonymisation, integrity and
confidentiality controls, encryption and access restrictions. In addition, any clinical
trial should be subject to ethical review.
(152) Since this Regulation amends Regulation (EU) No 536/2014 to establish a harmonised
framework for the processing of personal data in the context of clinical trials, Member
States should not be able to maintain or introduce under Article 9(4) of Regulation
(EU) 2016/679 further conditions, including limitations and specific provisions such
as requesting the consent of natural persons in the sense of that Regulation, with
regard to the processing of personal data, including genetic data or data concerning
health under Regulation (EU) No 536/2014 as amended by this Regulation.
(153) Personal data which is collected and processed under each authorised protocol in
accordance with Regulation (EU) No 536/2014 as amended by this Regulation may be
further processed by the same controller for the purposes of other clinical trials,
conducted in accordance with Regulation (EU) No 536/2014. Such data may include
names, contact details, health and genetic data of subjects. It should also be possible to
further process such personal data by the same controller for scientific research
purposes.
(154) To further address the issue of fragmentation within and across Member States on the
application of the measures applicable to the conduct of clinical trials and, as regards
certain aspect that remain national, and drive further harmonisation, it is necessary to
enable closer cooperation between and across Member States’ competent authorities
and ethics committees. For that purpose, the role and tasks of the Clinical Trials
Coordination and Advisory Group (CTAG) should be extended. The CTAG should in
particular be empowered to issue or endorse guidance documents related to clinical
trials conduct and supervision, to ensure uniform interpretation and harmonised
implementation of Regulation (EU) No 536/2014 across the Member States.
(155) Ethics committees involved in the assessment of clinical trials application should
collaborate in a dedicated forum with the objective to strengthen cooperation in the
area of ethical aspects of clinical trials which are of national competence.
(156) Regulation (EU) No 536/2014 outlines the responsibilities of Member States in
designating competent authorities and ethics committees for regulatory activities,
including oversight. To perform their roles as required by the provisions of this
Regulation amending Regulation (EU) No 536/2014, these competent authorities and
responsible ethics committees should be vested in the necessary powers, have at their
disposal qualified personnel and sufficient resources to perform their duties
effectively. Regulation (EU) 536/2014 emphasizes the importance of communication
and coordination to ensure consistent and efficient regulatory actions within Member
States. It is also essential to define how the Commission will verify the correct
implementation of the law by the competent authorities. Regulation (EU) No 536/2014
should be amended accordingly.
(157) The integration of AI in clinical trials presents opportunities to enhance the clinical
trials’ design, execution, and oversight. This technological advancement offers
substantial benefits to clinical trial sponsors, regulators, and ultimately patients.
Among the possible enhancements are improved endpoint determination, advanced
statistical analysis, optimized patient selection, enhanced data handling and analysis.
While AI tools aim to accelerate the development of medicinal products, it is
imperative that their use in clinical trials adheres to applicable legislation. This
EN 66 EN
includes, when applicable, compliance with Regulation (EU) 2024/1689, Regulation
(EU) 2017/746, Regulation (EU) 2017/745 and Regulation (EU) 2016/679.
(158) Sponsors hold the responsibility to evaluate the potential impact and risk of AI tools
on patient safety based on guidelines. Untested systems may introduce gender and
other biases and errors, risking unreliable outcomes or failures in interpreting medical
data accurately. Such risks could lead to misdiagnosis, incorrect treatment, or
inaccurate patient selection, especially hazardous in extensive clinical trials with
numerous participants. The guidelines on the developments and deployment of AI
tools developed by the Agency, in cooperation with the Clinical Trials Coordination
and Advisory Group, and as appropriate, with other expert groups established under
Union law, should assist the sponsors, national competent authorities and ethics
committees in assessment of AI tools benefits and risks in the context of the lifecycle
of clinical trials.
(159) To further strengthen the competitiveness of the European Union in clinical research
and ensure timely access of patients to innovative medicines, it is necessary to monitor
the effectiveness of the provisions in thisRegulation amending Regulation (EU) No
536/2014 to streamline and simplify the authorisation and conduct of multinational
clinical trials. Such monitoring should be based on key performance indicators such as
the increase in the number of clinical trials in the Union over the period of five years,
as this indicator reflects both the attractiveness of the Union and the capacity of the
European regulatory system to support clinical research with maintained high data
quality and patients’ safety standards. Regulation (EU) No 536/2014 should be
amended accordingly.
(160) The management of changes through the lifecycle of veterinary medicinal products is
subject to regulatory approvals. The handling of variations for biological products is
particularly critical because of the impact that changes in the source materials or the
manufacturing process can have on the safety and efficacy attributes of the finished
product. It is necessary to continue ensuring that changes introduced during the
lifecycle of a veterinary medicinal do not alter the positive benefit-risk balance while
avoiding unnecessary administrative burden. To this end, the process for
implementation of variations not requiring assessment laid down in Article 61 of
Regulation (EU) 2019/6 of the European Parliament and of the Council58 should be
further optimised.
(161) Advances in biotechnology bring new opportunities for the development of veterinary
medicinal products, including the possibility to develop vaccines with improved safety
and efficacy profiles in a much shorter timeframe. The possibility to deploy and use
vaccines quickly is essential to react to outbreaks of certain animal diseases thereby
reducing the risks for human health, contributing to animal welfare and reducing
economic losses for farmers.
(162) Safety for veterinary medicinal products is assessed during marketing authorisation
procedures in accordance with Regulation (EU) 2019/6. The competent authorities
responsible for the granting of marketing authorisations are required to verify the
safety for the target species, for the user, for consumers and for the environment.
Likewise, the conduct of clinical trials is subject to the approval and supervision by
58
Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on
veterinary medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 2, ELI:
http://data.europa.eu/eli/reg/2019/6/oj).
EN 67 EN
competent authorities responsible for veterinary medicinal products. Regulation (EU)
2019/6 further requires that such trials are conducted in accordance with Good Clinical
Practice, which includes the obligation for sponsors to ensure that there are no
environmental grounds precluding the conduct of the trial.
(163) Regulation (EU) 2019/6 and the Union GMO legislation (Directives 2001/18/EC59 and
2009/41/EC60, Regulations (EC) 1829/200361, 1830/200362 and 1946/200363 of the
European Parliament and of the Council share the same protection goals as regards the
protection of human and animal health and the environment from genetically modified
organisms. Since parallel assessments and documentation and increased administrative
burden is not conducive to increased protection of human health or the environment
and has negative effects on the use of biotechnology in veterinary medicine, the risks
for human and animal health and to the environment from veterinary medicinal
products containing or consisting of genetically modified organisms should be solely
assessed in accordance with Regulation (EU) 2019/6. This simplification should be
coupled with a reinforcement of existing obligations as regards the conduct of clinical
trials with veterinary medicinal products that contain or consists of GMOs.
(164) To remove any legal uncertainty for developers, marketing authorisation holders and
users, it should also be clarified that given the purpose of veterinary medicinal
products to treat animals, their administration does not bring the treated animals or
their products under the scope of the Union GMO legislation.
(165) The Commission should be empowered to adopt delegated acts to amend Annex II to
Regulation (EU) 2019/6 in order to adapt it to scientific and technical progress.
(166) Veterinary medicinal products developed by means of biotechnology processes to
diagnose, treat or prevent zoonotic diseases should be entitled to an extra year of
supplementary protection certificate (‘SPC’) in order to support their development.
(167) Scientific and technical progress in biotechnology enables the development of new
technologies, methods or products that may not fit into existing Union legislation. The
lack of harmonised requirements is an impediment to the development, marketing and
use of new concepts that may, however, bring benefit to animal healthcare. Regulatory
sandboxes may be established to facilitate the development, placing on the market or
use of innovative technologies, methods or products related to animal health which are
directly or indirectly related to the development, manufacturing or use of veterinary
medicinal products under conditions that ensure protection of animal and public health
as well as the environment. A regulatory sandbox should only be established if there is
no Union legislation governing the marketing and use of the relevant technology,
method or product.
59
Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the
deliberate release into the environment of genetically modified organisms and repealing Council
Directive 90/220/EEC (OJ L 106, 17.4.2001, p. 1).
60
Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained
use of genetically modified micro-organisms (OJ L 125, 21.5.2009, p. 75,).
61
Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September 2003
on genetically modified food and feed (OJ L 268, 18.10.2003, p. 1).
62
[Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September
2003on genetically modified food and feed (OJ L 268, 18.10.2003, p. 1).
63
Regulation (EC) No 1946/2003 of the European Parliament and of the Council of 15 July 2003 on
transboundary movements of genetically modified organisms (OJ L 287, 5.11.2003, p.1).
EN 68 EN
(168) A regulatory sandbox may be established by the Commission, by way of an
implementing act following a recommendation of the Agency which should analyse
expected potential benefits and risks as well as existing regulatory challenges.
Technical and scientific requirements for the technologies, methods or products under
the regulatory sandbox and procedures should be developed and published by the
Agency. The Agency should ensure that the requirements and procedures it develops
are proportionate and are adapted to the specific risks. A regulatory sandbox may be
terminated at any time where, following the identification of negative impacts on
animal or public health or the environment, the benefit-risk balance becomes negative
and there are no satisfactory risk mitigation measures that could be implemented.
(169) Technologies, methods or products developed under a regulatory sandbox should only
be placed on the market or used on the basis of an authorisation granted by the
Commission. Depending on the specific characteristics of the products concerned, a
class authorisation to market or use technologies, methods or products may be
possible. Member States should be empowered to take interim measures where serious
risks to animal or public health or the environment are identified. In such cases,
Member States should swiftly inform the Agency.
(170) To ensure legal certainty, the termination of a regulatory sandbox should not affect the
validity of the authorisations to place on the market or use technologies, methods or
products already granted, unless the regulatory sandbox has been terminated on
grounds related to the protection of public or animal health or the environment.
(171) To provide legal certainty to developers and competent authorities alike, time limits
should be established also in the Regulation (EU) 2024/1938 and for all actors
involved in the consultation process, at national and Union level, including the SoHO
competent authorities, the Substances of Human Origin Coordination Board (‘the
SCB’), established in that Regulation and advisory bodies established under other
relevant Union legislation. Consequently, Regulation (EU) 2024/1938 should be
amended to provide the power for the Commission to adopt implementing acts to
establish such time limits, that should be ambitious and determined based on
experience gathered with the consultation process as of the entry into application of
that Regulation.
(172) The field of substances of human origin is characterised by rapid scientific and
technological innovation, giving rise to health biotechnology approaches that may
present scientific or regulatory challenges under existing legal requirements. To
support the development of such innovations at early stages while maintaining public
health protection, Member States should be able to establish regulatory sandboxes for
substances of human origin that cannot yet be developed in full compliance with the
requirements of Regulation (EU) 2024/1938, provided that the innovative
characteristics or methods are expected to contribute distinctively to quality, safety,
effectiveness, or patient access to treatment. The sandbox activities should enable a
discussion on the development of common approaches and the potential adaptation of
legislative frameworks based on accumulated experience. Any substances of human
origin developed through regulatory sandboxes should only be distributed for human
application when properly authorised, with initial authorisations limited to the
regulatory sandbox duration. This framework should enable controlled
experimentation with innovative regulatory approaches while preserving the essential
safeguards for public health and safety. Regulation (EU)2024/1938 should be
amended accordingly.
EN 69 EN
(173) The regulatory sandboxes in the field of substances of human origin should be
conducted under the supervision of the concerned SoHO competent authorities, and,
where relevant, competent authorities under other Union and Member State legislation
concerned. The latter authorities should be in particular involved where the
preparation of the SoHO requires steps using products regulated under another Union
legislative framework, or where SoHO is presented as a therapy together with products
regulated under another such Union framework.
(174) In order to ensure uniform conditions for the implementation of this Regulation
regarding the recognition by the Commission of high impact biotechnology strategic
projects, the modalities for the processing of personal data necessary to achieve the
purpose of such projects in the form of biotechnology data quality accelerators and the
rules for the selection, composition, number of members, and functioning of the
Foresight Panel for Emerging Health Innovation, implementing powers should be
conferred on the Commission.
(175) In order to ensure uniform conditions for the implementation of this Regulation,
implementing power should be conferred on the Commission to detail the criteria to
clarify in what cases a project is to be deemed to have a strong systemic and catalytic
potential within the Union’s biotechnology ecosystem and accelerate innovation, detail
the criteria for the recognition of centres of excellence for advanced therapies,
including advanced therapy medicinal product, establish procedural rules for the
recognition of high impact health biotechnology strategic projects and the format of
the assessment report to be submitted by the designated authorities in relation to
applications for recognition of high impact health biotechnology strategic projects,
establish regulatory sandboxes for health biotechnology products and common
principles, criteria and practical arrangements for the assessment of applications
received from developers and for the establishment and supervision of the regulatory
sandboxes and related sandbox plans. Those powers should be exercised in accordance
with Regulation (EU) No 182/2011.
(176) The power to adopt acts in accordance with Article 290 of the Treaty on the
Functioning of the European Union should be delegated to the Commission in respect
of modifying Annex I to this Regulation listing the biotechnology products of concern.
It is of particular importance that the Commission carries out appropriate consultations
during its preparatory work, including at expert level, and that those consultations be
conducted in accordance with the principles laid down in the Interinstitutional
Agreement on Better Law-Making of 13 April 2016. In particular, to ensure equal
participation in the preparation of delegated acts, the European Parliament and the
Council receive all documents at the same time as Member States' experts, and their
experts systematically have access to meetings of Commission expert groups dealing
with the preparation of delegated acts.
(177) The European Data Protection Supervisor and the European Data Protection Board
were consulted in accordance with Article 42 of Regulation (EU) 2018/172564 and
delivered an opinion [date].
64
Regulation (EU) 2018/1725 of the European Parliament and of the Council of 23 October 2018 on the
protection of natural persons with regard to the processing of personal data by the Union institutions,
bodies, offices and agencies and on the free movement of such data, and repealing Regulation (EC) No
45/2001 and Decision No 1247/2002/EC, OJ L 295, 21.11.2018, pp. 39–
98, ELI: http://data.europa.eu/eli/reg/2018/1725/oj)
EN 70 EN
(178) Since the objectives of this Regulation cannot be sufficiently achieved by the Member
States but can rather, by reason of the scale or effects of the action, be better achieved
at Union level, the Union may adopt measures in accordance with the principle of
subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance
with the principle of proportionality as set out in that Article, this Regulation does not
go beyond what is necessary in order to achieve those objectives.
HAVE ADOPTED THIS REGULATION:
CHAPTER I
SUBJECT MATTER, SCOPE AND DEFINITIONS
Article 1
Subject matter and scope
1. This Regulation establishes a framework to strengthen the competitiveness of the
health biotechnology sector in the Union. It creates and reinforces favourable
conditions for health biotechnology as defined in Article 2(1), point (2), from
research and development to the timely placing on the Union market and production
of biotechnology innovations and products, while safeguarding high standards of
protection of human health, patient safety and animal health, the environment, ethics,
quality of products, food and feed safety and biosecurity.
2. This Regulation lays down measures regarding:
(a) the establishment of a framework for the recognition of, and support measures
for, health biotechnology strategic projects and high impact health
biotechnology strategic projects;
(b) novel health biotechnology products and regulatory sandboxes to support
innovation and take into account technological and scientific developments and
progress;
(c) the support to promoters of biotechnology projects, SMEs, start-ups and scale-
ups and non-profit developers of biotechnology products, by establishing an
EU Health Biotechnology Support Network;
(d) the support for funding of, investments in, and access to capital for
biotechnology companies and projects;
(e) the enhancement of the manufacturing capacity of, and expertise for
biosimilars in the Union, including through international cooperation;
(f) the application in a facilitated manner of advanced technologies, including AI
in biological applications, into the Union’s health biotechnology ecosystems,
while monitoring and mitigating, in line with the Union harmonisation
legislation on AI, biological risks arising from the use of such technologies;
(g) the placing on the market in particular of health biotechnology products and
biotechnology services in accelerated and streamlined procedures;
(h) the prevention of the misuse of biotechnologies and the strengthening of
biodefence capabilities, without prejudice to, and in complementarity with,
activities financed under any defence related Union funding programmes and
instruments.
EN 71 EN
3. This Regulation applies to health biotechnology innovations and products and their
ecosystem during their entire lifecycle, including related research, funding,
development, innovation, testing, validation, manufacturing, placing on the market,
and use activities.
4. The amendments to the Union legislation laid down in Articles 56 to 61 are not
limited to health biotechnology products and activities, but also relate to the other
products, services and activities that fall in the scope of that legislation.
5. This Regulation does not affect the application of Directive 2010/63/EU on the
protection of animals used for scientific purposes and of Regulation (EU) 1907/2006
concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals
(REACH).
6. This Regulation shall apply without prejudice to Regulation (EU) 2024/1689 laying
down harmonised rules on artificial intelligence.
7. This Regulation shall apply without prejudice to Regulation […][[Regulation on
speeding-up environmental impact assessments -permitting regulation].
Article 2
Definitions
1. For the purposes of this Regulation, the following definitions apply:
(1) ‘biotechnology’ means the application of science and technology to living
organisms, as well as parts, products and models thereof, to alter living or non-
living materials for the production of knowledge, products and services;
(2) ‘health biotechnology’ means the application of biotechnology for the
promotion, protection, or restoration of human health and biotechnological
applications relevant to animal health, plant health, veterinary public health,
and food safety, insofar as these areas contribute directly or indirectly to the
protection of human health and align with the Union’s public health objectives,
as set out under Article 168 of the Treaty on the Functioning of the European
Union;
(3) ‘biotechnology product’ means any good, technology or activity resulting from
the application of biotechnology, including any process, action, technique, tool
or knowledge involving biotechnology;
(4) ‘advanced biotechnology innovation’ means a biotechnology product, process,
service or enabling technology that demonstrates, on the basis of preliminary
scientific or technical evidence, the potential to achieve a substantial
improvement over existing solutions in terms of efficacy, safety, sustainability,
accessibility, and/or cost-effectiveness, and that, by reason of its novelty,
technical complexity and/or market-creating potential, entails a high level of
technological or commercial risk and it is likely to create new markets or
significantly disrupt existing ones;
(5) ‘biomanufacturing’ means the production of biotechnology products at a
commercial scale;
(6) ‘biotechnology cluster’ means a geographic concentration of interconnected
companies, research institutions and organisations focused on biotechnology
and life sciences, fostering collaboration and innovation;
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(7) ‘project promoter’ means any undertaking or consortium of undertakings
developing a health biotechnology strategic project referred to in Article 3 or a
high impact health biotechnology strategic project referred to in Article 4;
(8) ‘permit-granting process’ means a process that covers all relevant permits to
build, expand, convert and operate health biotechnology strategic projects and
high impact health biotechnology strategic projects, including building permits
and environmental assessments and authorisations where required, and
encompassing all applications and procedures from the acknowledgement that
the application for such permits is complete to the notification of the decision
on the outcome of the procedure by the single point of contact concerned;
(9) ‘deep tech’ means an innovation with the potential to deliver transformative
solutions and that is based on cutting-edge advances in science, technology and
engineering;
(10) ‘SME’ means a micro, small or medium-sized enterprise within the meaning of
the Annex to Commission Recommendation 2003/361/EC65;
(11) ‘European Investment Bank Group (EIBG)’ means the European Investment
Bank, the European Investment Fund or any subsidiary of the European
Investment Bank;
(12) ‘national promotion bank or institution’ means a legal entity as defined in
Article 2, point (21), of Regulation (EU) 2021/523 of the European Parliament
and of the Council66;
(13) ‘implementing partner’ means an entity implementing, in indirect management,
support under the EU health biotechnology investment pilot;
(14) ‘AI system’ means an AI system system as defined in Article 3(1) of
Regulation (EU) 2024/1689;
(15) ‘general-purpose AI model’ means an AI model as defined in Article 3point
(63) of Regulation (EU) 2024/1689;
(16) ‘general-purpose AI system’ means a general-purpose AI system as defined in
Article 3point (66) of Regulation (EU) 2024/1689;
(17) ‘clinical trial’ means a clinical trial as defined in Article 2(2), point (2) of
Regulation (EU) No 536/2014;
(18) ‘advanced therapy medicinal product’ means an advanced therapy medicinal
product as defined in Article 2(1) of Regulation (EC) No 1394/2007;
(19) ‘New Approach Methodologies (NAMs)’ means innovative methods that do
not involve live animals, such as in vitro (cell or tissue-based), in chemico
(chemical-based), or in silico (computer-based) approaches, as well as
combinations of these;
(20) ‘biological threats’ means risks posed by harmful biological agents such as
pathogens or toxins that can cause disease or significant societal consequences,
whether arising naturally, through accidental release, or via deliberate misuse;
65 Commission Recommendation of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises (Text with EEA relevance) (notified
under document number C(2003) 1422), OJ L 124, 20.5.2003, pp. 36–41. ELI: http://data.europa.eu/eli/reco/2003/361/oj
.
66 Regulation (EU) 2021/523 of the European Parliament and of the Council of 24 March 2021 establishing the InvestEU Programme and amending Regulation
(EU) 2015/1017, O
J L 107, 26.3.2021, pp. 30–89. ELI: http://data.europa.eu/eli/reg/2021/523/oj.
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(21) ‘biodefence’ means actions, policies, and measures that are designed, in
particular by state actors, for preventive, protective or peaceful purposes, to
counter biological threats, reduce risks, and prepare for, detect, assess, respond
to, and recover from biological threats;
(22) ‘biosecurity’ means the protection, control and accountability of high-
consequence biological agents, technologies, materials and toxins of concern,
as well as of critical relevant information against unauthorised access, loss,
theft, misuse, diversion or intentional release by those who intend to misuse
them;
(23) ‘biotechnology product of concern’ means any good, service or technology,
including software resulting from the application of science and technology to
living organisms, their parts, products or models with significant potential for
biological misuse that are listed in Annex I, including any thresholds or
exclusions;
(24) ‘benchtop nucleic acid synthesis equipment’ means any equipment that allows
a user to synthesise nucleic acids individually or in a core research facility.
2. For the purpose of the provisions regarding biosecurity and the prevention of
biotechnology misuse laid down in Chapter VIII, Section 2, the following definitions
apply:
(a) ‘making available’ means any supply, whether in return for payment or free of
charge;
(b) “legitimate” means in good faith, in the ordinary course of recognised
professional, research or commercial activities, and in accordance with
applicable Union and national law;
(c) ‘legitimate need’ in a biotechnology product of concern means the need for
such biotechnology for legitimate and peaceful purposes, including handling,
production, cultivation, experimentation, preservation, destruction, internal
transport, by a legitimate member of the scientific community or a legitimate
enterprise, consistent with applicable international treaties, laws, standards and
oversight;
(d) ‘suspicious transaction’ means any transaction concerning biotechnology
products of concern for which there are reasonable grounds, taking into
account all relevant factors, to doubt the legitimacy of the prospective
customer’s intentions.
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CHAPTER II
UNION HEALTH BIOTECHNOLOGY AND BIOMANUFACTURING
SECTION 1
RECOGNITION OF HEALTH BIOTECHNOLOGY STRATEGIC PROJECTS IN THE UNION
Article 3
Health biotechnology strategic projects
1. To enable access to the support measures laid down in Section 2 of Chapter II,
Member States shall recognise projects located in the Union, by means of a reasoned
decision, as health biotechnology strategic projects if they make a substantial
contribution to at least one of the following specific objectives:
(a) strengthening the industrial capacity and value chains in the health
biotechnology sector, through one or more of the following activities:
(i) pooling resources and expertise among research organisations,
biotechnology industry actors and/or public authorities within the Union;
(ii) creating new, or significantly expanding, production facilities for
biotechnology products, in particular in biotechnology sectors where
such facilities do not exist or where they are limited, including for
biosimilars;
(iii) creating or upgrading industrial scale biomanufacturing sites with
innovative, sustainable, safe and digitally enabled processes and
technologies;
(iv) reducing dependencies on third-country suppliers for key biotechnology
inputs and intermediates;
(v) integrating advanced digital and AI-driven manufacturing and supply-
chain management systems to enhance productivity, traceability and
sustainability across biotechnology value chains;
(b) scaling-up or upgrading critical research and technology infrastructures
underpinning the development, testing and validation of health biotechnology
products, including but not limited to pilot or testing infrastructures for
biomanufacturing, data and digital platforms, through one or more of the
following activities:
(i) establishing, expanding or upgrading pilot, testing and demonstration
infrastructures linking research, development, validation and industrial
deployment capacities for biotechnology products and processes; or
(ii) integrating advanced digital, data and AI capabilities to enhance
modelling, simulation and process optimisation; or
(iii) establishing interoperable infrastructures connecting research
organisations, industry and public authorities across the Union; or
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(iv) promoting and integrating the use of NAMs in areas such as biological
research, discovery and preclinical development, regulatory and quality
testing and production of medicinal products and medical technologies.
(c) accelerating innovation and technology deployment in health biotechnology
through one or more of the following activities:
(i) introducing or scaling up breakthrough innovations in biotechnology that
have the potential to strengthen the Union’s industrial competitiveness,
including AI-enabled technologies and tools;
(ii) supporting SMEs, start-ups and scale-ups, universities and research
centres in accessing advanced biomanufacturing and laboratory
capacities;
(iii) promoting technology transfer and collaboration with corresponding
facilities in third countries, where Union-led partnerships are established
under Union law.
(d) addressing talent and skills needs or preventing shortages of talent and skills
critical to all kinds of jobs in support of the strengthening of the health
biotechnology and biomanufacturing sectors, and supporting the creation and
maintenance of quality jobs in the EU through one or more of the following
activities:
(i) attracting and retaining talent in the Union and aiming to provide
adequate upskilling or reskilling opportunities covering the broad range
of skills required for biotechnology and biomanufacturing, including
technical skills, data science, AI, intellectual property and project
management, and entrepreneurial skills, through activities including
apprenticeships, traineeships, continuing education and training, in close
cooperation with regional and local authorities, education and training
institutions, businesses and social partners;
(ii) establishing public-private partnerships between universities, vocational
education and training providers, businesses, in particular SMEs, start-
ups and scale-ups, social partners and applied research institutes;
(iii) establishing university alliances, also in cooperation with employers, to
improve their delivery on innovation and the development of skills and
talent.
(e) contributing to strengthening the EU’s preparedness and response capacity to
priority health threats by supporting the development, manufacturing and
supply of medical countermeasures.
2. The projects referred to in paragraph 1 may be located on the territory of two or more
Member States.
Article 4
High impact health biotechnology strategic projects
1. To enable access to the support measures laid down in Section 2 of Chapter II,
projects located in the Union fulfilling the criteria to be recognised as health
biotechnology strategic projects, which demonstrate by virtue of their scale, scope or
cross-border relevance, a strong systemic and catalytic potential within the Union’s
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biotechnology ecosystem to accelerate innovation and enhance the translation of
research into market applications shall be recognised by the Commission as high
impact health biotechnology strategic projects, including in the following cases:
(a) the project is a biotechnology development accelerator that fulfils the
conditions laid down in Article 5;
(b) the project is a centre of excellence for advanced therapies, including for
advanced therapy medicinal products that fulfils the conditions laid down in
Article 6;
(c) the project contributes to an EU biotechnology late-stage capital booster pilot,
fulfilling the conditions laid down in Article 23;
(d) the project contributes to the development of trusted testing environments for
advanced biotechnology innovations, fulfilling the conditions laid down in
Article 32(1) or is a health biotechnology data quality accelerator, fulfilling the
conditions laid down in Article 33.
(e) the project contributes to the EU Biothreat Radar fulfilling the conditions laid
down in Article 41(1) or it is a biodefence capability high impact strategic
project fulfilling the conditions laid down in Article 42(1).
2. The Commission may adopt implementing acts to detail the conditions set out in
paragraph 1, to clarify in which cases a project is to be deemed to have a strong
systemic and catalytic potential within the Union’s biotechnology ecosystem to
accelerate innovation and enhance the translation of research into market
applications. These implementing acts shall be adopted in accordance with the
examination procedure referred to in Article 65(2).
Article 5
Biotechnology development accelerators
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high impact health
biotechnology strategic projects in the form of biotechnology development
accelerators, only where they comply with the conditions laid down in Article 4(1),
and they fulfil at least three of the following conditions:
(a) provide trusted testing or demonstration facilities replicating real-world
biomanufacturing processes, including good manufacturing practices (GMPs)
compliant processes, or their enabling technologies, for process testing,
validation, and small batch manufacturing, including for the investigational
medicinal products for early stages of clinical trials; such enabling technologies
may include digital technologies, with specific applicability in biotechnology
and biomanufacturing;
(b) aim to operate state-of-the-art equipment, laboratories and technical expertise
to support biotechnology and biomanufacturing processes and provide access
thereof;
(c) aim to support hands-on and work-based training programmes aligned with the
Union’s skills and workforce development objectives in the biotechnology and
biomanufacturing sectors or in relation to enabling technologies, such as digital
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technologies, with specific applicability in biotechnology and
biomanufacturing;
(d) conduct applied research in biotechnology or biomanufacturing, or in relation
to enabling technologies, with specific applicability in biotechnology and
biomanufacturing;
(e) seek to engage in partnerships among industry, academia, and public
authorities to ensure the integration of research, innovation, and training in
biotechnology and biomanufacturing or their enabling technologies.
Article 6
Centres of excellence for advanced therapies
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high impact health
biotechnology strategic projects in the form of centres of excellence for advanced
therapies, including for advanced therapy medicinal products (ATMPs), only where
they comply with the conditions laid down in Article 4[(1) and reinforce the Union’s
capability in the area of advanced therapies, by fulfilling all of the conditions set out
in paragraph 2 of this Article.
2. The centres referred to in paragraph 1 shall fulfil all of the following conditions:
(a) specialise in at least one advanced therapy, such as cell and gene therapies;
(b) provide or coordinate advanced infrastructures including downstream
processing, delivery models and the manufacturing of therapies referred to in
point (a);
(c) integrate quality, regulatory science, and safety testing functions supporting
Union-wide development of advanced therapies;
(d) establish structured cooperation among clinical centres, research organisations,
industrial developers of biotechnology products, investors and regulators;
(e) provide multiple services enabling the transition of advanced therapies from
laboratory research to commercial manufacturing, including:
(i) provide acceleration programmes to transform innovative ideas into
viable business propositions;
(ii) provide incubation programmes assisting early-stage companies
requiring GMP infrastructure, technical and regulatory expertise;
(iii) carry out networking and partnership facilitation to foster alliances;
(iv) ensure access to clinical and hospital settings, including for paediatric
patients, for testing, clinical validation, and feedback;
(v) provide education and training for researchers, clinicians, and
developers; and
(vi) ensure the possibility of cross-border access to users from any Member
State.
3. The Commission may adopt implementing acts to detail the conditions listed in
paragraph 2 of this Article, with a view to ensure a consistent approach in their
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implementation across the Member States. These implementing acts shall be adopted
in accordance with the examination procedure referred to in Article 65(2).
Article 7
Designation of the competent authority responsible for assessing applications for
recognition of health biotechnology strategic projects and high-impact health
biotechnology strategic projects
1. Member States shall designate an authority (‘the designated authority’) responsible
for assessing applications for recognition of health biotechnology strategic projects
and high impact health biotechnology strategic projects.
2. Member States shall inform the Commission within six months from the entry into
force of this Regulation of the authority designated pursuant to paragraph 1.
Article 8
Application for recognition of a health biotechnology strategic projects or a high impact
health biotechnology strategic project
1. An application for the recognition of a project as a health biotechnology strategic
project or as a high impact health biotechnology strategic project shall be submitted
by the project promoter to the designated authority referred to in Article 7 of a
Member State on whose territory the project is located.
2. The application referred to in paragraph 1 of this Article shall contain the
relevant evidence related to the fulfilment of the conditions laid down in Article 3 as
regards health biotechnology strategic projects or in Article 4, as regards high impact
health biotechnology strategic projects.
Article 9
Recognition by Member States of health biotechnology strategic projects
1. The designated authority shall assess the application for the recognition of a project
as a health biotechnology strategic project within one month of the receipt of the
complete application and communicate a reasoned decision to the project promoter.
The assessment process shall be fair and transparent.
2. Where the designated authority concludes that the project fulfils the conditions of
Article 3, it shall recognise the project as a health biotechnology strategic project.
3. Member States shall ensure that applicants have easy access to information on
procedures for the settlement of disputes concerning the recognition process,
including, where applicable, alternative dispute resolution mechanisms provided for
by national law.
4. Where a project is located on the territory of two or more Member States, the
decision recognising the project as a biotechnology strategic project issued by the
designated authority of a Member State shall be recognised by the designated
authorities of other Member States.
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Article 10
Recognition by the Commission of high impact health biotechnology strategic projects
1. The designated authority shall assess the application for the recognition of a project
as a high impact health biotechnology strategic project within one month of the
receipt of the complete application and shall communicate its assessment report to
the Commission. The assessment process shall be fair and transparent.
2. Where the designated authority concludes that the project fulfils the conditions of
Article 4, the Commission shall, by means of implementing acts, adopt a decision
approving or rejecting the application for recognition referred to in paragraph 1 of
this Article, based on the assessment referred to in that paragraph and taking into
account the views of the Steering Group referred to in Article 20.
3. By way of derogation from Article 8 and to paragraphs 1 and 2 of this Article, a
project may also be recognised as a high impact health biotechnology strategic
project in the framework of calls for proposals launched under Union programmes
for the purpose of identifying, selecting and funding such projects, in line with the
basic acts setting up those programmes.
The Commission shall recognise a project as a high impact health biotechnology
strategic project in the context of a call for proposals where it fulfils the conditions
set out in Article 4(1) and the specific criteria set out in those calls, based on the
evidence submitted by the applicant.
4. The Commission shall adopt implementing acts laying down the format of the
assessment report referred to in paragraph 1 of this Article and the procedural rules
for the recognition of high impact health biotechnology strategic projects. These
implementing acts shall be adopted in accordance with the examination procedure
referred to in Article 65(2).
SECTION [2]
SUPPORT OF HEALTH BIOTECHNOLOGY STRATEGIC PROJECTS AND HIGH IMPACT HEALTH
BIOTECHNOLOGY STRATEGIC PROJECTS
Article 11
Single points of contact
1. Each Member State shall designate one or more authorities as single points of contact
at the relevant administrative level to facilitate and coordinate the permit-granting
process for health biotechnology strategic projects and high impact health
biotechnology strategic projects and shall provide information on the general
administrative support and the technical and financial support set out in this [Section]
through a dedicated webpage.
2. This single point of contact shall be the same as the single point of contact referred to
in Article 3(2) of the Regulation (EU) ../.. [Regulation on speeding-up environmental
impact assessments -permitting regulation], responsible for facilitating and
coordinating all aspects of the environmental assessments, pursuant to applicable
Union and Member States rules.
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3. The single point of contact shall be the sole point of contact for the project promoter
during the permit-granting process and shall assist the project promoter in handling
any administrative matter relevant to the permit-granting process.
4. It shall coordinate the exchange of documents and information between the project
promoters and the competent authorities and shall notify the promoter of the outcome
of the decision-making process related to permit-granting, in accordance with
national administrative arrangements. The authorities involved in the permit-granting
process and other authorities concerned shall specify and make available to the single
point of contact concerned the requirements and the scope of information requested
of a project promoter.
5. The single point of contact shall direct project promoters to the relevant national and
regional antennas of the EU Health Biotechnology Support Network referred to in
Article 19.
6. Project promoters shall be allowed to submit to the single points of contact any
documents relevant to the permit-granting process in electronic form.
7. Member States shall promote the reuse of existing data, studies and authorisations in
order to avoid duplication of procedures, reduce administrative burden and ensure
consistency of decision-making. For that purpose, they shall ensure that, when
assessing an application, competent authorities duly take into account all relevant
studies, assessments and valid permits or authorisations already carried out or issued
for the same project or its components, provided that they remain applicable and up
to date.
8. Member States shall ensure that the single points of contact and all authorities
involved in the permit-granting process have a sufficient number of qualified staff
and adequate resources.
9. Member States shall ensure that applicants have easy access to information on
procedures for the settlement of disputes concerning the permit-granting process,
including, where applicable, alternative dispute resolution mechanisms provided for
by national law.
Article 12
Priority status of health biotechnology strategic projects
1. Health biotechnology strategic projects shall be considered as contributing to the
strengthening of the biomanufacturing capacity and to the supply resilience of
biotechnology products in the Union and, therefore, shall be considered to be of
public interest.
Health biotechnology strategic projects shall be deemed to contribute to the resilience
objectives referred to in Article 14 of Regulation [Regulation on speeding-up
environmental impact assessments – permitting regulation].
2. For the purposes of this Article, health biotechnology strategic projects shall be
understood to cover also high impact health biotechnology strategic projects.
3. High impact health biotechnology strategic projects shall be considered to be of
public interest and may be considered to have an overriding public interest with
specific consideration given to the high impact strategic nature of such projects in
accordance with Article 14 of Regulation [Regulation on speeding-up environmental
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impact assessments – permitting regulation ] and point I of the Annex to that
Regulation.
4. Where a project is recognised as a health biotechnology strategic project, Member
States shall grant that project the status of project with the highest national
significance possible, where such a status exists in national law and shall ensure that
the relevant process for permit-granting and the licensing procedures, including
environmental assessments and spatial planning, are treated in the most rapid way
possible in accordance with Union and national law and shall benefit from any
accelerated procedures provided for in applicable Union and national law.
5. Health biotechnology strategic projects shall also benefit, where applicable, from the
tacit-approval in accordance with Article 14 and point II of the Annex to [COM
Proposal 2025(984) for a Regulation on speeding-up environmental impact
assessments – permitting regulation].
6. The permit-granting process shall not exceed ten months for health biotechnology
strategic projects, and eight months for high impact health biotechnology strategic
projects, from the date of acknowledgement of the completeness of the permit
application. In duly justified cases requiring complex procedures under Union or
national legislation, such as in the case of multi-site or multi-purpose projects, the
competent authority may extend the period by up to three additional months,
provided that the reasons for such extension are communicated in writing to the
project promoter.
7. Where an environmental impact assessment is required pursuant to Directive
2011/92/EU, the step of the preparation of the environmental impact assessment
report referred to in Article 1(2), point (g)(i), of that Directive shall not be included
in the maximum duration of the permit-granting process referred to in paragraph [5]
of this Article.
8. No later than 45 days from the receipt of the permit-granting application, the single
point of contact shall acknowledge that the application is complete or, if the project
promoter has not sent all the information required to process the application, request
the project promoter to submit a complete application without undue delay,
specifying which information is missing. In the event that the submitted application
is deemed to be incomplete for a second time, the single point of contact may, within
30 days of the second submission, make a second request for information. The single
point of contact shall not request information in areas not covered in the first request
for additional information and shall be entitled only to request further evidence to
complete the identified missing information. The date of the acknowledgement of the
completeness of the application from the single point of contact shall serve as the
start of the permit-granting process for that particular application.
9. All dispute resolution procedures, litigation, appeals and judicial remedies relating to
health biotechnology strategic projects before any national court, tribunal or panel —
including mediation or arbitration — shall be treated as urgent, to the extent that
national law allows such urgency, and without prejudice to the normal rights of
defence of individuals or local communities. Project promoters of health
biotechnology strategic projects shall be able to avail themselves of such urgency
procedures, where applicable. This shall include the dispute-settlement provision in
accordance with Article 14 and point III of the Annex to the Regulation
[…][Regulation on speeding-up environmental impact assessments].
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Article [13]
Administrative support
1. Upon request of a project promoter, Member States shall provide administrative
support to biotechnology projects located on their territory, including health
biotechnology strategic projects and high impact health biotechnology strategic
projects and shall take all appropriate measures to facilitate their timely and effective
implementation, including:
(a) assistance to project promoters to ensure compliance with applicable
administrative, regulatory, and reporting obligations;
(b) support and facilitation of permitting and authorisation procedures; and
(c) assistance to inform the public and those in the vicinity of the project with the
aim of increasing public acceptance of the project;
2. High impact health biotechnology strategic projects shall benefit from priority access
to the administrative support measures referred to in paragraph 1,
3. The administrative support referred to in paragraphs 1 and 2 shall be provided
including through the single points of contact and the national and regional antennas
of the EU Health Biotechnology Support Network referred to in Article 19.
4. Member States shall provide online and in a centralised and easily accessible
manner, information relevant to promoters of biotechnology projects, including
health biotechnology strategic projects and high impact health biotechnology
strategic projects covering at least the following elements:
(a) the designated authority referred to in Article 7(1);
(b) the single points of contact referred to in Article 11;
(c) the national and regional antennas of the EU Health Biotechnology Support
Network referred to in Article 19;
(d) the permit-granting process, including information on dispute settlement;
(e) advice on financing and investment services;
(f) business support services, including corporate tax declaration, local tax rules
and labour law.
5. When providing the administrative support referred to in paragraph 1 of this Article,
Member States shall pay particular attention to SMEs, start-ups and scale-ups. Where
appropriate, Member States shall ensure that a dedicated channel for communication
with SMEs, start-ups and scale-ups is available within the single points of contact to
provide guidance and respond to queries related to the implementation of this
Regulation.
Article 14
Financial and technical support
1. Without prejudice to Articles 107 and 108 TFEU, Member States may make use,
where applicable, of the relevant frameworks for providing public support to health
biotechnology strategic projects and high impact health biotechnology strategic
projects, including national promotional banks and other relevant public support
instruments, as provided for in Article 24, paragraphs (4), (5) and (6). Where public
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support is granted, Member States shall ensure that such support is coordinated with
other support measures at Union or national level and is in line with applicable State
aid rules.
2. Projects recognised as high impact health biotechnology strategic projects:
(a) may be given particular consideration for Union financial support including in
the form of blended financing, under Union programmes, funds and financial
instruments and for national support as provided for in Article 25, if the basic
regulations setting up such Union programmes allow it;
(b) shall benefit from priority status in administrative procedures, including in the
permit-granting process, as provided for in Article 12]and of priority access to
administrative support referred to in Article 13.
3. The Commission, in cooperation with the Member States and, where appropriate,
with the Steering Group referred to in Article 20, shall take the following measures
to support the implementation of health biotechnology strategic projects and of high
impact health biotechnology strategic projects, including through the EU Health
Biotechnology Support Network referred to in Article 19:
(a) support project promoters in identifying funding opportunities at Union level,
and facilitate the liaison between project promoters and investors;
(b) promote actions that strengthen the biotechnology innovation ecosystem;
(c) facilitating access, in particular for SMEs, to relevant research and
technological infrastructures, including where such infrastructures are funded
through Union funding programmes, funds and financial instruments.
Article 15
Networks of health biotechnology clusters
1. The Commission and the Member States shall promote and facilitate the cooperation
and the establishment of networks among promoters of health biotechnology
strategic projects, of high impact health biotechnology strategic projects and other
relevant actors. A particular focus shall be placed on fostering cross-border synergies
between regional and national health biotechnology clusters, and on supporting the
networks constituted under the EU Competitiveness Coordination Tool pilot, in full
compliance with EU competition law.
2. Such networks shall fulfil one or more of the following activities:
(a) facilitate synergies between innovation ecosystems at local, regional and Union
levels;
(b) support the establishing of EU-wide interregional biotechnology value chains;
(c) pool national and Union resources and facilities across several Member States,
bridging and upscaling research, pilot and industrial-scale biomanufacturing,
including through cooperation between regional biotechnology clusters;
(d) provide transparent, open, and non-discriminatory cross-border access at
market prices to research organisations, SMEs, start-ups and scale-ups,
healthcare providers, and industrial actors from across the Union;
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(e) facilitate knowledge transfer, standardisation and inter-cluster collaboration, in
line with competition rules, and the dissemination of best practices;
(f) promote the development of infrastructure and digital platforms, and AI-
enabled technologies supporting biotechnology and biomanufacturing.
3. The networks referred to in this Article may establish governance arrangements
appropriate to their objectives and may, where necessary, constitute themselves as
legal entities under Union law, as appropriate for the implementation of specific
actions and investments.
4. The Steering Group referred to in Article 20 shall provide advice for the support of
the federation and networking of biotechnology clusters.
SECTION 3
ACCESS PRINCIPLES AND STRATEGIC MAPPING
Article 16
Access principles and security safeguards
1. Health biotechnology strategic projects and high impact health biotechnology
strategic projects recognised in accordance with this Regulation that receive financial
support in accordance with Union programmes shall offer open, non-discriminatory,
transparent, and criteria-based access at market prices to their facilities, equipment,
services and training programmes for users, including SMEs, start-ups and scale-ups
and other industrial actors, research organisations or training institutions.
The projects referred to in the first subparagraph shall ensure that access to, and the
operation of their infrastructures, facilities and services comply, where applicable,
with the requirements of Directive (EU) 2022/2555 of the European Parliament and
of the Council67, including with the relevant cybersecurity risk-management and
reporting obligations.
2. The access criteria referred to in paragraph 1 of this Article shall ensure
proportionality and fair treatment among users, while taking into account all of the
following:
(a) the objectives and capacity of the infrastructure concerned;
(b) the need to ensure equitable opportunities in particular for SMEs, start-ups and
scale-ups and research actors;
(c) any safeguards necessary for the protection of security, confidentiality or
economic-security interests, in particular those referred to in paragraph [3].
3. In order to safeguard the Union’s security, public order and strategic interests, access
to biotechnology infrastructures and biotechnology datasets of projects referred to in
67
Directive (EU) 2022/2555 of the European Parliament and of the Council of 14 December 2022 on
measures for a high common level of cybersecurity across the Union, amending Regulation (EU) No
910/2014 and Directive (EU) 2018/1972, and repealing Directive (EU) 2016/1148 (NIS 2 Directive)
(Text with EEA relevance), OJ L 333, 27.12.2022, pp. 80–152. ELI:
http://data.europa.eu/eli/dir/2022/2555/oj
EN 85 EN
paragraph 1 of this Article shall be governed by the rules laid down in the relevant
Union funding programmes under which those projects are funded.
Article 17
Strategic mapping of the Union’s biotechnology ecosystem
1. The Commission, in close cooperation with the Steering Group referred to in Article
20 and where appropriate the AI Board established under the Regulation (EU)
2024/1689, shall conduct, no later than six months after the entry into force of this
Regulation, and maintain thereafter a strategic mapping of the biotechnology
ecosystem in the Union.
2. The strategic mapping shall provide a comprehensive overview of the Union’s
biotechnology and biomanufacturing landscape, to assess existing capacities and
infrastructures, detect gaps, unused capacities, dependencies, and systemic
challenges across the value chains. It shall cover in particular the following areas:
(a) industrial capacity and infrastructures, including on critical intermediates and
key input, relevant to biotechnology research, development, testing, and
manufacturing, and assessment of their distribution, interconnections and
potential gaps;
(b) access to risk-tolerant capital, by analysing public and private funding sources
supporting biotechnology across all stages of development and identifying gaps
in risk-tolerant financing and market incentives;
(c) biotechnology clusters and biomanufacturing ecosystems, by mapping existing
and planned clusters across the Union and assessing opportunities for
coordination, investment, and both cross-border and interregional
collaboration;
(d) skills, upskilling and reskilling, by analysing current and projected workforce
needs, identifying gaps in education and training, and assessing measures to
attract, retain, and upskill talent;
(e) use of data and AI, by assessing access to data, computing and digital
infrastructures for biotechnology and identifying opportunities to foster
responsible AI-enabled innovation and mitigate related risks.
3. The strategic mapping shall be based on information from relevant Union bodies and
agencies, and, where appropriate, industry stakeholders and research organisations.
The Commission may request Member States to submit data necessary for this
purpose, while ensuring the protection of confidential and commercially sensitive
information. The Member States shall submit such data within 30 days from the
request of the Commission.
4. The Commission shall present the findings of the strategic mapping to the Steering
Group.
5. The results of the strategic mapping shall be used for the following purposes:
(a) supporting the identification and prioritisation by the Member States and the
Commission, as appropriate, of potential health biotechnology strategic
projects and high impact health biotechnology strategic projects;
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(b) informing Union policy and funding priorities in biotechnology and
biomanufacturing, including actions in accordance with this Regulation, as
well as initiatives under Union programmes supporting research, innovation,
skills development and industrial competitiveness;
(c) informing the advice of the Steering Group on health biotechnology strategic
projects and high-impact health biotechnology strategic projects and on
initiatives supporting research, innovation, skills and industrial competitiveness
in the biotechnology sector.
Article 18
More favourable treatment
The provisions of this Regulation regarding the permit granting process, the priority status of
health biotechnology strategic projects and of high impact health biotechnology strategic
projects and support for such projects shall apply without prejudice to more favourable
provisions laid down in other Union rules.
SECTION 4
EU HEALTH BIOTECHNOLOGY SUPPORT NETWORK
Article 19
EU Health Biotechnology Support Network
1. The Commission shall set up, coordinate and support an EU Health Biotechnology
Support Network (‘the Network’), consisting of national and regional antennas in the
Member States (‘the antennas’).
2. The Network shall assist and support the developers of health biotechnology
products, in particular SMEs, start-ups and scale-ups, the promoters of biotechnology
projects, including health biotechnology strategic projects and high impact health
biotechnology strategic projects (‘project promoters’) in identifying the relevant
applicable rules and funding, scaling-up and networking opportunities.
3. The Network shall fulfil in particular the following missions:
(a) provide information on the national and Union rules applicable to the
development and placing on the market of health biotechnology products,
including on the applicable authorisation procedures for health biotechnology
products;
(b) information for the identification and use of the applicable regulatory
frameworks and regulatory support mechanisms with regard to innovative
health biotechnology products, as provided for in Article 34;
(c) facilitate the interactions of project promoters with potential public and private
investors including venture-capital funds, corporate partners and national
promotional banks and relevant funding structures and existing networks of
investors, including with the European Innovation Council Trusted Investors
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Network68 through matchmaking initiatives, including host pitch sessions,
demo days and investor forums, in cooperation with the Steering Group
referred to in Article 20, the European Innovation Council and other relevant
Union initiatives;
(d) provide information and support to project promoters for intellectual property
procedures and technology transfer and promote investors’ awareness of Union
regulatory frameworks and responsible-innovation principles;
(e) support project promoters in the identification of scaling up resources,
including business support networks providing advice on commercial readiness
of health biotechnology projects and testing and training facilities, state-of-the-
art pilot plant facilities that simulate a real production environment, and
relevant research and technology infrastructures across the Union, including
technology centres, cutting-edge facilities, and data-sharing platforms to
support the development and testing of health biotechnologies;
(f) support biotechnology actors in the responsible and effective integration of AI,
by providing sector-specific guidance and promoting best practices and
standards for trustworthy AI, in coordination with the bodies established under
Regulation (EU) 2024/1689, and by providing information and support, in
particular to SMEs, start-ups and scale-ups;
(g) facilitate liaison and exchanges among project promoters with a view to
fostering networking and cooperation, including to support networks of health
biotechnology clusters referred to in Article 15;
(h) provide incubation, acceleration and mentorship programmes for
biotechnology start-ups and scale-ups and connect project promoters with
projects and initiatives that address skills and expertise needs in health
biotechnology and biomanufacturing, including with testing, training and
technical support facilities, and regional skills partnerships;
(i) support Member States and the single points of contact in facilitating projects
promoters’ access to administrative support provided in accordance with
Article 13.
4. The Network shall complement and, to the extent possible, rely on existing relevant
organisations and networks at Union and Member State and regional level, including
the European Enterprise Network.
5. The Commission shall select the members of the Network based on criteria made
public pertaining to the expertise and capabilities required to fulfil the missions
referred to in paragraph 3 of this Article, including to the ability to leverage,
complement and strenghten existing national and European networks that support
SMEs, start-ups and scale-ups, and innovators.
The Commission shall organise the management, coordination and support of the
Network.
68
The European Innovation Council (EIC) Trusted Investor Network brings together investors from
across Europe, including venture capital funds, public investment banks, foundations, and corporate
venture arms with experience and commitment to co-invest in promising deep tech start-ups in Europe,
alongside the European Innovation Council Fund. List of members accessible at:
https://eic.ec.europa.eu/eic-fund/trusted-investor-network_en
EN 88 EN
6. The Commission may support the Network through Union funds, programmes, and
instruments, in accordance with the objectives established in their respective basic
acts.
7. Member States shall take all necessary measures to facilitate the fulfilment of the
tasks of the Network.
SECTION 5
EUROPEAN HEALTH BIOTECHNOLOGY STEERING GROUP
Article 20
European Health Biotechnology Steering Group
1. The European Health Biotechnology Steering Group (the “Steering Group”) is
hereby established.
2. The Steering Group shall provide advice to the Commission and to the Member
States to facilitate the implementation of this Regulation and shall carry out the tasks
provided for in this Regulation.
Article 21
Composition and functioning of the Steering Group
1. The Steering Group shall be composed of representatives from all Member States
and the Commission. It shall be chaired by a representative of the Commission (the
‘Chair’).
2. Each Member State shall nominate a member and an alternate member as its
representatives to the Steering Group. Where relevant as regards function and
expertise, a Member State may nominate different representatives in relation to the
different subgroups of the Steering Group, while not exceeding a representative per
subgroup. Nominated permanent representatives shall ensure the necessary
coordination within their respective Member State. The Commission and the
Member States shall have voting rights.
3. The Steering Group shall, upon a proposal by the Commission, adopt its rules of
procedure by a simple majority of its members. Where appropriate, the Chair may
invite external experts to attend meetings of the Steering Group.
4. The Steering Group shall meet as needed in order to allow the effective performance
of its tasks provided for in this Regulation. Where necessary, the Steering Group
shall meet on the basis of a reasoned request by the Commission or by a Member
State. The Commission shall coordinate the work of the Steering Group by means of
a secretariat that provides technical and logistical support.
5. The Steering Group shall carry out the following tasks:
(a) facilitate the exchange of information and best practices among Member
States, the Commission, and relevant stakeholders in relation to the recognition
and the implementation of health biotechnology strategic projects and high
impact health biotechnology strategic projects;
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(b) discuss, at least once a year, the progress in the recognition of health
biotechnology strategic projects and high impact health biotechnology strategic
projects and provide advice including to overcome systemic challenges faced
by such projects;
(c) provide advice for supporting the federation and networking of biotechnology
clusters, as provided for in Article [15[(4)];
(d) discuss and coordinate funding for health biotechnology strategic projects,
including high-impact health biotechnology strategic projects, without
prejudice to the basic acts of the relevant Union programmes; this may include
facilitating the liaison between project promoters and potential private and
public investors, such as the European Investment Bank Group, national
promotional banks and institutions and export credit agencies, to mobilise
additional financing, including from private or venture capital sources;
(e) provide its views regarding the recognition of a project as a high impact health
biotechnology strategic project, in accordance with Article [10][(2)];
(f) facilitate the coordination and information exchange among the Member States
on enforcement of the biosecurity provisions in this Regulation and other
emerging biosecurity topics.
6. The Steering Group may establish subgroups for the purpose of this Regulation.
7. The Steering Group shall take the necessary measures to ensure the safe handling and
processing of confidential and commercially sensitive information.
8. The Steering Group shall use its best endeavours to reach consensus, where possible.
Members with diverging positions may request that their positions and the grounds
on which they are based be recorded in the Steering Group’s position.
CHAPTER III
ACCESS TO FUNDING
Article 22
EU health biotechnology investment pilot
1. To support the financing of, and investments in, companies and projects falling
within the scope of this Regulation, the Commission, together with the European
Investment Bank Group (EIBG) or other implementing partners, shall develop an EU
Health Biotechnology investment pilot (‘the pilot). The pilot is established for an
initial period of two years, after which it shall be reviewed.
2. The pilot shall support the full lifecycle of companies and projects in the area of
health biotechnology, including SMEs, start-ups and scale-ups through direct and
indirect financing, other than direct equity operations, without prejudice to the basic
acts to be agreed under the next Multiannual Financial Frameworks. It shall
complement and be developed in a coordinated manner with other EU financing
instruments.
3. The pilot shall be designed as a mechanism that may use and leverage different
funding streams and instruments to accelerate and catalyse investments into the
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health biotechnology sector. It may be used to provide Union support through Union
programmes.
4. The pilot shall pursue the following objectives:
(a) support early-stage applied research and innovation, technology transfer and
spin-offs, with appropriate financing mechanisms, including equity;
(b) provide support to projects, SMEs, including start-ups and scale-ups, and mid-
caps across the Union, which are providing solutions and developments that
contribute to the objectives of this Regulation;
(c) finance late-stage development initiatives, industrial scale-up and production
capacity build-up for companies that contribute to the objectives of this
Regulation, through venture loans and other suitable debt or quasi-equity
instruments;
(d) anchor growth and manufacturing activities in the Union in order to gain or
maintain strategic autonomy and resilience, as well as boost competitiveness of
the sector;
(e) mobilise private investments, including from institutional investors such as
pension funds, and strengthen the availability of long-term risk finance for
biotechnology companies established in the Union. Financial actors, including
private institutional investors, shall be targeted by leveraging expertise in
catalysing private capital and use appropriate risk-sharing mechanisms to
achieve this objective;
(f) assist early and growth-stage companies through blended and concessional
finance, encompassing equity or debt operations, complementing the direct
equity support provided by the European Innovation Council Fund and the
Scale-Up Europe Fund under the Horizon Europe, including via the
development of new products;
(g) provide advisory support throughout the investment cycle, encompassing
concrete capacity-building measures. These interventions shall be aimed at
reinforcing the competencies and institutional preparedness of developers and
promoters of projects and financial intermediaries to successfully develop and
implement their initiatives.
Article 23
EU biotechnology late-stage capital booster pilot
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union contributing to an EU
biotechnology late-stage capital booster as high-impact health biotechnology
strategic projects, only where in addition to the conditions laid down in Article
[4][(1)], the projects facilitate access to capital markets in accordance with applicable
law, and are led by private-sector operators or consortia, with the potential
participation of market-infrastructure providers and investors.
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2. The projects referred in paragraph 1 of this Article shall pursue at least one of the
following objectives or activities:
(a) facilitating cross-border investment in accordance with Union law;
(b) mobilising long-term capital and attracting private investment, including
institutional investors, and through private markets, with credible commitments
or structures that support liquidity and follow-on financing;
(c) improving cross-border investors’ access and issuers’ visibility through
practical steps and deliverables and demonstrating a credible issuance and
investor pipeline with target numbers and timelines;
(d) enhancing biotechnology sector-specific investment expertise through
exchange of best practices on these topics ;
(e) mobilising private capital through biotechnology accelerators and venture
builders, including potential use of risk-sharing mechanisms.
3. The projects referred in paragraph 1 shall:
(a) ensure non-discriminatory, transparent and criteria-based access for eligible
issuers;
(b) ensure the possibility of cross-border participation from any Member State;
(c) include proportionate risk-management, governance and reporting
arrangements and operate without prejudice to applicable Union financial
services legislation and the mandates of competent authorities.
4. The provisions of this Regulation regarding the application for, and the recognition
of, high-impact health biotechnology strategic projects laid down in Articles 8 and
[10], respectively, apply to projects referred to in this Article.
Article 24
Biotechnology as a strategic technology eligible for Union and national financial support
1. Union programmes may support biotechnology as a strategic technology for the
Union’s innovation capacity, sovereignty, resilience and leadership in line with the
objectives set out in the Regulations establishing those Union programmes.
2. The Commission may adopt calls, windows or compartments for biotechnology and
may establish instruments in the implementation of those programmes, funds and
instruments, that support biotechnology companies, projects and initiatives falling
within the scope of this Regulation, in line with the objectives and rules set out in the
regulations establishing those programmes, funds and instruments.
3. Companies, projects and initiatives falling within the scope of this Regulation may
be targeted for financial support from Union-led funding initiatives and from Union
funding programmes and instruments, as projects in a strategic technology and, as
appropriate, in a strategic deep tech area.
4. Member States may, in line with applicable State aid rules, provide financial support
to biotechnology as a strategic technology for the Union’s innovation capacity,
sovereignty, resilience and leadership.
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5. Member States shall pursue the support as referred to in paragraph 4, including for
health biotechnology strategic projects and high impact health biotechnology
strategic projects, in the implementation at national level of the relevant Union
programmes that are shared-management basic acts.
6. Where State aid instruments, designed in compliance with Union competition law
and making use of related EU guidance, are used by Member States for the purpose
of supporting the health biotechnology sector or parts thereof, Member States shall
give particular consideration to high-impact health biotechnology strategic projects
for support under such instruments.
Article 25
Funding for high impact health biotechnology strategic projects
1. High impact health biotechnology strategic projects may be given particular
consideration for financial support under Union funds, programmes and instruments
in accordance with the objectives set out in the regulations establishing those funds,
programmes and instruments.
2. Where high impact health biotechnology strategic projects benefit from financial
support under Union funds, programmes and instruments, in accordance with the
respective legal bases and eligibility criteria of those funds, programmes and
instruments, such support may be used in combination with financing from the
European Investment Bank Group, from national promotional banks and institutions
or from other development or public financial institutions, as well as in combination
with financing from private-sector finance institutions and from public-sector or
private-sector investors, including through public–public or public–private
partnerships.
3. When preparing and implementing the annual and multiannual work programmes of
the relevant Union funds, programmes and instruments referred to in paragraph 1, the
Commission may give particular consideration to actions supporting high-impact
health biotechnology strategic projects.
4. The Commission shall ensure the coordination and the complementarity among the
relevant Union funds, programmes and instruments that support actions under this
Regulation, and shall provide strategic guidance for the implementation of such
funds, programmes and instruments with regard in particular to the high impact
health biotechnology strategic projects, including in cooperation with the Steering
Group, referred to in Article 20, where appropriate.
Article 26
Coordination of financing for health biotechnology strategic projects
The Steering Group referred to in Article 20 may coordinate investments into health
biotechnology strategic projects, including high impact health biotechnology strategic
projects, with the project promoters and other relevant interested parties, in compliance with
Union competition law.
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CHAPTER IV
EXTENSION OF THE SUPPLEMENTARY PROTECTION CERTIFICATE
Article 27
Extension of the supplementary protection certificate concerning best-in-class
biotechnology medicines developed in the Union
1. Where a marketing authorisation is granted by the Union to a medicinal product for
human use developed by means of biotechnological processes referred to in
paragraph 1 of Annex I to Regulation (EU) …/… [reference to be added after
adoption cf. COM(2023) 193 final] or to an advanced therapy medicinal product
referred to in paragraph 2 of that Annex, and that is protected either by a
supplementary protection certificate in accordance with Regulation (EC) No
469/2009 of the European Parliament and of the Council69, or by a patent which
qualifies for the granting of such supplementary protection certificate, the holder of a
patent or of such certificate shall be entitled to a 12-month extension of the periods
referred to in Article 13, paragraphs (1) and (2), of Regulation (EC) No 469/2009,
provided that the marketing authorisation applicant demonstrates that all of the
following conditions are met:
(a) the medicinal product contains a new active substance distinctly different from
that of any authorised medicinal product in the Union;
(b) the medicinal product has a mechanism of action distinctly different and shows
a level of safety and efficacy which is at least equivalent to that of any
authorised medicinal product in the Union for the same disease;
(c) the clinical trials evaluating the efficacy of the medicinal product and
supporting its marketing authorisation were conducted in more than two
Member States;
(d) at least a manufacturing step, excluding packaging, quality testing and
certification is performed in the Union.
2. The European Medicines Agency (‘the Agency’) shall assess compliance with the
conditions referred to in paragraph 1 as part of the marketing authorisation procedure
concerned.
3. Where compliance is confirmed, the Agency shall issue a statement to that effect.
4. A copy of the statement referred to in paragraph 3 of this Article shall be included in
the application for a certificate lodged under article 7 of Regulation (EC) No
469/2009.
69
Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009
concerning the supplementary protection certificate for medicinal products, OJ L 152, 16.6.2009, pp. 1.
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CHAPTER V
ENHANCING COMPETITIVENESS IN BIOSIMILARS
Article 28
Guidance by the Agency on biosimilars
The Agency, in consultation with the Commission, shall develop and update non-binding
guidance on a tailored regulatory approach for the development of biosimilars, reflecting
advances in manufacturing and analytical testing. The guidance shall consider a potential
reduction of the clinical data required for the development and approval of biosimilars,
without affecting their quality, safety and efficacy.
Article 29
Biotechnology health strategic projects for biosimilars
To enable access to the support measures laid down in Section II of Chapter II, Member
States shall recognise projects located in the Union as biotechnology health strategic projects
in the form of biotechnology health strategic projects for biosimilars only where they make a
substantial contribution to at least one the specific objectives referred to in Article [3][(1)] and
fulfil either of the following conditions:
(a) they contribute to the setting up and extension of innovative biomanufacturing
capacity, and infrastructures for analytical testing procedures;
(b) they contribute to the research, development and marketing authorisation of
biosimilars, and where appropriate to strengthening the use of platform technologies;
this includes analytical methodologies that would reduce the need for clinical data
for biosimilars, without affecting their quality, safety and efficacy.
Article 30
International partnerships
Where appropriate, promoters of projects related to biosimilars and other companies working
in this area, shall explore opportunities to establish or strengthen cooperation with
international biotechnology clusters, including with a view to fulfilling the conditions referred
to in Article [29] for the recognition of biotechnology health strategic projects for biosimilars.
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CHAPTER VI
ARTIFICIAL INTELLIGENCE AND DATA AS BIOTECHNOLOGY ENABLERS
Article 31
Guidance on the deployment and use of systems based on advanced technologies,
including AI, in the lifecycle of medicinal products
1. The Agency shall publish and regularly update, as appropriate, non-binding guidance
on the deployment and use of systems based on advanced technologies, including
AI, in the lifecycle of medicinal products development, including during pre-clinical
research, clinical development and trials, manufacturing and post-authorisation
monitoring.
Such guidance shall be developed, updated and published in agreement with the
Commission, including with the AI Office.
Such guidance shall ensure full coherence with the requirements laid down in
Regulation (EU) 2024/1689 and with any guidance issued under that Regulation
regarding general-purpose AI models or AI systems.
2. In developing and updating the guidance referred to in paragraph 1, the Agency shall
consult the relevant authorities, at national and European level, and stakeholders as
appropriate.
To the extent that the guidance concerns the deployment and use of systems based on
advanced technologies, including AI, across the clinical trials lifecycle, the Agency
shall further cooperate with the Clinical Trials Coordination [and Advisory] Group
(‘CTAG’) referred to in Article [85] of Regulation (EU) No 536/2014, with the
Medical Device Coordination Group (‘MDCG’) referred to in Article 103 of
Regulation (EU) 2017/745 and with the Artificial Intelligence Board referred to in
Article 65 of Regulation (EU) 2024/1689, as appropriate and shall publish that
guidance in agreement with the consulted entities referred to in this subparagraph.
3. The Agency shall develop and publish in agreement with the Commission, including
the AI Office where appropriate, and in cooperation with the national competent
authorities, non-binding guidance on the deployment and use of advanced
technologies, including AI, in the procedures for the authorisation of medicinal
products.
Article 32
Biotechnology testing environments for advanced biotechnology innovations
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high impact health
biotechnology strategic projects in the form of trusted testing environments for
advanced health biotechnology innovations, where such innovations are enabled,
enhanced or significantly supported by AI or advanced computational methods, only
where they comply with the criteria laid down in Article 4(1) and substantially
strengthens the Union’s capacity for responsible experimentation, development,
testing and validation of such innovations and they fulfils all of the following
conditions:
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(a) operate under trusted conditions ensuring compliance and alignment with
relevant Union and national legislation and complements where appropriate
testing and experimentation facilities and AI regulatory sandboxes established
in accordance with Regulation (EU) 2024/1689, while ensuring consistency
and synergies in their implementation;
(b) seek, where appropriate, to leverage AI systems or other advanced
computational tools, alongside advanced technologies and analytics, to
optimise workflows and increase efficiency;
(c) aim to enable innovation in biotechnology areas where the use of AI-enabled or
computationally enhanced methods can be particularly impactful, such as
enhancing efficacy and safety of immunology treatments and of ATMP gene
therapies, or developing NAMs that combine advanced experimental and
computational approaches;
(d) make available, under fair and transparent conditions, evidence, results and
lessons learned generated within such testing environments, to inform Union
guidance, standardisation and best-practice frameworks, and, where
appropriate, the design or implementation of regulatory sandboxes in
accordance with Union or national law.
2. The Commission, in cooperation with the Member States, shall promote and
facilitate, including through existing networks such the European Digital Innovation
Hubs and testing and experimentation facilities and relevant expert groups
established under Union legislations, networking, knowledge-sharing and capacity-
building among projects and initiatives providing such testing environments.
3. The provisions of this Regulation regarding the application for, and the recognition
of, high-impact health biotechnology strategic projects laid down in Articles 8 and
10, respectively, apply to projects referred to in this Article.
Article 33
Biotechnology data quality accelerator
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high impact health
biotechnology strategic projects in the form of biotechnology data quality
accelerators, only where they comply with the criteria laid down in Article 4(1) and
fulfil the conditions laid down in paragraph 2 of this Article and they make a
significant contribution to the curation, maintenance and responsible use of high-
quality, appropriately annotated and provenance-verified datasets that are essential
for the training, validation and testing of AI systems and models used in health
biotechnology applications.
2. The projects referred to in paragraph 1 shall:
(a) aim to foster the development and deployment of trustworthy and competitive
AI systems in health biotechnologies, including large-scale and general-
purpose models relevant for biological, biomedical or biomanufacturing use
cases;
(b) assist entities that lawfully hold relevant data and, as regards health data,
holders as defined in Article 2(2), point (t), of Regulation (EU) 2025/327
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(‘health data holders’) to improve data quality, standardize and make other
improvements to such data as referred to in paragraph 1 of this Article;
(c) contribute to the development of Union standards and quality frameworks for
data representativeness, provenance, interoperability and annotation in
biotechnology;
(c) give due consideration to the interoperability with platforms deployed pursuant
to the European Health Data Space (EHDS) and other relevant data spaces;
(d) be aligned with and complement Union initiatives such as the Data Union
Strategy, including data labs and AI factories, while addressing the specific
requirements of biotechnology datasets, including biological metadata,
scientific taxonomies, experimental traceability and regulatory-grade data
quality.
3. The provisions of this Regulation regarding the application for, and the recognition
of, high-impact health biotechnology strategic projects laid down in Articles 8 and
10, respectively, apply to projects referred to in this Article.
4. The processing of personal data by the entities that lawfully hold the relevant
datasets enhanced as provided for in paragraph 2, point (b) of this Article, and by the
biotechnology data quality accelerator projects takes place in the public interest.
5. Entities that lawfully hold relevant datasets enhanced as provided for in paragraph 2,
point (b) of this Article, shall make available such datasets under fair, reasonable and
non-discriminatory conditions, ensuring equitable access for users including research
organisations, SMEs and public institutions, under the conditions referred to in
Article 16 of this Regulation.
Electronic health data referred to in Article 51 of Regulation (EU) 2025/327 shall be
made available in accordance with that Regulation.
6. Entities that lawfully hold relevant datasets enhanced as provided for in paragraph 2,
point (b) of the Article, shall support, where appropriate, the integration of such
datasets into Union infrastructures, including the European Research Area data
spaces, data labs, AI factories and the infrastructures operated by high impact health
biotechnology strategic projects.
7. The decision of the Commission regarding the recognition of a high impact health
biotechnology strategic project in the form of a biotechnology data quality
accelerators, referred to in Article 10(2), shall specify the modalities of processing of
personal data necessary to achieve the purpose of the project. In particular the
Commission shall specify the categories of data to be processed, the roles of the
entities participating in the project, the categories of the entities which may use the
curated data and the safeguards.
8. With regard to biotechnology data quality accelerators recognised in the context of a
call for proposals as provided for in Article 10(3), the Commission shall, by means
of implementing acts, adopt, before the launch of the related call, a decision
establishing the modalities of processing of personal data necessary to achieve the
purpose of the project. That decision shall specify the categories of data to be
processed, the roles of the entities participating in the project, the categories of the
entities which may use the curated data and the safeguards. The selected
beneficiaries shall comply with the conditions laid down in that decision.
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CHAPTER VII
REGULATORY TOOLS FOR NOVEL HEALTH BIOTECHNOLOGY PRODUCTS
SECTION 1
SUPPORT IN DETERMINING THE REGULATORY STATUS OF NOVEL HEALTH BIOTECHNOLOGY
PRODUCTS
Article 34
Assistance on regulatory procedural pathways
1. The EU Health Biotechnology Support Network referred to in Article 19 shall, upon
request, assist developers, in particular SMEs, start-ups and scale-ups, with
identifying and using the appropriate regulatory procedural pathway and regulatory
support mechanisms with regard to innovative health biotechnology products or
biotechnology services for human use that exhibit characteristics that raise questions
on the application or applicability of the Regulation (EU) 2017/745, Regulation (EU)
2017/746, Regulation (EU) 2024/1938, Regulation (EU) …/… [reference to be
added after adoption cf. COM(2023) 193 final] and Regulation (EU) …/…
[reference to be added after adoption cf. COM(2023) 192 final] Regulation (EC)
1394/2007 and Directive 2010/45/EU.
2. The support provided pursuant to this Article shall not duplicate procedures
pertaining to recommendations or opinions on regulatory status set out in with
Regulation (EU) 2017/745, Regulation (EU) 2017/746, Regulation (EU) 2024/1938,
Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 193
final] and Regulation (EU) …/… [reference to be added after adoption cf.
COM(2023) 192 final] .
3. The support referred to in paragraph 1 shall be provided in particular on the
following:
(a) procedures for seeking guidance on the regulatory status and on the nature and
scope of such guidance;
(b) applicable rules for the authorisation of health biotechnology products that
combine different products, technologies, processes, or components regulated
under different regulatory frameworks;
(c) regulatory sandboxes established in Article 40 and under [revised Regulation
(EU) 2017/745], [revised Regulation (EU) 2017/746], Regulation (EU)
2024/1938 and in Regulation (EU) …/… [reference to be added after adoption
cf. COM(2023) 193 final].
4. In providing the support referred to in this Article, the EU Health Biotechnology
Support Network referred to in Article 19 may request the assistance of the Foresight
Panel for Emerging Health Innovation.
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Article 35
Union regulatory status repository
1. The Commission shall compile, maintain, develop and make publicly available a
regulatory status repository (‘regulatory status repository’).
2. The regulatory status repository shall contain:
(a) decisions, opinions, scientific recommendations regarding the regulatory status
of a health innovations, issued pursuant to the mechanisms laid down in Article
4 of Regulation (EU) 2017/745, Articles 61 and 62 of Regulation (EU) …/…
[reference to be added after adoption cf. COM(2023) 193 final], Article 13 of
Regulation (EU) 2024/1938, and, where relevant, pursuant to similar
mechanisms laid down in other legislative acts;
(b) the summaries of the scientific recommendations delivered by the Agency,
prior to the application of Regulation (EU) …/… [reference to be added after
adoption cf. COM(2023) 193 final], in accordance with Article 17 of
Regulation (EC) No 1394/2007 on whether a product falls within the definition
of an advanced therapy medicinal product or not;
(c) the discussion papers delivered by the Foresight Panel for Emerging Health
Innovation.
3. Member States shall make publicly available, through the relevant national platforms
or registries, decisions, opinions, scientific recommendations, and other outputs
issued at national level concerning the regulatory status of health biotechnology
products. Member States shall inform the Commission where such information is
made available.
Article 36
Time limits in the regulatory status process
With a view to ensuring the timely assessment of the regulatory status of health biotechnology
products, the advisory bodies and other relevant entities mandated under [revised Regulation
(EU) 2017/745, [revised Regulation (EU) 2017/746], Regulation (EU) 2024/1938
Regulation], Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 193
final] and Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 192
final] to provide a recommendation or opinion, including preparatory consultations, on the
regulatory status of a product, shall act swiftly, without prejudice to the time limits for the
forming of such recommendations or opinions established in the above legal acts.
SECTION 2
FORESIGHT ON EMERGING HEALTH INNOVATION
Article 37
Foresight Panel for Emerging Health Innovation
1. A Foresight Panel for Emerging Health Innovation is hereby established ('the
Foresight Panel').
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2. The Foresight Panel shall provide regulatory, scientific and technical expertise on
emerging science and technology in the field of health underpinning the development
of health biotechnology products to the Commission, the Agency and to relevant
Union-level advisory bodies and competent authorities and other entities in the
Member States in the area of health. The Foresight Panel shall operate in accordance
with the Commission’s framework for expert groups.
3. The Foresight Panel shall carry out the following tasks:
(a) conduct horizon scanning by analysing, identifying and discussing emerging
science and technology with the potential to drive the development of health
biotechnology products, including upon request from the Commission, the
Agency, Union-level advisory bodies or competent authorities in the Member
States in the area of health, and develop and publish related considerations in
the form of discussion papers
(b) engage with the Agency and relevant Union-level advisory bodies and
competent authorities and other entities in the Member States in the area of
health, to facilitate cross-framework dialogue and consistency;
(c) engage with existing relevant networks to contribute to enhancing regulatory
expertise regarding health biotechnology products.
(d) accommodate exchanges among the authorities responsible for the setting up
and the operation of regulatory sandboxes in accordance with article 39(5).
4. For the purpose of performing the tasks referred to in paragraph 2, point (a), of this
Article, the Foresight Panel may engage in preliminary discussions with the Agency
or relevant Union level advisory bodies in the area of health, networks and informal
task forces, national competent authorities, developers, and other relevant actors and
shall implement a collaborative approach with a view to ensuring an effective uptake
of its discussion papers.
5. The Foresight Panel shall consist of scientific and regulatory experts from the SoHO
Coordination Board (‘the SCB’), the Medical Devices Coordination Group (‘the
MDCG’), the Coordination group on Health Technology Assessment (‘the
HTACG’), the Agency and the competent authorities of the Member States,
appointed by the Commission in view of their regulatory, scientific or technical
expertise in the relevant identified fields and frameworks. The panel may invite
external experts selected to assist with specific tasks when such relevant external
expertise is needed.
6. The Commission shall adopt an implementing act laying down detailed rules on the
selection, composition, number of members, and functioning of the Foresight panel.
The implementing act shall be adopted in accordance with the examination procedure
referred to in Article 65(2).
Article 38
Support to the Foresight Panel for Emerging Health Innovation
1. The Commission shall chair and provide the secretariat for the Foresight Panel and
shall provide the support necessary to ensure it can efficiently perform its tasks.
2. The Commission shall in particular have the following tasks:
(a) to provide administrative and technical support to the Foresight Panel;
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(b) to facilitate and manage remote and physical meetings of the Foresight Panel;
(c) to ensure that the work of the Foresight Panel is carried out in an independent
manner;
(d) to facilitate the dissemination of the discussion papers produced by the
Foresight Panel with relevant competent authorities and advisory bodies;
(e) to ensure that remuneration and expenses are provided to the experts
composing the Foresight Panel;
(f) to monitor compliance with the rules of procedure of the Foresight Panel;
(g) to issue annual reports on the work of the Foresight Panel, including on the
number of discussion papers delivered by the Panel.
3. The Foresight panel shall establish its own rules of procedure.
SECTION 3
REGULATORY SANDBOXES AS TOOLS FOR NOVEL HEALTH BIOTECHNOLOGY PRODUCTS
Article 39
Regulatory sandboxes provided for in the applicable frameworks and cross-framework
communication
1. Where a regulatory sandbox is established at Member State level for a health
biotechnology product in accordance with [revised Regulation (EU) 2017/745],
[revised Regulation (EU) 2017/746], Regulation (EU) 2024/1938, the authorities
responsible for the operation of that sandbox shall, where appropriate and in
accordance with the relevant legislative act referred to in this paragraph, conduct
consultations with the competent authorities and the Commission, responsible for the
operation of sandboxes under the other relevant Union legislative acts referred to in
this paragraph and in paragraph 2 of this Article, and with the Foresight Panel
referred to in Article 37, regarding the design and the implementation of the
regulatory sandbox.
2. Where a regulatory sandbox is established at Union level for a health biotechnology
product in accordance with Regulation (EU) …/… [reference to be added after
adoption cf. COM(2023) 193 final] or with Article [40] of this Regulation, the
Commission or the Agency shall consult, where appropriate and in accordance with
the legislative acts referred to in this paragraph, the Agency, the SCB, the MDCG,
and the Foresight Panel referred to in Article 37, regarding the design and the
implementation of the regulatory sandbox.
3. The authorities responsible, pursuant to the applicable legislative act, for setting up a
regulatory sandbox referred to in paragraphs 1 and 2 of this Article, shall ensure that
due consideration is given to the regulatory challenges posed by combination
products, and to consultations with the relevant authorities with expertise regarding
the associated parts of such products.
4. For the purposes of the consultations referred to in paragraphs 1 and 2 of this Article,
all authorities shall endeavour to provide their contribution swiftly, without prejudice
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to time limits set out in the provisions of the Union legislative acts in the area of
health governing the regulatory sandbox referred to in those paragraphs.
5. The Commission, the Agency, the MDCG and the SCB shall, through the Foresight
Panel, facilitate the exchange of views and experiences among the authorities
responsible for the setting up and the operation of regulatory sandboxes for health
biotechnology products. Those exchanges shall include the following:
(a) promoting knowledge sharing, by facilitating the exchange of information,
experiences and best practices, including on regulatory approaches,
technological challenges, and emerging scientific insights and the appropriate
regulatory responses (cross-framework knowledge sharing);
(b) identifying potential implications for the evolution or adaptation of the relevant
Union legislative acts in the area of health (cross-framework regulatory
learning).
Article 40
Regulatory sandboxes for novel health biotechnology products not falling under other
regulatory sandboxes in Union legislation in the area of health
1. Upon a substantiated request from developers, the Commission may set up a
regulatory sandbox that provides a controlled regulatory environment for the testing
and development of a health biotechnology product, that:
(a) cannot be appropriately accommodated in any of the regulatory sandboxes
available under the Union legislation in the area of health referred to in Article
39, paragraphs (1) and (2); and
(b) whose development is hindered by the challenge to identify a suitable
regulatory procedure in the area of health.
A regulatory sandbox shall not be set up for health biotechnology products which are
likely to fall under the scope of the Union legislation in the area of health referred to
in Article 39, paragraphs (1) and (2).
The sandbox shall be set up in accordance with this Article.
2. Such regulatory sandbox shall set out a time limited framework to allow for the
generation of evidence and data, in a real-world environment and under supervision
of one or more competent authorities.
3. Developers wishing to participate in a regulatory sandbox referred to in paragraph 1
shall submit a substantiated application to the Commission. That application shall
include the following:
(a) a justification for the establishment of a regulatory sandbox, including a
description of the product in question, its level of development, and a
justification with regard to the impossibility of appropriately accommodating
the proposed sandbox in any of the regulatory sandboxes available under the
Union legislation in the area of health referred to in Article 39, paragraphs (1)
and (2).
(b) the identification of existing regulatory challenges;
(c) the assessment of potential benefits and potential risks of the health
biotechnology product to be tested or developed.
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4. Where the Commission concludes, on the basis of its assessment, that the application
shall be accepted, it shall take a decision regarding the establishment of a regulatory
sandbox, by means of an implementing act, in accordance with the examination
procedure referred to in Article 65(2). That implementing act shall set out the
duration of the regulatory sandbox and the principles for operating the regulatory
sandbox.
5. The testing and development activities within the regulatory sandbox shall take place
in accordance with a sandbox plan developed and updated as appropriate by the
Commission based on the principles referred in paragraph 4 of this Article. The
regulatory sandbox plan shall:
(a) set out the objectives, the specific innovations to be tested in the regulatory
sandbox, the relevant activities to be carried out within the regulatory sandbox,
the geographical and temporal scope of those activities, as well as the relevant
conditions and requirements thereof;
(b) be informed by data provided by, and consultations with, the developer of the
health biotechnology product concerned;
(c) identify the participants in the regulatory sandbox and their respective roles;
(d) include appropriate measures to mitigate potential risks, in particular to health
and to the environment;
(e) include conditions regarding the suspension or the termination of the regulatory
sandbox;
(f) set out the supervision measures and the related responsibilities.
6. When assessing the applications received in accordance with paragraph 3 of this
Article and when developing and implementing the sandbox plan, the Commission
may consult the Agency, the SCB, the MDCG, or the Foresight Panel, as appropriate.
7. Participants in the regulatory sandbox, in particular the developer, shall remain liable
under applicable national legislation for any harm inflicted on third parties as a result
of the testing taking place in the sandbox. They shall inform the Commission without
undue delay of any information which might entail the amendment of the regulatory
sandbox or concerns the quality, safety or efficacy of products developed as part of a
regulatory sandbox.
8. The regulatory sandboxes shall not affect the supervisory and corrective powers of
the competent authorities. In case of identification of risks to public health or safety
concerns associated with the use of products covered by a sandbox, competent
authorities shall take immediate and adequate temporary measures in order to
suspend or restrict their use and inform the Commission. Where such mitigation is
not possible or proves to be ineffective, the development and testing process shall be
suspended without delay until an effective mitigation takes place.
9. When concluding the regulatory sandbox, the Commission shall, at the request of a
developer and after having consulted the bodies referred to in paragraph [6] of this
Article, deliver a recommendation on an existing appropriate regulatory procedural
pathway for authorising the placing on the market and post-marketing surveillance
and vigilance of the products concerned.
10. When a product is submitted for authorisation following a recommendation delivered
in accordance with paragraph 9 of this Article, due consideration by the authorities
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responsible for the assessment of the application for authorisation shall be given to
data and evidence collected in the regulatory sandbox.
11. The Commission, after consulting competent authorities of the Member States, and
after seeking the opinion of the bodies consulted in accordance with paragraph [6] of
this Article, may publish a report on the lessons learned from the regulatory sandbox
and, where appropriate, conclusions regarding possible measures at Union level for
the regulation of the health biotechnology product or similar innovation categories
concerned by the regulatory sandbox.
12. The Commission may, by means of implementing acts, lay down common principles,
criteria and practical arrangements for the assessment of applications received from
developers and for the establishment and supervision of the regulatory sandboxes and
for sandbox plans referred to in this article. These implementing acts shall be
adopted in accordance with the examination procedure referred to in Article 65(2).
CHAPTER VIII
BIODEFENCE AND PREVENTING BIOTECHNOLOGY MISUSE
SECTION 1
UNION BIODEFENCE AND BIOSECURITY
Article 41
EU biothreat radar high impact health biotechnology strategic projects
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high-impact health
biotechnology strategic projects contributing to the EU Biothreat Radar for the
detection, characterisation, identification, analysis and assessment of biological
threats, including novel, unknown and engineered pathogens to ensure pathogen-
agnostic cross-border surveillance and early threat detection, as well as the generation
and sharing of data required for this, only where they comply with the conditions laid
down in Article 4[(1)] and make a substantial contribution to at least one of the
following:
(a) detection, characterisation, identification, analysis and assessment of biological
threats, including novel, unknown and engineered pathogens;
(b) interoperable and pathogen-agnostic cross-border surveillance, as well as the
generation and sharing of data required for such surveillance;
(c) building sampling and detection infrastructure for early detection of novel pathogens
and situational awareness across environmental and clinical sources, including basic
logistics for collection and transport, and support for the deployment of advanced
detection methods, such as metagenomic sequencing;
(d) ensuring the appropriate use of internationally recognised pathogen data standards;
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(e) ensuring that sequencing data generated through early detection activities is shared in
a timely manner through the European Nucleotide Archive (ENA)70, to enable access
and use by actors across the Union for the development, validation and deployment
of advanced pathogen detection and characterisation methods, by engaging in
partnerships among industry, academia, public authorities and defence actors to
ensure data sharing and integration of warning systems.
2. The provisions of this Regulation regarding the application for, and the recognition
of, high-impact health biotechnology strategic projects laid down in Articles 8 and
10, respectively, apply to projects referred to in this Article.
Article 42
Biodefence capability high impact strategic project
1. To enable access to the support measures laid down in Section 2 of Chapter II, the
Commission shall recognise projects located in the Union as high impact health
biotechnology strategic projects for biodefence capability only where they comply
with the conditions laid down in Article 4(1) and make a substantial contribution to at
least one of the following:
(a) preventing or mitigating misuse of biotechnologies;
(b) rapid surge capacity for safe sampling, testing sequencing and swift manufacturing
of rapid diagnostics;
(c) analysis and assessment capacity of testing and sequencing data that can be
mobilised across Member States;
(d) robust pathogen-agnostic pharmaceutical and non-pharmaceutical defences against
biological threats;
(e) development, validation and benchmarking of methods for the detection and
attribution of genetic engineering, including the creation of open genetic engineering
detection tools;
(f) civilian and defence research, testing or demonstration infrastructures for
biotechnology activities relevant to defence, security and resilience, provided that
governance ensures clear separation of mandates and access regimes, with
appropriate confidentiality and security safeguards, in line with relevant
requirements arising from the Convention on the Prohibition of the Development,
Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and
on their Destruction (‘BTWC’), Union and national law.
2. The provisions of this Regulation regarding the application for, and the recognition
of, high-impact health biotechnology strategic projects laid down in Articles 8 and
10, respectively, apply to projects referred to in this Article.
70
ENA, https://www.ebi.ac.uk/ena.
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SECTION 2
PREVENTION OF BIOTECHNOLOGY MISUSE
Article 43
Biotechnology products of concern
1. Biotechnology products of concern in Annex I shall only be made available to,
introduced, or used by any natural or legal person in the Union, as well as made
available to any natural or legal person outside the Union, that has a legitimate need
for those products, in accordance with this Section.
2. The Commission is empowered to adopt delegated acts in accordance with Article 64
(2) to amend Annex I by adding, removing or modifying categories of biotechnology
products of concern, setting or adjusting thresholds or exclusions, and specifying
technical parameters, in order to reflect developments in scientific evidence,
biosecurity and biosafety risks or patterns of misuse, also considering the latest
developments under relevant international fora and instruments.
Article 44
Verification of legitimate need
1. An economic operator that makes available on the Union market, including through
online marketplaces, biotechnology products of concern, shall, for each transaction,
verify proof of identity of the prospective customer, record the transaction, including
the quantities ordered, and assess whether the customer has a legitimate need.
2. For the purposes of conducting the verification referred to in paragraph 1, the
economic operator shall request the following information from the prospective
customer prior to facilitating the exchange:
(a) proof of identity of the person;
(b) institutional or corporate affiliation;
(c) documentation establishing the legitimacy of the institution or corporation,
such as address, any official registration number, evidence of legal personality
and of a purpose, and, where applicable, evidence of authorisations,
certifications or biosafety approvals appropriate to the intended use;
(d) information on the intended use of the product.
The first subparagraph, with the exception of transaction recording, shall not apply
where the economic operator has conducted an equivalent verification for the same
customer within the preceding five years and the new transaction does not
significantly deviate in nature or scale from previous transactions.
3. When assessing legitimate need, the economic operator shall take into account all
relevant circumstances, in particular, as applicable:
(a) the demonstrable need for the biotechnology product of concern and the
legitimacy of its intended use;
(b) the background of the applicant;
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(c) the applicant’s compliance history with the economic operator and, where
available, with other operators, including past incidents or refused orders;
(d) credentials that demonstrate evidence of the legitimate need, including relevant
academic publications, history or track record in a related domain;
(e) documentation establishing the existence of suitable facilities, competencies
and biosafety arrangements appropriate to the intended use.
4. The economic operator shall refuse to make the biotechnology products of concern
available in the case of a suspicious transaction.
5. The economic operator shall report to the national contact point referred to in Article
46(3) any suspicious transaction, or attempted suspicious transaction, in accordance
with Article 46(5).
6. Economic operators shall keep and retain records of the transactions referred to in
this Article for three years and shall make them available without undue delay to the
competent authorities upon request.
7. Paragraphs 1 to 7 shall also apply by analogy to persons that are not economic
operators, except in the case where the biotechnology product of concern is supplied
to a person that is employed by the same legal entity.
Article 45
Benchtop equipment
Benchtop nucleic acid synthesis devices made available in the Union shall contain a
mechanism to screen for sequences of concern as defined in Annex I, provided that databases
of sequences of concern are not stored on the equipment itself, in an unencrypted manner or a
manner that could allow users to extract the database.
Article 46
Prevention and reporting of biotechnology misuse
1. For the purpose of preventing and detecting biotechnology misuse, economic
operators and online marketplaces shall report suspicious transactions, having regard
to all circumstances and in particular where the prospective customer:
(a) is not clear about their identity or affiliations, or provides information that
cannot be confirmed or verified, including inconsistent addresses or
unverifiable company details;
(b) would not be expected, in the normal course of business, to place such an
order, including where there is no link to life science research or
biotechnology, or no plausible requirement for biotechnology products of
concern;
(c) proposes an intended use that does not match their reported job role or
institutional affiliation;
(d) requests unusual labelling or shipping procedures, including misidentification
of goods on packaging or changes to the recipient’s name after the order has
been placed but before shipment;
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(e) proposes unusual methods of payment, including cash for high-value items,
personal credit cards for institutional purchases, or payment through non-bank
third parties, or offers unusually favourable terms including above market
prices;
(f) requests unusual confidentiality conditions regarding the order, including with
respect to their identity, the final destination or the destruction of transaction
records;
(g) requests delivery to an address without a legitimate biotechnology business or
research justification, including a residential address.
2. Economic operators and online marketplaces shall have appropriate, reasonable and
proportionate procedures in place to detect suspicious transactions, adapted to the
specific environment in which biotechnology products of concern are made
available.
3. Each Member State shall set up at least one national contact point with clearly
identified contact details, web form or other effective tool for the reporting of
suspicious transactions of biotechnology products of concern. The contact point shall
be part of or have direct links to law enforcement and national inspection authorities.
4. Economic operators and online marketplaces shall refuse a suspicious transaction.
They shall report any suspicious transaction or attempted suspicious transaction
within 24 hours of determining that it is suspicious. Reports shall include, where
possible, the identity of the prospective customer and the facts that led to the
suspicion and shall be addressed to the national contact point of the Member State
where the transaction was concluded or attempted.
5. Where a biotechnology product of concern falls also under categories regulated
under other EU legislation, to avoid duplication of reporting, where the transaction
for that biotechnology product of concern has already been reported as a suspicious
transaction under one legal framework, it shall not be reported again. Where in
doubt, its intended use should be prioritised for reporting obligations, pursuant to
Regulation (EU) 2021/821[71] and Regulation (EU) 2019/1148[72].
Article 47
Training and awareness-raising
1. Member States shall ensure adequate resources for, and the provision of, training for
law enforcement authorities, first responders and customs authorities to recognise
biotechnology products of concern and to react in a timely and appropriate manner to
suspicious activity.
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Regulation (EU) 2021/821 of the European Parliament and of the Council of 20 May 2021 setting up a
Union regime for the control of exports, brokering, technical assistance, transit and transfer of dual-use
items, OJ L 206, 11.6.2021, pp. 1–461. ELI: http://data.europa.eu/eli/reg/2021/821/oj.
72
Regulation (EU) 2019/1148 of the European Parliament and of the Council of 20 June 2019 on the
marketing and use of explosives precursors, amending Regulation (EC) No 1907/2006 and repealing
Regulation (EU) No 98/2013 (Text with EEA relevance), OJ L 186, 11.7.2019, pp. 1–20.
ELI: http://data.europa.eu/eli/reg/2019/1148/oj.
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2. Member States shall organise awareness-raising actions, including on the issue of
insider threats, adapted to the specificities of each sector that uses biotechnology
products of concern.
3. To facilitate cooperation and effective implementation, and avoid duplicate
reporting, Member States shall organise regular exchanges between law enforcement
authorities, national supervisory authorities, economic operators, online marketplaces
and representatives of sectors that use biotechnology products of concern.
4. Economic operators shall inform their personnel about the conditions under which
biotechnology products of concern may be made available and shall raise personnel’s
awareness accordingly.
Article 48
National inspection authorities
1. Each Member State shall designate a competent authority responsible for the
inspection and control of compliance with the obligations laid down in this Section.
2. Member States shall ensure that the national inspection authority has the resources
and investigative powers necessary to perform their tasks, including the power to
request information and records, to carry out on-site inspections and, where
appropriate, to conduct test purchases, including online.
3. Member States shall ensure that the national inspection authorities regularly run
simulation exercises to test the procedures in place and to ensure appropriate
response to incidents.
4. Member States shall ensure the participation of national inspection authorities, as
appropriate, in the relevant activities of the Steering Group, in particular for the
exchange of information on implementation practices, inspection findings and
emerging risks.Member States shall ensure risk-based audits of economic operators,
verifying, in particular, the existence and effectiveness of screening mechanisms for
legitimate need, record-keeping as provided for in Article [44][(6)] and detection of
suspicious transactions and incidents, and response procedures.
Article 49
Commission enforcement support and monitoring
The Commission may support and monitor national competent authorities in the enforcement
of this section, by taking actions such as requesting information and records and running
training exercises.
Article 50
Audits
Member States shall ensure risk-based audits of economic operators, verifying, in particular,
the existence and effectiveness of screening mechanisms for legitimate need, record-keeping
as provided for in Article 44[(6)] and detection of suspicious transactions and incidents, and
response procedures.
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Article 51
Penalties
1. Member States shall lay down the rules on penalties applicable to infringements of
this Section and shall take all measures necessary to ensure that they are
implemented. The penalties provided for shall be effective, proportionate and
dissuasive.
2. Member States may impose fines on economic operators not exceeding 5% of their
annual total worldwide turnover in the preceding financial year when Member States
finds that the provider intentionally or negligently infringed the relevant provisions
of this Section.
3. In fixing the amount of the fine or periodic penalty payment, regard shall be had to
the nature, gravity and duration of the infringement, taking due account of the
principles of proportionality and appropriateness.
Article 52
Advisory group on biosecurity
1. An Advisory Group on Biosecurity (‘the Advisory Group’) is hereby established.
2. The Advisory Group shall provide independent scientific advice to the Commission
on biosecurity risks arising from the rapid development of biotechnology, including
from AI models as described in Regulation (EU) 2024/1689 in biological
applications (‘AI models in biological applications’). It shall be selected and operate
in accordance with the Commission’s framework for expert groups73.
3. The tasks of the Advisory Group shall include:
(a) monitoring advances in biotechnology to advise the Commission on emerging
biosecurity challenges, including on any potentially necessary updates to the
list of biotechnology products of concern laid down in Annex I and on risk-
based audits of economic operators;
(b) monitoring the capabilities and risk profile of AI models in biological
applications throughout their life cycle;
(c) contributing to the preparation of Union guidance and best practices for
responsible innovation on AI models in biological applications;
(d) facilitate dialogue and coordination among scientific, industry, and security
stakeholders and support, where appropriate, international cooperation on
biosecurity.
4. Where the Advisory Group has reasonable grounds to suspect that an AI model in a
biological application not covered by Regulation (EU) 2024/1689, poses biological
systemic risk, it shall issue a qualified alert to the Commission and to the Member
States. A qualified alert may be issued following a decision of the Advisory Group or
at the initiative of at least 50% of its members. The alert shall be concise and duly
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Commission Decision establishing horizontal rules on the creation and operation of Commission expert
groups, C(2016)3301.
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reasoned and shall indicate at least the point of contact of the developer of the model
concerned and the factual basis for the alert.
5. Where the Advisory Group has reasonable grounds to suspect that an AI model
covered by Regulation (EU) 2024/1689 poses biological systemic risk, it shall inform
the scientific panel of independent experts referred to in Article 68 Regulation (EU)
2024/1689. That panel may issue a qualified alert to the AI Office in accordance with
Regulation (EU) 2019/1689.
6. The Advisory Group shall be composed of up to 25 globally leading independent
experts appointed by the Commission based on their recognized expertise in the
areas of biotechnology, biosecurity, biodefence and AI.
7. The members of the Advisory Group shall perform their tasks with impartiality and
objectivity. The Advisory Group shall liaise, where appropriate, with other Union
and international expert structures addressing biotechnology, AI, or biosecurity to
ensure coherence and efficiency, including the scientific panel referred to in Article
68 of Regulation (EU) 2024/1689.
8. The Advisory Group may adopt opinions, recommendations, or principles on matters
within its mandate.
Article 53
Biological systemic risk
1. The Commission shall monitor biological systemic risk from AI models in biological
applications and propose mitigating actions, based on advice provided by the
Advisory Group and in line with the Union harmonisation legislation on AI,
including boosting biodefence capabilities or regulation, including on assessment and
mitigation of systemic risk from those AI models, as appropriate.
2. Where a qualified alert is issued by the Advisory Group as referred to in Article
52(3), point (d), the Commission and the Member States shall take appropriate
measures to ensure a proper control of risks.
Article 54
Monitoring and guidance
The Commission, based on advice by the Advisory Group on Biosecurity, and where
appropriate, in cooperation with the Steering Group, may issue and regularly update guidance,
to assist actors in the supply chain and the competent authorities. The guidance may provide:
(a) clarifications regarding the biotechnology products of concern listed in the Annex I;
(b) clarification on the criteria for determining the sequences of concern referred to in
Annex I;
(c) information and methodologies for the assessment of legitimate need for the
purposes of this Section;
(d) information on how to exchange relevant information between competent authorities,
national contact points and among Member States;
(e) information on how to recognise, refuse, and report suspicious transactions;
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(f) obligations for natural or legal persons that are not economic operators that make
available biotechnology products of concern;
(g) requirements regarding benchtop nucleic acid synthesis equipment referred to in
Article 45;
(h) information on risk-based audits of economic operators referred to in Article 50;
(i) any other information deemed useful for effective implementation, including on the
investigative powers of national inspection authorities, test purchases, information
requests from, and resources of, such authorities, or requested by relevant economic
operators.
Article 55
Coordination on biosecurity and biosafety
The Steering Group referred to in Article 20 shall facilitate the coordination of and
information exchange on the enforcement of the provisions in this section among Member
States.
CHAPTER IX
AMENDMENTS TO REGULATIONS (EC) No 178/2002, (EC) No 1394/2007, (EU) No
536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938
Article 56
Amendments to Regulation (EC) No 178/2002
Regulation (EC) No 178/2002 is amended as follows:
(1) in Article 3, the following points 19, 20 and 21 are added:
‘19. ‘regulatory sandbox’ means a controlled environment where participants can
test innovative products or substances and related processes as well as data and
other regulatory requirements at a pre-market stage under a set of defined rules
and monitoring and for a limited period of time;
20. ‘regulatory sandbox plan’ means a plan setting out the scope, the requirements
and the conditions governing the operation of a specific regulatory sandbox;
21. ‘participants’ means any natural or legal person participating in a regulatory
sandbox to whom specific tasks are assigned in the regulatory sandbox plan,
such as business operators, Union and national agencies, final consumers,
academia and research institutions.’;
(2) in Article 22(5), point (a) is replaced by the following:
‘(a) scientific advice and scientific and technical support on human nutrition;’
(3) Article 28 is amended as follows:
(a) paragraph 3 is replaced by the following:
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‘3. The Scientific Committee shall be composed of the first Vice-Chairs of
the Scientific Panels and six independent scientific experts who do not
belong to any of the Scientific Panels.’
(b) paragraph 6 is replaced by the following:
‘6. The Scientific Committee and the Scientific Panels shall be chaired by
the staff of the Authority without the right to vote. The Scientific
Committee and the Scientific Panels shall each choose two Vice-Chairs
from among their members.’
(c) in paragraph 9, the following point (h) is added:
‘(h) the role of the Authority when chairing the Scientific Committee and the
Scientific Panels.’
(4) in Article 32a, paragraph 1 is replaced by the following:
‘1. Where Union law contains provisions for the Authority to provide a scientific
output, including a scientific opinion, the Authority shall, at the request of a
potential applicant or notifier, provide advice on the content of the application
or notification, prior to its submission, including the rules applicable to and the
required content thereof as well as on the design of the studies and testing
strategies to support such an application or notification. Such advice provided
by the Authority shall be without prejudice and non-committal as to any
subsequent assessment of applications or notifications by the Scientific Panels.’
(5) Article 32b is amended as follows:
(a) in paragraph 4, the third subparagraph is replaced by the following:
‘The assessment of the validity or the admissibility of such re-submitted
application or notification shall commence three months after the date of re-
submission of the application and provided that a notification of the studies
pursuant to the second subparagraph has taken place.’
(b) in paragraph 5, the third subparagraph is replaced by the following:
‘The assessment of the validity or admissibility of such re-submitted
application or notification shall commence three months after the date of re-
submission of the application and provided that all studies that had previously
been notified in accordance with paragraph 2 or 3 are included in the
resubmitted application or notification.’;
(c) paragraph 6 is replaced by the following:
‘6. Where the Authority detects, during its risk assessment, that studies
notified in accordance with paragraph 2 or 3 are not included in the
corresponding application or notification in full, and in the absence of a
valid justification of the applicant or notifier to that effect, the applicable
time limits within which the Authority is required to deliver its scientific
output shall be suspended. That suspension shall end three months after
the submission of all data of those studies.’
(6) in Article 32c, paragraph 1 is deleted.
(7) the following Chapter IIIA is inserted:
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‘CHAPTER IIIA
REGULATORY SANDBOXES
Article 49a
General provisions on regulatory sandboxes
1. A Member State or several Member States jointly may establish regulatory
sandboxes in accordance with this Article and the procedure set out in Article
49b.
2. Regulatory sandboxes may be established in relation to the following:
(a) all stages of the production, processing and distribution of food with the
exception of novel foods, and also of the feed produced for, or fed to
food-producing animals;
(b) food contact materials, with the exception of plastic recycled materials;
(c) products, other than food and feed, containing or consisting of
genetically modified organisms as defined in Article 2, point (2), of
Directive 2001/18/EC.
The making available of products within a regulatory sandbox shall not be
regarded as placing on the market.
3. Regulatory sandboxes shall pursue one or more of the following objectives:
(a) facilitating the development, testing and validation of technologies,
products and substances before they obtain authorisation or approval for
placing on the market, where so required by Union law;
(b) testing data requirements, including the type and design of studies
required for conducting a safety and/or efficacy assessment;
(c) testing alternative regulatory requirements and appraising their
performance as regards the attainment of the objectives of the applicable
Union sectoral law in comparison to the existing requirements; in the
areas where Union law provides for an approval or authorisation, as well
as in the area of food information to consumers.
4. Member States shall monitor and supervise the operation of regulatory
sandboxes that they establish and ensure compliance with the regulatory
sandbox plan.
5. A participant to an established regulatory sandbox shall immediately inform
the competent authorities of the Member State(s) concerned if it considers or
has reason to believe that the conditions of the regulatory sandbox plan have
not been complied with and/or there are potential risks to public health, animal
health or welfare, plant health or to the environment, which may require the
revocation of the regulatory sandbox or the amendment of the regulatory
sandbox plan to provide for mitigating measures. Participants shall also
immediately inform the competent authorities of any other information that
concerns the quality, safety or efficacy of the subject matter of the relevant
regulatory sandbox.
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6. Member States shall immediately notify to the Commission and, where
relevant, to the Authority any violation of the conditions set out in the
regulatory sandbox plan and/or the identification of any potential risks to
public health, animal health or welfare, plant health or to the environment.
7. Member States shall suspend or revoke a regulatory sandbox at any time on
their own motion, or at the request of the Commission in accordance with
paragraph 9, in either of the following cases:
(a) the requirements and conditions governing the regulatory sandbox plan
are not met;
(b) where necessary to protect public health, animal health or welfare, plant
health or the environment and there is no possibility for effective
mitigation measures.
Member States shall inform the Commission, the Authority and the other
Member States without delay of the suspension or revocation of a regulatory
sandbox and of the reasons.
8. Where after the setting up of a regulatory sandbox in their territory, a Member
State identifies risks to public health, animal health and welfare, plant health
and to the environment which can be fully mitigated by amendments to the
regulatory sandbox plan, it shall communicate to the Commission, the
Authority and the other Member States the draft amendments in accordance
with the procedure laid down in Article 49b.
9. Where the Commission considers that one of the cases referred to in paragraph
7 is fulfilled, it shall immediately adopt implementing acts in accordance with
the procedure referred to in Article 58(2) requesting the suspension or the
revocation of the regulatory sandbox concerned.
However, in emergencies, the Commission may provisionally adopt an
implementing act requesting the suspension of the regulatory sandbox
concerned after consulting the Member State(s) concerned and informing the
other Member States. As soon as possible, and at most within 10 working days,
the measure taken shall be confirmed, amended or revoked in accordance with
the procedure referred to in Article 58(2) and the reasons for the Commission’s
decision shall be made public without delay.
10. A Member State may prolong the duration once of a regulatory sandbox for a
limited time where this is justified by the need to attain the objective of the
specific regulatory sandbox at hand and shall inform the Commission, the
Authority and the other Member States thereof.
11. The Commission may, by means of implementing acts, specify common
principles or practical arrangements for the establishment and supervision of
regulatory sandboxes, including the establishment of sandboxes involving
several Member States pursuant to this Article, Article 49b and 49c. Those
implementing acts shall be adopted in accordance with the procedure referred
to in Article 58(2).
Article 49b
Establishment of regulatory sandboxes
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1. Where a Member State deems it appropriate to establish a regulatory sandbox,
it shall communicate to the Commission, the Authority and the other Member
States a draft regulatory sandbox plan, which shall contain the following
elements:
(a) the objectives of the regulatory sandbox;
(b) a description of the specific areas that the sandbox will cover, including
the products or substances, processes, technologies and practices;
(c) a clearly defined geographical scope;
(d) a clearly defined and limited temporal scope;
(e) the regulatory or scientific justifications for setting up the regulatory
sandbox;
(f) an identification of the relevant provisions of Union law that apply for
the purposes of the regulatory sandbox and those that do not apply or are
adapted;
(g) the procedure for the application and selection for participants, including
clearly defined eligibility criteria, the modalities governing the provision
of the explicit and prior consent from participating final consumers as
well as the modalities by which the participants may end their
participation;
(h) the possible involvement of the Authority, other Union agencies and
national agencies, where relevant, provided that they have expressed
interest to join the regulatory sandbox;
(i) the activities allowed to be carried out and the conditions and
requirements that apply;
(j) an assessment that identifies how potential risks to public health, animal
health or welfare, plant health or the environment are mitigated;
(k) details on how activities will be monitored, including responsibilities of
the competent authorities entrusted with the supervision of the
implementation of the sandbox plan.
2. Where several Member States deem it appropriate to jointly establish
regulatory sandboxes, they shall collectively communicate a draft regulatory
sandbox plan to the Commission, the Authority and the other Member States.
The regulatory sandbox plan shall specify the activities to take place in each of
the participating Member States in addition to the elements listed in paragraph
1.
3. Member States shall engage with relevant stakeholders during the preparation
of a draft regulatory sandbox plan to gather diverse perspectives and foster
collaboration.
4. The Member State(s) which deem it appropriate to set up a regulatory sandbox
alone or jointly, shall communicate the draft regulatory sandbox plan to the
Commission, the Authority and other Member States at least 60 days prior to
the intended commencement of the sandbox activities. Member State(s) shall
consider any feedback or recommendations from the Commission, the other
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Member States and the Authority before deciding whether to establish the
regulatory sandbox.
5. Member State(s) shall communicate to the Commission, the Authority and the
other Member States any subsequent draft amendment to regulatory sandbox
plans and the reasons thereof. Paragraphs 1 to 4 shall apply mutatis mutandis.
Article 49c
Other responsibilities, monitoring and reporting obligations regarding regulatory
sandboxes
1. Regulatory sandboxes shall not affect the enforcement and monitoring
responsibilities of the competent authorities set out in Article 17 and in other
sectoral legislation.
2. Participants, with the exception of final consumers, in particular the operator
that is the developer of the product or substance concerned, shall remain liable
under applicable national legislation for any harm inflicted on third parties as a
result from the testing taking place in the sandbox.
3. Member States shall submit annual reports to the Commission on the results
from the implementation of regulatory sandboxes, including good practices
developed, lessons learnt and recommendations on their setup and, where
relevant, on the application of the relevant sectorial Union legislation. Those
reports shall be made publicly available by the Commission.
4. The Authority shall also ensure the necessary revisions of its guidance where
relevant and appropriate on the basis of those annual reports.
Article 57
Amendments to Regulation (EC) No 1394/2007
Regulation (EC) No 1394/2007 is amended as follows:
(1) Article 2 is amended as follows:
(i) in paragraph 1, the following point (e) is added:
‘(e) ‘viral vector’ means a genetically modified virus that is used to deliver
genetic material into cells.’
(ii) the following paragraph 6 is added:
‘6. The Commission is empowered to adopt delegated acts in accordance
with Article 25a to amend this Regulation in order to amend the
definitions referred to in paragraph 1, regarding what constitutes a tissue
engineered product, in light of technical and scientific advancements in
the field of advance therapy medical products and taking into account
definitions agreed at Union and international level without extending the
scope of this definition. The delegated acts shall be adopted after
consultations with the European Medicines Agency and the SoHO
Coordination Board.’;
(2) The following Article 4a is inserted:
‘Article 4a
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Advanced therapy investigational medicinal products containing or consisting of
genetically modified organisms presenting no or negligible risks
1. By way of exemption from Article 5a of Regulation (EU) No 536/2014 [as
added by the revised Regulation No (EC) 726/2004], sponsors of clinical trials
that concern advanced therapy investigational medicinal products as defined in
Article 2(7) of that Regulation, consisting or containing GMOs, are not
required to submit an environmental risk assessment, if those products belong
to at least one of the following categories:
(a) non-viable or replication deficient viral vector that is used to deliver a
genetic sequence of human origin, and the vector does not carry an
antimicrobial resistance gene;
(b) genetically modified somatic cells, that cannot secrete or produce
infectious agents due to the genetic modification;
(c) genetically modified bacteria that do not carry an antimicrobial resistance
gene;
(d) genetic material altered using genome editing techniques (ex vivo or in
vivo), provided that it has generally negligible adverse effects on human
health and the environment.
2. The exemption provided for in paragraph 1 of this Article is subject to the
sponsor submitting, through the EU Portal and as part of the clinical trial
application dossier, a reasoned declaration confirming that the advanced
investigational therapy medicinal product concerned falls into one or more of
the categories referred to in points (a) to (d) of paragraph 1, of this Article. The
Committee for Medicinal Products for Human Use (CHMP) referred to in
Article [148] of Regulation […] [revised Regulation No (EC) 726/2004] shall
verify this declaration and the reasons provided, and the CHMP may, to this
end, access the information on the clinical trial application in the EU portal.
The CHMP shall communicate its opinion on the declaration to the sponsor and
to the reporting Member State within 21 days after the submission date referred
to in Article 5(1) of Regulation (EU) No 536/2014 [as revised by European
Biotech Act].
3. The reporting Member State, giving due consideration to the opinion of the
CHMP, shall assess if the conditions of paragraph 1 of this Article apply or if
the sponsor is to be requested to submit an environmental risk assessment
pursuant to Article 5a of Regulation (EU) No 536/2014 [as introduced by the
revised Regulation No (EC) 726/2004].
4. Sponsors of clinical trials concerning advanced investigational therapy
medicinal products that fall under paragraph 1 of this Article are also exempted
from complying with the GMO related requirements of Article 61(2), point (a),
of Regulation (EU) No 536/2014 [as introduced by the revised Regulation No
(EC) 726/2004] regarding the authorisation of manufacturing and import of
advanced investigational therapy medicinal products.
5. The exemptions provided for in this Article shall apply only for the duration of
the clinical trial, limited to the activities within the clinical trial.’;
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(3) Article 25a is replaced by the following:
‘Article 25a
Exercise of the delegation
1. The power to adopt delegated acts is conferred on the Commission subject to
the conditions laid down in this Article.
2. The power to adopt delegated referred to in Article 2, paragraph 6, and in
Article 24 shall be conferred on the Commission for a period of five years from
[insert date xx, from the entry into force of this Regulation].
The Commission shall draw up a report in respect of the delegation of power
not later than nine months before the end of the five-year period. The
delegation of power shall be tacitly extended for periods of an identical
duration, unless the European Parliament or the Council opposes such
extension not later than three months before the end of each period.
3. The delegation of power referred to in Article 2, paragraph 6, and in Article 24
may be revoked at any time by the European Parliament or by the Council. A
decision to revoke shall put an end to the delegation of the power specified in
that decision. It shall take effect the day following the publication of the
decision in the Official Journal of the European Union or at a later date
specified therein. It shall not affect the validity of any delegated acts already in
force.
4. Before adopting a delegated act, the Commission shall consult experts
designated by each Member State in accordance with the principles laid down
in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.
5. As soon as it adopts a delegated act, the Commission shall notify it
simultaneously to the European Parliament and to the Council.
6. A delegated act adopted pursuant to Article 2, paragraph 6, and Article 24 shall
enter into force only if no objection has been expressed either by the European
Parliament or by the Council within a period of two months of notification of
that act to the European Parliament and the Council or if, before the expiry of
that period, the European Parliament and the Council have both informed the
Commission that they will not object. That period shall be extended by two
months at the initiative of the European Parliament or of the Council.
Article 58
Amendments to Regulation (EU) No 536/2014
Regulation (EU) 536/2014 is amended as follows:
(1) Article 2 is amended as follows:
(a) point (3) is replaced by the following:
‘(3) ‘Low-intervention clinical trial’ means a clinical trial which fulfils all of
the following conditions:
(a) the investigational medicinal products, excluding placebos, are
authorised;
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(b) according to the protocol of the clinical trial, the use of the
investigational medicinal product is evidence-based and supported
by published scientific evidence on the safety and efficacy of those
investigational medicinal products concerned; and
(c) the additional diagnostic or monitoring procedures do not pose
more than minimal additional risk or burden to the safety of the
subjects compared to normal clinical practice in any Member State
concerned;’
(b) the following point (3a) is inserted:
‘(3a) ‘Minimal-intervention clinical trial’ means a clinical trial which fulfils all
of the following conditions:
(a) the investigational medicinal products are authorised;
(b) according to the protocol of the clinical trial, the investigational
medicinal products are used in accordance with the terms of
marketing authorisation; and
(c) the additional diagnostic or monitoring procedures do not pose
more than minimal additional risk or burden to the safety of the
subjects compared to normal clinical practice in any Member State
concerned’;
(c) points 12 and 13 are replaced by the following:
‘(12) ‘Member State concerned’ means the Member State where an application
for authorisation of a clinical trial or a combined study of a substantial
modification has been submitted under Chapters II, IIa or III of this
Regulation respectively;”
'(13) ‘Substantial modification’ means any change to any aspect of the clinical
trial which is made after the notification of a decision referred to in
Article 8 in at least one Member State concerned and which is likely to
have a substantial impact on the safety or rights of the subject or on the
reliability and robustness of data generated in the clinical trial;’
(d) the following point (13a) is inserted:
‘(13a) ‘Parallel substantial modification’ means a substantial modification for
which an application is submitted to a Member State concerned before a
decision on a previous application for a substantial modification to the
same clinical trial is notified by that Member State to the sponsor;’
(e) point (21) is replaced by the following:
‘(21) ‘Informed consent’ means a subject’s free and voluntary expression of
his or her willingness to participate in a particular clinical trial, after
having been informed of all aspects of the clinical trial that are relevant
to the subject’s decision to participate or, in case of minors and of
incapacitated subjects, an authorisation or agreement from their legally
designated representative to include them in a clinical trial, including
consent given through the use of electronic systems, methods and
processes, and signed electronically in accordance with Union law or
equivalent standards;’
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(f) the following points (36), to 47 are inserted:
(36) ‘Consideration’ means a justified concern or divergent view raised by a
Member State concerned in the process of an assessment of an
application for an authorisation of a clinical trial or for a substantial
modification on the aspects that, if unresolved, will result in a negative
decision on the clinical trial or substantial modification application;
(37) ‘Reporting Member State’ means the Member State concerned that:
(a) is responsible for the assessment and authorisation of the clinical
trial application in mono-national clinical trials, or
(b) is leading the assessment for the authorisation of a multinational
clinical trial or of a substantial modification regarding aspects
covered by Part I of the application dossier, or
(c) is leading the assessment for the authorisation of a multinational
combined study;
(38) ‘Investigational medicinal product core dossier’ means a dossier,
containing documents referred to in point (Ga), Part II of Annex I
concerning the investigational medicinal product, established at the
request of the sponsor in view of supporting the development of the
investigational medicinal product.
(39) ‘Core dossier depositary Member State’ means a Member State
responsible for assessing suitability and completeness of the
investigational medicinal product core dossier to be established and for
the regulatory oversight of an already established dossier;
(40) ‘Core dossier competent Member States’ means the Member States
concerned for all corresponding clinical trials and the Member States
indicated by a sponsor at the time of the initial request for the
establishment of the investigational medicinal product core dossier;
(41) ‘Corresponding clinical trial’ means a clinical trial tested to the
investigational medicinal product for which an establishment of an
investigational medicinal product core dossier has been requested and
any subsequent clinical trial tested to that investigational medicinal
product;
(42) ‘Distribution’ means all activities, consisting of procuring, holding,
supplying, shipping across Member States or exporting investigational
medicinal product or auxiliary medicinal products, , including delivery of
investigational and auxiliary medicinal products to the clinical trial
participants;
(43) ‘Direct delivery to the subject’ means controlled and documented direct
delivery of an investigational medicinal product or an auxiliary medicinal
product to the subject’s place of residence in a Member State, where the
clinical trial has been authorised;
(44) ‘Combined study’ means a clinical trial concerning one or more
medicinal products combined with a performance study of one or more in
vitro diagnostic medical devices, as defined in Article 2 point (42) of
Regulation (EU) 2017/746 of the European Parliament and of the
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Council *and/or clinical investigation of one or more medical devices as
defined in Article 2 point (45) of Regulation (EU) 2017/745 of the
European Parliament and of the Council **;
(45) 'Regulatory sandbox' means a regulatory framework that allows for the
development and testing of innovative or adapted regulatory approaches
in a controlled environment pursuant to a specific plan, for a limited time
and under regulatory supervision, that enables innovation driven
approaches to an authorisation and conduct of clinical trials that
otherwise would not be possible or appropriate given current legal
framework;’
(46) ‘AI system’ means AI system as defined in Article 3(1) of Regulation
(EU) 2024/1689 of the European Parliament and of the Council***;
(47) ‘serious cross-border threat to health’ means serious cross-border threat
to health as defined in Article 3(1) of Regulation (EU) 2022/2371 of the
European Parliament and of the Council****‘
* Regulation (EU) 2017/746 of the European Parliament and of the
Council of 5 April 2017 on in vitro diagnostic medical devices and
repealing Directive 98/79/EC and Commission Decision 2010/227/EU
(JO 5.5.2017, L117/176., ELI: http://data.europa.eu/eli/reg/2017/746/oj).
** Regulation (EU) 2017/745 of the European Parliament and of the
Council of 5 April 2017 on medical devices, amending Directive
2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No
1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC
(JO 5.5.2017, L 117/1., ELI: http://data.europa.eu/eli/reg/2017/745/oj).
*** Regulation (EU) 2024/1689 of the European Parliament and of the
Council of 13 June 2024 laying down harmonised rules on artificial
intelligence and amending Regulations (EC) No 300/2008, (EU) No
167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU)
2019/2144 and Directives 2014/90/EU, (EU) 2016/797 and (EU)
2020/1828 (OJ L, 2024/1689, 12.7.2024,
ELI: http://data.europa.eu/eli/reg/2024/1689/oj)
**** Regulation (EU) 2022/2371 of the European Parliament and of the
Council of 23 November 2022 on serious cross-border threats to health
and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022, p. 26,
http://data.europa.eu/eli/reg/2022/2371/oj).
(2) Article 3 is replaced by the following:
‘Article 3
General principles
1. A clinical trial may be conducted only if:
(a) the rights, safety, dignity and well-being of subjects are protected and
prevail over all other interests; and
(b) it is designed to generate reliable and robust data.
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2. Member States concerned shall cooperate closely and efficiently to ensure the
effective and timely application of the provisions of this Regulation.
3. Member States shall take into account whether a clinical trial is a minimal-
intervention or low-intervention clinical trial and, where this is the case, adapt
the regulatory requirements throughout the lifecycle of such clinical trial, in
particular with regard to the application dossier, the authorisation procedures,
the safety reporting and oversight.’
(3) Articles 4 and 5 are replaced by the following:
’Article 4
Prior authorisation
A clinical trial shall be conducted only if it has been authorised by the Member State
concerned in accordance with this Regulation. Applications for an authorisation shall
be subject to scientific and ethical review.
In clinical trials concerning more than one Member States (multinational clinical
trials) all the Member States concerned including the reporting Member State shall
cooperate in good faith and in spirit of mutual trust and reliance. The reporting
Member State shall have a leading role in the assessments.
The ethical review shall be performed by an ethics committee in accordance with the
law of the Member State concerned. The reporting Member State shall involve its
ethics committee in the assessment of ethical aspects of Part I of the application
dossier referred to in Article 6.
Each Member State shall ensure that the organisation, timelines and procedures for
the review by an ethics committee are compatible with the timelines and procedures
set out in this Regulation for the assessment of the application for authorisation of a
clinical trial and substantial modifications thereof.
Article 5
Submission of an application
1. In order to obtain an authorisation, the sponsor shall submit an application
dossier to the intended Member States concerned throughout the Portal referred
to in Article 80 (‘the EU portal’) referred to in Article 25. The date on which
the sponsor submits the application for an authorisation of a clinical trial is
referred to within this Chapter as the submission date.
2. The authorisation procedure of a clinical trial consists of three steps:
(a) a validation of the application dossier, as set out in Article 5b;
(b) an assessment, that consists of:
– an assessment of Part I, as set out in Article 6, of the elements of
the application dossier listed in Part I of Annex I, that constitute
Part I of the assessment dossier, and
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– an assessment of Part II, as set out Article 7 of the application
dossier, of the elements listed in Part II of Annex I, that constitute
Part II of the application dossier.
(c) a decision resulting either an authorisation, conditional authorisation or
refusal of an authorisation, as set out in Article 8.’
(4) the following Articles 5a and Article 5b are inserted:
“Article 5a
Appointment of the reporting Member State
1. In clinical trials concerning only one Member State, this Member State is the
reporting Member State.
2. In clinical trials concerning more than one Member States, the sponsor shall
propose one of the Member States concerned as the reporting Member State.
All Member States concerned willing to become the reporting Member State
shall declare their willingness through the EU portal.
The sponsor shall, when applying for a low-intervention clinical trial propose
one of the Member States concerned where the use of the investigational
medicinal product is evidence-based as a reporting Member State.
3. If the proposed Member State accepts the proposal by expressing willingness
to become the reporting Member State, it shall be the reporting Member State.
4. If the proposed Member State does not accept the proposal, the following rules
shall apply, and their application shall be supported by the EU Portal:
(a) where there is only one other Member State concerned willing to become
the reporting Member State, that Member State shall become the
reporting Member State;
(b) where there is more than one Member State concerned willing to become
the reporting Member State or none of the Member States concerned is
willing to become the reporting Member State, the reporting Member
State shall be designated automatically by the EU Portal in application of
the recommendation referred to in article 85(2)(c).
5. Within three days from the submission date, all Member States concerned, the
sponsor and the reporting Member State shall be notified by the EU Portal of
the appointment of the reporting Member State.
Article 5b
Validation of Part I of the application dossier
1. Within seven days from the submission date, the reporting Member State shall
validate Part I of application dossier referred to in Article 6 and notify the
sponsor, through the EU portal, of the following:
(a) whether the clinical trial applied for falls within the scope of this
Regulation;
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(b) whether the application dossier is complete in accordance with Part I of
Annex I;
(c) whether it confirms that the clinical trial is a minimal-intervention or a
low- intervention clinical trial, respectively, if such a claim was made by
the sponsor.
2. Where the reporting Member State has not notified the sponsor within the
period referred to in paragraph 1, the clinical trial applied for shall be deemed
to fall within the scope of this Regulation and the application dossier shall be
considered complete and, if applicable, the clinical trial shall be considered a
minimal-intervention or low-intervention clinical trial.
3. Where the reporting Member State finds that the application dossier is not
complete, or that the clinical trial applied for does not fall within the scope of
this Regulation, or, if applicable, has doubts whether the clinical trial is a
minimal-intervention or low-intervention clinical trial, the reporting Member
State shall:
(a) inform the sponsor thereof through the EU portal and shall set a deadline
of maximum seven days for the sponsor to comment on the application or
to complete the application dossier through the EU portal;
(b) within seven days from the submission of the comments or the completed
application dossier referred to in point (a) notify the sponsor as to
whether or not the application complies with the requirements set out in
paragraph 1 points (a), (b) and (c).
In case the reporting Member State requests the sponsor to comment on the
application pursuant to this paragraph, the period referred to in paragraph 1
may be extended by a maximum of 14 days.
4. Where the reporting Member State has not notified the sponsor within the
period referred to in paragraph 3, point (b), the clinical trial applied for shall be
deemed to fall within the scope of this Regulation, the application dossier shall
be considered complete in accordance with Part I of Annex I and the clinical
trials is deemed to be a minimal-intervention or a low-intervention clinical
trial, if claimed by the sponsor.
5. Where the sponsor has not provided comments or completed the application
dossier within the period referred to in paragraph 3, point (a), the application
shall be deemed to have lapsed in all Member States concerned.
6. For the purpose of this Chapter, the date on which the sponsor is notified in
accordance with paragraph 1 or paragraph 3, point (b) shall be the validation
date of the application. Where the sponsor is not notified within these time
periods, the validation date shall be the last day of respective periods referred
to in paragraph 1 or paragraph 3, point (b).”
(5) Article 6 is replaced by the following:
’Article 6
Assessment report – Aspects covered by Part I of the assessment report
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1. The reporting Member State shall assess the application relying on the
information and the documents listed in Part I of Annex I, with regard to the
following aspects:
(a) compliance with Chapter V as with respect to the following:
(i) the anticipated therapeutic and public health benefits taking
account of all of the following:
– characteristic of and knowledge about the investigational
medicinal products;
– relevance of the clinical trial, including whether the groups of
subjects participating in the clinical trial represent the
population to be treated, or if not, the explanation and
justification provided in accordance with point 17(y) of Part I
of Annex I; the current state of scientific knowledge; whether
the clinical trial has been recommended or imposed by
regulatory authorities in charge of the assessment and
authorisation of the placing on the market of medicinal
products; where applicable, taking into account any opinion
formulated by the Paediatric Committee on paediatric
investigational plan in accordance with Chapter VII of
Regulation (EU) …/…[reference to be added after adoption
cf. COM(2023)196final];
– reliability and robustness of the data generated in clinical
trial, taking into account of statistical approaches, design of
the clinical trial and methodology, including sample size and
randomisation, comparator and endpoints;
(ii) risk and inconveniencies for the subjects, taking into account all of
the following:
– characteristic of and knowledge about the investigational
medicinal product and the auxiliary medicinal product;
– characteristic of the investigational medicinal product;
– safety measures, including provisions for risk minimisation
measures, monitoring, safety reporting, and the safety plan;
– risk to subjects’ health posed by the medical condition for
which the investigational medicinal product is being
investigated;
– aspects related to the protection of the subjects’ safety, well-
being and fundamental rights as a clinical trial participant.
(b) compliance with the requirements concerning the manufacturing and
import of investigational medicinal product set out in Chapter IX;
(c) compliance with the labelling requirements set out in Chapter X;
(d) completeness and adequacy of the investigator’s brochure.
The adequacy of the translations of the documents, when translations are
required pursuant to Article 26 and Article 69, submitted in Part I shall be
assessed in Part II.
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2. The reporting Member State shall draw up an assessment report. The
assessment of the aspects referred to in paragraph 1 shall constitute Part I of the
assessment report.
The ethics committee of the reporting Member State shall review, from the
ethical perspective, aspects covered by Part I of the assessment report. That
ethical review shall complement the scientific and regulatory assessment and
shall cover Part I of the application dossier in order to evaluate whether the
subjects’ rights, safety and well-being are being ensured in the clinical trial.”
2a. Notwithstanding paragraph 2, where the clinical trial is a minimal-intervention
clinical trial, the assessment of the reporting Member State shall be limited to
an ethical review by its ethics committee of the aspects referred to points (a)
and (d) of paragraph 1.
3. The assessment report shall contain one of the following conclusions
concerning the aspects addressed in Part I of the assessment report:
(a) the conduct of the clinical trial is acceptable in view of the requirements
set out in this Regulation:
(b) the conduct of the clinical trial is acceptable in view of the requirements
set out in this Regulation, but subject to compliance with specific
conditions which shall be specifically listed in that conclusion; or
(c) the conduct of the clinical trial is not acceptable in view of the
requirements set out in this Regulation.
4. The reporting Member state shall submit, through EU portal, the final Part I of
the assessment report, including its conclusions, to the sponsors and to the
other Member States concerned within 42 days from the submission date.
5. For clinical trials involving more than one Member State concerned, the
assessment process shall include three phases:
(a) an initial assessment phase within 28 days from the submission date;
(b) a review phase within seven days from the end of the initial assessment;
(c) a consolidation phase within seven days from the end date of the review
phase.
During the initial assessment phase, the reporting Member State shall assess
Part I of the application dossier and draw up a draft Part I of the assessment
report and circulate it to all other Member States concerned within 28 days
from the submission date.
During the review phase, within seven days from the circulation of the draft
assessment report all Member States concerned shall review the application
based on the draft Part I of the assessment report and shall share considerations
for their Member States relevant to the application. The consideration may be
raised only on one of the following grounds:
(a) one of the grounds referred to in Article 8(2);
(b) issues that would lead to a negative opinion of the ethics committee of
the Member State concerned.
During the consolidation phase, the reporting Member State shall take due
account of the considerations of the other Member States concerned and
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finalise Part I of the assessment report and shall record how all considerations
have been dealt with. The reporting Member State shall submit the final Part I
of the assessment report to the sponsor and all other Member States concerned
within seven days from the end of the review phase.”
5a. Where the clinical trial is a minimal-intervention clinical trial, other Member
States concerned may only raise during the review phase considerations
referred to in paragraph 5related to ethical aspects of the draft assessment
report.”
6. For the purpose of this Chapter, the date on which the final Part I of the
assessment report is submitted by the reporting Member State to the sponsor
and to the other Member States concerned through the EU portal shall be the
reporting date.”
7. Between the validation date and the reporting date, only the reporting Member
State may request additional information from the sponsor, taking into account
the considerations referred to in paragraph 5.
For the purpose of obtaining and reviewing this additional information from
the sponsor, the reporting Member State may extend the period referred to in
paragraph 4 by maximum of 28 days.
The sponsor shall submit the requested information within the period set by the
reporting Member State which shall not exceed 14 days from the receipt of the
request.
Upon receipt of the requested additional information, the Member State
concerned shall review additional information provided by the sponsor and
shall identify and share with the reporting Member State any unaddressed
considerations, relevant for the application. The coordinated review shall be
performed within maximum 7 days of the receipt of the additional information
and the further consolidation shall be performed within maximum seven days
of the end of the coordinated review. When finalising Part I of the assessment
report, the reporting Member State shall take due account of the considerations
of the other Member States concerned and shall record how the considerations
have been dealt with.
Where the sponsor does not provide additional information within the period
set by the reporting Member State in accordance with the third subparagraph,
the application shall be deemed to have lapsed in all Member States concerned.
The request for additional information and additional information shall be
submitted through the EU Portal.’
(6) Article 7 is replaced by the following:
‘Article 7
Assessment report – Aspects covered by Part II of the application dossier
1. Each Member State concerned shall assess, for its own territory, the application
with respect to the following aspects. Such assessment shall constitute Part II
of the assessment report:
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(a) compliance with the requirements for informed consent set out in
Chapter V;
(b) compliance of the arrangements for rewarding or compensating subjects
with the requirements set out in Chapter V;
(c) compliance of the arrangements for recruitment of subjects with the
requirements set out in Chapter V;
(d) compliance with Regulation (EU) 2016/679 of the European Parliament
and of the Council*;
(e) compliance with Article 49;
(f) compliance with Article 50;
(g) compliance with Article 76;
(h) compliance with applicable rules for the collection, storage and future
use of biological samples of the subject;
(i) accuracy of the translations of the documents and information submitted
in Part I of the application dossier, when such documents are required to
be submitted in the national language in accordance with Article 26 and
69.
2. Each Member State concerned shall complete the assessment within 42 days
from the submission date and submit, through the EU portal, Part II of the
assessment report, including its conclusions, to the sponsor.
Each Member State concerned may within the period referred to in this
paragraph, and through EU portal, request on duly justified grounds additional
information , from the sponsor regarding the aspects covered in paragraph 1 or
to request to complement the documentation, required pursuant to Part II of
Annex I, if such documentation is missing or documentation provided is not
adequate or is incomplete.
The Member State concerned may decide within 28 days of the submission
date to rely on the ethical review of the ethics committee of the reporting
Member State of the common elements of the application dossier of Part II and
inform the sponsor accordingly.
3. Each Member State concerned may extend the assessment period referred to in
paragraph 2 by a maximum of 28 days:
(a) to requests additional documentation or information, as referred in
paragraph 2, from the sponsor regarding Part II of the assessment for its
territory;
(b) to align with the timeline for the assessment referred to in Article 6,
when it has been extended to allow for a request for information by the
reporting Member State related to Part I assessment and its review.
The sponsor shall submit the requested additional information and
documentation within the period set by the Member State concerned which
shall not exceed 14 days from the receipt of the request.
Upon receipt of the additional information and documentation, the Member
State concerned shall complete its assessment within maximum of 14 days
from the submission of the requested information by the sponsor.
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Where the sponsor does not provide additional information and documentation
within the period set by the Member State concerned in accordance with this
paragraph, the application shall be deemed to have lapsed in that Member State
concerned.
* Regulation (EU) 2016/679 of the European Parliament and of the Council of
27 April 2016 on the protection of natural persons with regard to the
processing of personal data and on the free movement of such data, and
repealing Directive 95/46/EC (General Data Protection Regulation), OJ L 119,
4.5.2016., ELI: http://data.europa.eu/eli/reg/2016/679/oj.’
(7) in Article 8, paragraphs 1 and 2 are replaced by the following:
‘1. Each Member State concerned shall notify the sponsor through the EU portal
and by way of one single decision as to whether the clinical trial is authorised,
authorised subject to conditions, or whether authorisation is refused.
The notification shall be made within five days from the reporting date or from
the last day of the assessment referred to in Article 7, whichever is later.
2. Where the conclusion of the reporting Member State as regards Part I of the
assessment report is that the conduct of the clinical trial is acceptable or
acceptable subject to compliance with specific conditions, that conclusion shall
be deemed to be the conclusion of the Member States concerned.
A clinical trial subject to conditions may start, unless the Member State
concerned specified that the condition is suspensive. Unless otherwise
specified, a fulfilment of the condition shall not require a submission of a
request for a substantial modification.
Notwithstanding the first subparagraph of this paragraph, a Member State
concerned may disagree with the conclusion of the reporting Member State as
regards Part I of the assessment report only on the following grounds, provided
that the corresponding consideration was raised during the process pursuant to
Article 6(5) point (b) and the Member State concerned considers that it was not
sufficiently addressed:
(a) participation in the clinical trial would lead to a subject receiving an
inferior treatment than in normal clinical practice in the Member State
concerned; or
(b) infringement of its national law as referred to in Article 90.
Where a Member State concerned disagrees with the conclusion, it shall
communicate its disagreement, together with a detailed justification, through
the EU portal, to the Commission, to all Member States, and to the sponsor.’
(8) Article 9 is replaced by the following:
‘Article 9
Persons assessing the application
1. Member States shall ensure, including through the institutional safeguards, that
persons validating and assessing the application do not have conflicts of
interest, are independent of the sponsors, or the clinical trial site and the
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investigators involved and of persons financing the clinical trial, as well as free
of any other undue influence and ensure their sufficient independence in
performance of their tasks.
In order to guarantee independency and transparency, the Member States shall
ensure that persons validating and assessing the application as regards the
aspects covered in Parts I and II of the assessment report have no financial or
personal interests which could affect their impartiality. These persons shall
make an annual declaration of their financial interest.
2. Member States shall ensure that the assessment is done by persons who
collectively have the necessary qualifications and experience.
These persons shall be sufficiently equipped and empowered to perform their
tasks.
3. At least one layperson shall participate in the assessment.’
(9) in Article 10, the following paragraph 6 is added:
’6. Where potential subjects of a clinical trial belong to vulnerable populations,
Member States concerned and sponsors shall consider and weigh the harms and
benefits of their inclusion as opposed to their exclusion from a clinical trial.
The Member States concerned and sponsors shall assess in particular whether
the exclusion of those subjects from a clinical trial could inadvertently
perpetuate or exacerbate their vulnerabilities, particularly in relation to their
specific health needs.’
(10) Article 11 is replaced by the following:
‘ Article 11
Submission and assessment of applications limited to aspects covered by Part I of the
assessment report
1. Where the sponsor so requests, the application for authorisation of a clinical
trial, its assessment and the conclusion shall be limited to the aspects covered
by Part I of the assessment report.
After the notification of the conclusion on the aspects covered by Part I of the
assessment report, the sponsor may, within two years, apply for an
authorisation limited to aspects covered by Part II of the assessment report.
Where the sponsor submits only Part I of the application dossier to all of the
Member States concerned, the sponsor shall declare at the time of the first
submission of Part II of the application dossier to any of the Member States
concerned that the sponsor is not aware of any new substantial scientific
information that would change the validity of any item submitted in the
application on the aspects covered by Part I of the assessment report. If an
update of Part I of the application dossier is necessary, the sponsor shall submit
a substantial modification of Part I of the application dossier, at the latest, at
the same time as the submission of Part II of the application dossier to at least
one of the Member States concerned.
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The Part II of the application dossier shall be assessed in accordance with
Article 7 and the Member State concerned shall notify the decision on clinical
trial in accordance with Article 8.
In those Member States concerned where the sponsor does not apply for an
authorisation limited to aspects covered by Part II of the assessment report
within two years, the application on the aspects covered by Part I of the
assessment report shall be deemed to have lapsed.
2. When the sponsor submits a substantial modification of Part I of the
application dossier with regard to clinical trial that is subject to a request
referred to in paragraph 1 and has been authorised or authorised subject to
conditions by at least one Member State concerned, all Member States
concerned that received the initial application shall participate in the
assessment of that substantial modification in accordance with Article 18 or 22
as appropriate.’
(11) Article 14 is amended as follows:
(a) paragraph 1 is replaced by the following:
‘1. Where the sponsor wishes to extend an authorised clinical trial to another
Member State (additional Member State concerned), the sponsor shall
submit an application dossier to that Member State through the EU
portal.
The application dossier may be submitted only after the notification date
of the first initial authorisation decision by at least one Member State
concerned.’
(b) paragraph 3 is replaced by the following:
‘3. The additional Member State concerned shall notify the sponsor, through
the EU portal, within 47 days from the date of submission of the
application dossier referred to in paragraph 1 of this Article, by way of
one single decision as to whether the clinical trial is authorised, whether
it is authorised subject to conditions, or whether the authorisation is
refused. Article 8(2), (3), (4) and (5) apply to the decision of the
additional Member State concerned.’
(c) paragraph 4 is deleted;
(d) paragraph 5 to 8 are replaced by the following:
‘5. Within 42 days following the submission date referred to in paragraph 1,
the additional Member State concerned may communicate to the
reporting Member State and the other Member States concerned any
considerations through the EU portal.’
(e) paragraphs 6, 7 and 8 are replaced by the following:
‘6. Between the submission date referred to in paragraph 1 and the expiry of
the period referred to in paragraph 3, only the reporting Member State
may request additional information from the sponsor concerning the
aspects covered in Part I of the assessment report, taking into account the
considerations referred to in paragraph 5.
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For the purpose of obtaining and reviewing this additional information
from the sponsor in accordance with the third and fourth subparagraphs,
the reporting Member State may extend the period referred to in the first
subparagraph of paragraph 3 by a maximum of 28 days.
The sponsor shall submit the requested additional information within the
period set by the reporting Member State, which shall not exceed 14 days
from receipt of the request.
Upon receipt of the additional information the reporting Member State,
the additional Member State concerned and all other Member States
concerned shall review any additional information provided by the
sponsor together with the original application and shall share any
unaddressed considerations relevant to the application. The coordinated
review shall be performed within a maximum of seven days from the
receipt of the additional information and the further consolidation shall
be performed within a maximum of seven days from the end of the
coordinated review. The reporting Member State shall take due account
of the considerations of the Member States concerned and shall record
how the considerations have been dealt with.
Where the sponsor does not provide additional information within the
period set by the reporting Member State in accordance with the third
subparagraph, the application shall be deemed to have lapsed in the
additional Member State concerned.
The request for additional information and the additional information
shall be submitted through the EU portal
7. The additional Member State concerned shall assess, for its territory, the
aspects covered in Part II of the assessment report and submit Part II
assessment report, including its conclusions, through the EU portal, to the
sponsor.
Within period referred to in paragraph 3, additional Member State may
request, through the EU portal, with justified reasons, additional
information from the sponsor regarding aspects covered in Part II of the
assessment report as far as its territory is concerned.’
8. For the purpose of obtaining and reviewing the additional information
referred to in paragraph 6 or 7 the additional Member State concerned
may extend the period referred to in paragraph 5 by maximum of 28
days.
The sponsor shall submit the requested additional information within the
period set be the additional Member State concerned, which shall not
exceed 14 days from the receipt of the request.
Upon receipt of the additional information, the Member State concerned
shall compete its assessment within a maximum of 14 days.
Where the sponsor does not provide additional information within the
period set by the additional Member State concerned in accordance with
second subparagraph, the application shall be deemed to have lapsed in
the additional Member State concerned.’
(f) paragraphs 9 and 10 are deleted;
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(g) paragraphs 11 and 12 are replaced by the following:
‘11. Where the additional Member State concerned has not notified the
sponsor of its decision within the period referred to in paragraph 3, or in
case that period has been extended in accordance with paragraph 6 or 8
and where that additional Member State concerned has not notified the
sponsor of its decision within the extended period, the conclusion on Part
I of the assessment report shall be deemed to be the decision of that
additional Member State concerned on the application for authorisation
of the clinical trial.”
12. A sponsor shall not submit an application dossier in accordance with this
Article where a procedure for a substantial modification of Part I of the
assessment report, set out in Chapter III, is pending as regards that
clinical trial.’
(12) the following Article 14a is inserted:
’Article 14a
Appointment of a new reporting Member State
1. The reporting Member State may initiate the procedure for an appointment of a
new reporting Member State if:
(a) the reporting Member State has notified its decision refusing the
authorisation of the clinical trial; or
(b) the clinical trial is no longer taking place in the reporting Member State.
2. The procedure can only be launched after the clinical trial has been authorised
in at least one Member State concerned.
3. The reporting Member State shall notify the sponsor and other Member States
concerned of its intention to cease to be a reporting Member State.
4. The Member States concerned shall declare their willingness to become new
reporting Member State. The selection of new reporting Member State shall
follow the rules established Article 5a (4) and (5).
5. Following the initiation of the procedure for the appointment of a new
reporting Member State, the initial reporting Member State shall continue to
carry out its tasks until all of the ongoing assessments and records are
completed and the respective final assessment reports are submitted to the EU
portal.
6. The new reporting Member State shall become responsible for the assessment
of any application related to Part I of the assessment report, including an
application based on Article 14, that has been submitted after it has been
notified as the reporting Member State to the sponsor and all Member States
concerned by the EU portal.’
(13) the following Chapter IIa is inserted:
‘Chapter IIa
SPECIAL AUTHORISATION PROCEDURES
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Article 14b
Accelerated procedure for the authorisation of multinational clinical trials in the context of
public health emergencies
1. During a recognised public health emergency at Union level pursuant to Article
23 of Regulation (EU) 2022/2371 of the European Parliament and of the
Council, Member States shall apply an accelerated procedure for the
authorisation of multinational clinical trials for medicinal products intended for
the treatment, prevention or medical diagnosis of the disease or condition
which are directly related to the public health emergency.
2. To address an emergence or development of a serious cross-border threat to
health as defined in Article 3(1) of Regulation 2022/2371 that is likely to lead
to the recognition of a public health emergency at Union level in accordance
with Article 23(1) of Regulation (EU) 2022/2371, Member States shall apply
an accelerated procedure for the authorisation of multinational clinical trials
when this procedure is declared applicable in accordance with the criteria in
paragraph 3 of this Article. The application of the accelerated procedure shall
ensure the availability of medicinal products in order to prevent or swiftly
contain the emerging serious cross-border health threat, to provide timely
treatment options grounded in scientifically robust evidence or to facilitate
medical diagnosis of the disease or condition directly related to the specific
serious cross-border health threat.
3. The Commission shall, by means of implementing acts, lay down the detailed
criteria and the processes for declaring applicability of the accelerated
authorisation procedure to address an emergence or development of serious
cross-border threat to health that is likely to lead to the recognition of a public
health emergency at Union level in accordance with Article 23 (1) of
Regulation (EU) 2022/2371, .
The criteria for declaring applicability of an accelerated authorisation
procedure shall at least include the epidemiological situation and its dynamics
as well as the availability of treatment, prevention and diagnostics options
addressing the emerging serious cross-border threat to health. The process of
declaring applicability of the accelerated authorisation procedure shall involve
consultations with relevant Union agencies, expert groups and advisory bodies
in the field of public health and clinical trials.
The implementing acts referred to in the first subparagraph shall be adopted in
accordance with the examination procedure referred to in Article 88.
4. When submitting the application for the clinical trial authorisation during a
public health emergency as referred to in paragraph 1 or when the accelerated
procedure referred to in paragraph 2 is declared applicable to address an
emerging serious cross-border health threat, pursuant to the procedure referred
to in paragraph 3, the sponsor shall indicate whether the investigational
medicinal products are intended for the treatment, prevention or medical
diagnosis of a disease or a condition directly related to the specific serious
cross-border threat to health. The reporting Member State shall confirm
whether the accelerated procedure is applicable to the clinical trial application.
5. The Commission shall adopt delegated acts in accordance with Article 89 to
supplement this Regulation by setting out the procedures for an accelerated
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authorisation of multinational clinical trials, including timelines, criteria for
evaluating whether a clinical trial qualifies for an accelerated procedure and an
integrated ethical review, and by laying down simplified requirements for the
application dossier.
Article 14c
Combined studies
1. This Article applies to combined studies in which a clinical trial is combined
with a performance study of an in vitro diagnostic medical device that is
subject to authorisation pursuant to Article 58(1) of Regulation (EU) 2017/746,
or is combined with a clinical investigation of a medical device that is subject
to authorisation according to Article 62 of Regulation (EU) 2017/745.
2. By way of derogation from Article 5, the sponsor of a combined study referred
to in paragraph 1, which is to be conducted in one or more Member States, may
submit a single application for authorisation.
3. The single application referred to in paragraph 2 shall be submitted
electronically through the EU Portal to all Member States in which the
combined study is to be conducted (‘Member States concerned’). Where a
combined study has more than one sponsor, the sponsors shall designate one
coordinating sponsor.
4. The Member States concerned shall assess the single application by means of a
coordinated assessment procedure under the direction of a reporting Member
State chosen from among the Member States concerned. If a combined study
involves only one Member State, that Member State shall be the reporting
Member State.
5. The coordinated assessment procedure shall include the assessment by the
competent authorities and review by ethics committees. During the assessment
procedure, the Member States concerned may only raise considerations related
to the following:
(a) the grounds referred to in Article 14a(5) of this Regulation, Article 78(8)
of Regulation (EU) 2017/746 or Article 74(8) of Regulation (EU)
2017/745; or
(b) issues that would lead to ethics committee of the Member State
concerned issuing a negative opinion.
6. Where the conclusion of the reporting Member State as regards the area of
coordinated assessment is that the conduct of the combined study is acceptable,
or acceptable subject to compliance with specific conditions, that conclusion
shall be deemed to be the conclusion of all Member States concerned.
Notwithstanding the first subparagraph of this paragraph, a Member State
concerned may disagree with the conclusion of the reporting Member State
concerning the area of coordinated assessment but only on one of the following
grounds, provided that the corresponding consideration was raised during the
assessment process and the Member State concerned has substantiated
comments that were not sufficiently addressed:
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(a) participation in the combined study would lead to a subject receiving an
inferior treatment than in normal clinical practice in the Member State
concerned;
(b) infringement of its national law;
(c) with regard to the assessment of the medical device or in vitro medical
device, grounds referred to in Article 78(8) of Regulation 2017/746 or
Article 74(8) of Regulation (EU) 2017/745, respectively
7. Where a Member State concerned disagrees with the conclusion on the basis of
paragraph 5, it shall communicate its disagreement, together with a detailed
justification, through the EU Portal, to the Commission, to all other Member
States concerned, and to the coordinating sponsor referred to in paragraph 2.
8. Each Member State concerned shall issue a single decision as to whether the
combined study is authorised, whether it is authorised subject to conditions, or
whether authorisation is refused and shall notify the coordinating sponsor
referred to in paragraph 2.
9. The Commission shall, by means of a delegated act in accordance with Article
89, amend or supplement, as necessary, the provisions of Chapters II to V, VII,
XIII, XIV and XVI and Articles 71 and 72 of this Regulation in order to:
(a) enable a streamlined procedure for an authorisation of combined studies,
including the coordinated assessment of initial applications, coordinated
assessment of the request for substantial modifications and additions of
Member State concerned;
(b) set the requirements applicable during the conduct of the combined
studies, including as regards to the specific safety reporting requirements;
(a) clarify the responsibilities of the combined studies’ sponsors and
investigators;
(b) ensure supervision;
(c) determine the functionalities of the EU portal and EU database necessary
to support application of this Article.
10. When doing so, the Commission shall take into consideration, where relevant,
provisions of Chapter VI and Annex XV of Regulation (EU) 2017/745 or
Chapter VI and Annexes XIII and XIV of Regulation (EU) 2017/746
concerning the investigational device(s) or device(s) for performance study
which are covered by the combined study, as applicable.
Article 14d
Persons assessing the applications
Article 9 applies to assessments made under this Chapter.’
(14) Article 16 is replaced by the following:
‘Article 16
Submission of application
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In order to obtain an authorisation, the sponsor shall submit an application dossier to
the Member States concerned through the EU portal. The date on which the sponsor
submitted the application for an authorisation of a substantial modification is referred
to within this Chapter as the submission date.’;
(15) the following Article 16a is inserted:
‘Article 16a
Parallel substantial modification
1. The sponsor may submit to the reporting Member State, through the EU portal,
an application for a parallel substantial modification regarding aspects covered
by Part I of the assessment report, prior to the notification of a decision on an
ongoing assessment of a substantial modification in accordance with Article
19(1) or Article 23(1).
2. The sponsor may submit to the same Member State concerned, through the EU
portal, an application for a parallel substantial modification of an aspect
covered by Part II of the assessment report prior to the notification of a
decision on an ongoing assessment of a substantial modification in accordance
with Article 20(5) or Article 23(1) by the same Member State concerned.
3. The reporting Member State or Member state concerned, as applicable, shall
accept the application for a parallel substantial modification if the parallel
substantial modification concerns distinct and independent aspects of the
application dossier and may be assessed concurrently by the same Member
State concerned or reporting Member State.
4. When scope of the application for the parallel substantial modification covers
both Part I and Part II of the assessment report, the sponsor shall seek the
agreement of both, the reporting Member State and the relevant Member States
concerned. The relevant Member State concerned may oppose the agreement if
the substantial modification concerns aspects of Part II covered by an ongoing
assessment.’
(16) Article 17 is amended as follows:
(a) paragraphs 1 and 2 are replaced by the following:
‘1. The reporting Member State for the authorisation of the substantial
modification shall be the reporting Member State for the initial
authorisation procedure.
2. Within four days from the submission date, the reporting Member State
shall validate the application and notify the sponsor through the EU
portal as to whether:
(a) the substantial modification concerns an aspect covered by Part I of
the assessment report;
(b) the application dossier is complete in accordance with Annex II;
and
(c) in case of parallel substantial modification to Part I, whether such a
parallel substantial modification is acceptable taking into account
the requirements of Article 16a.
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When applicable, in the context of a substantial modification of Part I,
the Member State concerned shall verify whether the translation or
translations in the national language or languages in accordance with the
requirements of Articles 26 and 69 has or have been submitted as a
substantial modification of Part II. Article 21 applies to the assessment of
the accuracy of translations.’
(b) paragraph 4 is replaced by the following:
‘4. Where the reporting Member State finds that the application does not
concern an aspect covered by Part I of the assessment report or that the
application dossier is not complete or, where applicable, that the parallel
substantial modification is not acceptable, it shall inform the sponsor
thereof though the EU portal and shall set a maximum of four days for
the sponsor to comment on the application of to complete the application
dossier though the EU portal.
The reporting Member State shall notify the sponsor within 14 days from
the submission date, as to whether or not the application complies with
the requirements set out in paragraph 2, points (a), (b), and when
applicable point (c).
Where the reporting Member State has not notified the sponsor within the
period referred to in the second subparagraph, the substantial
modification applied for shall be deemed to concern an aspect covered by
Part I of the assessment report, the application dossier shall be deemed to
be complete and, when applicable, the parallel substantial modification
shall be deemed to be acceptable taking into account the requirements of
Article 16a.
Where the sponsor has not provided comments or completed the
application dossier within the period referred to in the first subparagraph,
the application shall be deemed to have lapsed in all the Member States
concerned.’
(17) Article 18 is amended as follows:
(a) paragraphs 3 and 4 are replaced by the following:
‘3. The reporting Member State shall submit, through the EU portal, the final
assessment report including its conclusions, to the sponsor and to the
other Member States concerned within 28 days from the submission date.
For the purpose of this Article and of Articles 19 and 23, the reporting
date shall be the date on which the final assessment report is submitted to
the sponsor and the other Member States concerned.
4. For clinical trials involving more than one Member State the assessment
process of substantial modification shall include three phases:
(a) an assessment phase performed by the reporting Member State
within 21 days from the submission date. The assessment phase
shall end when the reporting Member State circulates the draft
assessment report;
(b) a review phase performed within three days from the end of the
assessment phase, involving all the Member States concerned, and;
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(c) a coordination phase performed within four days from the end of
the review phase.
During the assessment phase, the reporting Member State shall develop a
draft assessment report and circulate it to all the Member States
concerned.
During the review phase, all Member States concerned shall review the
application on the basis of the draft assessment report and shall share
considerations for their Member State that are relevant to the application.
Considerations may only be raised on:
– one or more grounds referred to in Article 19(2) of this Regulation.
– on matters that would lead the ethics committee issuing negative
opinion.
During the consolidation phase, the reporting Member State shall take
due account of the considerations of the other Member States concerned
when finalizing the assessment report and shall record how the
considerations have been addressed. The reporting Member State shall
submit the final assessment report to the sponsor and all the other
Member States concerned by the reporting date.’
(b) paragraph 5 is deleted;
(c) paragraph 6 is replaced by the following:
‘6. Between the validation date and the reporting date, only the reporting
Member State may request additional information from the sponsor,
taking into account the considerations referred to in paragraph 4.
For the purpose of obtaining and reviewing this additional information
from the sponsor in accordance with the third and fourth subparagraph,
the reporting Member State may extend the period referred to in the first
subparagraph of paragraph 3 by a maximum of 14 days.
The sponsor shall submit the requested additional information within the
period set by the reporting Member State. This period shall not extend
beyond seven days from the receipt of the request.
Upon receipt of the additional information, the Member States concerned
shall review any additional information provided by the sponsor and shall
share any unaddressed considerations relevant to the application. The
review shall be performed within a maximum of three days from the
receipt of the additional information and further consolidation shall be
performed within a maximum of seven days from the receipt of
additional information from the sponsor. When finalising the assessment
report, the reporting Member State shall take due account of the
considerations of the other Member States concerned and shall record
how the considerations have been dealt with.’;
(18) Article 19 is amended as follows:
(a) paragraphs 1 and 2 are replaced by the following:
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‘1. Each Member State concerned shall notify the sponsor through the EU
portal as to whether the substantial modification is authorised, whether it
is authorised subject to conditions, or whether authorisation is refused.
Notification shall be done by way of a single decision within five days
from the reporting date.
Where the conclusion of the reporting Member State is that the
substantial modification is acceptable or acceptable subject to
compliance with specific conditions, that conclusions shall be deemed to
be the conclusions of the Member State concerned.
A substantial modification subject to condition may be implemented
unless the Member State concerned specified that the condition is
suspensive. Unless otherwise specified, the fulfilment of the condition
does not require a submission of a request for another substantial
modification.
Notwithstanding the first subparagraph, a Member State concerned may
disagree with that conclusion of the reporting Member State only on the
following grounds, provided that the consideration was raised during the
process pursuant to Article 18(4) and it considers that it was not
sufficiently addressed:
(a) when it considers that participation in the clinical trial would lead
to a subject receiving an inferior treatment than in normal clinical
practice in the Member State concerned;
(b) infringement of its national law as referred to in article 90.
2. Where the Member State concerned disagrees with the conclusion on the
basis of the second subparagraph, it shall communicate its disagreement,
together with a detailed justification, through the EU portal, to the
Commission, to all Member States and to the sponsor.
A Member State concerned shall refuse to authorise a substantial
modification if it disagrees with the conclusion of the reporting Member
State as regards Part I of the assessment report on any of the grounds
referred to in the second paragraph or where an ethics committee has
issued a negative opinion which, in accordance with the law of that
Member State concerned, is valid for the entire Member State. That
Member State shall provide for an appeal procedure in respect of such
refusal.’
(19) Article 20 is amended as follows:
(a) paragraphs 1 and 2 are replaced by the following:
‘1. Within four days from the submission of the application dossier, the
Member State concerned shall notify the sponsor though the EU portal of
the following:
(a) whether the substantial modification concerns an aspect covered by
Part II of the assessment report;
(b) whether the application dossier is complete in accordance with
Annex II;
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(c) in case of parallel modification to Part I, whether the submission is
acceptable taking into account the requirements of Article 16a.
‘2. Where the Member State concerned has not notified the sponsor within
the period referred to in paragraph 1, the substantial modification applied
for shall be deemed to concern an aspect covered by Part II of the
assessment report and the application dossier shall be deemed to be
complete and, when applicable, the parallel substantial modification shall
be deemed to be acceptable taking into account the requirements of
Article 16a.’
(b) in paragraph 3, the two first subparagraphs are replaced by the following:
‘Where the Member State concerned finds that the substantial modification
does not concern an aspect covered by Part II of the assessment report or that
the application dossier is not complete, or, where applicable, that the parallel
substantial modification is not acceptable, it shall inform the sponsor thereof
through the EU portal and shall set a maximum of five days for the sponsor to
comment on the application or to complete the application dossier through the
EU portal.
Within 14 days from the submission date the reporting Member State shall
notify the sponsor as to whether or not the application complies with the
requirements set out in paragraph 1 points (a), (b), and if applicable, (c).’
(c) in paragraph 5, the second and third subparagraphs are replaced by the
following:
‘Notification shall be done by way of a single decision within 28 days from the
submission date.
A substantial modification subject to condition may be implemented unless the
Member State concerned specified that the condition is suspensive. Unless
otherwise specified, a fulfilment of the condition does not require a submission
of a request for another substantial modification.’
(d) in paragraph 6, the second, third and fourth subparagraphs are replaced by the
following:
‘For the purpose of obtaining and reviewing this additional information from
the sponsor, the Member State concerned may extend the period referred to in
the paragraph 5, second subparagraph, by a maximum of 14 days.
The sponsor shall submit the requested additional information within the period
set by the Member State concerned, which shall not exceed seven days from
the receipt of the request.
Upon receipt of the additional information, the Member State concerned shall
complete its assessment within a maximum seven days.’;
(20) in Article 21, paragraph 1 is replaced by the following:
‘1. Where a substantial modification relates to aspects covered by Parts I and II of
the assessment report, the application for an authorisation of that substantial
modification shall be validated in accordance with Articles 17 and 20.’;
(21) Article 22 is amended as follows:
(a) paragraph 1 is replaced by the following:
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‘1. Each Member State concerned shall assess, for its own territory, the
aspects of the substantial modification which are covered by Part II of the
assessment report and submit, through the EU portal, that report,
including its conclusion, to the sponsor within 28 days from the
submission date. If the reporting Member State requested additional
information regarding aspects covered by Part I of the assessment report
as per Article 21(2) in conjunction with Article 18(6), or when a Member
State concerned requests additional information from the sponsor
regarding Part II aspects of the application, Member States concerned
may extend this period by 14 days.’
(b) paragraph 2 is deleted;
(c) paragraph 3 is replaced by the following:
‘3. The sponsor shall submit the requested additional information within the
period set by the Member State concerned, which shall not exceed seven
days from the receipt of the request.
Upon receipt of the additional information, the Member State concerned
shall complete its assessment within a maximum of seven days from the
submission of the requested information by the sponsor.
Where the sponsor does not provide the requested additional information
within the period set by the Member State concerned the application shall
be deemed to have lapsed in that Member State.
The request for additional information and the additional information
shall be submitted through the EU portal.’
(22) Article 23 is amended as follows:
(a) in paragraph 1, the third subparagraph is replaced by the following:
‘A substantial modification subject to condition may be implemented unless
the Member State concerned specified that the condition is suspensive. Unless
otherwise specified, a fulfilment of the condition does not require a submission
of a request for another substantial modification.’
(b) in paragraph 2, the second subparagraph, is replaced by the following:
’Notwithstanding the first subparagraph, a Member State concerned may
disagree with the conclusion of the reporting Member State only on the
following grounds, provided that the consideration was raised during the
process pursuant to Article 18(4) and it considers that it was not sufficiently
addressed:
(a) when it considers that participation in the clinical trial would lead to a
subject receiving an inferior treatment than in normal clinical practice in
the Member State concerned;
(b) infringement of its national law as referred to in Article 90.’
(23) Article 25 is amended as follows:
(a) paragraph 1 is amended as follows:
(i) in the first subparagraph, point (e) is replaced aby the following:
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‘(e) justification as to why the clinical trial is a minimal-intervention or
low-intervention clinical trial, in cases where this is claimed by the
sponsor.’;
(ii) the second subparagraph is replaced by the following:
‘The list of required documentation and information for Part I is set out
in Part I of Annex I. The list of required documentation for Part II is set
out in Part II of Annex I.’;
(b) the following paragraphs 1a, 1b and 1c are inserted:
‘1a. The requirements for Part I may be adapted for minimal-intervention or
low-intervention clinical trials.”
‘1b. The sponsor shall use harmonised templates, where such templates are
available, for the submission of documents for Part II of the application
dossier necessary for the authorisation of the clinical trial, in accordance
with the requirements described in Article 7(1) of this Regulation.
1c. To draw up and update, when necessary, harmonised templates to be
used by sponsors, the Commission shall be empowered to adopt
implementing acts in accordance with Article 88. The harmonised
templates may include standardised sections for documents referred to in
Article 7(2) and in Annex I.’
(c) the following paragraph 2a is inserted:
’2a. The requirements referred to in paragraph 2 may be adapted for minimal-
intervention and low-intervention clinical trials.’
(d) the following paragraphs 8 and 9 are added:
‘8. An application dossier for an authorisation of a clinical trial or for an
authorisation of a substantial modification may rely on health data
accessed under Chapter IV of Regulation (EU) 2025/327 of the European
Parliament and of the Council*
9. National competent authorities and ethics committees shall ensure that
the persons validating or assessing the initial application and substantial
modification requests only documents which are listed in Part I and Part
II of Annex I and Annex II.’
* Regulation (EU) 2025/327 of the European Parliament and of the
Council of 11 February 2025 on the European Health Data Space and
amending Directive 2011/24/EU and Regulation (EU) 2024/2847 (OJ L,
2025/327, 5.3.2025. ELI: http://data.europa.eu/eli/reg/2025/327/oj).
(24) the following Chapters IVa and IVb are inserted:
‘Chapter IVa
INVESTIGATIONAL MEDICINAL PRODUCT CORE DOSSIER
Article 27a
Establishment of an investigational medicinal product core dossier
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1. At the time of submission of a clinical trial application referred to in Articles 5
and 11 the sponsor may request through the EU portal the establishment of an
investigational medicinal product core dossier. To this end, the sponsor shall
provide data and information referred to in point (Ga) of Part I of Annex I.
2. The sponsor shall submit the request for the establishment of the
investigational medicinal product core dossier to all Member States concerned
of the initial trial. The sponsor may extend this request to other Member States
than the Member States concerned. The reporting Member State of the initial
clinical trial shall become the depositary Member State.
3. The depositary Member State shall verify the completeness and suitability of
the core dossier for the purposes of the initial clinical trial. At the latest by the
time when the conclusion of the assessment of Part I is due in accordance with
Article 6(3) the depositary Member State shall notify the sponsor and the other
core dossier competent Member States through the EU portal of the
establishment of the investigational medicinal products core dossier where the
assessment is positive.
4. The investigational product core dossier shall be relied upon by the reporting
Member State and the Member States concerned in the process of authorising
the initial clinical trial referred to in paragraph 1.
5. Once established, the investigational medicinal product core dossier shall be
referred to in all subsequent applications concerning the clinical trial in the
context of which the investigational medicinal products core dossier was
established and any other corresponding clinical trial.
Article 27b
Maintenance and changes of the investigational medicinal products core dossier
1. The sponsor shall keep the investigational medicinal product core dossier
updated and shall review it at least once per year. When the sponsor identifies a
necessity to update the investigational products core dossier, paragraph 2
applies.
2. When new information, relevant to maintain the suitability and completeness
of an established investigational product core dossier becomes known to the
sponsor, the sponsor shall submit to the depositary Member State, through the
EU portal, a request for a change of the investigational medicinal product core
dossier.
3. In case of a new application for an authorisation of a new corresponding
clinical trial, the reporting Member State of that clinical trial together with the
depositary Member State shall assess the suitability of the investigational
product core dossier for the purpose of the authorisation of the trial application,
that is;
(a) whether the investigational product core dossier is complete as regards
the information on the characteristics and knowledge about the
investigational medicinal products;
(b) if appropriate, the compliance with the requirements concerning the
manufacturing and import of investigational medicinal products set out in
Chapter IX;
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(c) whether the investigator’s brochure and the IMPD is adequate and
complete for the scope of use as proposed by the sponsor in the
application in accordance point Ga, Part I of Annex I.
The reporting Member State of the corresponding clinical trial shall
communicate the results of its assessment to the depositary Member State.
If the investigational product core dossier does not contain all the information
necessary for the authorisation of the clinical trial, the reporting Member State
may request the sponsor to change the investigational product core dossier.
The sponsor shall in such situations request a change of the investigational
medicinal product core dossier in accordance with paragraph 2.
4. After receiving the request for a change to the core dossier, independently of
whether a change is submitted in the context of an assessment of an application
related to a corresponding clinical trial or independently, the depositary
Member State shall verify whether the core dossier, once changed, will
continue to fulfil the requirements listed in paragraph 3 points (a), (b) and (c).
The Member State concerned with the core dossier shall not duplicate the
assessment of the depositary Member State. The depositary Member State may
consult the Member State concerned as appropriate.
5. If a request for a core dossier change is submitted in the context of an ongoing
assessment related to a corresponding clinical trial, the timeline for change of
the core dossier shall allow for timely approval of the clinical trial.
6. The sponsor shall assess whether a change to the investigational product core
dossier makes it necessary to submit a substantial modification in
corresponding clinical trials that are ongoing.
Article 27c
Procedural aspects related to the establishment and maintenance of the investigational
medicinal products core dossier
The Commission shall set out the detailed rules governing the submission of a
request for the establishment of an investigational product core dossier, its
assessment and maintenance by means of implementing acts, including the rules for
cooperation between the core dossier competent Member States and the change of
depositary Member State. Those implementing acts shall be adopted in accordance
with the examination procedure referred to in Article 88.”
Chapter IVb
REGULATORY SANDBOXES AND USE OF AI
Article 27d
Regulatory sandbox
1. The Commission may, pursuant to the procedure set out in paragraph 7,
establish and operate a regulatory sandbox at Union level that provides a
controlled and time-limited framework to enable, under real-world conditions,
the testing of innovative approaches in clinical trials to which the full
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application of certain requirements of this Regulation is not possible or
appropriate and which therefore may require adaptations.
2. The regulatory sandbox under this Regulation may encompass approaches to
the authorisation and conduct of the clinical trials and where appropriate,
maybe be implemented in coordination and synergies with the regulatory
sandboxes established pursuant to Regulation (EU) 2024/1689 with full
involvement of competent authorities supervising the sandbox under
Regulation (EU) 2024/1689 and in accordance with the relevant procedures
and rules for participating in those AI regulatory sandboxes.
3. The activities within a regulatory sandbox shall take place pursuant to a
specific plan, for eligible clinical trials, which may be conducted under
enhanced regulatory oversight of the Member States concerned. The plan shall
clearly identify the requirements of this Regulation that are temporarily
adapted or derogated from in the sandbox and that may relate to, as necessary,
to source data and documentation requirements, recruitment and informed
consent procedures, monitoring and reporting requirements, trial design rules,
investigational medicines handling rules, safety reporting rules, site
requirements. The plan shall also identify the roles and responsibilities of
sponsors, investigators, and manufacturers.
4. A regulatory sandbox may be established only if the following conditions are
met:
(a) it is not possible to authorise or conduct a clinical trial in full compliance
with the requirements of this Regulation due to innovative approaches in
the clinical trial or due to the specificity of the investigational medicinal
product;
(b) the approaches referred to in point (a) are expected to contribute to at
least one of the following objectives:
(i) increasing the robustness of the data generated in the trial;
(ii) considerably decreasing clinical trial length, and increasing the
efficiency of the clinical trial;
(iii) enabling new technologies and approaches in the development of
medicinal products that have the potential to positively and
distinctively contribute to better prevention, diagnosis, and
treatment, as well as increase adherence to treatment plans or
improve the efficiency of the provision of health care;
(c) the sandbox provides safeguards to ensure the safety, well-being, and
fundamental rights of clinical trial participants, data robustness, and
maintained integrity of the clinical trials within the sandbox.
5. The regulatory sandbox shall not affect the supervisory or corrective powers of
the Member States concerned and shall operate under the direct supervision of
the competent authorities in the Member State concerned for activities that take
place on its territory.
6. Before setting up a sandbox, the Commission shall request an opinion of the
CTAG.
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7. The Commission may establish a regulatory sandbox by means of
implementing acts, after taking into consideration opinions referred to in
paragraph 6. Those implementing acts shall be adopted in accordance with the
examination procedure referred to in Article 88.
8. Member States shall notify the Commission of any risk to health and safety or
fundamental rights or integrity and robustness of data identified during the
operation of a sandbox. In these cases, the Commission may, by means of
implementing acts, suspend or revoke a regulatory sandbox.
8. Without prejudice to Article 114(1) of [Regulation (EU) …/… of the European
Parliament and the Council [reference to be added after adoption cf.
COM(2023) 193 final], where in the context of a regulatory sandbox under
Article 113 of Regulation (EU) …/… of the European Parliament and the
Council [reference to be added after adoption cf. COM(2023) 193 final] is
considered that new regulatory approaches in clinical trial are necessary for the
product development, the Commission may consider to establish a regulatory
sandbox under this Regulation to complement the regulatory sandbox
established under Regulation (EU) …/… of the European Parliament and the
Council [reference to be added after adoption cf. COM(2023) 193 final].
Article 27e
Use of Artificial Intelligence in Clinical Trials
1. For those clinical trials where the sponsor plan to use AI models or systems,
the sponsor shall evaluate the benefits and risks related to patient safety and
data robustness of the use of the AI in the context of a specific clinical trial for
a specific purpose taking into account the guidelines laid down in Article 37 of
Regulation [...] [Biotech Act].
2. The sponsor shall provide information in the protocol on the specific purpose
of the use of AI models or systems and the description of the process in the
context of the specific clinical trial.
3. When the investigation of a medicinal product in a clinical trial is combined
with a performance study of an AI in vitro diagnostic medical device or a
clinical investigation of an AI medical device, the provisions of Article 14 on
coordinated assessment for authorising combined studies shall apply.
4. In cooperation with the CTAG and, where appropriate, the Medical Device
Coordination Group, the Artificial Intelligence Board, the Agency shall
develop guidelines referred to in paragraph 1 of this Article.
** Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND
OF THE COUNCIL laying down Union procedures for the authorisation and
supervision of medicinal products for human use and establishing rules
governing the European Medicines Agency, amending Regulation (EC) No
1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC)
No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No
1901/2006, COM/2023/193final
(25) Article 28 is amended as follows:
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(a) paragraph 2 is deleted.
(b) in paragraph 3, the last sentence is deleted.
(26) in Article 29(1), the following subparagraph is added:
‘The communication in the context of an interview between the investigator and the
subject or the investigator and the subject and its legally designated representative, as
applicable, may be done remotely through use of electronic means. The record of the
informed consent procedure may have an electronic form and shall be signed relying
on electronic identification means complying with Regulation (EU) No 910/2014 of
the European Parliament and of the Council* or the equivalent standards.
* Regulation (EU) No 910/2014 of the European Parliament and of the Council of
23 July 2014 on electronic identification and trust services for electronic transactions
in the internal market and repealing Directive 1999/93/EC, OJ L 257,
28.8.2014.ELI: http://data.europa.eu/eli/reg/2014/910/oj.’’
(27) in Article 30(3), point (c) is replaced by the following:
‘(c) the clinical trial is a minimal-intervention clinical trial;’
(28) in Article 31(1), point (e) is deleted;
(29) in Article 32 (1), point (e) is deleted;
(30) in Article 33, the following second paragraph is inserted:
’Women who become pregnant or begin breastfeeding while participating in a
clinical trial shall not be automatically excluded from participation in the clinical
trial.’
(31) in Article 41, the following paragraph 5 is added:
’5. Reporting requirements of adverse events and serious adverse events for
minimal-intervention and low-intervention clinical trials shall be simplified by
applying a risk-based approach. Any such adaptation should be clearly stated
and justified in the protocol by the sponsor.:
(32) in Article 48, point (a) is replaced by the following:
‘(a) whether the clinical trial is a minimal-intervention or low-intervention clinical
trial;’:
(33) the following Article 50a is inserted:
’Article 50a
Delivery of investigational and auxiliary medicinal products through a dispensing pharmacy,
an authorised person or directly to the subject
When justified in the protocol, the delivery of investigational medicinal products and
auxiliary medicinal products to the clinical trials subjects may be ensured at a
distance under the supervision of the investigator.
In case of a minimal-intervention and a low-intervention clinical trial, the
distribution of the investigational medicinal products can be ensured in a Member
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State where the clinical trial has been authorised, under the responsibility of the
investigator, through the dispensing pharmacies or by persons authorised to supply
medicinal products to thesubject.
The protocol and investigator’s brochure shall describe the arrangements for direct
delivery to subjects or through dispensing pharmacies or persons authorised to
supply to the patients, including the roles and responsibilities of all parties involved
and procedures for secure handling, storage.
The direct delivery to subjects shall comply with the guidelines referred to in
paragraph 1 of Article 63a.’:
(34) in Article 51(1), first subparagraph is replaced by the following:
’Investigational medicinal products shall be traceable. They shall be stored, returned
and/or destroyed as appropriate and proportionate to ensure the safety of the subject
and the reliability and robustness of the data generated in the clinical trial, in
particular, taking into account whether the investigational medicinal product is an
authorised investi-gational medicinal product, and whether the clinical trial is a
minimal-intervention or low-inter-vention clinical trial.’;
(35) in Article 53(2), the first sentence is replaced by the following:
’The sponsor shall submit to the Member States concerned, through the EU portal,
inspection reports of third country authorities concerning the clinical trial and
relevant to subject safety .’
(36) in Article 57, the first subparagraph is replaced by the following:
’The sponsor and the investigator shall keep a clinical trial master file. The clinical
trial master file shall at all times contain the essential documents relating to that
clinical trial which allow verification of the conduct of a clinical trial and the quality
of the data generated, taking into account all characteristics of the clinical trial,
including in particular whether the clinical trial is a minimal-intervention or low-
intervention clinical trial.’;
(37) Article 61 is amended as follows:
(a) paragraph 6 is replaced by the following:
‘6. Member States shall make the processes set out in paragraph 5 subject to
appropriate and proportionate requirements to ensure subject safety and
reliability and robustness of the data generated in the clinical trial while
taking into account the guidelines referred to in paragraph 7. They shall
subject the processes to regular inspections.’;
(b) the following paragraph 7 is added:
‘7. The inspection working groups referred to in Article 142, point (k) of
Regulation (EU) …/… of the European Parliament and the Council
[reference to be added after adoption cf. COM(2023) 193 final]*, in
agreement with the Commission, may draw up guidelines on general
principles applicable to the processes set out in paragraph 5, including for
auxiliary medicinal products, and revise them as necessary in order to
take account of technical and scientific progress.
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*Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND
OF THE COUNCIL laying down Union procedures for the authorisation and
supervision of medicinal products for human use and establishing rules
governing the European Medicines Agency, amending Regulation (EC) No
1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC)
No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No
1901/2006, COM/2023/193final.’
(38) in Article 63, paragraph 4 is replaced by the following:
‘4. The Member States shall ensure compliance with the requirements of this
Article by means of inspections. Articles 188, with exception of its paragraph 3
and 4, and 189 of Directive (EU) …/… [reference to be added after adoption
cf. COM(2023) 192 final]* and article 52 of Regulation (EU) …/… of the
European Parliament and the Council [reference to be added after adoption cf.
COM(2023) 193 final]** apply mutatis mutandis.
* Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE
COUNCIL on the Union code relating to medicinal products for human use, and
repealing Directive 2001/83/EC and Directive 2009/35/EC COM/2023/192final
** Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF
THE COUNCIL laying down Union procedures for the authorisation and supervision
of medicinal products for human use and establishing rules governing the European
Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU)
No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No
141/2000 and Regulation (EC) No 1901/2006, COM/2023/193final’
(39) the following Article 63a is inserted:
’Article 63a
Distribution
1. The distribution of investigational medicinal shall comply with standards that
shall ensure their quality and integrity. The Commission shall adopt delegated
acts supplementing this Regulation by determining the standards of good
distribution practices for investigational and auxiliary medicinal products
taking into account the input of the inspection working groups referred to in
Article 142, point (k) of Regulation (EU) …/… of the European Parliament
and the Council [reference to be added after adoption cf. COM(2023) 193
final], and update them if necessary to take account of scientific and technical
progress.
2. Where the competent authority of the Member State considers it necessary, in
particular where there are grounds for suspecting non-compliance with the
requirements of this Article, it may carry out inspections to verify the
compliance.
3. Arrangements for inspections referred to in Article 63(1) apply mutatis
mutandis to inspections of good distribution practices for investigational and
auxiliary medicinal products.’;
(40) in Article 76, paragraph 3 is replaced by the following:
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‘3. Member States shall not require any additional use of the system referred to in
paragraph 1 from the sponsor for minimal or low-intervention clinical trials, if
any possible damage that could be suffered by a subject resulting from the use
of the investigational medicinal product in accordance with the protocol of that
specific clinical trial on the territory of that Member State is covered by the
applicable compen-sation system already in place.’;
(41) Article 78 is amended as follows:
(a) paragraph 1 is replaced by the following:
’1. The national competent authorities shall organize inspections in order to
supervise compliance with this Regulation.
Member States shall appoint inspectors to perform the inspections in
order to supervise compliance with this Regulation.
The competent authority of the Member State shall have in place a
system of supervision that shall include the following measures:
(a) announced, and where appropriate, unannounced on-site
inspections;
(b) remote inspections conducted where justified;
(c) compliance control;
(d) the effective follow up of the measures referred to in points (a), (b)
and (c).’;
(b) aragraph 6 is replaced by the following:
“6. Following an inspection, the Member State under whose responsibility
the inspection has been conducted, shall draw up an inspection report.
That Member State shall make the inspection report available to the
inspected entity and the sponsor of the relevant clinical trial and shall
submit the inspection report through the EU portal within 90 days after
conducting the inspection.”;
(c) paragraphs 8, 9 and 10 are added:
‘8. Upon a request by one or more competent authorities of the Member
State, the inspection referred to in paragraph 1 may be carried out jointly
by the inspectors from more than one Member State and the inspectors
from the Agency.
9. Member States may delegate to another Member State or the Agency the
conduct of a good clinical practice inspection. The Commission may
adopt a delegated act in accordance with Article 89 to supplement this
Regulation by laying down the procedures applicable to joint inspections
and delegation of inspections.
10. This Article does not apply to the good manufacturing practice
inspections and the good distribution practices inspections related to
application of this Regulation, in accordance with Articles 63 and 63a
respectively.’;
(42) Article 79 is replaced by the following:
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’Article 79
Union controls
1. The Commission may conduct controls in order to verify:
(a) whether the Member States correctly supervise compliance with this
Regulation;
(b) whether regulatory system applicable to clinical trials conducted outside
the Union ensures that the clinical trials references in the applications for
marketing authorisations in the Union are designed, implemented and
reported on what good clinical practice and ethical principle are
concerned, on the basis of principles that are equivalent to the ones
established in this Regulation;
(c) whether the regulatory system applicable to clinical trials conducted
outside the Union ensures that Article 25(5) of this Regulation is
complied with .
1a. In order to perform the Union controls referred to in paragraph (1) point (a),
the Commission may verify whether competent authorities and ethics
committees have in place adequate and effective mechanisms to ensure
compliance with this Regulation as regards in particular the requirements
related to:
(a) validation of the clinical trial application as referred to in Articles 5(3),
17(2) and Article 20;
(b) scientific and ethical review as referred to in Article 4, Articles 6(1),
7(1), 8, 9 and 10, assessment of substantial modifications as referred to in
Articles 17 to 22, safety assessment referred to in Article 44;
(c) communication and coordination with other Member States as referred to
in Articles 5 to 8, Article 14, Article 17 to 19, Article 22 and 23;
(d) manufacturing and import of investigational medicinal products as
referred to in Articles 61 and 63(4);
(e) application of corrective measures and penalties as referred to in Article
77 and 94;
(f) conduct inspections as referred to in Articles 78, 63 and 63a.
2. The Commission shall organise the controls referred to in paragraph 1 in
cooperation with the national authorities and shall carry them out in a manner
that avoids unnecessary administrative burden.
3. When performing the controls referred to in paragraph 1, the Commission shall
consult the relevant best practices.
4. The Commission, in carrying out the controls referred to in paragraph 1, may
be supported by experts from the competent authorities or ethics committees.
5. Following each control, the Commission shall:
(a) prepare a draft report on the findings and, where appropriate, include
recommendations addressing the shortcomings identified;
(b) send a copy of the draft report referred to in point (a) to the clinical trials
national authority concerned for its comments;
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(c) take the comments referred to in point (b) into account in preparing the
final report; and
(d) submit the final report through the EU portal.”;
(43) the following Article 79a is inserted:
’Article 79a
Obligations as regards Union controls
Member States shall cooperate with the Commission in respect of the performance of
the Union controls referred to in Article 79 (1). In particular, they shall:
(a) ensure that the necessary technical assistance and the relevant documentation,
upon justified request, is being provided to the Commission as well as provide
any other support that the Commission requests to enable it to perform controls
efficiently and effectively, including facilitating access to all premises or any
part thereof, to personnel (interviews) and data, including IT systems of the
competent authority that is relevant for the execution of their duties.
(b) take appropriate follow-up measures to remedy the shortcomings identified
through those Commission controls;’
(44) Article 81 is amended as follows:
(a) paragraph 2 is replaced by the following:
’2. The EU database shall be established to enable cooperation between the
competent authorities of the Member States concerned to the extent that
it is necessary for the application of this Regulation and to search for
specific clinical trials. It shall also enable communication between
sponsors and Member States concerned and reporting Member State as
appropriate for the purpose of swift regulatory procedures. It shall enable
sponsors to refer to previous submissions of an application for
authorisation of a clinical trial or a substantial modification. It shall also
enable citizens of the Union to have access to clinical information about
medicinal products. To this end all data held in the EU database shall be
in an easily searchable format, all related data shall be grouped together
by way of the EU trial number, and hyperlinks shall be provided to link
together related data and documents held on the EU database and other
databases managed by the Agency.’;
(b) paragraph 9 is replaced by the following:
’9. The sponsor shall permanently update in the EU database information on
any changes to the clinical trials which are not substantial modifications
but are relevant for the supervision of the clinical trial. The sponsor shall
also update the EU portal to satisfy the condition to which an
authorisation decision is subject to. An update may trigger a corrective
measure from the reporting Member State or the Member State
concerned requiring from the sponsor to submit a substantial
modification concerning this change. The Member State concerned may
issue such corrective measure within 7 days from the date of the update.
The sponsor shall submit the substantial modification within period
defined in the corrective measure by the Member State.’;
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(45) Article 83 is replaced by the following:
‘Article 83
Competent authorities and ethics committees
1. Member States shall designate one national contact point to which they confer
responsibility for the implementation and practical application of this
Regulation. The Commission shall publish a list of national contact points.
2. Each Member State shall communicate the contact point referred to in
paragraph 1 to the Commission. Member States shall ensure that competent
authorities and ethics committees:
(a) have the necessary powers to perform all the necessary regulatory actions
and inspections, pursuant to this Regulation.
(b) have, or have access to, a sufficient number of suitably qualified and
experienced personnel, human and financial resources, operational
capacity, and expertise, including technical expertise, for the effective
and efficient performance of their tasks they have been made responsible
for pursuant to this Regulation.’;
(46) the following Article 83a is inserted:
’Article 83a
Communication and coordination between competent authorities and between ethics
committees
1. Where more than one competent authority and ethics committee are
responsible for performing regulatory activities or inspections in a Member
State for the purpose of applying this Regulation, Member States shall ensure
efficient and effective coordination among all the competent authorities and
ethics committees concerned in order to guarantee the consistency and
effectiveness of the regulatory activities or inspections performed on their
territory.
2. Within those Member States, the competent authorities shall cooperate with
each other. They shall communicate information to each other for the effective
implementation of the regulatory activities and inspections provided for in this
Regulation.’;
(47) Article 85 is replaced by the following:
‘Article 85
Clinical Trials Coordination and Advisory Group
1. A Clinical Trials Coordination and Advisory Group (CTAG) is hereby
established.
2. Each Member State shall appoint to the CTAG, for a three-year term which
may be renewed once, one member and one alternate each with expertise in the
field of clinical trials. The members of the CTAG shall be chosen for their
competence and experience in the field of clinical trials. They shall represent
the competent national authorities and the ethics committees of the Member
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States. The names and affiliations of members and alternates shall be made
public by the Commission. The alternates shall represent and vote for the
members in their absence.
3. For the purpose of the fulfilment of their tasks, CTAG members shall be able
to rely on the contribution of experts from national competent authorities and
ethics committees. These experts shall participate in CTAG meetings where
relevant.
4. The CTAG shall use its best endeavors to reach consensus. If such consensus
cannot be reached, the CTAG shall decide by a majority of its members.
Members with diverging positions may request that their position and the
grounds on which they are based are recorded.
5. The CTAG shall in particular have the following tasks:
(a) to support the exchange of information between the Member States and
the Commission on the experience acquired with regard to the
implementation of this Regulation;
(b) to assist the Commission in providing the support referred to in the
second paragraph of Article 84;
(c) to prepare recommendations on criteria regarding the selection of a
reporting Member State;
(d) to provide strategic steering on a common approach for the application of
this Regulation and on the support of the clinical trials ecosystem in the
Union;
(e) to contribute to the development of guidance aiming to ensure effective
and harmonised implementation of this Regulation.
(f) to contribute to the development of guidelines on the use of the artificial
intelligence models and systems in clinical trials in accordance with
Article [xx] Regulation (EU) …/… [European Biotech Act]*;
(g) to provide advice, either of its own initiative or at the request of the
Commission, in the assessment of any issue related to the implementation
of this Regulation;
(h) to contribute to harmonised administrative practice with regard to clinical
trials in the Member States;
(i) to provide a recommendation before setting up a regulatory sandbox.
6. The CTAG shall be chaired by a representative of the Commission. The chair
shall not take part in votes of the CTAG.
7. The CTAG may issue recommendations and opinions on matters related to
clinical trials and shall endorse any guidance related to the application of this
Regulation. The Commission shall publish the guidelines endorsed by the
CTAG.
8. The CTAG shall meet at regular intervals and whenever the situation requires,
on a request from the Commission or a Member State. Any item of the agenda
of the meeting shall be placed at the request of the Commission or a Member
State.
9. The secretariat shall be provided by the Commission.
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10. The CTAG shall draw up its rules of procedure. The rules of procedure shall be
made public.
(48) Article 93 is replaced by the following:
’Article 93
Data protection
1. When carrying out their tasks pursuant to this Regulation, sponsors are
required to process personal data, including genetic data or data concerning
health for the following purposes:
(a) for the submission of applications in accordance with Articles 5, 11, 14
and 16;
(b) to perform research activities in the context of a clinical trial in
accordance with the protocol as authorised by the national competent
authorities in accordance with point D, Part I of Annex I;
(c) to perform safety operations and reporting in accordance with Articles 41
to 43 and 52 to 54;
(d) to record, process, handle and store information in accordance with
Article 56;
(e) to perform archiving in accordance with Article 58;
(f) to submit to the EU portal the summary of the results of the clinical trial,
the lay summary, the clinical study report and, where applicable, raw
data, in accordance with Article 37(4).
2. When carrying out their tasks pursuant to this Regulation, investigators are
required to process personal data, including genetic data or data concerning
health for the following purposes:
(a) to perform research activities in the context of a clinical trial in
accordance with the protocol as authorised by the national competent
authorities in accordance with point D, Part I, Annex I;
(b) to perform safety reporting in accordance with Articles 41 and 54;
(c) to record, process, handle and store information in accordance with
Article 56;
(d) to perform archiving in accordance with Article 58.
3. Sponsors and investigators shall make available personal data, including
genetic data or data concerning health:
(a) to the competent authorities of the Member States for the purposes of
oversight activities, including inspections, in accordance with Article 78;
(b) to the Commission for the purposes of controls, in accordance with
Article 79.
4. For the processing assessment leading to the authorisation of clinical trial
applications and operations referred to in this Article, sponsors and
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investigators are controllers within the meaning of Article 4(7) of Regulation
(EU) 2016/679.
5. Personal data, including genetic data or data concerning health, shall be
retained as long as required pursuant to Article 58 and in accordance with the
conditions laid down therein.
6. Personal data collected and processed in accordance with this Regulation may
be further processed by the same controller for the purposes of other clinical
trials conducted under this Regulation, or for scientific research with the aim of
protecting public health, improving standard of care and fostering the
innovation capacity of European medical research.
7. By derogation from Article 9(4) of Regulation (EU) 2016/679, Member States
may not maintain or introduce further conditions, including limitations, with
regard to the processing of personal data, including genetic data or data
concerning health in the context of clinical trials carried out in accordance with
this Regulation.
8. Processing of personal data referred to in this Article shall be subject to
appropriate technical and organisational measures to ensure the protection of
the rights and freedoms of data subject. In particular, the controller shall obtain
informed consent of the subject in accordance with Article 29 of this
Regulation. The controllers shall also apply confidentiality rules concerning
access to records and personal data of subjects and apply further safeguards
that are appropriate for a specific clinical trial as requested in point D, Part I of
Annex I (ak), (al), (am).
(49) Article 97 is replaced by the following:
“Article 97
Review
Five years after the date referred to in Article 99, second subparagpah, and every ten
years thereafter, the Commission shall present a report to the European Parliament
and to the Council on the application of this Regulation. That report shall include an
assessment of the impact that the Regulation has had on scientific and technological
progress, comprehensive information on the different types of clinical trials
authorised pursuant to this Regulation, and the measures required in order to
maintain the competitiveness of European clinical research. The report shall also
assess progress made by monitoring as a key performance indicator the number of
addition multinational clinical trials authorised in the Union over the 5-year period of
the reporting, compared to the average number of such clinical trials authorised per
year in the Union as of 2025;
The Commission shall, if appropriate, present a legislative proposal based on that
report in order to update the provisions set out in this Regulation”
(50 in Article 98, paragraph 1 is replaced by the following:
‘1. This Regulation, as applicable on [Publication Office: please insert the date of
the day before the date of application of Biotechnology Regulation] shall
continue to apply to the procedures for authorisation, substantial modification
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of addition of a Member State concerned of a clinical trial where the request
for the authorisation has been submitted before the date of entry into
application as referred in Article 67(3), point (a), of Regulation […][European
Biotech Act].’
(51) the following Article 98a is inserted;
‘Article 98a
Development plan for the EU Portal and database
The Agency shall be responsible for reporting, on the development, maintenance
and, where relevant, adjustment of the EU portal in terms of timing, budgetary
compliance and quality.
This would include a submission, after consulting the Commission, of a revised
development plan for EU Portal and database to the Agency’s Management Board 1
month after entry into force of Regulation (EU)…/… of the European Parliament and
of the Council [include reference to Biotech Act proposal].* The development plan
shall ensure that all required system functionalities are available by the date of
application as defined in Article [..] of Regulation (EU)…/…[Biotech Act proposal].
The summary of the development plan with key milestones and timelines [once
approved by the Management Board of the Agency] shall be made publicly available
at the website of the Agency.’
*Biotechnology proposal
(52) Annex I is amended in accordance with Annex I to this Regulation.
Article 59
Amendments to Regulation (EU) 2019/6
Regulation (EU) 2019/6 is amended as follows:
(1) in Article 3, the following paragraph 3 is inserted:
“The Union GMO legislation shall not apply to veterinary medicinal products
containing or consisting of genetically modified organisms that are authorised or
manufactured in accordance with this Regulation. The administration of veterinary
medicinal products shall not bring the treated animal or their products under the
scope of the GMO rules.”
(2) in Article 4, the following points (45), (46) and (47) are added:
(45) “zoonosis’ means any disease and/or infection which is naturally transmissible
directly or indirectly between animals and humans
(46) “‘veterinary medicinal products containing or consisting of genetically
modified organisms’ means veterinary medicinal products that contain or
consist of genetically modified organisms as defined in Article 2 point (2) of
Directive 2001/18/EC” excluding organisms obtained through the techniques
of genetic modification listed in Annex I B to Directive 2001/18/EC”;
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(47) ‘‘regulatory sandbox’ means a time-limited regulatory framework that enables
the development, placing on the market or use, under regulatory supervision, of
innovative technologies, methods or products related to animal health which
are directly or indirectly related to the development, manufacturing or use of
veterinary medicinal products and which are not regulated under Union
legislation’;
(3) in Article 8, paragraph 5 is deleted;
(4) Article 9 is amended as follows:
(a) the following paragraph 2a is inserted:
‘2a. In case of clinical trials with veterinary medicinal products containing or
consisting of genetically modified organisms, the competent authorities
shall assess potential adverse effects on human health and the
environment, having regard to the specific characteristics of the product
and in accordance with the principles for environmental risk assessment
set out in Annex II. Where appropriate, the implementation of risk
mitigation measures shall be required’.
(b) in paragraph (3), the following subparagraph is added:
‘During this period, where the trial concerns a veterinary medicinal product
containing or consisting of genetically modified organisms, the competent
authorities may consult with the bodies set up by the Union or Member States
in accordance with under Directive 2001/18/EC, in particular in case of novel
questions or fist-in-class veterinary medicinal products. The consulted bodies
shall ensure protection of commercially confidential information and security
of exchange of information.’
(c) In paragraph (4), the following subparagraph is added:
‘In the context of the sponsor’s obligation to determine that there are no
environmental grounds precluding the conduct of the study, in case of clinical
trials with veterinary medicinal products containing or consisting of genetically
modified organisms, where a risk to the environment or human health is
identified, mitigation measures shall be implemented before the start of the
trial, having regard to the specific characteristics of the product, the magnitude
of the possible hazard and likelihood of that adverse effect occurring.’
(5) In Article 28, paragraph 2 is replaced by the following:
‘During the process of examination of applications for marketing authorisations for
veterinary medicinal products containing or consisting of genetically modified
organisms, the Agency may hold consultations with the bodies set up by the Union or
Member States in accordance with Directive 2001/18/EC, in particular for first-in-
class products or when a novel question arises. The consulted bodies shall ensure
protection of commercially confidential information and security of exchange of
information.’
(6) The following Article 40a is inserted:
‘Article 40a
Extension of the supplementary protection certificate concerning biotechnology
medicinal products treating zoonoses developed and authorised in the Union
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1. Where a marketing authorisation is granted by the Union to a veterinary
medicinal product developed by means of a biotechnology process referred to
in paragraphs 2(a) of Article 42 of Regulation (EU) 2019/6 that is intended to
diagnose, treat or prevent zoonotic diseases, and that is protected either by a
supplementary protection certificate in accordance with Regulation (EC) No
469/200974 of the European Parliament and of the Council , or by a patent
which qualifies for the granting of such supplementary protection certificate,
the holder of a patent or of such certificate shall be entitled to a 12-month
extension of the periods referred to in Article 13, paragraphs 1 and 2 of
Regulation (EC) No 469/2009, provided that the marketing authorisation
applicant demonstrates that all of the following conditions are met:
(a) the medicinal product contains a new active substance distinctly different
from that of any authorised medicinal product in the Union;
(b) the veterinary medicinal product has a mechanism of action distinctly
different and shows a level of safety and efficacy which at least euivalent
to that that of any authorised veterinary medicinal product in the Union
for the same zoonotic disease; and
(c) at least a manufacturing step, excluding packaging, quality testing and
certification is performed in the Union.
2. The Agency shall assess compliance with the conditions referred to ins
paragraph 1 as part of the marketing authorisation procedure concerned.
3. Where compliance is confirmed, the Agency´s opinion shall issue a statement
to that effect.
4. A copy of the statement referred to in paragraph 3 shall be included in the
application for a certificate lodged under article 7 of of Regulation (EC) No
469/2009.
(7) Article 61 is replaced by the following:
‘Article 61
Variations that do not require assessment
1. Marketing authorisation holders shall be entitled to implement variations
included in the list established in accordance with Article 60(1), under the
conditions specified therein.
2. Where a variation referred to in paragraph (1) affects the summary of product
characteristics, the labelling or package leaflet, the marketing authorisation
holder shall record the change in the product database within 30 days after its
implementation.
The competent authority that granted the marketing authorisation or, in the case
of veterinary medicinal products authorised under the centralised procedure,
the Commission following an opinion by the Agency, shall amend the
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Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009
concerning the supplementary protection certificate for medicinal products, OJ L 152, 16.6.2009, pp. 1
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marketing authorisation in accordance with the change recorded by the
marketing authorisation holder in the product database.
For veterinary medicinal products authorised under the centralised procedure,
the amendment of the marketing authorisation shall be made by means of
implementing acts which shall be adopted in accordance with the examination
procedure referred to in Article 145(2).
3. Where a variation as referred to in paragraph (1) does not affect the summary
of product characteristics, labelling or package leaflet, the marketing
authorisation holder shall record the change in the product database within one
year after its implementation.
4. Variations implemented by marketing authorisation holders in circumvention
of the conditions laid down in the implementing act referred to in Article 60(1)
shall not be valid.’
(8) the following Chapter IX is added:
‘CHAPTER IX
REGULATORY SANDBOX
Article 136a
Regulatory sandbox
1. The Commission may set up a regulatory sandbox in accordance with the
procedure set out in paragraphs 2 and 4 for innovative technologies, methods
or products related to animal health which are directly or indirectly related to
the development, manufacturing or use of veterinary medicinal products and
which are not regulated under other Union legislation, where the following
conditions are met:
(a) it can be expected that those technologies, methods or products will have
a positive impact on animal health without unacceptable negative impacts
on human health or the environment;
(b) the development, placing on the market or use of the technologies,
methods or products concerned is hindered by the lack of a harmonised
legal framework.
2. Developers of technologies, methods or products related to animal health
which are directly or indirectly related to the development, manufacturing or
use of veterinary medicinal products and which are not regulated under other
Union legislation may send an application to the Agency requesting the
development of a regulatory sandbox. The Agency shall assess applications
received and, based on its assessment, may submit a recommendation to the
Commission which shall include all of the following:
(a) a justification for the regulatory sandbox, including a description of the
proposed technologies, methods or products to be included;
(b) identification of existing regulatory challenges;
(c) estimation of potential benefits and potential risks to animal or human
health or the environment;
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(d) mapping of existing expertise available to the Agency required to address
potential benefits and risks referred to in point (c). Where no relevant
expertise is readily available to the Agency, it shall present a plan on how
it intends to address the points identified under point (c);
(e) a proposal for the duration of the regulatory sandbox.
3. Upon receipt of the Agency’s recommendation, the Commission shall take a
decision, by means of an implementing act, in accordance with the examination
procedure referred to in Article 145(2). Where the Commission agrees to the
establishment of a regulatory sandbox, the implementing act shall specify the
duration of the regulatory sandbox.
4. After a regulatory sandbox is established, the Agency shall take the following
measures:
(a) develop and make publicly available technical and scientific
requirements for technologies, methods or products developed under the
regulatory sandbox, taking due account of the potential risks of thereof
for human and animal health and the environment;
(b) develop rules of procedure which ensure that the confidentiality of
information exchanged is maintained;
(c) provide relevant scientific advice;
(d) assess the benefits and risks of technologies, methods or products
developed under the regulatory sandbox and, where it considers that the
benefits outweigh the risks, it shall address to the Commission a
recommendation for their placing on the market or use.
The Agency shall levy a fee from the applicants in accordance with Article 4 of
Regulation (EU) 2024/56875 for the activities referred to in points c) and d) of
the first subparagraph. The applicable amounts shall be published on the
website of the Agency.
5. The Commission may, by means of an implementing act, authorise the placing
on the market or the use of the technologies, methods or products developed
under a regulatory sandbox in accordance with the examination procedure
referred to in Article 145(2).
Technologies, methods or products developed under a regulatory sandbox shall
not be placed on the market or used until they have been authorised by the
Commission.
6. Where a serious risk to public or animal health or to the environment
associated with the use of technologies, methods or products developed under
a regulatory sandbox is identified by national competent authorities, they shall
swiftly inform the Agency. Pending the adoption of a Commission decision
pursuant to paragraph 8, national competent authorities may take interim
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Regulation (EU) 2024/568 of the European Parliament and of the Council of 7 February 2024 on fees
and charges payable to the European Medicines Agency, amending Regulations (EU) 2017/745 and
(EU) 2022/123 of the European Parliament and of the Council and repealing Regulation (EU)
No 658/2014 of the European Parliament and of the Council and Council Regulation (EC) No 297/95
(OJ L OJ L 568, 14.2.2024)
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measures, including the suspension of their placing on the market, the
suspension of use, or recall measures.
7. Where the Agency is notified of a serious risk in accordance with paragraph 6,
it shall swiftly assess the referred matter and, where appropriate, any possible
impact for similar technologies, methods or products placed on the market
which have been developed or used under a regulatory sandbox. In its
assessment, the Agency shall consider the benefits for animal health and the
identified risks.
8. Where the assessment referred to in paragraph 7 concludes that the benefit-risk
balance is negative and there are no satisfactory risk mitigation measures that
can be implemented, the Agency shall recommend the suspension or
withdrawal of authorisation for placing on the market or use. The Commission
shall take a decision, by means of an implementing act, in accordance with the
examination procedure referred to in Article 145(2).
9. Following the assessment referred to in paragraphs 7, the Agency may
recommend the Commission to put an end to the regulatory sandbox. The
Agency’s recommendation shall advise on appropriate actions concerning the
technologies, methods or products in development under the regulatory
sandbox. The Commission may, by means of an implementing act, terminate a
regulatory sandbox in accordance with the examination procedure referred to in
Article 145(2).
10. Two years before the end of the period of validity of an established regulatory
sandbox, the Agency shall submit an assessment report on the progress of the
regulatory sandbox to the Commission, including recommendations for a
regulatory framework after the end of the regulatory sandbox. Where
appropriate, it may recommend the extension of the duration of the regulatory
sandbox.
11. The Commission shall review the assessment report referred to in paragraph 10
and may take appropriate actions as regards the regulatory requirements for the
marketing or use of technologies, methods or products under the scope of the
regulatory sandbox after the termination thereof. Where appropriate, the
Commission may extend the duration of a regulatory sandbox, by means of an
implementing act, in accordance with the examination procedure referred to in
Article 145(2).
12. The Agency shall keep a registry of regulatory sandboxes established in
accordance with this Regulation. It shall prepare and publish each year a report
on the implementation of the regulatory sandbox.’
(9) Article 146 is replaced by the following:
‘Article 146
Amendments to Annex II
‘The Commission is empowered to adopt delegated acts in accordance with Article
147(2) in order to amend Annex II to take due account of technical and scientific
progress.’
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(10) Annex II to Regulation (EU) 2019/6 is amended in accordance with Annex III to this
Regulation.
Article 60
Amendments to Regulation (EU) 2024/795
Regulation (EU) 2024/795 is amended as follows:
(a) in Article 2, the following paragraph 9 is added:
‘9. Health biotechnology strategic projects, including high-impact health
biotechnology strategic projects recognised in accordance with Regulation […]
[European Biotech Act ] shall be deemed to contribute to the STEP objectives
referred to in paragraph 1, point (a)(iii) or point (b), as appropriate.
(b) in Article 4, paragraph 7 is replaced by the following:
‘7. Strategic projects recognised in accordance with the relevant provisions of the
Regulation (EU) 2024/1735, Regulation (EU) 2024/1252, Regulation […]
[Critical Medicines Act] and health biotechnology strategic projects, including
high-impact health biotechnology strategic projects recognised in accordance
with Regulation […] [European Biotech Act] that fall within the scope of
Article 2 of this Regulation and that receive a contribution under the
programmes referred to in Article 3 of this Regulation may also receive a
contribution from any other Union programme, including funds under shared
management, provided that those contributions do not cover the same costs.
The rules of the relevant Union programme shall apply to the corresponding
contribution to the strategic project. The cumulative funding shall not exceed
the total eligible costs of the strategic project. The support from the different
Union programmes may be calculated on a pro rata basis in accordance with
the documents setting out the conditions for support.’;
(c) in Article 6(1), point (c) is replaced by the following:
‘(c) details of projects that have been recognized as strategic projects under
Regulation (EU) 2024/1735, Regulation (EU) 2024/1252 and Regulation […]
[Critical Medicines Act] and as health biotechnology strategic projects,
including as high-impact health biotechnology strategic projects under
Regulation […] [European Biotech Act], to the extent that they fall within the
scope of Article 2 of this Regulation.’.
Article 61
Amendment to Regulation (EU) 2024/1938
Regulation (EU) 2024/1938 is amended as follows:
(1) In Article 3, the following point (60) is added:
‘(60) ‘regulatory sandbox’ means a regulatory framework which allows to develop,
assess and test innovative or adapted regulatory solutions within a controlled
environment pursuant to a specific plan, for a limited time and under regulatory
supervision and which facilitates the development, assessment, authorisation or
monitoring of innovative activities or substances which are likely to fall within
the scope of this Regulation.’
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(2) in Article 13, the following paragraph 3a is inserted:
‘3a. The Commission may adopt implementing acts, setting out time limits for the
provision, by the competent authorities consulted in accordance with paragraph
2, of a reply on the regulatory status of a substance, product or activity.
Those implementing acts shall be adopted in accordance with the examination
procedure referred to in Article 79(2).’
(3) in Article 69(2), the first subparagraph is replaced by the following:
‘The Commission may adopt implementing acts setting out time limits for the SCB,
to issue its opinions on the regulatory status of a substance, product or activity, in
accordance with Article 13(3), first subparagraph.
The Commission may adopt implementing acts setting out criteria and procedures for
the consultation of advisory bodies established under other relevant Union legislation
in relation to the performance of the SCB tasks, including time limits for those
bodies to issue their opinions in the framework of such consultation.
Those implementing acts shall be adopted in accordance with the examination
procedure referred to in Article 79(2)
(4) the following Article 39a is inserted:
Article 39a
SoHO regulatory sandboxes
1. On a substantiated request from a SoHO entity, a Member State may set up
regulatory sandboxes that provide a time limited controlled environment to
facilitate the development and testing of innovative products, services,
processes or substances in the field of SoHO, under the supervision of one or
more competent authorities and where the following conditions are met:
(a) the characteristics or methods of those innovations and technologies are
expected to distinctively contribute to the safety, quality, including the
effectiveness of the SoHO or the SoHO activity or to provide a major
contribution to patient access to treatment;
(b) the application of the requirements of this Regulation would impede or
significantly delay the development of those innovations and
technologies, due to scientific or regulatory challenges arising from the
characteristics or methods related to that innovation or technology.
2. Member States may jointly set up the regulatory sandboxes referred to in
paragraph 1. The Commission shall support such cooperation in accordance
with Article 72 (1).
3. The regulatory sandbox shall seek to allow the assessment of the innovations
referred to in paragraph 1 in a real-world environment under strict regulatory
supervision, to ensure that the necessary evidence and data is generated to
demonstrate their safety quality, including effectiveness in view of their
distribution.
4. The regulatory sandbox may include clearly described derogations from the
requirements set out in this Regulation. Those derogations may entail adapted,
enhanced, waived or deferred requirements. Each derogation shall be limited to
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what is apt and strictly necessary to attain the objectives pursued and shall be
duly justified and specified in the sandbox plan referred to in paragraph [6].
However, the regulatory sandbox shall not include derogations from the
provisions on standards concerning voluntary and unpaid nature of SoHO
donations laid down in Article 54.
5. The regulatory sandboxes shall be conducted under the supervision of the
SoHO competent authorities, and, where appropriate, in cooperation with
competent authorities acting in accordance with other relevant Union
legislative acts in the area of health or national legislation.
6. The activities within the regulatory sandbox shall take place in accordance with
a specific regulatory sandbox plan developed by the SoHO competent
authorities. The sandbox plan shall:
(a) be informed by data provided by, and established following consultations
with, the developers of the concerned innovations;
(b) identify the participants in the regulatory sandbox and their respective
roles;
(c) identify the requirements of this Regulation that cannot be complied
with, from which derogations are considered necessary and the adapted,
enhanced, waived or deferred requirements entailed by such derogations;
(d) include appropriate measures to mitigate potential risks to health and to
the environment;
(e) establish the duration of the regulatory sandbox.
(f) explain the monitoring framework for the regulatory sandboxes including
what aspects will be reported on, the frequency of reporting and data
sources.
7. When establishing the regulatory sandbox, the SoHO competent authorities
shall consult, where appropriate, the SCB, including by requesting scientific,
technical or regulatory advice for the design of the sandbox plan. The SCB
shall provide support and shall seek to foster a common approach for the
design and the implementation of the regulatory sandboxes referred to in this
Article.
For the purposes of the support to SoHO competent authorities referred to in
the first subparagraph, the SCB may:
(a) request information and data from holders of authorisations of SoHO
preparations, leveraging information on the EU SoHO platform
established under article 74 of this Regulation, developers, independent
experts and researchers, representatives of healthcare professionals and
patients and may engage with them in preliminary discussions;
(b) collaborate with the Foresight Panel for Emerging Health Innovation
referred to in article 38 of Regulation (EU) …/…[European Biotech Act].
8. When setting up the regulatory sandbox, the SOHO competent authorities shall
provide detailed, non-confidential information to the Commission, regarding
the regulatory framework governing the specific regulatory sandbox set out in
a regulatory sandbox plan. The Commission shall publish the information
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received, on theEU SoHO platform established under article 74 of this
Regulation.
9. Upon the termination of the regulatory sandbox, the competent authorities shall
submit to the SCB and to the Commission a detailed report on the regulatory
sandbox and any possible follow up concerning in particular changes in the
regulatory framework for the innovations or categories of innovations
concerned, based on the learnings from the regulatory sandbox. The SCB shall
publish the information received.
The information referred to in the first subparagraph may also be provided at
regular intervals during the implementation of the sandbox.
10. A SoHO preparation resulting from an innovation developed as part of a
regulatory sandbox may be distributed for human application only where
authorised in accordance with Article 38(1). The initial validity of such
authorisation shall not exceed the duration of the regulatory sandbox. The
authorisation may be extended by the competent authority at the request of the
relevant SoHO entity.
11. The regulatory sandboxes shall not affect the enforcement and monitoring
responsibilities of the SoHO competent authorities pursuant to this Regulation
and to other Union legislation.
12. Participants in the regulatory sandbox, in particular the developer shall remain
liable under applicable national legislation for any harm inflicted on third
parties as a result from the testing taking place in the regulatory sandbox. They
shall inform the national SoHO competent authorities without undue delay of
any information which might entail the amendment of the regulatory sandbox
or concerns the quality, safety or efficacy of products developed as part of a
regulatory sandbox.
13. In case of identification of risks to public health or safety concerns or the
environment associated with the use of the innovation covered by a regulatory
sandbox, the sandbox participants shall immediately inform the SoHO
competent authorities of the action taken to prevent those risks. The SoHO
competent authorities shall take immediate and adequate temporary corrective
measures, including to suspend, revoke or restrict the scope of the regulatory
sandbox and shall inform the SCB and the Commission thereof.
CHAPTER [X]
FINAL PROVISIONS
Article 62
Monitoring
The Commission shall publish and keep up to date a list of health biotechnology strategic
projects and high impact health biotechnology strategic projects.
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Article 63
Evaluation
1. No sooner than [insert date, five years after the date of entry into application of this
Regulation...], the Commission shall evaluate this Regulation in light of the general
objective that it pursues and referred to in Article 1(1)]and present a report on its
main findings to the European Parliament and to the Council, the European
Economic and Social Committee, and the Committee of the Regions, in particular on
the impact of this Regulation and progress towards that objective.
2. The Member States shall, upon request, provide the Commission with any relevant
information they have and that the Commission may need for its assessment pursuant
to in paragraph 1.
Article 64
Exercise of the delegation
1. The power to adopt delegated acts is conferred on the Commission subject to the
conditions laid down in this Article.
2. The power to adopt delegated acts referred to in Article 43(2) shall be conferred on
the Commission for a period of five years from [insert date of entry into force of this
Regulation]. The Commission shall draw up a report in respect of the delegation of
power not later than nine months before the end of the five-year period. The
delegation of power shall be tacitly extended for periods of an identical duration,
unless the European Parliament or the Council opposes such extension not later than
three months before the end of each period.
3. The delegation of power referred to in Articles 43(2) may be revoked at any time by
the European Parliament or by the Council. A decision to revoke shall put an end to
the delegation of the power specified in that decision. It shall take effect the day
following the publication of the decision in the Official Journal of the European
Union or at a later date specified therein. It shall not affect the validity of any
delegated acts already in force.
4. Before adopting a delegated act, the Commission shall consult experts designated by
each Member State in accordance with the principles laid down in the
Interinstitutional Agreement on Better Law-Making of 13 April 2016.
5. As soon as it adopts a delegated act, the Commission shall notify it simultaneously to
the European Parliament and to the Council.
6. A delegated act adopted pursuant to Articles 43(2), shall enter into force only if no
objection has been expressed either by the European Parliament or by the Council
within a period of two months of notification of that act to the European Parliament
and the Council or if, before the expiry of that period, the European Parliament and
the Council have both informed the Commission that they will not object. That
period shall be extended by two months at the initiative of the European Parliament
or of the Council.
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Article 65
Committee procedure
1. The Commission shall be assisted by the Standing Committee on Biotechnology.
That committee shall be a committee within the meaning of Regulation (EU) No
182/2011.
2. Where reference is made to this paragraph, Article 5 of Regulation (EU) No
182/2011 shall apply.
Article 66
Handling of confidential information
1. Information acquired in the course of implementing this Regulation shall be used
only for the purposes of this Regulation and shall be protected by the relevant Union
and national law.
2. Member States and the Commission shall ensure the protection of trade and business
secrets and other sensitive, confidential and classified information obtained and
processed in application of this Regulation, including recommendations and
measures to be taken, in accordance with Union and relevant national law.
3. The Commission and Member States shall ensure that classified information
provided or exchanged pursuant to this Regulation is not downgraded or declassified
without the prior written consent of the originator in accordance with relevant Union
or national law.
4. The Commission and the national authorities, their officials, employees and other
persons working under the supervision of those authorities shall ensure the
confidentiality of information obtained in carrying out their tasks and activities in
accordance with relevant Union or national law. This obligation also applies to all
representatives of Member States, observers, experts and other participants attending
meetings of the Steering Group.
Article 67
Entry into force and application
1. This Regulation shall enter into force on the twentieth day following that of its
publication in the Official Journal of the European Union.
2. It shall apply as of the day of entry into force.
3. By way of derogation from paragraph 2:
(a) Article 58, points (5) to (12) and points (15) to (24) shall apply as of [OP,
please insert date: six months after entry into force of this Regulation];
(b) Article 58, point (13) shall apply as of [OP, please insert date: nine months
after entry into force of this Regulation];
(c) Article 58, point (25) shall apply as of [OP, please insert date: nine months
after entry into force of this Regulation].
EN 171 EN
This Regulation shall be binding in its entirety and directly applicable in all Member States.
Done at Strasbourg,
For the European Parliament For the Council
The President The President
EN 172 EN
LEGISLATIVE FINANCIAL AND DIGITAL STATEMENT- AGENCIES
TABLE OF CONTENTS
LEGISLATIVE FINANCIAL AND DIGITAL STATEMENT ................................................ 1
1. FRAMEWORK OF THE PROPOSAL/INITIATIVE ................................................ 3
1.1. Title of the proposal/initiative ...................................................................................... 3
1.2. Policy area(s) concerned ............................................................................................. 3
1.3. Objective(s) .................................................................................................................. 3
1.3.1. General objective(s) ..................................................................................................... 3
1.3.2. Specific objective(s) ..................................................................................................... 3
1.3.3. Expected result(s) and impact ...................................................................................... 4
1.3.4. Indicators of performance ............................................................................................ 4
1.4. The proposal/initiative relates to: ................................................................................ 4
1.5. Grounds for the proposal/initiative ............................................................................. 5
1.5.1. Requirement(s) to be met in the short or long term including a detailed timeline for
roll-out of the implementation of the initiative ............................................................ 5
1.5.2. Added value of EU involvement (it may result from different factors, e.g.
coordination gains, legal certainty, greater effectiveness or complementarities). For
the purposes of this section 'added value of EU involvement' is the value resulting
from EU action, that is additional to the value that would have been otherwise
created by Member States alone. ................................................................................. 5
1.5.3. Lessons learned from similar experiences in the past .................................................. 6
1.5.4. Compatibility with the multiannual financial framework and possible synergies with
other appropriate instruments ....................................................................................... 6
1.5.5. Assessment of the different available financing options, including scope for
redeployment ................................................................................................................ 7
1.6. Duration of the proposal/initiative and of its financial impact .................................... 8
1.7. Method(s) of budget implementation planned ............................................................ 8
2. MANAGEMENT MEASURES ................................................................................ 10
2.1. Monitoring and reporting rules ................................................................................. 10
2.2. Management and control system(s) .......................................................................... 10
2.2.1. Justification of the budget implementation method(s), the funding implementation
mechanism(s), the payment modalities and the control strategy proposed ................ 10
2.2.2. Information concerning the risks identified and the internal control system(s) set up
to mitigate them.......................................................................................................... 11
2.2.3. Estimation and justification of the cost-effectiveness of the controls (ratio between
the control costs and the value of the related funds managed), and assessment of the
expected levels of risk of error (at payment & at closure) ........................................ 12
2.3. Measures to prevent fraud and irregularities ............................................................. 12
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3. ESTIMATED FINANCIAL IMPACT OF THE PROPOSAL/INITIATIVE ........... 14
3.1. Heading(s) of the multiannual financial framework and expenditure budget line(s)
affected ...................................................................................................................... 14
3.2. Estimated financial impact of the proposal on appropriations .................................. 15
3.2.1. Summary of estimated impact on operational appropriations ................................... 15
3.2.1.1. Appropriations from voted budget ............................................................................. 15
3.2.3. Summary of estimated impact on administrative appropriations .............................. 20
3.2.3.1. Appropriations from voted budget .............................................................................. 20
3.2.4. Estimated requirements of human resources ............................................................. 20
3.2.4.1. Financed from voted budget....................................................................................... 21
3.2.5. Overview of estimated impact on digital technology-related investments ................ 24
3.2.6. Compatibility with the current multiannual financial framework ............................. 25
3.2.7. Third-party contributions .......................................................................................... 25
3.2.8. Estimated human resources and the use of appropriations required in a decentralised
agency ....................................................................................................................... 26
4. Digital dimensions ..................................................................................................... 35
4.1. Requirements of digital relevance .............................................................................. 35
4.2. Data ............................................................................................................................ 71
4.3. Digital solutions ......................................................................................................... 78
4.4. Interoperability assessment ........................................................................................ 79
4.5. Measures to support digital implementation .............................................................. 83
EN 2 EN
1. FRAMEWORK OF THE PROPOSAL/INITIATIVE
1.1. Title of the proposal/initiative
Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF
THE COUNCIL on establishing a framework of measures for strengthening
Europe’s biotechnology and biomanufacturing sectors and amending Regulations
(EU) No 536/2014 (‘Clinical Trials Regulation’), (EC) No 1394/2007 (ATMP), (EU)
2024/1938 (SoHO), (EU) 2019/6 (Veterinary Medicine Products Regulation), and
Regulation (EC) No 178/2002 (General Food Law) ('EU Biotech Act')
1.2. Policy area(s) concerned
Priority Area: Competitiveness, prosperity and security
Health, Biotech, Agriculture and Bioeconomy
1.3. Objective(s)
1.3.1. General objective(s)
(i) to improve the functioning of the internal market by establishing a framework to
strengthen the competitiveness of the health biotechnology sector, from research to
production,
(ii) to create the conditions for the development and timely placing on the Union
market, of biotechnology innovations, products and services,
(iii) while safeguarding high standards for the protection of human health, animal
health, patients and consumers, the environment, ethics, quality, food and feed
safety, and biosecurity.
1.3.2. Specific objective(s)
This general objective translates into the following specific objectives:
(i) strengthen the biotechnology sector and reinforce the Union’s research,
development and production capabilities, by establishing a framework for the
recognition of, and support measures for, strategic health biotechnology projects and
high impact strategic health biotechnology projects (pillar 1);
(ii) support funding of, investments in, and access to capital for, biotechnology
companies and projects, including through the setting up of an EU health
biotechnology investment pilot to fill the gap in spending on biotechnology
innovation (pillar 2);
(iii) improve the EU manufacturing capacity of, and expertise in biosimilars,
including through international cooperation (pillar 3);
(iv) facilitate the application of AI into the Union’s biotechnology and health
technology manufacturing ecosystems and frameworks, in line with the Regulation
(EU) 2024/1689 (pillar 4);
(v) ensure a legislative framework that encourages innovation and takes account of
technological and scientific developments and progress, by establishing provisions
for health biotechnology products (pillar 5);
(vi) prevent the misuse of biotechnologies and strengthen biodefence capabilities
(pillar 6).
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(vii) enable the effectiveness of the measures under the pillars 1 to 6 through a
legislative framework conducive to the use of biotechnology innovations, by
amending Union legislation in particular on clinical trials, veterinary medicinal
products, food and feed safety and related legislation (pillar 7).
1.3.3. Expected result(s) and impact
Specify the effects which the proposal/initiative should have on the
beneficiaries/groups targeted.
Overall, the Biotech Act is expected to support a smooth function of the Union
internal market and the resilience and competitiveness of the Union biotechnology
and biomanufacturing sector, while allowing allow end-users - including patients - to
benefit from the availability of innovative technologies in the EU.
The Biotech Act will have the following expected results:
– - regulatory procedures to place products on the market are predictable,
simplified and shorter, with reduced administrative burden;
– - innovation is supported by specific regulatory procedures that are fit for
technological and scientific progress;
– - operators have better access to funding throughout the different stages of their
development;
– - the EU’s capabilities in research, development and production are reinforced,
including for biodefence
– - availability of a skilled biotechnology workforce in the Union is improved;
– - there are clear rules preventing the misuse of biotechnologies.
1.3.4. Indicators of performance
Specify the indicators for monitoring progress and achievements.
Progress towards the objectives of the Biotech Act will be monitored using a set of
quantitative and qualitative indicators. This assessment will draw on the strategic
mapping of the Union’s biotechnology ecosystem, to be established and maintained
by the Commission.
Such monitoring shall be based on key performance indicators such as the increase in
the number of clinical trials in the Union over the period of five years, as this
indicator reflects both the attractiveness of the Union and the capacity of the
European regulatory system to support clinical research with maintained high data
quality and patients’ safety standards.
1.4. The proposal/initiative relates to:
a new action
¨ a new action following a pilot project / preparatory action1
1
As referred to in Article 58(2), point (a) or (b) of the Financial Regulation.
EN 4 EN
the extension of an existing action
¨ a merger or redirection of one or more actions towards another/a new action
1.5. Grounds for the proposal/initiative
1.5.1. Requirement(s) to be met in the short or long term including a detailed timeline for
roll-out of the implementation of the initiative
In the short term, the initiative requires the Commission to complete the strategic
mapping of the Union’s biotechnology ecosystem within six months of entry into
force and to initiate the establishment of the new governance and support structures
foreseen in the Regulation, including the EU Health Biotechnology Support
Network, the Emerging Innovation Foresight Panel and the European Health
Biotechnology Steering Group. The Commission would also proceed with adopting
the necessary implementing and delegated acts, including those detailing the criteria
and procedures for the recognition of health biotechnology strategic projects and
high-impact health biotechnology strategic projects. In parallel, Member States must
designate national single points of contact and begin applying the streamlined
regulatory procedures.
The Commission and the Agencies will have to update and/or develop new tools and
ways of operation to implement workflows resulting from the amendments to EU
legislative frameworks in the health and food area. These amendments aim at
simplifying regulatory procedures and creating regulatory environments conducive to
innovation.
In the medium term, the strategic mapping would be updated and used to guide the
selection of projects and the deployment of Union support, as well as further
developments in Union policy for biotechnology.
1.5.2. Added value of EU involvement (it may result from different factors, e.g.
coordination gains, legal certainty, greater effectiveness or complementarities). For
the purposes of this section 'added value of EU involvement' is the value resulting
from EU action, that is additional to the value that would have been otherwise
created by Member States alone.
Reasons for action at EU level (ex-ante)
European companies are not competitive enough and face several market and
regulatory barriers. Whilst several Member States have taken action to boost
innovation in this field, many bottlenecks persist, and improvements are not expected
to achieve the necessary levels for the Union to compete at a global scale.
Important regulatory barriers identified stem from EU legislation, therefore the
proposed amendments seek to simplify EU legislations, enhance their legal clarity
and certainty and make them fit to scientific and technological development.
Furthermore, the market drivers are occurring across the EU, affecting the
functioning of the Union single market and EU’s businesses competitiveness in the
Union and globally. These hurdles result from insufficient capacity of EU companies
to access private finance at a competitive scale, especially at later stages of
development. Biotechnology clusters in the EU are scattered across Member States,
without cross-border connections and continental scale, thus not able to compete
globally. Compounded by the low level of storage, access and sharing of data in the
area of biotechnology - including cross-borders -, the development and deployment
EN 5 EN
of AI solutions for biotechnology in the Union are not reaching their full potential.
Finally, the gap in developing and retaining an adequately skilled workforce has been
observed across the Union. These challenges are systemic, transnational in nature
and cannot be addressed effectively through isolated national measures alone.
Expected generated EU added value (ex-post)
A harmonised but simplified EU regulatory framework, supported by strengthened
collaboration in selected policy areas (access to capital, skills, AI and data) is
expected to ensure all patients, users and citizens can benefit from these innovations
to same extent in the EU, a level playing field for operations in the Union single
market as well as to enhance the overall competitiveness of the EU. Coordinated EU
action will generate economies of scale, reduce duplication of efforts, increase legal
certainty for entrepreneurs operating across borders, and unlock cross-border
investments, infrastructures and skills development that Member States acting alone
could not achieve. It will also reinforce the EU’s strategic autonomy in a critical
technological area foster the development of adequate biosecurity capabilities.
1.5.3. Lessons learned from similar experiences in the past
Developments in the biotechnology sector over the last decades shows that Europe’s
strong scientific base does not automatically translate into industrial competitiveness.
Fragmented and complex regulatory frameworks, slow and divergent procedures,
limited access to risk-tolerant capital, insufficient data sharing and interoperability,
shallow public equity markets, and persistent skills shortages have repeatedly
hindered the ability of EU innovators to scale and commercialise their technologies.
Past efforts have also demonstrated that lack of coordinated EU action leads to
duplication, delays, and missed opportunities for deploying biotechnology at scale,
while emerging technologies such as AI raise regulatory and biosecurity challenges
that cannot be adequately addressed at national level.
Experience from other strategic sectors saw targeted EU-level initiatives, combining
regulatory simplification, coordinated investment, and infrastructure support, being
deployed to address systemic bottlenecks - such as in the case of the Net-Zero
Industry Act and the Critical Raw Materials Act. The same lessons apply to
biotechnology: only a coherent and integrated EU approach can unlock the sector’s
full potential, strengthen competitiveness, and accelerate the safe deployment of
biotechnology innovative across the Single Market.
1.5.4. Compatibility with the multiannual financial framework and possible synergies with
other appropriate instruments
In order to maximise its positive impact, the Biotech Act will build upon the strong
knowledge base The objectives of the Biotech Act may be supported under the future
European Competitiveness Fund, in particular under the Health, Biotech, Agriculture
and Bioeconomy Window. Horizon Europe may also be leveraged to complement
the Biotech Act’s objective of bringing biotechnology products to the market by
supporting all stages of research and development of innovative ideas.
EN 6 EN
1.5.5. Assessment of the different available financing options, including scope for
redeployment
N/A
EN 7 EN
1.6. Duration of the proposal/initiative and of its financial impact
¨ limited duration
– ¨ in effect from [DD/MM]YYYY to [DD/MM]YYYY
– ¨ financial impact from YYYY to YYYY for commitment appropriations and
from YYYY to YYYY for payment appropriations.
unlimited duration
– Implementation with a start-up period from 2028 to 2029,
– followed by full-scale operation.
1.7. Method(s) of budget implementation planned2
Direct management by the Commission
– by its departments, including by its staff in the Union delegations;
– by the executive agencies
– ¨ Shared management with the Member States
x Indirect management by entrusting budget implementation tasks to:
– ¨ third countries or the bodies they have designated
– ¨ international organisations and their agencies (to be specified)
– the European Investment Bank and the European Investment Fund
– ¨ bodies referred to in Articles 70 and 71 of the Financial Regulation
– ¨ public law bodies
– bodies governed by private law with a public service mission to the extent that
they are provided with adequate financial guarantees
– bodies governed by the private law of a Member State that are entrusted with
the implementation of a public-private partnership and that are provided with
adequate financial guarantees
– ¨ bodies or persons entrusted with the implementation of specific actions in the
common foreign and security policy pursuant to Title V of the Treaty on
European Union, and identified in the relevant basic act
– bodies established in a Member State, governed by the private law of a
Member State or Union law and eligible to be entrusted, in accordance with
sector-specific rules, with the implementation of Union funds or budgetary
guarantees, to the extent that such bodies are controlled by public law bodies or
by bodies governed by private law with a public service mission, and are provided
with adequate financial guarantees in the form of joint and several Soho by the
controlling bodies or equivalent financial guarantees and which may be, for each
action, limited to the maximum amount of the Union support.
Comments:
2
Details of budget implementation methods and references to the Financial Regulation may be found on
the BUDGpedia site: https://myintracomm.ec.europa.eu/corp/budget/financial-rules/budget-
implementation/Pages/implementation-methods.aspx.
EN 8 EN
The proposal envisions two main vehicles for biotechnology investment in the EU:
Support to High Impact Health Biotechnology Strategic Projects
High Impact Health Biotechnology Strategic projects will boost the European ecosystem by
expanding shared pilot facilities open to SMEs and academia alike, financially supporting
Member State innovation procurement to create predictable demand for innovative products,
and harnessing the potential of data and AI for Biotechnology
A Biotechnology Investment Pilot
The Pilot aims to provide a full lifecycle approach to biotechnology finance by supporting
both the intermediate equity approach for biotechnology equity investments and venture loans
into the sector. This would enable European innovators to move from discovery to industrial
scale by bridging the most capital-intensive stages of development. A company may, for
instance, start with early-stage backing from a VC fund, then access tailored venture loans to
build production capacity, securing co-investment along the financing journey. By linking
these steps, the Pilot ensures that Europe’s biotechnology champions can grow, manufacture
and stay anchored in Europe.
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2. MANAGEMENT MEASURES
2.1. Monitoring and reporting rules
The proposal relies on existing legislations and initiatives in the European
Commission and the European Medicines Agency, which will facilitate monitoring of
several indicators. For these, continuous data/information will be available.
In addition, five years after the Regulation’s entry into application, and every five
years thereafter, the Commission will evaluate its implementation, effectiveness and
impact.
2.2. Management and control system(s)
2.2.1. Justification of the budget implementation method(s), the funding implementation
mechanism(s), the payment modalities and the control strategy proposed
The actions for establishing a framework of measures for strengthening Europe's
biotechnology and biomanufacturing sector will be implemented through direct and
indirect management, using the implementation modes offered by the Financial
Regulation, mainly being grants and procurement for the direct management mode.
Direct management allows to establish grant agreements/contracts with
beneficiaries/contractors directly engaged in activities that serve Union policies. The
Commission ensures direct monitoring over the outcome of the actions financed. The
payment modalities of the actions funded will be adapted to the risks pertaining to the
financial transactions.
In order to ensure the effectiveness, efficiency and economy of the Commission
controls, the control strategy will be oriented towards a balance of ex-ante and ex-post
checks and focus on three key stages of grant/contract implementation, in accordance
with the Financial Regulation and/ or the specific contractual provisions:
- Selection of proposals/award the contract to tenders that fit the policy objectives;
- Operational, monitoring and (ex ante) technical desk reviews that cover project
implementation, public procurement, pre-financing, interim and final payments,
management of guarantees;
- Ex-post controls at the beneficiaries will also be carried out on a sample of
transactions. The selection of these transactions will combine a risk assessment and a
random selection.
The annual EU subsidy will be transferred to the Agencies in accordance with their
payment needs and upon their requests. The Agencies will be subject to administrative
controls including budgetary control, internal audit, annual reports by the European
Court of Auditors, the annual discharge for the execution of the Union budget and
possible investigations conducted by OLAF to ensure, in particular, that the resources
allocated to the Agencies are put to proper use. Through its representation in the
Agencies' Management Board and Audit Committee, the Commission will receive
audit reports and ensures that adequate actions are defined and timely implemented by
the Agencies to address the issues identified. All payments will remain pre-financing
payments until the Agencies’ accounts have been audited by the European Court of
Auditors and the Agencies has submitted its final accounts. If necessary, the
Commission will recover unspent amounts of the instalments paid to the Agencies.
EN 10 EN
For provisions of this Regulation that require long-term coordination and large-scale
public and private investment (i.e. for high impact health biotechnology strategic
projects), the Commission may propose European Partnerships where the Union
together with private and/or public partners, acting in full compliance with
competition rules, commit to jointly supporting the development and implementation
of a programme activities, including those related to market, regulatory or policy
uptake.
The activities of the Agencies will also be subject to the supervision of the
Ombudsman in accordance with Article 228 of the Treaty. These administrative
controls provide a number of procedural safeguards to ensure that account is taken of
the interests of the stakeholders.
2.2.2. Information concerning the risks identified and the internal control system(s) set up
to mitigate them
The main risks relate to the Agencies’ performance and independence in
implementing the tasks entrusted to them. Underperformance or impaired
independence could hamper the achievement of the objectives of this initiative and
also reflect negatively on the Commission’s reputation.
The Commission and the Agencies have put in place internal procedures that aim at
covering the risks identified above. The internal procedures are in full compliance
with the Financial Regulation and include anti-fraud measures and cost-benefit
considerations.
First and foremost, sufficient resources should be made available to the Agencies in
both financial and staffing terms to achieve the objectives of this initiative.
Furthermore, quality management will include both the integrated quality-
management activities and risk-management activities within the Agencies. A risk
review is conducted annually, with risks being assessed at a residual level, i.e. taking
into account controls and mitigations already in place. Conducting self-assessments
(as part of the EU Agencies benchmarking programme), annual reviews of sensitive
functions and ex-post controls also fall within this area, as does maintain a register of
exceptions.
To preserve impartiality and objectivity in every aspect of the Agencies’ work, a
number of policies and rules on management of competing interests have been put in
place and will be regularly updated, describing specific arrangements, requirements
and processes applying to the Agencies’ Management Board, scientific committee
members and experts, the Agencies’ staff and candidates, as well as consultants and
contractors. The Commission will be informed timely of relevant management and
independence issues encountered by the Agencies and will react upon notified issues
timely and adequately.
The proposal also envisages that the Commission promotes Biotechnology
Investment Pilot for biotechnology investment in the EU.
The main risks are the following:
• Risk of not fully achieving the objectives of the Regulation due to insufficient
uptake or quality/delays in the implementation of the selected projects or contracts;
• Risk of inefficient or non-economic use of investments awarded;
EN 11 EN
• Reputational risk for the Commission, if fraud or criminal activities are discovered;
only partial assurance can be drawn from the third parties' internal control systems
due to the rather large number of heterogeneous contractors and beneficiaries, each
operating their own control system.
The Commission will allocate the necessary human and financial resources for the
proper implementation of this Regulation and will put in place internal procedures
that aim at covering the risks identified above. The internal procedures will be in full
compliance with the Financial Regulation and include anti-fraud measures and cost-
benefit considerations.
.
2.2.3. Estimation and justification of the cost-effectiveness of the controls (ratio between
the control costs and the value of the related funds managed), and assessment of the
expected levels of risk of error (at payment & at closure)
The Commission’s and the Agencies’ internal control strategies take into
consideration the main cost drivers, and the efforts already taken over several years
to reduce the cost of controls, without compromising the effectiveness of controls.
The existing control systems proved to be able to prevent and/or to detect errors
and/or irregularities, and in case of errors or irregularities, to correct them.
In the past five years, the Commission’s yearly costs of controls under indirect
management represented less than 1% of the annual budget spent on subsidies paid to
the EMA and EFSA. The Agencies allocated less than 0,5% (EMA) and 5% (EFSA)
of their total annual budget on control activities centring around integrated quality
management, audit, anti-fraud measures, finance and verification processes,
corporate risk management and self-assessment activities.
2.3. Measures to prevent fraud and irregularities
Preventing and detecting fraud is a key governance issue and a common control
objective for all Commission’s departments who have, in practical terms, the
obligation to put in place the appropriate management and internal control
procedures designed to deter, detect, correct or sanction irregularities and fraud, in
line with articles 317 and 325 TFEU and article 36 FR.
As for its activities in indirect management, the Commission shall take appropriate
measures ensuring that the financial interests of the European Union are protected by
the application of preventive measures against fraud, corruption and any other illegal
activities, by effective checks and, if irregularities are detected, by the recovery of
the amounts wrongly paid and, where appropriate, by effective, proportional and
deterrent penalties. To this effect, the Commission adopted an anti-fraud strategy,
latest update of April 2019 (COM(2019)176), covering preventive, detective and
corrective measures. The Commission or its representatives and the European Court
of Auditors shall have the power of audit, on the basis of documents and on-the-spot,
over all grant beneficiaries, contractors and subcontractors who have received Union
funds. OLAF shall be authorised to carry out on-the-spot checks and inspections on
economic operators concerned indirectly by such funding.
As regards the European Medicines Agency, the anti-fraud measures are provided for
in Article 69 of Regulation (EC) No 726/2004 and the framework financial
Regulation (2019/715). The Executive Director and the Management Board of the
Agency will take the appropriate measures in accordance with the Internal Control
EN 12 EN
Principles applied across all EU institutions. In line with the Common Approach and
Article 42 of the framework financial Regulation, an anti-fraud strategy has been
developed and is followed by the Agency. The Agency’s Anti-fraud strategy covers
3-year period and is accompanied by a corresponding action plan, outlining both
specific focus areas and actions for the next years, and several continuous actions
that are carried out every year, such as a specific standalone fraud risk assessment,
with the identified fraud risks included in the overall Agency risk register. Anti-fraud
trainings are organised as part of the induction training and via mandatory anti-fraud
e-learning training for newcomers. Staff are made aware of how to report any
suspects of wrongdoings and disciplinary procedures are in place as per the rules of
the Staff Regulations.
As regards the European Food Safety Authority, the anti-fraud measures are
provided for in Article 25 of Regulation (EC) No 178/2002 and the framework
financial Regulation (2019/715). The Management Board will take the appropriate
measures in accordance with the Internal Control Principles applied across all EU
institutions. In line with the Common Approach and Article 42 of the framework
financial Regulation, an anti-fraud strategy has been developed and is followed by
the Authority. The Authority’s Anti-fraud strategy is accompained by a
corresponding action plan, outlining both specific focus areas and actions for the next
years, and several continuous actions that are carried out every year, such as a
specific standalone fraud risk assessment, with the identified fraud risks included in
the overall Agency risk register. Mandatory anti-fraud trainings are organised as part
of the awareness anti-fraud sessions. Staff are made aware of how to report any
suspects of wrongdoings and disciplinary procedures are in place as per the rules of
the Staff Regulations.
EN 13 EN
3. ESTIMATED FINANCIAL IMPACT OF THE PROPOSAL/INITIATIVE
3.1. Heading(s) of the multiannual financial framework and expenditure budget
line(s) affected
• Existing budget lines
In order of multiannual financial framework headings and budget lines.
Type of
Budget line expendit Contribution
ure
Heading
of from
multiann candidat
ual From
from e
financial Number other other
Diff./No EFTA countrie
framewo third assigned
n-diff.1 countri s and
rk countri revenue
es2 potential
es
candidat
es3
2 Support expenditure of the programme Non-diff YES YES YES NO
Union contribution to the European Non-
2 YES YES YES NO
Medicines Agency diff.
2 Union contribution to the European Diff. YES YES YES NO
Food Safety Agency
20 01 02 01 - Headquarters and Non-
4 Representation offices - officials and NO NO NO NO
diff.
temporary staff
20 02 01 and 20 02 02 – External
personnel – Headquarters and Non-
4 Representation offices NO NO NO NO
diff.
20 02 06 02 - Conference and meeting Non-
4 NO NO NO NO
costs diff.
20 02 06 01 - Missions, conferences Non-
4 NO NO NO NO
and representation expenses diff.
1
Diff. = Differentiated appropriations / Non-diff. = Non-differentiated appropriations.
2
EFTA: European Free Trade Association.
3
Candidate countries and, where applicable, potential candidates from the Western Balkans.
EN 14 EN
3.2. Estimated financial impact of the proposal on appropriations
3.2.1. Summary of estimated impact on operational appropriations
– The proposal/initiative does not require the use of operational appropriations
– The proposal/initiative requires the use of operational appropriations, as explained below
3.2.1.1. Appropriations from voted budget
Amounts are indicative and do not prejudge the outcome of the ongoing negotiations on the next MFF.
EUR million (to three decimal places)
Year Year Year Year Year Year Year TOTAL
DG: SANTE MFF
2028 2029 2030 2031 2032 2033 2034 2028-2034
Operational appropriations
Commitments (1a) p.m. p.m. p.m. p.m. p.m. p.m. p.m. p.m.
Programme Budget line
Payments (2a) p.m. p.m. p.m. p.m. p.m. p.m. p.m. p.m.
Appropriations of an administrative nature financed from the envelope of specific programmes
Budget line - Technical
(3) 2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382
Assistance -Support credits
TOTAL appropriations Commitments =1a+1b+3 2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382
for DG SANTE Payments =2a+2b+3 2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382
EN 15 EN
EU contribution to decentralised agencies
EUR million (to three decimal places)
Year Year Year Year Year Year Year POST
[Agency]: TOTAL
<EMA .> 2028 - 2034 2034 annual
2028 2029 2030 2031 2032 2033 2034
expenditure)
Budget line:
EMA / EU
Budget 10,055 8,153 2,196 2,240 2,285 2,330 2,377 29,635 2,425
contribution to
the agency
EUR million (to three decimal places)
Year Year Year Year Year Year Year TOTAL POST
EFSA 2028- 2034(annual
2028 2029 2030 2031 2032 2033 2034
2034 expenditure)
Budget line: EFSA/ EU Budget contribution to
0,882 1,800 1,836 1,872 1,910 1,948 1,987 12,235 2,027
the agency
For EFSA and EMA for the first year only 50 % of the average staff costs are taken into account as it is expected that not all positions will
be filled from the beginning of the year
EN 16 EN
Without prejudice to the negotiations on the next MFF, the appropriations allocated to the agencies from 2028 onwards will be compensated via
redeployments from programmes under the 2028-2034 MFF. If a compensatory reduction is needed, the resources allocated to the agencies and
their funding streams and sources may need to be revised.
EUR million (to three decimal places)
Year Year Year Year Year Year Year TOTAL
MFF
2028 2029 2030 2031 2032 2033 2034 2028-2034
TOTAL operational Commitments (4) 10,938 9,953 4,032 4,112 4,194 4,278 4,364 41,870
appropriations
(including
contribution to EMA Payments (5) 10,938 9,953 4,032 4,112 4,194 4,278 4,364 41,870
and EFSA)
TOTAL appropriations of an
administrative nature financed from (6) 2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382
the envelope for specific programmes
TOTAL
appropriations
Commitments =4+6 13,564 12,579 6,658 6,738 6,820 6,904 6,990 60,252
under HEADING
SANTE
of the multiannual
Payments =5+6 13,564 12,579 6,658 6,738 6,820 6,904 6,990 60,252
financial framework
Without prejudice to the negotiations on the next MFF, the appropriations allocated to the agencies from 2028 onwards will be
compensated via redeployments from programmes under the 2028-2034 MFF. If a compensatory reduction is needed, the resources
allocated to the agencies and their funding streams and sources may need to be revised.
EN 17 EN
EUR million (to three decimal places)
Heading of multiannual financial framework 4 ‘Administrative expenditure’
Year Year Year Year Year Year Year TOTAL
MFF
DG: SANTE
2028 2029 2030 2031 2032 2033 2034 2028-
2034
Human resources 6,371 6,371 6,371 6,371 6,371 6,371 6,371 44,597
Other administrative expenditure 0,010 0,010 0,010 0,011 0,011 0,011 0,011 0,075
TOTAL DG SANTE Appropriations 6,381 6,381 6,381 6,382 6,382 6,382 6,382 44,672
(Total
TOTAL appropriations
commitments
under HEADING 4 6,381 6,381 6,381 6,382 6,382 6,382 6,382 44,672
= Total
of the multiannual financial framework
payments)
– Amounts are indicative and do not prejudge the outcome of the ongoing negotiations on the next MFF.
EN 18 EN
TOTAL HEADING 1 to 4 C1
Year Year Year Year Year Year Year TOTAL MFF
2028 2029 2030 2031 2032 2033 2034 2028-2034
TOTAL
appropriations
under Commitments 19,945 18,960 13,039 13,120 13,202 13,286 13,372 104,924
HEADINGS 1
to 4
of the
multiannual
Payments 19,945 18,960 13,039 13,120 13,202 13,286 13,372 104,924
financial
framework
* Figures in the table above are all strictly indicative pending the outcome of the 2028-2034 MFF negotiations which cannot be prejudged.
3.2.2. Estimated output funded from operational appropriations (not to be completed for decentralised agencies)
The output funded from operational appropriations cannot be calculated as the outcome of the 2028-2034 MFF negotiations, still ongoing at time
of completing the LFDS, cannot be prejudged.
EN 19 EN
3.2.3. Summary of estimated impact on administrative appropriations (not to be completed
for decentralised agencies)
– ¨ The proposal/initiative does not require the use of appropriations of an
administrative nature
– x The proposal/initiative requires the use of appropriations of an administrative
nature, as explained below
– 3.2.3.1 Appropriations from voted budget
Year Year Year Year Year Year Year TOTAL POST
VOTED
2028 - 2034(annual
APPROPRIATIONS 2028 2029 2030 2031 2032 2033 2034 2034 expenditure)
HEADING 4
Human resources 6,371 6,371 6,371 6,371 6,371 6,371 6,371 44,597 6,371
Other administrative
0,010 0,010 0,010 0,011 0,011 0,011 0,011 0,075 0,011
expenditure
Subtotal HEADING 4 6,381 6,381 6,381 6,382 6,382 6,382 6,382 44,672 6,382
Outside HEADING 4
Human resources 2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382 2,626
Other expenditure of an
0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000
administrative nature
Subtotal outside
2,626 2,626 2,626 2,626 2,626 2,626 2,626 18,382 2,626
HEADING 4
TOTAL 9,007 9,007 9,007 9,008 9,008 9,008 9,008 63,054 9,008
– * Figures in the tables above are all strictly indicative pending the outcome of the
2028-2034 MFF negotiations which cannot be prejudged.
===================================================================
3.2.4. Estimated requirements of human resources (not to be completed for decentralised
agencies)
– ¨ The proposal/initiative does not require the use of human resources
– The proposal/initiative requires the use of human resources, as explained
below
EN 20 EN
3.2.4.1. Financed from voted budget
Estimate to be expressed in full-time equivalent units (FTEs)1
TOTAL Year Year Year Year Year Year Year POST
VOTED APPROPRIATIONS
+ 2034(annual
EXTERNAL ASSIGNED 2028 2029 2030 2031 2032 2033 2034
expenditure)
REVENUES
Establishment plan posts (officials and temporary staff)
20 01 02 01 (Headquarters
and Commission’s 29 29 29 29 29 29 29 29
Representation Offices)
20 01 02 03 (EU Delegations) 0 0 0 0 0 0 0 0
01 01 01 01 (Indirect
0 0 0 0 0 0 0 0
research)
01 01 01 11 (Direct research) 0 0 0 0 0 0 0 0
Other budget lines (specify) 0 0 0 0 0 0 0 0
• External staff (in Full Time Equivalent unit: FTE)
20 02 01 (AC, END from the
9 9 9 9 9 9 9 9
‘global envelope’)
20 02 03 (AC, AL, END and
0 0 0 0 0 0 0 0
JPD in the EU Delegations)
Admin. Support - at
0 0 0 0 0 0 0 0
line Headquarters
[XX.01.YY.YY] - in EU
0 0 0 0 0 0 0 0
[2] Delegations
01 01 01 02 (AC, END -
0 0 0 0 0 0 0 0
Indirect research)
01 01 01 12 (AC, END -
0 0 0 0 0 0 0 0
Direct research)
Other budget lines (specify) -
0 0 0 0 0 0 0 0
Heading 4
Other budget lines (specify) -
26 26 26 26 26 26 26 26
Outside Heading 4
TOTAL 64 64 64 64 64 64 64 64
* Figures in the tables above are all strictly indicative pending the outcome of the 2028-2034
MFF negotiations which cannot be prejudged.
Considering the overall strained situation in Heading 4, in terms of both staffing and the level of
appropriations, the human resources required will be only partly met by staff from the DG who are
already assigned to the management of the action and/or have been redeployed within the DG.
1
Please specify below the table how many FTEs within the number indicated are already assigned to the
management of the action and/or can be redeployed within your DG and what are your net needs.
EN 21 EN
24 additional establishment plan posts which are required to implement the proposal and 4 SNEs
(in FTEs) to be covered with additional staff to be financed under heading 4. 26 CAs will be
financed from appropriations of an administrative nature financed from the envelope of specific
programmes. 5ADs, 4 CAs and 1 SNE posts to be covered by current staff available in the
Commission services.
The staff required to implement the proposal (in FTEs):
To be covered by Exceptional additional staff*
current staff
available in the
Commission
services
To be financed To be financed To be financed
under Heading 4 from BA line from fees
or Research
Establishment 5 ADs 19 ADs N/A
plan posts 5 ASTs
External staff 4 CAs (FIV) and 1 4 SNEs 20 CAs FGIV
(CA, SNEs, INT) SNE 6 CAs FGIII
The provisions of the Biotech Act, focused on health and food applications in the
biotechnology sector, were developed by a temporary taskforce in DG SANTE with support
of line units fully resourced to other tasks across different directorates. To fully implement the
Act's provisions — which aim to streamline and future proof the regulatory system, enhance
research, development, manufacturing and financing of biotechnology products, enable use of
AI, foster skills and safe use of biotechnology — additional dedicated personnel will be
needed, as presented in the table above and detailed below.
Description of tasks to be carried out by SANTE:
Officials 24 FTEs (AD profiles) to:
and
temporary • Manage the workload related to the revision and implementation of the following
staff legislation
o Amendment to Regulation (EU) 2024/1938 (SoHO): handle increased
number of cases concerting the development of novel nologysandboxes in
the field of SoHO.
o Amendments to Regulation (EC) No 1394/2007 on Advanced
Therapeutic Medicinal Products (ATMPs): draft delegated acts in
relation to what constitute an ATMP in line with amendments to Regulation
(EC) No 1394/2007 foreseen by this Regulation.
o Amendments to Regulation (EU) No 536/2014 (‘Clinical Trials
Regulation’): prepare the delegated acts and implementing acts related to
the changes of CTR, support the work of expert groups developing
EN 22 EN
guidance and best practices, coordinate with relevant authorities for
coherence with other regulatory frameworks, monitor the preparedness of
Member States for the harmonised implementation of the changes to the
CTR, monitor and steer the changes to the Clinical Trials Information
System.
o Amendments to Regulation (EC) No 178/2002 (‘General Food Law’):
comment on behalf of the Commission prior to the commencement of a
proposed regulatory sandbox and of any adaptations thereof; Develop of
implementing acts , review annual reports of Member States that have set
up regulatory sandboxes, proceed to the necessary adaptations of the
applicable legislative framework where required.
• Manage a panel of experts advising the Commission on new biotechnology
developments i.e., Foresight Panel for Emerging Health Innovation.
• Set up and manage the regulatory sandboxes for novel health biotechnology
products not falling in any other legislation in the area of health.
• Develop implementing acts as needed, detail criteria, draft call for proposals and
follow the implementation of High Impact Health Biotechnology strategic
projects on: biotechnology research and development, availability of late-stage
capital, AI biotechnology applications and biosecurity.
• Draft call for proposals and follow the implementation of innovative and
precommercial procurement projects, the establishment of an EU Health
Biotechnology Support Network of local antennas supporting biotechnology
undertakings;
• Provide policy and legal guidance to and coordinate with:
o EMA on AI systems Deployment and Use in the Lifecycle of Medicinal
Products.
o Implementing partners on the management of the Biotechnology Investment
Pilot.
o Member States on the supervision of economic operators handling potential
biosecurity risk products.
5 (AST profiles) to:
• Provide administrative and logistic support to experts’ meetings of the Advisory
Group on Biosecurity and Artificial Intelligence and to meetings of Member
States and the Commission in the European Health Biotechnology Steering
Group.
• Support the process of projects selection and assessment for High Impact Health
Biotechnology strategic projects and assist with information management.
• Develop and maintain a Union Regulatory Status Repository to assist developers
in navigating cases of health biotechnology products.
External 5 SNEs and 24 CAs (FGV) to support ADs with:
staff
• Expert selection and appointment and dissemination of discussion papers produced
EN 23 EN
by the Foresight Panel for emerging health innovation, support content
preparation of panels meetings.
• Setting up and management of Regulatory Sandbox for novel health
biotechnology products not falling in any other legislation in the area of health
• Commenting on proposed regulatory sandboxes in the framework of the General
Food Law and with the development of implementing and delegated acts.
• Drafting of calls for proposal for Hight Impact Health Biotechnology Strategic
Projects and follow their implementation, in different areas (biotechnology
research and development, availability of late-stage capital, AI biotechnology
applications and biosecurity) and for the establishment of the and the EU Health
Biotechnology Support Network.
• Providing technical content development of the AI-Biotechnology Support Module
and its continued maintenance and update with information to be disseminated by
the Biotechnology Support Network.
• Ensuring coordination in management of funding and liaison with implementing
partners in the context of the EU Biotechnology Investment Pilot.
• Drafting of guidelines on the enforcement of biosecurity provision to be enforced in
cooperation with Member States and relevant delegated or implementing acts,
monitor and analyse landscape to identify promising technologies and to support
ADs in developing and following calls for capability projects.
• Preparing meeting content and support management of the meetings of the
Advisory Group on Biosecurity and Artificial Intelligence and the European
Health Biotechnology Steering Group.
6 CAs (FGIII) to:
• Provide administrative support to the organisation of the experts’ meetings of the
Foresight Panel for emerging health innovation.
• Promote and facilitate the networking and cooperation among projects and maintain
updated lists of High Impact Health Biotechnology Strategic Project.
• Support with workflow of queries and management of information of the EU
Health Biotechnology Support Network.
3.2.5. Overview of estimated impact on digital technology-related investments (not to be
completed for decentralised agencies)
Compulsory: the best estimate of the digital technology-related investments entailed
by the proposal/initiative should be included in the table below.
Exceptionally, when required for the implementation of the proposal/initiative, the
appropriations under Heading 4 should be presented in the designated line.
The appropriations under Headings 1-3 should be reflected as “Policy IT expenditure
on operational programmes”. This expenditure refers to the operational budget to be
used to re-use/ buy/ develop IT platforms/ tools directly linked to the implementation
of the initiative and their associated investments (e.g. licences, studies, data storage
etc). The information provided in this table should be consistent with details
presented under Section 4 “Digital dimensions”.
TOTAL TOTAL
Year Year Year Year Year Year Year
Digital and IT MFF
EN 24 EN
appropriations 2028 -
2028 2029 2030 2031 2032 2033 2034
2034
HEADING 4
IT expenditure
0 0 0 0 0 0 0 0
(corporate)
Subtotal
0 0 0 0 0 0 0 0
HEADING 4
Outside HEADING 4
Policy IT
expenditure on
0 0 0 0 0 0 0 0
operational
programmes
Subtotal
outside 0 0 0 0 0 0 0 0
HEADING 4
TOTAL 0 0 0 0 0 0 0 0
3.2.6. Compatibility with the current multiannual financial framework (not to be completed
for decentralised agencies)
The proposal/initiative:
– can be fully financed through redeployment within the relevant heading of the
multiannual financial framework (MFF)
The initiative will be fully financed via redeployments from programmes under the
2028-2034 MFF
– ¨ requires use of the unallocated margin under the relevant heading of the MFF
and/or use of the special instruments as defined in the MFF Regulation
– ¨ requires a revision of the MFF
3.2.7. Third-party contributions (not to be completed for decentralised agencies)
The proposal/initiative:
– does not provide for co-financing by third parties
– provides for the co-financing by third parties estimated below:
Appropriations in EUR million (to three decimal places)
Year Year Year Year Year Year Year
Total
2028 2029 2030 2031 2032 2033 2034
Specify the
co-financing
body
EN 25 EN
TOTAL
appropriations
co-financed
3.2.8. Estimated human resources and the use of appropriations required in EMA
.
Staff requirements (full-time equivalent units)
[Agency]: <EMA .> Year Year Year Year Year Year Year POST
2028 2029 2030 2031 2032 2033 2034 2034
Temporary agents (AD
5 5 5 5 5 5 5 5
Grades)
Temporary agents (AST
2 2 2 2 2 2 2 2
grades)
Temporary agents
7 7 7 7 7 7 7 7
(AD+AST) subtotal
Contract staff 5 5 5 5 5 5 5 5
Seconded National Experts
Contract agents and SNE
5 5 5 5 5 5 5 5
subtotal
TOTAL staff 12 12 12 12 12 12 12 12
Appropriations covered by the EU budget contribution in EUR million (to three decimal
places)
Year Year Year Year Year Year Year TOTAL POST
[Agency]:
2032 2033 2034 2028 - 2034(annual
<EMA .> 2028 2029 2030 2031
2034 expenditure)
Title 1: Staff
1,055 2,153 2,196 2,240 2,285 2,330 2,377 14,635 2,425
expenditure
Title 2:
Infrastructure
and operating
9,000 6,000 15,000
expenditure (
IT investments)
=
Title 3:
Operational 0,000
expenditure
EN 26 EN
TOTAL of
appropriations
10,055 8,153 2,196 2,240 2,285 2,330 2,377 29,635 2,425
covered by the
EU Budget
IT investments: EMA currently maintains the Clinical Trials Information System (CTIS)
development and maintenance. This Regulation contains major new provisions directly
impacting CTIS and need its strengthening. The core objectives of the amendments to the
Clinical Trials Regulation (EU 526/2014) will be implementable only following significant IT
developments and establishment of new workflows. We anticipate that these new provisions
will necessitate fundamental redesign and build of CTIS followed by long-term maintenance
including technology refresh.
Overview/summary of human resources and appropriations (in EUR million) required
by the proposal/initiative in a decentralised agency
Year Year Year Year Year Year Year TOTAL POST
[Agency]: <EMA .> 2028 -
2028 2029 2030 2031 2032 2033 2034 2034
2034
Temporary agents
7 7 7 7 7 7 7 12
(AD+AST)
Contract agents 5 5 5 5 5 5 5 5
Seconded National Experts 0 0 0 0 0 0 0
Total staff 12 12 12 12 12 12 12 12
Appropriations covered by
10,055 8,153 2,196 2,240 2,285 2,330 2,377 29,635 2,425
the EU Budget
Appropriations covered by
0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000
fees
Appropriations co-financed
0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000
(if applicable)
TOTAL appropriations 10,055 8,153 2,196 2,240 2,285 2,330 2,377 29,635 2,425
Appropriations covered by fees: Veterinary sandboxes established in this Regulation will be
supported by fees, however being a completely new use case for which EMA will not be able
to establish the fee level before the coming into effect of this Regulation, it is impossible to
establish an amount and assess the level of contribution at this stage.
Without prejudice to the negotiations on the next MFF, the appropriations allocated to the
agencies from 2028 onwards will be compensated via redeployments from programmes under
the 2028-2034 MFF. If a compensatory reduction is needed, the resources allocated to the
agencies and their funding streams and sources may need to be revised.
Description of tasks to be carried out by the European Medicines Agency (EMA):
Officials and temporary The Biotech Act proposal will contain major new provisions on the
staff management of Clinical Trials. These include multiple new workflows,
parallel submissions, amended dossier requirement, a core product dossier
and extension to combined studies including in-vitro diagnostics, among
others.
The requested 5 ADs will be:
• Managing the significantly increased daily operations of Clinical Trial
EN 27 EN
Information System (CTIS) including the access and tasks of its >20,000
users and close to 3000 initial clinical trial applications and thousands
of substantial modification applications.
• Identifying, designing, reviewing and ensuring oversight
of the delivery process for new functionalities and modules in CTIS in
line with relevant legal provisions.
• Monitoring the performance of the contractor,
• Working with CTIS subject matter experts and stakeholders,
to prioritise and validate CTIS technical specifications, in line with
relevant legal provisions.
• Performing CTIS testing activities, including for the new functionalities
and modules.
• Planning and performing change management activities.
• Performing communication, engagement and training of all relevant
stakeholders (e.g. sponsors, Member State regulatory bodies ).
• Maintaining the training materials up to date.
• Monitoring the KPIs of the IT system and the CTR for regular reporting
• Delivering reports when requested
• Regulatory compliance check of the IT system
2 AST will:
• Support AD organization of meetings with sponsors and/or experts and
drafting minutes.
• Support and coordinate engagement with CTIS subject matter experts and
stakeholders.
Support and coordinate communication and training activities with
sponsors, member state authorities, ethics bodies etc.
External staff The requested 5 FTE will be supporting ADs in:
• Overall support to the ADs, and as appropriate, in the case of national
experts, they provide expertise
• Implementation of the development plan
• Contribute to coordination tasks
• Maintaining continuous availability and operation of CTIS.
• Managing post-delivery maintenance, providing support to relevant
EN 28 EN
stakeholders (e.g. IT and business service desk).
• performing continuous monitoring of the CTIS function
and performance.
• Providing programme and project management.
• Response to queries from stakeholders
• Support the development of CTIS training material
• Stakeholder communication (e.g. CTIS Forum and other events)
The extra resources are absolutely necessary since timely
implementation of the amendments targeting competitiveness are
dependent on substantial IT development that would need to be set up in
short time.
3.2.9. Estimated human resources and the use of appropriations required in EFSA
Staff requirements (full-time equivalent units)
[Agency]: <EFSA> Year Year Year Year Year Year Year POST
2028 2029 2030 2031 2032 2033 2034 2034
Temporary agents (AD Grades) 5 5 5 5 5 5 5 5
Temporary agents (AST
1 1 1 1 1 1 1 1
grades)
Temporary agents (AD+AST)
6 6 6 6 6 6 6 6
subtotal
Contract staff 8 8 8 8 8 8 8 8
Seconded National Experts
Contract agents and SNE
8 8 8 8 8 8 8 8
subtotal
TOTAL staff 14 14 14 14 14 14 14 14
EN 29 EN
Overview/summary of human resources and appropriations (in EUR million) required
by the proposal/initiative in a decentralised agency
Year Year Year Year Year Year Year TOTA POST
[Agency]: 203 203 203 L 2034(annual
202 202 203 203
<EFSA> 2 3 4 2028 - expenditure
8 9 0 1
2034 )
Title 1: Staff
0,882 1,800 1,836 1,872 1,910 1,948 1,987 12,235 2,027
expenditure
Title 2:
Infrastructure
0,000
and operating
expenditure
Title 3:
Operational 0,000
expenditure
TOTAL of
appropriation
0,882 1,800 1,836 1,872 1,910 1,948 1,987 12,235 2,027
s covered by
the EU Budget
Year Year Year Year Year Year Year TOTAL POST
[Agency]: <EFSA> 2028 -
2028 2029 2030 2031 2032 2033 2034 2034
2034
Temporary agents
6 6 6 6 6 6 6 6
(AD+AST)
Contract agents 8 8 8 8 8 8 8 8
Seconded National Experts 0 0 0 0 0 0 0
Total staff 14 14 14 14 14 14 14 14
Appropriations covered by
0,882 1,800 1,836 1,872 1,910 1,948 1,987 12,235 2,027
the EU Budget
Appropriations covered by
0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000
fees
Appropriations co-financed
0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000
(if applicable)
TOTAL appropriations 0,882 1,800 1,836 1,872 1,910 1,948 1,987 12,235 2,027
EN 30 EN
Without prejudice to the negotiations on the next MFF, the appropriations allocated to the
agencies from 2028 onwards will be compensated via redeployments from programmes under
the 2028-2034 MFF. If a compensatory reduction is needed, the resources allocated to the
agencies and their funding streams and sources may need to be revised.
Description of tasks to be carried out by the European Food Safety Agency (EFSA):
Officials and temporary staff Currently, there are a lot of delays during the EU risk assessment as
EFSA receives low quality dossiers, for which it has to frequently stop
the EU risk assessment process and request applicants to provide
clarifications and/or additional information. To enhance innovation and
to ensure that applicants, and especially SMEs, submit high
quality/comprehensive application dossiers it is imperative to support
them at pre-submission phase. This will ensure that the EU risk
assessment finishes within the time provided increasing the applicants’
chances of reaching the market as quickly as they can (while keeping
funding from investors).
Currently EFSA provides pre-submission advice only as regards what
an application dossier needs to contain (administrative/regulatory
aspects). Given the restricted scope of pre-submission advice (PSA), the
uptake of the existing PSA is limited; applicants primarily need support
on the scientific aspects of preparing a dossier.
The provisions of the Biotech Act will significantly increase EFSA
workload, in particular due to the enlarged scope of PSA which will
now cover also scientific advice (i.e. what kind of studies, advice on
the appropriate study design depending on the subject matter at
issue, etc). Given the considerable attractiveness of the proposed
changes for applicants, especially for SMEs, this is expected to result in
a significant increased uptake of pre-submission advice (PSA)
especially by SMEs both in terms of numbers of requests for pre-
submission advice but also in the breadth and coverage of advice to be
given.
As regards numbers, EFSA expects about 200 requests per year
across all authorisation domains in the food chain – which are many
and diverse – both for new products/substances and renewals where
applicable (e.g. novel foods, food additives/enzymes/flavourings, feed
additives, plant protection products, maximum residue limits of
pesticides, GM food and feed, food contact materials, health claims,
EN 31 EN
addition of vitamins and minerals and other substances to foods, etc).
As regards the breadth and coverage of the advice to be given, EFSA
will now be required to carry out a closer evaluation of the request at
hand and provide tailor-made advice covering both
administrative/regulatory aspects but also scientific aspects on each
individual case.
Thus, the requested -5 ADs are necessary to:
- Prepare and provide tailor-made pre-submission advice
consisting of scientific advice including on the type and design
of studies to be submitted in support of an
application/notification and on the content of the
application/notification at hand. The scientific advice will be
particularly demanding as it needs to be specific to the needs of
each induvial application taking also into account the profile of
the applicant at hand (e.g. SME that has no experience with
applications) as well as the subject matter (type of product,
applicable sectoral legislation, type of approval, e.g. new or
renewal etc). This includes additional tasks such as:
o coordinate with subject matter units for the needed
tasks, involvement of working group Experts, Panel
experts, who might also later be involved in dossier
assessment; In this respect, additional research and
work would need to be carried out as regards
previous scientific outputs of the EFSA of all 11
Panels across all authorisation procedures in the food
chain, data requirements set out in sectoral legislation
and all relevant scientific guidances, where such exist
as well as the latest scientific information that may be
relevant for the applicant concerned;
o coordinate with Member State experts in the relevant
EFSA networks/fora but also with other EU agencies
where needed – in the area of pesticides where the
approval system of active substances is semi-
decentralised this will need additional effort to
coordinate with the relevant MS authorities to ensure the
provision of PSA from EFSA and from the MS
authorities in a consistent manner;
o exchange with the requestor (on acceptability, requests
for clarifications);
o regular consultation with EFSA’s legal department to
provide advice in line with the applicable rules (remit of
pre-submission advice, public disclosure of the advice
EN 32 EN
given once corresponding valid applications are made
etc.) ensure the clarity and consistency of the pre-
submission advice to all requestors across all
authorisation procedures, especially where applicants
would need to apply for more than 1 authorisation
process for placing products on the market (application
for novel foods and subsequently application for a health
claim);
o coordinate the timely handling of all PSA requests in a
manner that provides added value to the applicants and
ensure that high quality dossiers are subsequently
submitted.
- promotion of the pre-submission advice provided by EFSA
upon request among applicants and particularly SMEs, who are
often one-time applicant and have no experience on how to
prepare application dossiers for risk assessment purposes;
- to effectively explain the ‘pre-submission advice (PSA)’
process to potential requestors;
- to ensure appropriate training to the subject matter units
and/or relevant experts both on the required content of dossiers
and on the scientific front taking into account the EFSA
scientific guidance documents and data requirements laid down
in the sector specific legislation.
The permanent 5 AD positions will ensure clarity and consistency in the
provision of PSA, maintain the uptake of PSA to ensure that high
quality dossiers are later submitted that would accelerate the risk
assessment process and that the knowledge is retained within EFSA in
the most effective manner.
1 Assistant staff (AST) is needed for:
- organization of tele-meetings with the requestor and/or experts
(if needed) and drafting minutes;
- developing a knowledge database and ensuring its maintenance,
monitoring, reporting, auditing of the requests;
- following up on the continuous improvement of the service and
support IT tool improvements;
- supporting applicants on the characteristics of the service and the
IT Tools;
- disseminating the service among applicants and SMEs,
supporting the publication of summary in Open EFSA,
publication of full advice at the time of a validated dossier.
External staff Given the expected considerable increased uptake of the PSA in the
EN 33 EN
early years of entry into application of this enlarged service, the
permanent staff would need the support of 8 CAs (FGIV) to set in
motion the relevant process and the establishment/maintenance in terms
of content of a knowledge database for future use for all the tasks
outlined and for all authorisation procedures across the food chain for
which EFSA is responsible to provide scientific advice. More
specifically:
- perform reception and triage of the request;
- analyse the request and ensure appropriate understanding what is
needed to provide tailor-made advice;
- liaise with the technical units and identify the relevant and
appropriate profile of scientific experts (either from the
established panels or their working groups or even from the
reserve list of experts) that could support the scientific aspects of
PSA depending on each individual request; ensure their
participation, analysis and input to the provision of the PSA;
- perform literature review and preparatory work to support the
scientific experts and ensure also the provision of PSA on
administrative/regulatory aspects;
- exchanges with the requestor (on acceptability, requests for
clarifications) and setting up where appropriate PSA meetings;
- review of written replies and summaries to ensure consistency;
- ensure that the replies provided are introduced into a knowledge
database to keep records of past advice for future use depending
on the relevant needs of the requests at hand;
- drafting of the written advice to be sent to the requestor,
finalisation of the advice and ensure that public disclosure of the
PSA advice does not contain personal data or other confidential
information.
If such staffing is not guaranteed and given the considerable
increase of PSA that is expected, EFSA would not be able to deliver
on the PSA advice without moving staff from its ‘core business’ –
which is the provision of risk assessment – to the pre-submission phase.
This will result in even more delays than currently occur in the
delivery of scientific outputs, defeating the very purpose of the
Biotech act, which is to stimulate innovation and ensure that the time to
the market for innovators is reduced.
Therefore, it is absolutely imperative for ensuring the objectives of the
Biotech act to guarantee the EFSA additional resources so as to avoid
any direct negative impact on the timeliness and speed of delivery of
scientific opinions..
EN 34 EN
3.3. Estimated impact on revenue
– The proposal/initiative has no financial impact on revenue.
– The proposal/initiative has the following financial impact:
– on own resources
– on other revenue
– please indicate, if the revenue is assigned to expenditure lines
EUR million (to three decimal places)
Appropriations Impact of the proposal/initiative2
Budget revenue available for
line: the current Year Year Year Year Year Year Year
financial year 2028 2029 2030 2031 2032 2033 2034
Article
………….
For assigned revenue, specify the budget expenditure line(s) affected.
[…]
Other remarks (e.g. method/formula used for calculating the impact on revenue or
any other information).
[…]
4. DIGITAL DIMENSIONS
4.1. Requirements of digital relevance
High-level description of the requirements of digital relevance and related categories (data,
process digitalisation & automation, digital solutions and/or digital public services)
Actors
affected or
Reference to the Requirement High-level
concerned by Categories
requirement description Processes
the
requirement
Scaling-up or
upgrading critical Member State
Technical
Article [3] 1b research and authorities,
documentation,
Health technology Research Data, Digital
Data
Biotechnology organisations, Solution
infrastructures generation,
Strategic Projects Biotechnology
underpinning the Data processing
industry actors
development,
2
As regards traditional own resources (customs duties, sugar levies), the amounts indicated must be net
amounts, i.e. gross amounts after deduction of 20% for collection costs.
EN 35 EN
testing and
validation of
biotechnology
products,
including but not
limited to pilot or
testing
infrastructures for
biomanufacturing,
data and digital
platforms;
accelerating
innovation and
technology
deployment
through one or
more of the
following features:
(i) introducing or Commission,
scaling up Member State Technical
Article [3] 1c
breakthrough authorities, documentation,
Health Data, Digital
innovations in Research Data
Biotechnology Solution
biotechnology that organisations, generation,
Strategic Projects
Biotechnology Data processing
have the potential
industry actors
to strengthen the
Union’s industrial
competitiveness,
including AI-
enabled
technologies and
tools;
Article [4] 1d High the project Commission, Data Data, Digital
Impact Health contributes to the Member State generation, Solution
Biotechnology development of authorities, Data processing
Strategic Projects trusted testing Research
environments for organisations,
AI-enabled Biotechnology
biotechnology industry actors
innovations,
fulfilling the
conditions laid
down in Article
[36], paragraph [1]
or it is
Biotechnology
Data Quality
EN 36 EN
Accelerator High
Impact Project,
fulfilling the
conditions laid
down in Article
[37]
Article [5] a it provides trusted Commission, Data Data, Digital
testing or Member State generation, Solution
Biotechnology
demonstration authorities, Data processing
Development
facilities Research
Accelerator
replicating real- organisations,
world Biotechnology
biomanufacturing industry actors
processes,
including general
manufacturing
practices (GMPs)
compliant
processes, or their
enabling
technologies, for
process testing,
validation, and
small batch
manufacturing,
including for the
initial phases of
clinical trials; such
enabling
technologies may
include digital
technologies,
including AI with
specific
applicability in
biotechnology and
biomanufacturing;
Article [5] c it aims to support Commission, Technical Data, Digital
Biotechnology hands-on and Member State documentation, Solution
Development work-based authorities, Information
Accelerator training Research exchange
programmes organisations,
aligned with the Biotechnology
Union’s skills and industry actors
workforce
development
objectives in the
biotechnology and
biomanufacturing
EN 37 EN
sectors or in
relation to
enabling
technologies, such
as digital
technologies
including AI, with
specific
applicability in
biotechnology and
biomanufacturing;
Article [5] d it conducts applied Research Data Data, Digital
Biotechnology research in organisations, generation, data Solution
Development biotechnology or Biotechnology processing
Accelerator biomanufacturing, industry actors
or in relation to
enabling
technologies, such
as digital
technologies
including AI, with
specific
applicability in
biotechnology and
biomanufacturing
Article [11] 7 Member States Member State Reuse of Data
of shall promote the authorities existing data
Single Points
reuse of existing
Contact
data, studies and
authorisations in
order to avoid
duplication of
procedures, reduce
administrative
burden and ensure
consistency of
decision-making.
For that purpose,
they shall ensure
that, when
assessing an
application,
competent
authorities duly
take into account
all relevant
studies,
assessments and
valid permits or
EN 38 EN
authorisations
already carried out
or issued for the
same project or its
components,
provided that they
remain applicable
and up to date.
Article [15] 2e Such networking Commission, Information Data
Networks of Health and cooperation Member State exchange
Biotechnology should aim to: e) authorities,
Clusters promote the Research
development of organisations,
interoperable Biotechnology
infrastructure and industry actors
digital platforms,
and AI-enabled
technologies
supporting
biotechnology and
biomanufacturing
Article [16] 6a access by a non- Non- Access to data Data
Access Principles associated third associated
and Security country or by a third country,
Safeguards non-associated Non-
third-country associated
entity to sensitive third-country
information is entity,
prevented and the Member
employees or States,
other persons Associated
involved have countries
national security
clearance issued
by a Member State
or an associated
country, where
appropriate;
Article [16] 6b intellectual Non- Access to Data
Access Principles property arising associated infrastructures
and Security from, and the third country, and datasets
Safeguards results of, the Non-
activities related associated
to the access to third-country
infrastructures and entity,
datasets remain Member
within the legal States,
entity that is Associated
EN 39 EN
granted access, countries
during and after
such access, are
not subject to
control or
restriction by a
non-associated
third country or by
a non-associated
third-country
entity, and are
neither exported
outside the Union
or outside
associated
countries nor
accessible from
outside the Union
or outside
associated
countries without
the approval of the
Member State or
the associated
country in which
the legal entity is
established and in
accordance with
the objectives of
this Regulation
Article [17] 2e use of data and Union bodies Mapping Data
Strategic Mapping artificial and agencies,
of the Union’s intelligence, by industry
Biotechnology assessing access to stakeholders
Ecosystem data, computing and research
and digital organisations
infrastructures for
biotechnology and
identifying
opportunities to
foster responsible
AI-enabled
innovation and
contribute to the
mitigation of
related risks.
Article [21] 5a facilitate the Members of Information Data, Digital
and exchange of the Steering exchange Public Service
Composition
information and Group,
EN 40 EN
Functioning of the best practices Commission,
Steering Group among Member Member State
States, the authorities,
Commission, and research
relevant organisations,
stakeholders in biotechnology
relation to the industry actors
recognition and
the
implementation of
health
biotechnology
strategic projects
and high impact
health
biotechnology
strategic projects;
Article [21] 5h facilitate the Commission, Information Data, Digital
coordination and Member State exchange public service
Composition and
information authorities
Functioning of the
exchange among
Steering Group
the Member States
on enforcement of
the biosecurity
provisions in this
regulation and
other emerging
biosecurity topics
as provided for in
Article
Article [29]b it contributes to Member State Use of platform Data
the research, authorities technologies
Health
development and
Biotechnology
Strategic Projects marketing
authorisation of
for Biosimilars
biosimilar
products, and
where appropriate
to strengthen the
use of platform
technologies. It
includes analytical
methodologies
that would reduce
the need for
clinical data for
biosimilar
EN 41 EN
medicinal
products, without
affecting their
quality, safety and
efficacy.
Article [31] The European Commission, Technical The European
Medicines Agency EU Agencies, documentation Medicines
Guidance on the
(‘the Agency’) Member State Agency (‘the
deployment and use
shall develop authorities, Agency’)
of systems based on
guidance on the industry shall develop
advanced
deployment and stakeholders guidance on
technologies,
use of artificial- and research the
including AI, in the
intelligence organisations deployment
lifecycle of
systems (‘AI and use of
medicinal products
systems’) and of artificial-
general-purpose intelligence
AI models in the systems (‘AI
lifecycle of systems’) and
medicinal of general-
products purpose AI
development, models in the
including during lifecycle of
pre-clinical medicinal
research, clinical products
development and development,
trials, including
manufacturing and during pre-
post-authorisation clinical
monitoring. research,
clinical
Such guidance
development
shall comply with
and trials,
relevant EU
manufacturing
legislation and
and post-
shall be developed
authorisation
and updated in
monitoring.
cooperation with
the Commission. Such
guidance shall
comply with
relevant EU
legislation
and shall be
developed and
updated in
cooperation
with the
Commission.
Article [32]1 A project located Commission, Data Data
EN 42 EN
Biotechnology in the Union that Member State generation,
testing contributes to the authorities Data
environments for development of processing,
advanced trusted testing setting up
biotechnology environments for testing
innovations AI-enabled environments
biotechnology for AI
innovations shall
be recognised as a
high-impact health
biotechnology
strategic project
where, in addition
to the conditions
laid down in
Article [6],
paragraph [1], it
substantially
strengthens the
Union’s capacity
for responsible
experimentation,
development,
testing and
validation of such
innovations and it
fulfils all of the
following
conditions:
Article [33] 2a aim to foster the Research Development Data
Biotechnology Data development and organisations, and deployment
deployment of Biotechnology of AI solutions
Quality Accelerator
trustworthy and industry actors
competitive AI
applications in
health
biotechnologies,
including large-
scale and general-
purpose models;
Article [33] 2b ensure that Research Data Data
Biotechnology Data datasets are organisations, generation, data
established, Biotechnology processing
Quality Accelerator
managed and industry actors
processed in
accordance with
applicable Union
legislation on data
governance, ethics
EN 43 EN
and fundamental
rights, including
Regulation (EU)
2025/327
[European Health
Data Space],
Regulation (EU)
2016/679 [General
Data Protection
Regulation].
Article [33] 2c make such Research Data access Data
datasets, or the organisations,
Biotechnology Data
Quality Accelerator metadata and Biotechnology
reference industry actors
annotations
thereof, available
under fair,
reasonable and
non-
discriminatory
conditions,
ensuring equitable
access for users
including research
organisations,
SMEs and public
institutions, in
compliance with
the provisions of
Article [9] of this
Regulation.
Article [33] 2d contribute to the Research Data Data
Biotechnology Data development of organisations, interoperability,
Union standards Biotechnology Standard
Quality Accelerator
and quality industry actors Development
frameworks for
data
representativeness,
provenance,
interoperability
and annotation in
biotechnology;
Article [33] 2e support, where Research Infrastructure Data
Biotechnology Data appropriate, the organisations, interoperability,
integration of Biotechnology Data integration
Quality Accelerator
these datasets into industry actors
Union
infrastructures,
EN 44 EN
including the
European Health
Data Space,
European
Research Area
data spaces, or
other, including
the infrastructures
operated by high
impact health
biotechnology
strategic projects.
Article [33] 2f give due Research Platform Data
Biotechnology Data consideration to organisations, interoperability
Quality Accelerator the Biotechnology
interoperability industry actors
with platforms
deployed pursuant
to the EHDS and
other relevant data
spaces.
Article [35] 1 The Commission Member State Technical Data
shall compile, authorities, documentation,
Union Regulatory
maintain, develop Commission Information
Status Repository
and make publicly exchange
available a
Regulatory Status
Repository to
assist developers
in navigating
cases of novel
biotechnology
products
(‘Regulatory
Status
Repository’).
Article [35] 2 The Regulatory Member State Technical Data
Status Repository authorities, documentation,
Union Regulatory
shall contain: Commission Information
Status Repository
exchange
a) decisions,
opinions,
scientific
recommendations
regarding the
regulatory status
of a health
innovations,
EN 45 EN
issued pursuant to
the mechanisms
laid down in
Article 4 of
[revised
Regulation (EU)
2017/745],
Articles 61 and 62
of [revised
Regulation (EC)
No 726/2004] and
Articles 13 and 69
of Regulation
(EU) 2024/1938;
b) the summaries
of the scientific
recommendations
delivered by the
European
Medicines Agency
in accordance with
Article 17 of
Regulation (EC)
No 1394/2007 on
whether a product
falls within the
definition of an
advanced therapy
medicinal product
or not;
c) the discussion
papers delivered
by the Foresight
Panel for
Emerging Health
Innovation.
Article [35] 3 Member States Member State Technical Data
Union Regulatory shall make authorities, documentation,
publicly available, Commission Information
Status Repository
through the exchange
relevant national
platforms or
registries,
decisions,
opinions,
scientific
recommendations,
and other outputs
issued at national
EN 46 EN
level concerning
the regulatory
status of novel
biotechnology
products. Member
States shall inform
the Commission
where such
information is
made available.
Article [39] The European Member State Technical Data, Digital
Regulatory Medicines authorities, documentation, public service
Sandboxes provided Agency, the Commission Information
for in the MDCG, the SCB exchange
applicable and the Foresight
frameworks and Panel, as
Cross Framework applicable, shall
Communication facilitate dialogue
among the
authorities
responsible for the
setting up and the
implementation of
regulatory
sandboxes for
novel health
biotechnology
products. This
dialogue shall
focus on
exchanging
mutual learnings
and findings,
specifically
including:
(a) promoting
knowledge
sharing, by
facilitating the
exchange of
information,
experiences and
best practices,
including on
regulatory
approaches,
technological
challenges
EN 47 EN
Article [40] The Commission Commission Technical Digital public
may, by means of documentation service
Regulatory implementing
sandboxes for novel acts, lay down
health common
biotechnology principles, criteria
products not falling and practical
under other arrangements for
the assessment of
sandboxes in Union
applications
legislation received from
developers and for
the establishment
and the
supervision of the
regulatory
sandboxes and for
sandbox plans.
Article [41] d ensure that Commission, Surveillance, Data
sequencing data Member State data sharing
EU Biothreat Radar
Impact generated through authorities,
High
early detection Biotechnology
Projects
activities is shared industry
in a timely manner actors,
via the European Research
Nucleotide Organisations
Archive (ENA), to
enable access and
use by actors
across the Union
for the
development,
validation and
deployment of
advanced
pathogen detection
and
characterisation
methods; engage
in partnerships
among industry,
academia, public
authorities and
defence actors to
ensure data
sharing and
integration of
warning systems;
EN 48 EN
Article [42] f development, Commission, Health cross Data
validation and Member State border
Biodefence
benchmarking of authorities Surveillance,
capability high
strategic methods for the data sharing
impact
detection and
project
attribution of
genetic
engineering,
including the
creation of open
genetic
engineering
detection tools
[44] An economic
Article Economic Identity Data
Verification of operator that operator, verification
Legitimate Need makes available prospective
on the Union customer
market, including
through online
marketplaces,
biotechnology
products of
concern, shall, for
each transaction,
verify proof of
identity of the
prospective
customer, record
the transaction,
including the
quantities ordered,
and assess
whether the
customer has a
legitimate need.
Article [46] For the purpose of Economic Data reporting, Data
Prevention and preventing and operators, Information
Reporting of Misuse detecting Online exchange
biotechnology marketplaces
misuse, economic
operators and
online
marketplaces shall
EN 49 EN
report suspicious
transactions,
Article [48] 2 Member States Commission, Information Data
National Inspection shall ensure that Member State exchange
the national authorities
Authorities
inspection
authority has the
resources and
investigative
powers necessary
to perform their
tasks, including
the power to
request
information and
records, to carry
out on-site
inspections and,
where appropriate,
to conduct test
purchases,
including online.
Article [48] 4 Member States Commission, Information Data (data
shall ensure the Member State exchange flow)
National Inspection
participation of authorities
Authorities
national inspection
authorities, as
appropriate, in the
relevant activities
of the Steering
Group, in
particular for the
exchange of
information on
implementation
practices,
inspection
findings and
emerging risks.
Article [49] The Commission Commission Monitoring, Data, Digital
may support and requesting public service
Commission
monitor national information
Enforcement
Support and competent
authorities in the
Monitoring
enforcement of
this section, by
taking actions
such as requesting
EN 50 EN
information and
records and
running training
exercises.
Article [52] AI models in Commission, Monitoring, Data, Digital
Advisory Group on biological Member State access to data, public service
applications. The authorities, Technical
Biosecurity
Commission, Actors in the guidelines
based on advice supply chain
by the Advisory
Group on
Biosecurity, and
where appropriate,
in cooperation
with the Steering
Group, may issue
and regularly
update guidance,
to assist actors in
the supply chain
and the competent
authorities, and to
facilitate
cooperation
between them.
Article [53] The Commission Commission, Monitoring Data
Biological Systemic shall monitor Member State systemic risk
systemic risk from authorities
Risk
AI models in
biological
applications and
propose mitigating
actions, based on
advice provided
by the Scientific
Panel, including
boosting
biodefense
capabilities or
regulation,
including on
assessment and
mitigation of
systemic risk from
those models, as
appropriate.
Article [54] information on Commission, Information Data
how to exchange Member State
EN 51 EN
Monitoring and relevant authorities exchange
Guidance information
between
competent
authorities,
national contact
points and among
Member States;
Article [55] The Steering Commission, Information Data, Digital
Coordination on Group in Member State exchange, Public Service
Biosecurity and cooperation with authorities Technical
Biosafety the Commission, Guidelines
facilitates
coordination and
information
exchange on
emerging AI-
enabled bio-risks;
Article [56] ‘regulatory Commission, Technical Data
Amendments to sandbox’ means a Member State documentation,
Regulation (EC) No controlled authorities Information
178/2002 (General environment Exchange
Food Law): Article where participants
3 can test innovative
products or
substances and
related processes
as well as data and
other regulatory
requirements at a
pre-market stage
under a set of
defined rules and
monitoring and for
a limited period of
time.
Article [56] Regulatory Member Facilitating the Technologies,
Amendments to sandboxes may be States development, Data
Regulation (EC) No established in testing, and
178/2002 (General relation to the validation of
Food Law): Article following: (a) all technologies;
49a (3)General stages of the Testing data
provisions on production, requirements
regulatory processing and
sandboxes distribution of Testing
food with the alternative
exception of regulatory
novel foods, and requirements
EN 52 EN
also of the feed (such as digital
produced for, or labelling
fed to food- instead of
producing actual labels on
animals; (b) food food products).
contact materials,
with the
exception of
plastic recycled
materials; (c)
products, other
than food and
feed, containing
or consisting of
genetically
modified
organisms as
defined in Article
2, point (2), of
Directive
2001/18/EC,
excluding
organisms
obtained through
the techniques of
genetic
modification
listed in Annex I
B to Directive
2001/18/EC. The
making available
of products within
a regulatory
sandbox shall not
be regarded as
placing on the
market.
Regulatory
sandboxes shall
have the following
objectives:
(a) facilitating
the development,
testing and
validation of
technologies,
products and
substances before
they obtain
authorisation or
EN 53 EN
approval for
placing on the
market, where so
required by Union
law;
(b) testing data
requirements,
including the type
and design of
studies required
for conducting a
safety and/or
efficacy
assessment;
(c) testing
alternative
regulatory
requirements and
appraising their
performance as
regards the
attainment of the
objectives of the
applicable Union
sectoral law in
comparison to the
existing
requirements; in
the areas where
Union law
provides for an
approval or
authorisation, as
well as in the area
of food
information to
consumers
Article [56] ‘regulatory Commission, Technical Data
Amendments to sandbox’ means a Member State documentation,
Regulation (EC) No controlled authorities Information
178/2002 (General environment Exchange
Food Law): Article where participants
3 can test innovative
products or
substances and
related processes
as well as data and
other regulatory
requirements at a
EN 54 EN
pre-market stage
under a set of
defined rules and
monitoring and for
a limited period of
time.
Article [56] Regulatory Member Facilitating the Technologies,
Amendments to sandboxes may be States development, Data
Regulation (EC) No established in testing, and
178/2002 (General relation to the validation of
Food Law): Article following: (a) all technologies;
49a (3)General stages of the
Testing data
provisions on production, requirements
regulatory processing and
sandboxes distribution of Testing
food with the alternative
exception of regulatory
novel foods, and requirements
also of the feed (such as digital
produced for, or labelling
fed to food- instead of
producing actual labels on
animals; (b) food food products).
contact materials,
with the
exception of
plastic recycled
materials; (c)
products, other
than food and
feed, containing
or consisting of
genetically
modified
organisms as
defined in Article
2, point (2), of
Directive
2001/18/EC,
excluding
organisms
obtained through
the techniques of
genetic
modification
listed in Annex I
B to Directive
2001/18/EC. The
making available
EN 55 EN
of products within
a regulatory
sandbox shall not
be regarded as
placing on the
market.
Regulatory
sandboxes shall
have the following
objectives:
(a) facilitating
the development,
testing and
validation of
technologies,
products and
substances before
they obtain
authorisation or
approval for
placing on the
market, where so
required by Union
law;
(b) testing data
requirements,
including the type
and design of
studies required
for conducting a
safety and/or
efficacy
assessment;
(c) testing
alternative
regulatory
requirements and
appraising their
performance as
regards the
attainment of the
objectives of the
applicable Union
sectoral law in
comparison to the
existing
requirements; in
the areas where
Union law
EN 56 EN
provides for an
approval or
authorisation, as
well as in the area
of food
information to
consumers
Article [56] Member States Member Monitoring and Data
Amendments to shall monitor and States, Supervision,
Regulation (EC) No supervise the Commission Information
178/2002 (General operation of exchange
Food Law): Article regulatory
49a sandboxes that
they establish and
General provisions
ensure
on regulatory
compliance with
sandboxes
the regulatory
sandbox plan.
A participant to
an established
regulatory
sandbox shall
immediately
inform the
competent
authorities of the
Member State(s)
concerned if it
considers or has
reason to believe
that the conditions
of the regulatory
sandbox plan have
not been complied
with and/or there
are potential risks
to public health,
animal health or
welfare, plant
health or to the
environment,
which may
require the
revocation of the
regulatory
sandbox or the
amendment of the
regulatory
sandbox plan to
EN 57 EN
provide for
mitigating
measures.
Participants shall
also immediately
inform the
competent
authorities of any
other information
that concerns the
quality, safety or
efficacy of the
subject matter of
the relevant
regulatory
sandbox.
Member States
shall immediately
notify to the
Commission and,
where relevant, to
the Authority any
violation of the
conditions set out
in the regulatory
sandbox plan
and/or the
identification of
any potential risks
to public health,
animal health or
welfare, plant
health or to the
environment.
Member States
shall suspend or
revoke a
regulatory
sandbox at any
time on their own
motion, or at the
request of the
Commission in
accordance with
paragraph 9, in
either of the
following cases:
(a) the
requirements and
conditions
EN 58 EN
governing the
regulatory
sandbox plan are
not met; (b) where
necessary to
protect public
health, animal
health or welfare,
plant health or the
environment and
there is no
possibility for
effective
mitigation
measures.
Member States
shall inform the
Commission, the
Authority and the
other Member
States without
delay of the
suspension or
revocation of a
regulatory
sandbox and of the
reasons.
Where after the
setting up of a
regulatory
sandbox in their
territory, a
Member State
identifies risks to
public health,
animal health and
welfare, plant
health and to the
environment
which can be fully
mitigated by
amendments to the
regulatory
sandbox plan, it
shall communicate
to the
Commission, the
Authority and the
other Member
States the draft
EN 59 EN
amendments in
accordance with
the procedure laid
down in Article
49b.
Where the
Commission
considers that one
of the cases
referred to in
paragraph 7 is
fulfilled, it shall
immediately adopt
implementing
acts.in accordance
with the procedure
referred to in
Article 58(2)
requesting the
suspension or the
revocation of the
regulatory
sandbox
concerned.
However, in
emergencies, the
Commission may
provisionally
adopt an
implementing act
requesting the
suspension of the
regulatory
sandbox
concerned after
consulting the
Member State(s)
concerned and
informing the
other Member
States. As soon as
possible, and at
most within 10
working days, the
measure taken
shall be
confirmed,
amended or
revoked in
accordance with
EN 60 EN
the procedure
referred to in
Article 58(2) and
the reasons for the
Commission’s
decision shall be
made public
without delay.
A Member State
may prolong the
duration once of a
regulatory
sandbox for a
limited time where
this is justified by
the need to attain
the objective of
the specific
regulatory
sandbox at hand
and shall inform
the Commission,
the Authority and
the other Member
States thereof.
The Commission
may, by means of
implementing
acts, specify
common
principles or
practical
arrangements for
the establishment
and supervision of
regulatory
sandboxes,
including the
establishment of
sandboxes
involving several
Member States
pursuant to this
Article, Article
49b and 49c
.Those
implementing acts
shall be adopted in
accordance with
the procedure
EN 61 EN
referred to in
Article 58(2).
Where a Member
Article [56] Commission, Information Data
Amendments to State deems it EFSA, exchange
Regulation (EC) No appropriate to Member State
178/2002 (General establish a authorities
Food Law): Article regulatory
49b sandbox pursuant
to Article 49a, it
Establishment of
regulatory shall communicate
sandboxes at to the
national level Commission, the
Authority and the
other Member
States a draft
regulatory
sandbox plan 60
days prior to the
commencement
Article [56] Regulatory Commission, Monitoring, Data
Amendments to sandboxes shall Agency Information
Regulation (EC) No not affect the (EFSA), exchange
178/2002 (General enforcement and Member State
Food Law): Article monitoring authorities
49c responsibilities of
the competent
Other
authorities set out
responsibilities,
in Article 17 and in
monitoring and
other sectoral
reporting
legislation.
obligations
Participants, with
regarding
the exception of
regulatory
final consumers, in
sandboxes
particular the
operator that is the
developer of the
product or
substance
concerned, shall
remain liable under
applicable national
legislation for any
harm inflicted on
third parties as a
result from the
EN 62 EN
testing taking place
in the sandbox.
Member States
shall submit annual
reports to the
Commission on the
results from the
implementation of
regulatory
sandboxes,
including good
practices
developed, lessons
learnt and
recommendations
on their setup and,
where relevant, on
the application of
the relevant
sectorial Union
legislation. Those
reports shall be
made publicly
available by the
Commission.
The Authority
shall also ensure
the necessary
revisions of its
guidance where
relevant and
appropriate on the
basis of those
annual reports.
Article [58] Article 5: Biotechnology Submission of Data, Process
Amendments to Submission of an industry an application, automation,
Regulation (EU) No application actors, Information EU portal
536/2014 (‘Clinical through EU portal Commission, exchange,
Trials Regulation’) Article 6: Agency, access to
Assessment report Member application
by the reporting States
Member State—
Aspects covered
by Part I
Article 7:
Assessment report
EN 63 EN
- Aspects covered
by Part II
Article 8:
Decision on the
clinical trial by
Member States to
sponsor
Article 9: Persons
assessing the
application
Article 14c:
Coordinated
assessment for the
authorisation of
combined studies
Article 17:
Validation of an
application for the
authorisation of a
substantial
modification of an
aspect covered by
Part I of the
assessment report
Article 19:
Decision on the
substantial
modification of an
aspect covered by
Part I of the
assessment report
Article 20:
validation,
assessment and
decision regarding
a substantial
modification of an
aspect covered by
Part II of the
assessment report
Article 21:
Substantial
modification of
aspects covered by
Parts I and II of
the assessment
report
EN 64 EN
Article 25: Data
submitted in the
application dossier
Article [58] Sponsors shall Biotechnology Evaluation of Data
Amendments to evaluate AI industry AI models
Regulation (EU) No models or AI actors,
536/2014 (‘Clinical systems proposed Commission,
Trials to be used in the Agency,
Regulation’)/Article context of the Member
27e: Use of AI in lifecycle of the States
Clinical Trials
specific clinical
trial
Article 41:
Article [58] Biotechnology Reporting Data, EU
Amendments to Reporting of industry portal
Regulation (EU) No adverse events and actors,
536/2014 (‘Clinical serious adverse Commission,
Trials Regulation’) events by the Agency,
Articles 41 –46, 55, investigator to the Member
56-58, 79a sponsor States
regarding reporting Article 42:
requirements Reporting of
suspected
unexpected
serious adverse
reactions by the
sponsor to the
Agency
Article 43: Annual
reporting by the
sponsor to the
Agency
Article 44:
Assessment by
Member States
Article 46:
Reporting with
regard to auxiliary
medicinal
products
Article 48:
Monitoring
Article 52:
Reporting of
serious breaches
EN 65 EN
Article 55:
Investigator’s
brochure
Article 56:
Recording,
processing,
handling and
storage of clinical
trial information:
Article 57:
Clinical trial
master file
Article 58:
Archiving of the
clinical trial
master file
Article 79a:
Obligations as
regards Union
controls: Ensure
that the necessary
technical
assistance and the
available
documentation,
upon justified
request, is being
provided to the
Commission as
well as any other
support that the
Commission
requests
Article 81 is
Article [58] Commission, Reporting Data, digital
Amendments to amended: The Agency solution,
Regulation (EU) No sponsor shall (EMA), process
536/2014 (‘Clinical permanently Member automation,
Trials Regulation’) update in the EU States EU portal, EU
database database
information on
any changes to the
clinical trials
which are not
substantial
modifications but
are relevant for the
EN 66 EN
supervision of the
clinical trial. The
sponsor shall also
update the EU
portal to satisfy a
condition to which
an authorisation
decision is subject
to.
Article 93: Data
Article [58] Biotechnology Data protection Data
Amendments to protection: industry
Regulation (EU) No Sponsors shall actors,
536/2014 (‘Clinical comply with Commission,
Trials Regulation’) Regulation (EU) Agency,
2016/679 to Member
process personal States
data, including
data concerning
health, in the
public interest of
health in the
context of the
entire lifecycle of
a clinical trial,
from the
preparation of the
application for the
authorisation of
the clinical trial to
the end of the
archiving period
Article [59] Article 61 (2). Commission, Information Data
Amendments to Where a variation Member State exchange
Regulation (EU) as referred to in authorities,
2019/6 (Veterinary paragraph (1) Agency
Medicine Products affects the
Regulation) summary of
product
characteristics,
labelling or
package leaflet,
the marketing
authorisation
holder shall record
the change in the
product database
within 30 days
EN 67 EN
after its
implementation.
Article [59] ‘CHAPTER IX Commission, Technical Data
REGULATORY Member State documentation,
Amendments to
SANDBOX authorities Information
Regulation (EU)
Article 136a Exchange
2019/6 (Veterinary
Regulatory
Medicine Products
sandbox 5.After a
Regulation)
sandbox is
established, the
Agency shall:
a)develop and
make publicly
available technical
and scientific
requirements for
technologies,
methods or
products
developed under
the sandbox,
taking due account
of the potential
risks of thereof for
human and animal
health and the
environment;
Article [61]
The regulatory Member State Assessment of Data
Amendments to
sandbox shall aim authorities, innovations
Regulation (EC) No
to allow the Commission
2024/1938 Article
assessment of the
[39a] 3 innovations
SoHO regulatory referred to in
paragraph 1 in a
sandboxes
real-world
environment under
strict regulatory
supervision, to
ensure that the
necessary
evidence and data
is generated to
demonstrate their,
safety quality,
including
effectiveness in
view of their
distribution.
EN 68 EN
Article [61]
request Member State Data access, Data
Amendments to
information and authorities, information
Regulation (EC) No
data from holders developers, exchange,
2024/1398 of authorisations independent leveraging
of SoHO experts and information
Article [39a] 7a
preparations, researchers, published on
SoHO regulatory developers representatives the EU SoHO
sandboxes independent of healthcare platform (art
experts and professionals 74.3(b) of
researchers, and patients Regulation
representatives of (EU)2024/1938,
healthcare
professionals and
patients and may
engage with them
in preliminary
discussions;
Article [63] The national Commission, Information Data
Evaluation authorities and the Member State exchange
economic authorities,
operators shall, research
upon request, organisations,
provide the biotechnology
Commission with industry actors
any relevant
information they
have and that the
Commission may
need for its
assessment
pursuant to in
paragraph 1
Article [66] Member States Commission, Information Data, Digital
of and the Member exchange solution
Handling
Commission shall States
Confidential
ensure the
Information
protection of trade
and business
secrets and other
sensitive,
confidential and
classified
information
obtained and
processed in
application of this
Regulation,
EN 69 EN
including
recommendations
and measures to
be taken, in
accordance with
Union and
relevant national
law.
The Commission
and Member
States shall ensure
that classified
information
provided or
exchanged
pursuant to this
Regulation is not
downgraded or
declassified
without the prior
written consent of
the originator in
accordance with
relevant Union or
national law.
EN 70 EN
4.2. Data
High-level description of the data in scope
Type of data Reference to the Standard and/or specification
requirement(s) (if applicable)
Data required for testing and Article [3]1 Health N.A.
validation of biotechnology Biotechnology
products Strategic Projects
Article [4] 1 High
Impact Health
Biotechnology
Strategic Projects
Article [15] 2e
Networks of Health
Biotechnology
Clusters
Article [5]
Biotechnology
Development
Accelerator
Article [30] Strategic
Projects for
Biosimilars
Article [32]
Biotechnology
Testing Environments
for advanced
biotechnology
innovations
Article [33] 2
Biotechnology Data
Quality Accelerator
Article [59]
Amendments to
Regulation (EU)
2019/6 (Veterinary
Medicine Products
Regulation)
Article [61]
Amendments to
Regulation (EC) No
2024/1938/ Article
[39a] 3 SoHO
regulatory sandboxes
Article [49a] General
EN 71 EN
provisions on
regulatory sandboxes
Sensitive information, Article [16] Access N.A.
biotechnology datasets Principles and
Security Safeguards
Mapping of existing Article [17] Strategic N.A.
infrastructures Mapping of the
Union’s
Biotechnology
Ecosystem
Guidance on the use and Article [31] N.A.
deployment of AI Guidance on the
deployment and use
of systems based on
advanced
technologies
including AI Systems
in the Lifecycle of
Medicinal Products
Regulatory decisions, opinions, Article [35] 1 Union N.A.
recommendations Regulatory Status
Repository
Personal health data, clinical Article [58] N.A.
data Amendments to
Regulation (EU) No
536/2014 (‘Clinical
Trials Regulation’)
Cross-border surveillance of Article [41] One implementing
biological threats EU Biothreat Radar Act/Delegated Act foreseen
High Impact Projects
Article [42]
Biodefence capability
high impact strategic
project
Article [44]
Verification of
Legitimate Need
Article [46]
Prevention and
Reporting of Misuse
EN 72 EN
Article [48]
National Inspection
Authorities
Article [49]
Commission
Enforcement Support
and Monitoring
Article [52]
Advisory Group on
Biosecurity
Article [53]
Biological Systemic
Risk
Article [54]
Monitoring and
Guidance
Article [55]
Coordination on
Biosecurity and
Biosafety
Handling of confidential Article [66] Handling N.A.
information of Confidential
Information
Alignment with the European Data Strategy
Explanation of how the requirement(s) are aligned with the European Data Strategy
EN 73 EN
Article [33] Biotechnology Data Quality Accelerator High Impact Health Biotechnology
Strategic Projects will ensure that datasets are established, managed and processed in
accordance with applicable Union legislation on data governance, ethics and fundamental
rights, including Regulation (EU) 2025/327 [European Health Data Space], Regulation (EU)
2016/679 [General Data Protection Regulation].
Alignment with the once-only principle
Explanation of how the once-only principle has been considered and how the possibility to
reuse existing data has been explored
The legal provision allows for the reuse of data and evidence that has already been submitted
for the purposes of a first registration.
Explanation of how newly created data is findable, accessible, interoperable and reusable,
and meets high-quality standards
Through Union programmes and infrastructures, the Act promotes fair, reasonable and non-
discriminatory access to high-quality data resources for researchers, SMEs and public
institutions, thereby accelerating innovation while ensuring compliance with Union standards
on data protection, ethics and security.
Data flows
High-level description of the data flows
Type of data Reference(s) Actors who Actors who Trigger for Frequenc
to the provide the receive the the data y (if
requirement( data data exchange applicabl
s) e)
Data required Article [3]1 Biotechnolo Member Testing and N.A.
for testing and Health gy industry States, validation of
validation of Biotechnology actors, Commission, innovations
biotechnology Strategic Research Agencies
products Projects organization (EMA,
s EFSA)
Article [4] 1
High Impact
Health
Biotechnology
Strategic
Projects
Article [5]
Biotechnology
Development
Accelerator
Article [15]
2e Networks
EN 74 EN
of Health
Biotechnology
Clusters
Article [29]
Strategic
Projects for
Biosimilars
Article [32
Article [32]
Biotechnology
testing
environments
for advanced
biotechnology
innovations
Article [33]
Biotechnology
Data Quality
Accelerator
Article [56]
Amendments
to Regulation
(EC) No
178/2002
(General
Food Law):
Article [49a]
General
Article [59]
Amendments
to Regulation
(EU) 2019/6
(Veterinary
Medicine
Products
Regulation)
Article [61]
Amendments
to Regulation
(EC) No
2024/1398/
Article [39a]
3 SoHO
regulatory
sandboxes
provisions on
regulatory
EN 75 EN
sandboxes
Reuse of Article [11] Biotechnolo Member permit-
existing data Single Points gy industry States, granting
of Contact actors, Commission process for
Research strategic
organization biotechnology
s projects and
high impact
biotechnology
projects
Guidance on Article [31] Member Biotechnolo Guidance for
the use and Guidance on States, gy industry biotechnology
deployment of the Agency actors, industry actors
AI deployment (EMA), Research and research
and use of Commission organization organizations
systems based s on the
on advanced deployment
technologies and use of AI
including AI, systems and
in the general
Lifecycle of purpose AI
Medicinal models in the
Products lifecycle of
medicinal
product
development
Regulatory Article [35] 1 Member Biotechnolo Repository
decisions, Union States, gy industry will assist
opinions, Regulatory Agency actors, developers in
recommendatio Status (EMA), Research navigating
ns Repository Commission organization cases of novel
s biotechnology
health
biotechnology
products
Personal health Article [58] Biotechnolo Member Submission of
data, clinical Amendments gy industry States, clinical trial
data to Regulation actors, Agency
(EU) No Research (EMA)
536/2014 organization Commission
(‘Clinical s
Trials
Regulation’)
Cross-border Article [41] Biotechnolo Member Detection,
surveillance of EU Biothreat gy industry States, characterisatio
biological actors, n,
EN 76 EN
threats Radar High Research Commission identification,
Impact organization analysis and
Projects s assessment of
biological
Article [42]
threats
Biodefence
capability
high impact
strategic
project
Article [44]
Verification of
Legitimate
Need
Article [46]
Prevention
and Reporting
of Misuse
Article [48]
National
Inspection
Authorities
Article [49]
Commission
Enforcement
Support and
Monitoring
Article [52]
Advisory
Group on
Biosecurity
Article [53]
Biological
Systemic Risk
Article [54]
Monitoring
and Guidance
Article [55]
Coordination
on Biosecurity
and Biosafety
Handling of Article [66] Member Biotechnolo Information
EN 77 EN
confidential Handling of States, gy industry acquired in the
information Confidential Commission actors, course of
Information Research regulation,
organization trade and
s business
secrets
4.3. Digital solutions
High-level description of digital solutions
How is How is Use of AI
Reference(s Main
accessibil reusabilit technolog
Digital ) to the mandated Responsib
ity y ies (if
solution requiremen functionalit le body
catered considere applicabl
t(s) ies
for? d? e)
Biotechnol Article [32] Developme Commissi Yes
ogy testing Biotechnolo nt of trusted on,
environmen gy testing testing Member
ts for environment environmen States
advanced s for ts
biotechnolo advanced biotechnolo
gy biotechnolog gy
innovations y innovations
innovations
- high-
impact
biotechnolog
y strategic
projects
For each digital solution, explanation of how the digital solution complies with applicable
digital policies and legislative enactments
Digital solution #1: Biotechnology testing Environments for advanced biotechnology
innovations
Digital and/or Explanation on how it aligns
sectorial policy
(when these are
applicable)
AI Act Development and testing of AI
enabled biotechnology solutions
is in line with Article 51. It
ensures that these systems fulfil
the obligations set out in
EN 78 EN
Articles 53-55 of the act.
EU Cybersecurity Article 10 “Access Principles
framework and Security Safeguards”
provides that health
biotechnology strategic projects,
high impact biotechnology
strategic projects, and any other
entities operating infrastructures,
facilities and services established
or supported in accordance with
this Regulation shall ensure that
access to and the operation of
their infrastructures, facilities
and services complies, where
applicable, with Directive (EU)
2022/2555 of the European
Parliament and of the Council
(NIS2 Directive), including the
relevant cybersecurity risk-
management and reporting
obligations.
eIDAS Individuals and organisations
will use electronic identification
in line with EU legislation.
Single Digital N.A.
Gateway and IMI
Others
4.4. Interoperability assessment
High-level description of the digital public service(s) affected by the requirements
Digital public Description Reference(s) to Interoperable Other
service or the Europe Solution(s) interoperability
category of requirement(s) solution(s)
digital public (NOT
services APPLICABLE)
Biotechnology Biotechnology Article [33] //
Data Quality Data Quality Biotechnology
Accelerator Accelerator, Data Quality
aimed at Accelerator
improving data
EN 79 EN
quality at
source,
enhancing
interoperability
and annotation,
and fostering
the creation,
curation,
maintenance
and use of
shared datasets
for the
development
and refinement
of AI systems
and models in
health
biotechnology.
Category of //
digital public
services
according to
COFOG #1
EN 80 EN
Impact of the requirement(s) as per digital public service on cross-border interoperability
Digital public service #1 Biotechnology Data Quality Accelerator
Assessment Measure(s) Potential remaining barriers (if
applicable)
Alignment with The Biotechnology Data N.A.
existing digital and Quality Accelerator will
sectorial policies operate in accordance with
applicable Union legislation
Please list the
on data governance, ethics
applicable digital and
and fundamental rights,
sectorial policies
including Regulation (EU)
identified
2025/327 [European Health
Data Space], Regulation
(EU) 2016/679 [General
Data Protection
Regulation].
It will support, where N.A.
Organisational
measures for a smooth appropriate, the integration
cross-border digital of these datasets into Union
public services infrastructures, including
delivery the European Health Data
Please list the Space, European Research
governance measures Area data spaces, or other,
foreseen including the infrastructures
operated by high impact
health biotechnology
strategic projects.
Datasets, or the metadata N.A.
Measures taken to
and reference annotations
ensure a shared
thereof, will be available
understanding of the
under fair, reasonable and
data
non-discriminatory
Please list such conditions, ensuring
measures equitable access for users
including research
organisations, SMEs and
public institutions.
It will contribute to the N.A.
Use of commonly
agreed open technical development of Union
specifications and standards and quality
standards frameworks for data
Please list such representativeness,
measures provenance, interoperability
EN 81 EN
and annotation in
biotechnology
EN 82 EN
4.5. Measures to support digital implementation
High-level description of measures supporting digital implementation
Description of the Reference(s) to the Commission Actors to be Expected
measure requirement(s) role involved timeline
(if applicable) (if applicable) (if
applicable)
Adopting guidelines Article [4] High Commission Agency (EMA,
Impact Health will produce EFSA),
Biotechnology guidelines or Advisory
Strategic Projects will be Groups
involved in composed of
Article [14]
the Member State
Financial and
production of Representatives
technical support
guidelines
Article [15]
Networks of Health
Biotechnology
Clusters
Article [39]
Regulatory
Sandboxes provided
for in the applicable
frameworks and
Cross Framework
Communication
Article [58]
Amendments to
Regulation (EU) No
536/2014 (‘Clinical
Trials Regulation’):
• Article 37:
End of a
clinical trial,
temporary
halt and early
termination
of a clinical
trial and
submission
of the results
• Article 47:
Compliance
with the
protocol and
good clinical
EN 83 EN
practice
• Article 63:
Manufacturin
g and import
• Article 85:
Clinical
Trials
Coordination
and Advisory
Group
Designing policy Article [15] Commission Member States,
implementation Networks of Health will Biotechnology
pilots Biotechnology participate Industry actors,
Clusters through the Research
Steering organizations
Group
Sandboxing Article [39] Commission Member States
Regulatory shall
sandboxes provided encourage
for in the applicablesetting up
frameworks and regulatory
cross-framework sandboxes for
communication AI
biotechnology
Article [40]
solutions,
Regulatory
Substances of
sandboxes or novel
health biotechnology Human
Origin
products not falling
under other
sandboxes in Union
legislation
Article [58]
Amendments to
Regulation (EU) No
536/2014 (‘Clinical
Trials
Regulation’)/Article
85: Clinical Trials
Coordination and
Advisory Group
Article [59]
Amendments to
Regulation (EU)
2019/6 (Veterinary
Medicine Products
Regulation) Article
136a: Regulatory
EN 84 EN
sandbox
Article [61]
Amendment to
Regulation (EU)
2024/1938
(SoHO)/Article 39a:
SOHO regulatory
sandboxes
EN 85 EN
EUROPEAN
COMMISSION
Strasbourg, 16.12.2025
COM(2025) 1022 final
ANNEXES 1 to 3
ANNEXES
to the
Proposal for a
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on establishing a framework of measures for strengthening Union’s biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations
(EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795
and (EU) 2024/1938 (European Biotech Act)
{SWD(2025) 1055 final}
EN EN
ANNEX I
Biotechnology Products of Concern
1. Benchtop nucleic acid synthesis equipment
Any instrument designed, marketed or configured to de novo synthesise nucleic acids
(DNA, RNA) or their base-pairing analogues, including LNA, PNA and XNA, by
chemical or enzymatic means for use by an individual user, laboratory or facility.
2. Sequences of concern
Molecules of polymeric nucleic acids that have been synthesized de novo (without
template), including single- or double-stranded RNA or DNA that is at least 50
nucleotides in length, or the corresponding amino acid sequence of at least 17 amino
acids, and meets at least one of the following criteria:
(a) is an exact match or best match to a sequence of an agent listed on
internationally recognised control lists that is either (i) specific to any listed
virus or (ii) specific to any listed bacterium that, in itself or through its
transcribed or translated products represents a significant hazard to human,
animal or plant health. This criterion shall exclude cases where the matched
sequence is a non-harmful element demonstrably present in an unregulated
agent, including housekeeping genes without pathogenic function;
(b) is reasonably expected, based on international standards, current scientific
evidence and industry best practices for predicting biological function from
sequence, to increase a biological agent's ability to be used to deliberately
cause disease or death, by contributions to pathogenicity, toxicity, or other
criteria, even if not derived from a listed agent;
(c) has the potential to be assembled into a sequence that is at least 200 nucleotides
in length and meets point (a) or (b) if combined with other synthetic nucleic
acids supplied by the same economic operator to that customer in a bulk order
or across multiple orders over the previous12 months.
EN 1 EN
ANNEX II
Annexes to Regulation (EU) 536/2014 are amended as follows:
(1) Annex I is replaced by the following:
‘Annex I
Part I
A. INTRODUCTION AND GENERAL PRINCIPLES
1. The sponsor shall, where appropriate, refer to any previous applications. If
these applications have been submitted by another sponsor, the written
agreement from that sponsor shall be submitted.
2. Where a clinical trial has more than one sponsor, detailed information of the
responsibilities of each of the sponsors shall be submitted in the application
dossier.
3. The application shall be signed by the sponsor or a representative of the
sponsor. This signature confirms that the sponsor is satisfied that:
(a) the information provided is complete;
(b) the attached documents contain an accurate account of the information
available;
(c) the clinical trial is to be conducted in accordance with the protocol; and
(d) the clinical trial is to be conducted in accordance with this Regulation.
4. The application dossier for an application limited to Part I of the assessment
report referred to in Article 11 shall be limited to sections B to J and Q of this
Annex.
5. (deleted)
B. COVER LETTER
6. The cover letter shall specify the EU trial number and the universal trial
number and shall draw attention to any features which are particular to the
clinical trial.
7. However, in the cover letter it is not necessary to reproduce information
already contained in the EU application form, with the following exceptions:
(a) specific features of the clinical trial population, such as subjects not able
to give informed consent, minors and pregnant or breastfeeding women;
(b) whether the clinical trial involves the first administration of a new active
substance to humans;
(c) whether scientific advice relating to the clinical trial or the
investigational medicinal product has been given by the Agency, a
Member State or a third country;
(d) whether the clinical trial is part or is intended to be part of a Paediatric
Investigation Plan (PIP) as referred to in Title II, Chapter 3, of
Regulation (EC) No 1901/2006 (if the Agency has already issued a
decision on the PIP, the cover letter contains the link to the decision of
the Agency on its website);
EN 2 EN
(e) whether investigational medicinal products or auxiliary medicinal
products are a narcotic, psychotropic or radiopharmaceutical;
(f) whether the investigational medicinal products consist of or contain a
genetically-modified organism or organisms;
(fbis) whether the investigational medicinal products consist or contain
genetically-modified organism(s) and, where applicable, whether they
fall within one or more of the categories listed in Article 4a(1), points (a)
to (d), of Regulation(EC) No 1394/2007;
(g) whether the sponsor has obtained an orphan designation for the
investigational medicinal product for an orphan condition;
(h) a comprehensive list, including the regulatory status, of all
investigational medicinal products and a list of all auxiliary medicinal
products; and
(i) a list of medical devices which are to be investigated in the clinical trial
but which are not part of the investigational medicinal product or
products, together with a statement as to whether the medical devices are
CE-marked for the intended use.
8. The cover letter shall indicate where the information listed in paragraph 7 is
contained in the application dossier.
9. The cover letter shall indicate if the clinical trial is considered by the sponsor to
be a minimal or low-intervention clinical trial and shall contain a detailed
justification thereof.
10. The cover letter shall indicate if the methodology of the clinical trial requires
that groups of subjects rather than individual subjects are allocated to receive
different investigational medicinal products in a clinical trial, and as a
consequence whether informed consent will be obtained by simplified means.
11. The cover letter shall indicate the location in the application dossier of the
information necessary for assessing whether an adverse reaction is a suspected
unexpected serious adverse reaction, that is the reference safety information.
12. In the case of a resubmission, the cover letter shall specify the EU trial number
for the previous clinical trial application, highlight the changes as compared to
the previous submission and, if applicable, specify how any unresolved issues
in the first submission have been addressed.
12a. The cover letter shall include a summary of the activities that are planned to
conduct outside traditional trial sites, enabled by digital technologies, remote
procedures, and alternative delivery models in clinical trials.
C. EU APPLICATION FORM
13. The EU application form duly completed.
D. PROTOCOL
14. The protocol shall describe the objective, design, methodology, statistical
considerations, purpose and organisation of the clinical trial.
15. The protocol shall be identified by:
(a) the title of the clinical trial;
EN 3 EN
(b) the EU trial number;
(c) the sponsor's protocol code number specific for all versions of it (if
relevant);
(d) the date and number of the version, to be updated when it is amended;
(e) a short title or name assigned to the protocol; and
(f) the name and address of the sponsor, as well as the name and function of
the representative or representatives of the sponsor authorised to sign the
protocol or any substantial modification to the protocol.
16. The protocol shall, when possible, be written in an easily accessible and
searchable format, rather than scanned images.
17. The protocol shall at least include:
(a) a statement that the clinical trial is to be conducted in compliance with
the protocol, with this Regulation and with the principles of good clinical
practice;
(b) a comprehensive list of all investigational medicinal products and of all
auxiliary medicinal products;
(c) a summary of findings from non-clinical studies that potentially have
clinical significance and from other clinical trials that are relevant to the
clinical trial;
(d) a summary of the known and potential risks and benefits including an
evaluation of the anticipated benefits and risks to allow assessment in
accordance with Article 6; for subjects in a clinical trial in an emergency
situation, the scientific grounds for expecting that the participation of the
subjects has the potential to produce a direct clinically relevant benefit
shall be documented;
(e) where patients were involved in the design of the clinical trial, a
description of their involvement;
(f) a description of, and justification for, the dosage, the dosage regime, the
route and mode of administration, and the treatment period for all
investigational medicinal products and auxiliary medicinal products;
(g) a statement of whether the investigational medicinal products and
auxiliary medicinal products used in the clinical trial are authorised; if
authorised, whether they are to be used in the clinical trial in accordance
with the terms of their marketing authorisations, and, if not authorised, a
justification for the use of non-authorised auxiliary medicinal products in
the clinical trial;
(h) a description of the groups and subgroups of the subjects participating in
the clinical trial, including, where relevant, groups of subjects with
specific needs, for example. age, gender, participation of healthy
volunteers, subjects with rare and ultra rare diseases;
(i) references to literature and data that are relevant to the clinical trial, and
that provide background for the clinical trial;
(j) a discussion of the relevance of the clinical trial in order to allow
assessment in accordance with Article 6;
EN 4 EN
(k) a description of the type of clinical trial to be conducted and a discussion
of the trial design (including a schematic diagram of trial design,
procedures and stages, if relevant);
(l) a specification of the primary end-points and the secondary endpoints, if
any, to be measured during the clinical trial;
(m) a description of the measures taken to minimise bias, including, if
applicable, randomisation and blinding;
(n) a description of the expected duration of subject participation and a
description of the sequence and duration of all clinical trial periods,
including follow-up, if relevant;
(o) a clear and unambiguous definition of the end of the clinical trial in
question and, if it is not the date of the last visit of the last subject, a
specification of the estimated end date and a justification thereof;
(p) a description of the criteria for discontinuing parts of the clinical trial or
the entire clinical trial;
(q) arrangements for the maintenance of clinical trial treatment
randomisation codes and procedures for breaking codes, if relevant;
(r) a description of procedures for the identification of data to be recorded
directly on the Case Report Forms considered as source data;
(s) a description of the arrangements to comply with the applicable rules for
the collection, storage and future use of biological samples from clinical
trial subjects, where applicable, unless contained in a separate document;
(t) a description of the arrangements for tracing, storing, destroying and
returning the investigational medicinal product and unauthorised
auxiliary medicinal product in accordance with Article 51;
(u) a description of the statistical methods to be employed, including, if
relevant:
– timing of any planned interim analysis and the number of subjects
planned to be enrolled;
– reasons for choice of sample size;
– calculations of the power of the clinical trial and clinical relevance;
– the level of significance to be used;
– criteria for the termination of the clinical trial;
– procedures for accounting for missing, unused, and spurious data
and for reporting any deviation from the original statistical plan;
and
– the selection of subjects to be included in the analyses;
(v) a description of the subject inclusion and exclusion criteria, including
criteria for withdrawing individual subjects from treatment or from the
clinical trial;
(w) a description of procedures relating to the withdrawal of subjects from
treatment or from the clinical trial including procedures for the collection
EN 5 EN
of data regarding withdrawn subjects, procedures for replacement of
subjects and the follow-up of subjects that have withdrawn from
treatment or from the clinical trial;
(x) a justification for including subjects who are incapable of giving
informed consent or other special populations, such as minors;
(y) a justification for the gender and age allocation of subjects and, if a
specific gender or age group is excluded from or underrepresented in the
clinical trials, an explanation of the reasons and justification for these
exclusion criteria;
(z) a detailed description of the recruitment and informed consent procedure,
especially when subjects are incapable of giving informed consent;
(aa) a description of the treatments, including medicinal products, which are
permitted or not permitted, before or during the clinical trial;
(ab) a description of the accountability procedures for the supply and
administration of medicinal products to subjects including the
maintenance of blinding, if applicable;
(ac) a description of procedures for monitoring subject compliance, if
applicable;
(ad) a description of arrangements for monitoring the conduct of the clinical
trial;
(ae) a description of the arrangements for taking care of the subjects after
their participation in the clinical trial has ended, where such additional
care is necessary because of the subjects' participation in the clinical trial
and where it differs from that normally expected for the medical
condition in question;
(af) a specification of the efficacy and safety parameters as well as the
methods and timing for assessing, recording, and analysing these
parameters;
(ag) a description of ethical considerations relating to the clinical trial if those
have not been described elsewhere;
(ah) a statement from the sponsor (either in the protocol or in a separate
document) confirming that the investigators and institutions involved in
the clinical trial are to permit clinical trial- related monitoring, audits and
regulatory inspections, including provision of direct access to source data
and documents;
(ai) a description of the publication policy;
(aj) duly substantiated reasons for the submission of the summary of the
results of the clinical trials after more than one year;
(ak) a description of the arrangements to comply with the applicable rules on
the protection of personal data; in particular organisational and technical
arrangements that will be implemented to avoid unauthorised access,
disclosure, dissemination, alteration or loss of information and personal
data processed;
EN 6 EN
(al) a description of measures that will be implemented to ensure
confidentiality of records and personal data of subjects;
(am) a description of measures that will be implemented in case of data
security breach in order to mitigate the possible adverse effects.
(an) justification of allowing for a direct delivery to subject of an
investigational medicinal products;
(ao) a detailed description of the management of investigational or auxiliary
medicinal products delivered directly to the subject (‘direct delivery to
subject’) shall be provided, including aspects of privacy protection and
confidentiality. Information shall be included on ensuring that the
product reaches the intended recipient (e.g., the participant or their
designee) and on maintaining the integrity and quality of the medicinal
product (e.g., blinding, storage) throughout the supply chain
(ap) a justification for inclusion of subjects that can only provide an informed
consent through electronic means shall be provided.
(aq) if the sponsor used an AI tool, a clear explanation of the specific purpose
of the use of that tool and a description of the processes in which it is
used. If an AI tool is certified according to Regulation (EU) 2024/1689
laying down harmonised rules on artificial intelligence, the sponsor shall
provide the information contained in the certificate.
18. If a clinical trial is conducted with an active substance available in the Union
under different trade names in a number of authorised medicinal products, the
protocol may define the treatment in terms of the active substance or
Anatomical Therapeutic Chemical (ATC) code (level 3-5) only and not specify
the trade name of each product.
19. With regard to the notification of adverse events, the protocol shall identify the
categories of:
(a) adverse events or laboratory anomalies that are critical to safety
evaluations and must be reported by the investigator to the sponsor, and
(b) serious adverse events which do not require immediate reporting by the
investigator to the sponsor.
20. The protocol shall describe the procedures for:
(a) eliciting and recording adverse events by the investigator, and the
reporting of relevant adverse events by the investigator to the sponsor;
(b) reporting by the investigator to the sponsor of those serious adverse
events which have been identified in the protocol as not requiring
immediate reporting;
(c) reporting of suspected unexpected serious adverse reactions by the
sponsor to the Eudravigilance database; and
(d) follow-up of subjects after adverse reactions including the type and
duration of follow-up.
21. In case the sponsor intends to submit a single safety report on all
investigational medicinal products used in the clinical trial in accordance with
Article 43(2), the protocol shall indicate the reasons thereof.
EN 7 EN
22. Issues regarding labelling and the unblinding of investigational medicinal
products shall be addressed in the protocol, where necessary.
23. The protocol shall be accompanied by the Charter of the Data Safety
Monitoring Committee, if applicable.
24. The protocol shall be accompanied by a synopsis of the protocol.
E. INVESTIGATOR'S BROCHURE (IB)
25. An IB, which has been prepared in accordance with the state of scientific
knowledge and international guidance, shall be submitted.
26. The purpose of the IB is to provide the investigators and others involved in the
clinical trial with information to facilitate their understanding of the rationale
for, and their compliance with, key features of the protocol, such as the dose,
dose frequency/interval, methods of administration, and safety monitoring
procedures.
27. The information in the IB shall be presented in a concise, simple, objective,
balanced and non-promotional form that enables a clinician or investigator to
understand it and make an unbiased risk-benefit assessment of the
appropriateness of the proposed clinical trial. It shall be prepared from all
available information and evidence that
supports the rationale for the proposed clinical trial and the safe use of the
investigational medicinal product in the clinical trial and be presented in the
form of summaries.
28. If the investigational medicinal product is authorised, and is used in accordance
with the terms of the marketing authorisation, the approved summary of
product characteristics (SmPC) shall be the IB. If the conditions of use in the
clinical trial differ from those authorised, the SmPC shall be supplemented
with a summary of relevant non-clinical and clinical data that support the use
of the investigational medicinal product in the clinical trial. Where the
investigational medicinal product is identified in the protocol only by its active
substance, the sponsor shall select one SmPC as equivalent to the IB for all
medicinal products that contain that active substance and are used at any
clinical trial site.
29. For a multinational clinical trial where the medicinal product to be used in each
Member State concerned is authorised at national level, and the SmPC varies
among Member States concerned, the sponsor shall choose one SmPC for the
whole clinical trial. This SmPC shall be the one best suited to ensure patient
safety.
30. If the IB is not an SmPC, it shall contain a clearly identifiable section called the
‘Reference Safety Information’ (RSI). In accordance with paragraphs 10 and
11 of Annex III, the RSI shall contain product information on the
investigational medicinal product and on how to determine what adverse
reactions are to be considered as expected adverse reactions, and on the
frequency and nature of those adverse reactions.
EN 8 EN
F. DOCUMENTATION RELATING TO COMPLIANCE WITH GOOD
MANUFACTURING PRACTICE (GMP) FOR THE INVESTIGATIONAL
MEDICINAL PRODUCT
31. As regards documentation relating to GMP compliance, the following shall
apply.
32. No documentation needs to be submitted where the investigational medicinal
product is authorised and is not modified, whether or not it is manufactured in
the Union.
33. If the investigational medicinal product is not authorised, and does not have a
marketing authorisation from a third country that is party to the International
Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH), and is not manufactured in the Union,
the following documentation shall be submitted:
(a) a copy of the authorisation referred to in Article 61; and
(b) certification by the qualified person in the Union that the manufacturing
complies with GMP at least equivalent to the GMP in the Union, unless
there are specific arrangements provided for in mutual recognition
agreements between the Union and third countries.
34. In all other cases, a copy of the authorisation referred to in Article 61 shall be
submitted.
35. For processes related to investigational medicinal products set out in Article
61(5), which are not subject to an authorisation in accordance with Article 61,
documentation to demonstrate compliance with the requirements referred to in
Article 61(6) shall be submitted.
G. INVESTIGATIONAL MEDICINAL PRODUCT DOSSIER (IMPD)
36. The IMPD shall give information on the quality of any investigational
medicinal product, the manufacture and control of the investigational medicinal
product, and data from non-clinical studies and from its clinical use.
36bis. Where applicable, in the case of advanced therapy investigational medicinal
products, a declaration of the sponsor, in accordance with Article 4a(2) of
Regulation (EC) No 1394/2007.
36.1. Data relating to the investigational medicinal product
Introduction
37. Regarding data, the IMPD may be replaced by other documentation which may
be submitted alone or with a simplified IMPD. The details of this ‘simplified
IMPD’ are set out in section 1.2 ‘Simplified IMPD by referring to other
documentation’.
38. Each section of the IMPD shall be prefaced with a detailed table of contents
and a glossary of terms.
39. The information in the IMPD shall be concise. The IMPD must not be
unnecessarily voluminous. It is preferable to present data in tabular form
accompanied by a brief narrative highlighting the main salient points.
Quality data
EN 9 EN
40. Quality data shall be submitted in a logical structure such as that of Module 3
of the ICH Common Technical Document format.
Non-clinical pharmacology and toxicology data
41. The IMPD shall also contain summaries of non-clinical pharmacology and
toxicology data for any investigational medicinal product used in the clinical
trial in accordance with international guidance. It shall contain a reference list
of studies conducted and appropriate literature references. Wherever
appropriate, it is preferable to present data in tabular form accompanied by a
brief narrative highlighting the main salient points. The summaries of the
studies conducted shall allow an assessment of the adequacy of the study and
whether the study has been conducted according to an acceptable protocol.
42. Non-clinical pharmacology and toxicology data shall be submitted in a logical
structure, such as that of Module 4 of the ICH Common Technical Document
format.
43. The IMPD shall provide a critical analysis of the data, including justification
for omissions of data, and an assessment of the safety of the product in the
context of the proposed clinical trial rather than a mere factual summary of the
studies conducted.
44. The IMPD shall contain a statement of the good laboratory practice status or
equivalent standards, as referred to in Article 25(3).
45. The test material used in toxicity studies shall be representative of that of the
clinical trial use in terms of qualitative and quantitative impurity profiles. The
preparation of the test material shall be subject to the controls necessary to
ensure this and thus support the validity of the study.
▼B
Data from previous clinical trials and human experience
46. Data from previous clinical trials and human experience shall be submitted in a
logical structure, such as that of Module 5 of the ICH Common Technical
Document format.
47. This section shall provide summaries of all available data from previous
clinical trials and human experience with the investigational medicinal
products.
It shall also contain a statement of the compliance with good clinical practice
of those previous clinical trials, as well as a reference to the public entry
referred to in Article 25(6).
Overall risk and benefit assessment
48. This section shall provide a brief integrated summary that critically analyses
the non-clinical and clinical data in relation to the potential risks and benefits
of the investigational medicinal product in the proposed clinical trial unless this
information is already provided in the protocol. In the latter case, it shall cross-
refer to the relevant section in the protocol. The text shall identify any studies
that were terminated prematurely and discuss the reasons. Any evaluation of
foreseeable risks and anticipated benefits for studies on minors or incapacitated
adults shall take account of the specific provisions set out in this Regulation.
EN 10 EN
49. Where appropriate, safety margins shall be discussed in terms of relative
systemic exposure to the investigational medicinal product, preferably based on
‘area under the curve’ (AUC) data, or peak concentration (Cmax) data,
whichever is considered more relevant, rather than in terms of applied dose.
The clinical relevance of any findings in the non-clinical and clinical studies
along with any recommendations for further monitoring of effects and safety in
the clinical trials shall also be discussed.
49.1. Simplified IMPD by referring to other documentation
50. The applicant may refer to other documentation submitted alone or with a
simplified IMPD.
Possibility of referring to the IB
51. The applicant may either provide a stand-alone IMPD or cross-refer to the IB
for the reference safety information and the summaries of pre- clinical and
clinical parts of the IMPD. In the latter case, the summaries of pre-clinical
information and clinical information shall include data, preferably in tables,
providing sufficient detail to allow assessors to reach a decision on the
potential toxicity of the investigational medicinal product and the safety of its
use in the proposed clinical trial. If there is some special aspect of the pre-
clinical data or clinical data that requires a detailed expert explanation or
discussion beyond what would usually be included in the IB, the pre-clinical
and clinical information shall be submitted as part of the IMPD.
Possibility of referring to the SmPC
52. The applicant may submit the version of the SmPC valid at the time of
application, as the IMPD if the investigational medicinal product is authorised.
The exact requirements are detailed in Table 1. Where new data are provided,
it should be clearly identified.
EN 11 EN
▼B
Table 1: Content of the simplified IMPD
Quality data Non-clinical Clinical
Types of previous assessment
data data
The investigational medicinal
product is authorised or has a
marketing authorisation in an
ICH country and is used in the
SmPC
clinical trial:
SmPC If appropriate If appropriate
— within the conditions of the
P+A SmPC SmPC
SmPC
— outside
Another pharmaceutical
the conditionsform or SmPC+P+A Yes
of the Yes
strength
SmPC of the investigational
medicinal
— after product is authorised
modification (for
or has a marketing
example blinding)authorisation
in an ICH country and the
investigational medicinal
The investigational medicinal
product is supplied by the
product is not authorised and
marketing authorisation holder
has no marketing authorisation
in an ICH country but the active
substance is contained in an
authorised medicinal product, SmPC+P+A Yes Yes
and
SmPC+S+P+ Yes Yes
— is supplied by the same A
Themanufacturer
investigational medicinal
product
— is was subject
supplied to a
by another
previous
manufacturerclinical trial
application and authorised in at
least 2 Member States and has Reference to previous submission
not been modified, and
— no new data are available New data New data New data
since last amendment to the
clinical trial application,
— new data are available since If appropriate If appropriate If appropriate
(S: Data relating last
to the amendment
active substance;to P:the
Data relating to the investigational medicinal product; A:
clinical trial application,
Additional information on Facilities and Equipment, Adventitious Agents Safety Evaluation, Novel
Excipients, and
—Solvents
is usedfor Reconstitution and Diluents)
under different
conditions
53. If the investigational medicinal product is defined in the protocol in terms of
active substance or ATC code (see above, paragraph 18), the applicant may
replace the IMPD by one representative SmPC for each active substance/active
substance pertaining to that ATC group. Alternatively, the applicant may
provide a collated document containing information equivalent to that in the
representative SmPCs for each active substance that could be used as an
investigational medicinal product in the clinical trial.
1.3. IMPD in cases of placebo
EN 12 EN
54. If the investigational medicinal product is a placebo, the information
requirements shall be limited to quality data. No additional documentation is
required if the placebo has the same composition as the tested investigational
medicinal product (with the exception of the active substance), is manufactured
by the same manufacturer, and is not sterile.
Ga – CORE DOSSIER
54a. The IMP-CD as a tool to support the development of the investigational
medicinal product shall gather information relevant to regulatory processes.
The IMP-CD shall describe the scope of authorised use in clinical trials,
including the intended population(s), route(s) and mode(s) of administration,
dosage range(s), exposure range, development stage(s), and as appropriate,
relevant parameters that determine its applicability to clinical trials.
The IMP-CD contains product specific data and information in the IB and
IMPD in agreement with Annex I points E and G. GMP-related documentation
may be included in accordance with Annex I point F.
When using a reference to an approved IMP-CD in a clinical trial application,
the sponsor shall confirm that the intended corresponding clinical trial falls
within its defined scope as described in point 1.
Complementary, clinical trial specific information may be provided in the
application dossier of the corresponding clinical trial.
Gb – POSSIBILITY TO REFERR TO SIMPLIFIED IMPD
54b. Possibility to refer to an active substance master file, an additional master file,
a platform technology master file or a corresponding certificate, or a certificate
confirming that the quality of the substance is suitably controlled by the
relevant monograph of the European Pharmacopeia, or a certified platform
technology master file as referred to in [REVISED Directive
2001/83/EC]. Where applicable, the sponsor may, instead of submitting all the
relevant information on the quality of the active substance or any other
substance present or used in the manufacture of the investigational medicinal
product, include in the IMPD quality section an active substance master file
(ASMF), or any other additional quality master file or a corresponding valid
certificate, or a certificate confirming that the quality of the substance is
suitably controlled by the relevant monograph of the European Pharmacopeia,
or where relevant a certified platform technology master file as referred to
in [revised Directive 2001/83/EC] provided that the active substance is
produced in accordance with the master file or its certificate. Such reference
shall be accompanied by a letter of access from the substance manufacturer
when the substance is not manufactured by the sponsor. The manufacturer or
certificate holder shall, however, provide the sponsor with all of the data which
may be necessary for the latter to take responsibility for the medicinal product.
The manufacturer shall confirm in writing to the sponsor that it shall ensure
batch to batch consistency. The holders of the master files or related
certificates shall not modify the details of the master file without informing the
sponsor. Documents and particulars supporting the application for such a
change shall be supplied to the competent authorities and sponsor, as
EN 13 EN
applicable. The sponsor shall include in the simplified IMPD any relevant data
to the active substance or its manufacturing which is not covered in the
referenced master file or certificate. In addition, all quality data relating to the
investigational medicinal product and its manufacturing together with the non-
clinical and clinical data shall be provided.
H. AUXILIARY MEDICINAL PRODUCT DOSSIER
55. Without prejudice to Article 65, the documentation requirements set out in
sections F and G shall also apply to auxiliary medicinal products. However,
where the auxiliary medicinal product is authorised in the Member State
concerned, no additional information is required.
I. SCIENTIFIC ADVICE AND PAEDIATRIC INVESTIGATION PLAN (PIP)
56. If available, a copy of the summary of scientific advice of the Agency, or of
any Member State or third country, with regard to the clinical trial shall be
submitted.
57. If the clinical trial is part of an agreed PIP, a copy of the Agency's decision on
the agreement on the PIP, and the opinion of the Paediatric Committee, unless
these documents are fully accessible via the internet shall be submitted. In the
latter case, a link to this documentation in the cover letter is sufficient (see
section B).
J. CONTENT OF THE LABELLING OF THE INVESTIGATIONAL
MEDICINAL PRODUCTS
58. A description of the content of the labelling of the investigational medicinal
product in accordance with Annex VI shall be provided.
Part II
General principle:
Without prejudice to Article 26 and Article 69 concerning translations of part I
documents, the application dossier for an application limited to Part II of the
assessment report referred to in Article 11 and the application dossier for an
application referred to in Article 14 shall be limited to sections K to S of this Annex.
K. RECRUITMENT ARRANGEMENTS (INFORMATION PER MEMBER
STATE CONCERNED)
59. Unless described in the protocol, a separate document shall describe in detail
the procedures for inclusion of subjects and shall provide a clear indication of
what the first act of recruitment is.
60. Where the recruitment of subjects is done through advertisement, copies of the
advertising material shall be submitted, including any printed materials, and
audio or visual recordings. The procedures proposed for handling responses to
the advertisement shall be outlined. This includes copies of communications
used to invite subjects to participate in the clinical trial and arrangements for
EN 14 EN
information or advice to the respondents found not to be suitable for inclusion
in the clinical trial.
L. SUBJECT INFORMATION, INFORMED CONSENT FORM AND
INFORMED CONSENT PROCEDURE (INFORMATION PER
MEMBER STATE CONCERNED)
61. All information given to the subjects (or, where applicable, to their legally
designated representatives) before their decision to participate or abstain from
participation shall be submitted together with the form for written informed
consent, or other alternative means according to Article 29(1) for recording
informed consent. If electronic means are used, the sponsor shall ensure that
the systems used have proportionate security levels, and that safeguards
regarding confidentiality are in place.
62. A description of procedures relating to informed consent for all subjects, and in
particular:
(a) in clinical trials with minors or incapacitated subjects, the procedures to
obtain informed consent from the legally designated representatives, and
the involvement of the minor or incapacitated subject shall be described;
(b) if a procedure with consent witnessed by an impartial witness is to be
used, relevant information on the reason for using an impartial witness,
on the selection of the impartial witness and on the procedure for
obtaining informed consent shall be provided;
(c) in the case of clinical trials in emergency situations as referred to in
Article 35, the procedure for obtaining the informed consent of the
subject or the legally designated representative to continue the clinical
trial shall be described;
(d) in the case of clinical trials in emergency situations as referred to in
Article 35, the description of the procedures followed to identify the
urgency of the situation and to document it;
(e) in the case of clinical trials where their methodology requires that groups
of subjects rather than individual subjects are allocated to receive
different investigational medicinal products, as referred to in Article 30,
and where, as a consequence, simplified means for obtaining informed
consent will be used, the simplified means shall be described.
(f) in case of using electronic informed consent, a description of the
electronic system and the procedure to inform, obtain, document and
store the informed consent.
63. In the cases set out in paragraph 62, the information given to the subject and to
his or her legally designated representative shall be submitted.
M. SUITABILITY OF THE INVESTIGATOR (INFORMATION PER MEMBER
STATE CONCERNED)
64. A list of the planned clinical trial sites, the name and position of the principal
investigators and the planned number of subjects at the sites shall be submitted.
EN 15 EN
65. Description of the qualification of the investigators in a current curriculum
vitae and other relevant documents shall be submitted. Any previous training in
the principles of good clinical practice or experience obtained from work with
clinical trials and patient care shall be described.
66. Any conditions, such as economic interests and institutional affiliations, that
might influence the impartiality of the investigators shall be presented.
N. SUITABILITY OF THE FACILITIES (INFORMATION PER MEMBER
STATE CONCERNED)
67. A duly justified written statement on the suitability of the clinical trial sites
adapted to the nature and use of the investigational medicinal product and
including a description of the suitability of facilities, equipment, human
resources and description of expertise, issued by the head of the
clinic/institution at the clinical trial site or by some other responsible person,
according to the system in the Member State concerned, shall be submitted.
O. PROOF OF INSURANCE COVER OR INDEMNIFICATION (INFORMATION
PER MEMBER STATE CONCERNED)
68. Proof of insurance, a guarantee, or a similar arrangement shall be submitted, if
applicable.
P. FINANCIAL AND OTHER ARRANGEMENTS (INFORMATION PER
MEMBER STATE CONCERNED)
69. A brief description of the financing of the clinical trial.
70. Information on financial transactions and compensation paid to subjects and
investigator/site for participating in the clinical trial shall be submitted.
71. Description of any other agreement between the sponsor and the site shall be
submitted.
Q. PROOF OF PAYMENT OF FEE (INFORMATION PER MEMBER STATE
CONCERNED)
72. Proof of payment shall be submitted, if applicable.
R. PROOF THAT DATA WILL BE PROCESSED IN COMPLIANCE WITH
UNION LAW ON DATA PROTECTION
73. A statement by the sponsor or his or her representative that data will be
collected and processed in accordance with Directive 95/46/EEC shall be
provided.
S. ANY TRANSLATION OF DOCUMENTS FROM ANNEX Ia REQUIRED IN
THE NATIONAL LANGUAGE OF THE MEMBER STATE CONCERNED in
accordance with Article 26 and Article 69
EN 16 EN
This submission may include, depending on the requirements of the Member State
concerned, but is not limited to, Cover Letter, Scientific synopsis, Lay summary,
Labels and Patient-facing documents from Part I of the application dossier.’
EN 17 EN
ANNEX III
Annex II to Regulation (EU) 2019/6 is amended as follows:
(1) Section I.1.8 is deleted.
(2) In section IIIa.2C2.1, point (7) is deleted.
(3) Section IIIa.3A6 is amended as follows:
(i) the heading IIIa.3A6.1 is deleted
(ii) in point (1), the following paragraph is added:
‘Details of the environmental risk assessment shall be provided in accordance
with guidance published by the Agency. Where the environmental risks for a
veterinary medicinal product have already been assessed, relevant justification
for not submitting a new environmental risk assessment may be provided.’
(iii) in point (2), the first paragraph is replaced by the following:
‘The environmental risk assessment shall follow a stepwise approach. The first
phase shall assess the potential exposure of the environment to the product and
the level of risk associated with any such exposure taking into account in
particular the following items:’
(iv) in point (3), the first paragraph is replaced by the following:
‘Where the conclusions of the first phase indicate a relevant potential risk for
the environment, the applicant shall proceed to the second phase. In the second
phase, further specific investigation of the fate and effects of the product on
particular ecosystems shall be conducted, in accordance with guidance
published by the Agency. The extent of exposure of the product to the
environment, and the available information about the physical/chemical,
pharmacological and/or toxicological properties of the substance(s) concerned,
including metabolites in case of an identified risk, which has been obtained
during the conduct of the other tests and trials required by this Regulation, shall
be taken into consideration.’
(v) the following point (4) is added:
‘For veterinary medicinal products containing or consisting of genetically
modified organisms, the following elements, which are based on the general
principles laid down in Annex II to Directive 2001/18/EC, shall be addressed
in the environmental risk assessment:
(a) description of the genetically modified organism, the modifications
introduced and the characteristics of the finished product; 1 cross-
reference to other parts of the application is acceptable.;
(b) identification and characterisation of hazards for the environment,
animals and for human health;
(c) exposure characterisation assessing the likelihood or probability that the
identified hazards materialise;
1
Cross-reference to other parts of the application is possible.
EN 18 EN
(d) risk characterisation taking into account the magnitude of each possible
hazard and the likelihood or probability of that adverse effect occurring;
(e) risk minimisation strategies proposed to address the identified risks.’
(vi) Section IIIa.3A6.2 is deleted.
(4) In section IIIb.2C2.1, point (5) is deleted.
(5) Section IIIb.3D is amended as follows:
(i) in point (1), the following paragraph is added:
‘Details of the environmental risk assessment shall be provided in accordance
with guidance published by the Agency. Where the environmental risks for a
veterinary medicinal product have already been assessed, relevant justification
for not submitting a new environmental risk assessment may be provided.’
(ii) in point (2), the first paragraph is replaced by the following:
‘The environmental risk assessment shall follow a stepwise approach. The first
phase shall assess the potential exposure of the environment to the product and
the level of risk associated with any such exposure taking into account in
particular the following items:’
(iii) point (5) is replaced by the following:
‘For veterinary medicinal products containing or consisting of genetically
organisms, the following elements, which are based on the general principles
laid down in Annex II to Directive 2001/18/EC, shall be addressed in the
environmental risk assessment:
(a) description of the genetically modified organism, the modifications
introduced and the characteristics of the finished product; cross-reference
to other parts of the application is acceptable;
(b) identification and characterisation of hazards for the environment,
animals and for human health;
(c) exposure characterisation assessing the likelihood or probability that the
identified hazards materialise;
(d) risk characterisation taking into account the magnitude of each possible
hazard and the likelihood or probability of that adverse effect occurring
(e) risk minimisation strategies proposed to address the identified risks.’
(6) Section IIIb.3E. is deleted
(7) Section V.1.3.2 is deleted.
EN 19 EN
.
Resolutsiooni liik: Riigikantselei resolutsioon
Viide: Sotsiaalministeerium / / ; Riigikantselei / / 2-5/26-00105
Resolutsiooni teema: Biotehnoloogia pakett
Adressaat: Sotsiaalministeerium
Ülesanne: Tulenevalt Riigikogu kodu- ja töökorra seaduse § 152` lg 1 p 2 ning Vabariigi Valitsuse
reglemendi § 3 lg 4 palun valmistada ette Vabariigi Valitsuse seisukohtade ja otsuste eelnõud
järgmiste algatuste kohta, kaasates seejuures olulisi huvigruppe ja osapooli:
- Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on establishing a framework of measures for strengthening Union’s biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations (EC) No 178
/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938
(European Biotech Act), COM(2025)1022
- Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
amending Directives 2001/18/EC and 2010/53/EU as regards the placing on the market of
genetically modified micro-organisms and the processing of organs, COM(2025)1031
EISi toimiku nr: 26-0025
Tähtaeg: 13.03.2026
Adressaat: Haridus- ja Teadusministeerium, Justiits- ja Digiministeerium, Kaitseministeerium,
Kliimaministeerium, Majandus- ja Kommunikatsiooniministeerium, Rahandusministeerium,
Regionaal- ja Põllumajandusministeerium, Riigikantselei, Siseministeerium, Välisministeerium
Ülesanne: Palun esitada oma sisend Sotsiaalministeeriumile seisukohtade kujundamiseks antud
eelnõu kohta (eelnõude infosüsteemi (EIS) kaudu).
Tähtaeg: 30.01.2026
Lisainfo: Eelnõusid on kavas arutada valitsuse 02.04.2026 istungil ja Vabariigi Valitsuse reglemendi
§ 6 lg 6 kohaselt sellele eelneval nädalal (18.03.2026) EL koordinatsioonikogus. Esialgsed
materjalid EL koordinatsioonikoguks palume esitada hiljemalt 13.03.2026.
Kinnitaja: Merli Vahar, Euroopa Liidu asjade direktori asetäitja
Kinnitamise kuupäev: 16.01.2026
Resolutsiooni koostaja: Sandra Metste
[email protected],
15.01.2026
Ettepanek:
Biotehnoloogia pakett (COM (2025) 1022, COM (2025) 1031)
Otsuse ettepanek koordinatsioonikogule
Kujundada seisukoht
Kaasvastutaja sisendi tähtpäev 30.01.2026
KOKi esitamise tähtpäev 18.03.2026
VV esitamise tähtpäev 2.04.2026
Vastutav ministeerium: Sotsiaalministeerium
Kaasvastutajad:
Majandus- ja Kommunikatsiooniministeerium, Justiits- ja Digiministeerium,
Rahandusministeerium, Kliimaministeerium, Regionaalministeerium, Haridus- ja
Teadusministeerium, Välisministeerium, Kaitseministeerium, Siseministeerium,
Riigikantselei Julgeoleku ja riigikaitse koordinatsioonibüroo
Seisukoha valitsusse toomise alus ja põhjendus
Algatuse vastuvõtmisega kaasneks oluline majanduslik või sotsiaalne mõju (RKKTS §
152¹ lg 1 p 2)
Algatuse reguleerimisala nõuab vastavalt Eesti Vabariigi põhiseadusele seaduse või
Riigikogu otsuse vastuvõtmist, muutmist või kehtetuks tunnistamist (RKKTS § 152¹ lg 1
p 1)
Sisukokkuvõte
Euroopa Komisjon avaldas 16.12.25 tervisevaldkonna algatuste paketi, mille eesmärk on
tugevdada ELi biotehnoloogiasektorit, kiirendada innovaatiliste ravimeetodite
arendamist, lihtsustada meditsiiniseadmete reegleid ning aidata ELi-üleselt ennetada ja
ravida südame-veresoonkonna haigusi.
Pakett koosneb järgmistest algatustest:
Biotehnoloogia määruse eelnõust1
1
Communication on an EU cardiovascular health plan: the Safe Hearts Plan - Public Health
Direktiivi eelnõust2, millega muudetakse geneetiliselt muundatud organismide
tahtliku keskkonda viimise direktiivi ja siirdamiseks ettenähtud inimelundite
kvaliteedi- ja ohutusstandardite direktiivi (vajalik biotehnoloogia määruse tõhusaks
rakendamiseks);
Meditsiiniseadmete ja in vitro diagnostikameditsiiniseadmete reeglite
lihtsustamise määruse eelnõust3
Komisjoni teatisest4 EL südame-veresoonkonna tervise kava ehk „Safe Hearts
Plan“ kohta
Biotehnoloogia edendamiseks esitatud kaks eelnõud loovad meetmete raamistiku EL-s
biotehnoloogia ja biotootmise sektorite tugevdamiseks, eelkõige tervise valdkonnas.
Eesmärgid
Biotehnoloogia määruse eelnõu keskendub tervisesektori biotehnoloogia arenduste ja
tootmisvõimekuse toetamisele. Näiteks määratletakse strateegiliste projektide
kriteeriumid ja tunnustamise kord, neile ette nähtud administratiivne, tehniline ja
regulatiivne tugi. Samuti käsitletakse rahastusinstrumentidele juurdepääsu, sh ELi
tervisebiotehnoloogia investeerimispiloot koos Euroopa Investeerimispangaga, et
kaasata erasektori kapitali. Suure mõjuga projektid saavad eristaatuse ning võivad
taotleda ELi ja liikmesriikide rahalist toetust vastavalt riigiabi reeglitele. Nähakse ette
täiendav patendikaitse periood teatud uuenduslikele ravimitele: kehtestatakse 12-kuuline
täiendav kaitsetunnistuse (SPC) pikendus biotehnoloogiliste ravimite ja täiustatud
teraapiate jaoks. Toetatakse sarnaste bioloogiliste ravimite (biosimilars) arendamist,
tootmist ja turulesaamist. Edendatakse tehisintellekti kasutamist - AI kasutamine ravimite
kogu elutsükli jooksul, usaldusväärsed AI testkeskkonnad ja andmekvaliteedi kiirendid.
Nähakse ette paindlik regulatiivne lähenemine uutele toodetele - ELi-ülene regulatiivse
staatuse register, tulevikusuundumuste nõuandev kogu, regulatiivne liivakast varajases
arendusjärgus toodetele. Luuakse raamistik biotehnoloogia väärkasutuse ennetamiseks,
sh kahtlaste tehingute jälgimiseks ja kontrollimiseks. Biokaitse projektid võivad saada
suure mõjuga strateegilise projekti staatuse ja eelistatud rahastuse. Lisaks muudetakse
juba kehtivaid EL õigusakte, kõige mahukamad muudatused käsitlevad kliiniliste
uuringute määrust.
Biotehnoloogia määruse eelnõuga koos esitatud direktiivi eelnõu käsitleb geneetiliselt
muundatud mikroorganismide turulepanemist ja elundite töötlemist muudetakse
kehtivaid direktiive, mis reguleerivad geneetiliselt muundatud organismide tahtliku
2
Proposal for a regulation to simplify rules on medical and in vitro diagnostic devices - Public Health
3
Directive regarding the placing on the market of genetically modified micro-organisms and the
processing of organs - Public Health
4
Proposal for a Regulation to establish measures to strengthen the Union's biotechnology and
biomanufacturing sectors (European Biotech Act) - Public Health
2
keskkonda viimist (2001/18/EC) ja siirdamiseks ettenähtud inimelundite kvaliteedi- ja
ohutusstandardeid (2010/53/EU).
- Muudatused geneetiliselt muundatud mikroorganismide (GMM) direktiivis
(2001/18/EÜ) – lihtsustatakse GMMide (v.a toit ja sööt) turuleviimise korda,
säilitades kõrge ohutustaseme. Täpsustatakse riskihindamist, muudetakse load
tähtajatuks ning kehtestatakse madala riskiga GMMide jaoks lihtsustatud
loamenetlus ja paindlikum järelevalve.
- Muudatused elundite töötlemise direktiivis 2010/53/EL - direktiivi kohaldamisala
laiendatakse elundite töötlemisele ja täpsustatakse mõisteid. Kehtestatakse
elundite töötlemise lubade, kasu–riski hindamise ja järelevalve raamistik ning
nõuded seoste korral ravimite, meditsiiniseadmete ja inimpäritolu materjalidest
preparaatidega. Elundi töötlemine lisatakse ka nõutavasse dokumentatsiooni.
Kas EL algatus reguleerib karistusi või haldustrahve? Jah. Liikmesriigid peavad määruse
eelnõu kohaselt kehtestama määruse jõustamiseks karistuste eeskirjad ning võtma kõik
vajalikud meetmed nende rakendamise tagamiseks. Karistused peavad olema tõhusad,
proportsionaalsed ja hoiatavad.
Kas nähakse ette uue asutuse loomine (järelevalvelised või muud asutused)? Ei
Kas lahenduse rakendamine vajab IT-arendusi? Vajab täiendavat analüüsi.
Mõju ja sihtrühm
Majandus
Ettevõtlus
Sihtrühm: Biotehnoloogia ja biotootmise ettevõtted (sh idu- ja kasvufirmad, tootjad,
arendajad)
Mõju: Meetmed aitavad (i) soodustada ELi biotehnoloogia ja biotootmise tööstuse kasvu;
(ii) parandada ELi biotehnoloogiaettevõtete ülemaailmset konkurentsivõimet ja
innovatsioonivõimekust; ning (iii) suurendada ELi strateegilist autonoomiat kriitilistes
tehnoloogiavaldkondades.
ELi biotehnoloogiaettevõtete, eriti nende, kellel on potentsiaal kogu ökosüsteemi oluliselt
mõjutada, juurdepääs kapitalile paraneb kogu arendustsükli vältel ning paraneb ligipääs
taristule, mis on vajalik innovatsiooni tööstusliku potentsiaali hindamiseks. See aitab
kaasa elujõulise biotehnoloogia ja biotootmise ökosüsteemi kujunemisele ELis.
Ettepanekuga toetatavad strateegilised biotehnoloogiaprojektid võivad hõlmata ka
tegevusi, mis tegelevad kasvava oskustööjõu puudujäägiga biotehnoloogia ja
biotootmise valdkonnas, ning aitavad kujundada tööjõudu, mis suudab toetada
innovatsiooni, tööstuslikku laienemist ja pikaajalist konkurentsivõimet. Investorid ja
3
finantsvahendajad saavad kasu etteaimatavamast projektivoost ja suuremast
regulatiivsest selgusest, mis toetab suurema riskitaluvusega kapitali kättesaadavust ELis.
Algatus soodustab kooskõlas ELi tehisintellekti poliitika ja õigusaktidega tehisintellekti
kasutamist kogu biotehnoloogia ökosüsteemis, pakkudes ettevõtetele – eelkõige
VKEdele – rohkem juhiseid ja võimalusi usaldusväärsete ja kvaliteetsete
tehisintellektilahenduste integreerimiseks teadus-, katse- ja tootmisprotsessidesse.
Halduskoormus
Sihtrühm: biotehnoloogia sektoris tegutsevad teadusasutused ja ettevõtjad, samuti
riiklikud ametiasutused.
Mõju: Muudatused on suunatud kehtivate nõuete lihtsustamisele ja regulatiivkoormuste
kõrvaldamisele, mis takistavad ELi ettevõtjate innovatsiooni ja konkurentsivõimet.
Eelkõige on meetmete eesmärk selgitada ja lühendada menetlustähtaegu kogu
arendustsükli vältel (nt leevendades keerukaid ja ebaproportsionaalseid nõudeid) ning
pakkuda kiiresti kasvavale ja innovaatilisele biotehnoloogia sektorile paindlikku
regulatiivset keskkonda (nt regulatiivsete liivakastide kaudu ning võimaldades andmete ja
tehisintellekti laiemat kasutamist). Seeläbi saavad kõik osalejad, eelkõige ettevõtted,
kasu etteaimatavamast ELi regulatiivraamistikust, st suuremast õiguskindlusest,
lühematest menetlustähtaegadest ning paindlikust ja koostööpõhisest regulatiivsest
keskkonnast. Üldiselt eeldatakse, et need meetmed võimaldavad ettevõtetel
innovatsiooni kiiremini turule tuua. Eelkõige peaksid meetmetest kasu saama VKEd, kuna
biotehnoloogia valdkonnas vähenevad turuletuleku tõkked. Toetavad meetmed on samuti
suunatud VKEde, iduettevõtete ja kasvufirmade vajadustele.
Sotsiaalala
Tervis ja tervishoiukorraldus/ Inimeste heaolu ja sotsiaalne kaitse/Inimeste õigused
Sihtrühm: elanikkond.
Mõju: Ettepanekuga tagatakse tervise ja keskkonna kõrgetasemeline kaitse. Samuti
tagavad meetmed, mille eesmärk on vältida biotehnoloogiate väärkasutust ja tugevdada
ELi biokaitsevõimekust, sh tehisintellektil põhinevate bioloogiliste riskide seiret, et
innovatsiooniga kaasneksid tugevad avaliku tervise ja julgeoleku kaitsemeetmed.
Lõppkasutajad, sealhulgas patsiendid ja kodanikud, saavad kasu
biotehnoloogiatoodetest, mis vastavad nende vajadustele. Kiirem turulejõudmine ja
kliiniliste uuringute parem tulemuslikkus peaksid võimaldama varasemat juurdepääsu
ohututele, tõhusatele, kvaliteetsetele ja taskukohastele biotehnoloogiatoodetele,
sealhulgas arenenud ravimeetoditele, diagnostikale, biosimilaaridele ja innovatiivsetele
biotootmise toodetele, millest võidavad ka tervishoiusüsteemid.
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Riigivalitsemine
Riigieelarve
Sihtrühm: riiklikud/pädevad asutused.
Mõju: Riigiasutused saavad kasu sujuvamatest ja ühtsematest menetlustest ning
paremast koordineeritusest, mis vähendab töö dubleerimist ja toetab järjepidevamaid
regulatiivseid otsuseid. Töökoormuse suurt langust samas ei ole oodata, kuna lootus on
sektori poolt senisest aktiivsem arendustegevus valdkonnas ja uute toodete turule
toomine.
Kaasamine
Kaasata kõik asjassepuutuvad partnerid ja huvirühmad, sh bio- ja tervisetehnoloogia
valdkonna ettevõtted (nt ravimitööstus), teadusasutused ja ülikoolid (TalTech, Tartu
Ülikool, Eesti Maaülikool), Geenivaramu, tervishoiusektori esindajad (arstide, haiglate,
kliiniliste uuringute keskuste esindajad), patsiendiorganisatsioonid, bioohutuse ja
biojulgeolekuga seotud osapooled, samuti investorid ja rahastajad (sh EAS).
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Eelnõude infosüsteemis (EIS) on antud täitmiseks ülesanne.
Eelnõu toimik: 18.1.1/26-0025 - COM(2025) 1022 Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on establishing a framework of measures for strengthening Union’s biotechnology and biomanufacturing sectors particularly in the area of health and amending Regulations (EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938 (European Biotech Act)
Arvamuse andmine eelnõu kohta sotsiaalministeeriumile vastavalt Riigikantselei 16.01.2026 resolutsioonile.
Osapooled: Majandus- ja Kommunikatsiooniministeerium; Haridus- ja Teadusministeerium; Justiits- ja Digiministeerium; Riigikantselei; Kaitseministeerium; Siseministeerium; Regionaal- ja Põllumajandusministeerium; Rahandusministeerium; Kliimaministeerium; Välisministeerium
Tähtaeg: 30.01.2026 23:59
Link eelnõu toimiku vaatele: https://eelnoud.valitsus.ee/main/mount/docList/2b46f6f0-a442-4b83-8ee2-d4e787d485cf
Link menetlusetapile: https://eelnoud.valitsus.ee/main/mount/docList/2b46f6f0-a442-4b83-8ee2-d4e787d485cf?activity=2
Eelnõude infosüsteem (EIS)
https://eelnoud.valitsus.ee/main