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European Association of Nuclear Medicine (EANM) suggested amendments on 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 June 2024 Radiopharmaceuticals (radioactive medicinal products) have seen a tremendous development over the past two decades and are becoming ever more important for many clinical applications in both diagnosis and therapy. Therefore, the European Association of Nuclear Medicine (EANM) has proposed adaptation of the regulatory framework, namely the Directive 2001/83/EC. However, the recent proposal for the revision of the EU Pharmaceutical Legislation by the European Commission as well as the compromised amendments voted by the European Parliament in April 2024 do not contain any changes regarding radiopharmaceuticals reflecting these developments. The EANM therefore proposes three changes to the current proposal aiming at refining definitions and paragraphs relating to radionuclides, kits and starting materials with the aim: 1.) To ensure patient access to radiopharmaceuticals by overcoming unclear requirements for the local preparation in hospitals and Nuclear Medicine departments leading to significant national differences and health care practices. 2.) To harmonise regulatory views and requirements in the preparation of radiopharmaceuticals that cannot be centrally supplied and, therefore, have to be prepared locally. 3.) To clarify legal requirements for producers providing novel technologies (including radionuclides and starting materials), ensuring Europe`s leading role in this field Technical details and extended justifications can be found in the below table with the proposed amendments. European Commission legislative proposal EANM suggested amendment Rationale/Justification Article (20) ‘kit’ means any preparation to (20) ‘kit for radiopharmaceutical The short half-life of radionuclides in radiopharmaceuticals, and/or instability of the 4- be reconstituted or combined preparation’ means a pre- radiolabelled compound (by e.g. radiolysis), often results in a very short shelf-life of the Definit with radionuclides in the final formulated medicinal product final product. ions radiopharmaceutical, usually prior containing all ingredients This requires unique strategies for industry to develop and provide a drug product with to its administration; required to directly prepare a high and consistent quality. A kit for radiolabelling provides a safe and effective solution radiopharmaceutical, with the for this unique situation, with the preparation of the final radiopharmaceutical conducted exception of the radionuclide; close to the patient. Manufactures of kits provide a fully developed medicinal product, with a specific formulation of defined quality and clinical studies ensuring safety and efficacy (performed with the final radiolabelled formulation), which is the basis for a marketing authorization for the kit. Since there are immediate consequences resulting from the use of “kits” (exemption from the need for a marketing authorization of the final product in Article 16, Nr. 2 of both the commission’s proposal and the “old” directive (Dir 2001/83, Article 7)), a clear and unambiguous definition of a “kit” is mandatory. The current definition of “kit” is based on the practices available at the time of the 2004 directive amendment but does not reflect the technological advances and future developments in the field, in particular in the context of “complex radiopharmaceutical preparations”, where chemical precursor alone or technical tools for radiosynthesis such as reagent sets or cassettes are being used, which should not fall under exemption of Art. 16, No2, but be supervised via the final product. Additionally, without a clear distinction between “kits” and other starting materials providers of these types of starting materials (reagent sets, cassettes etc.) will withdraw their products, in particular related to the need to provide safety and efficacy data. This is, from a scientific point of view, not appropriate and often not possible for starting materials, which often are not linked to a specific final product.  Impact: So called “kits” rightfully require a marketing authorization by the manufacturer based on clinical data to show safety and efficacy thereby exempting the final product prepared locally. A large number of other starting materials should clearly not fall under this umbrella. This proposal ensures that clinically established diagnostic radiopharmaceuticals and their supply will remain available for patients in need of these products in many member states and innovation and development in this field, in which Europe is playing a leading role, is not hampered. . 1. A marketing authorisation shall 1. A marketing authorisation shall The suggested change removes the link to the marketing authorisation of the final be required for radionuclide be required for radionuclide product for which the radionuclide, kit or radionuclide generator is a starting material. generators, kits, and radionuclide generators, kits, and radionuclide The proposal by the Commission would exempt only starting materials from the need for precursors, unless they are used precursors, unless they are used a marketing authorization if the final product is covered by a marketing authorization. A as starting material, active as starting material, active large number of radiopharmaceuticals has to be prepared in-house in a hospital substance or intermediate of substance or intermediate of pharmacy (or equivalent department) for immediate application to the patient due to radiopharmaceuticals covered by radiopharmaceuticals. reasons of stability and physical half-life. These radiopharmaceuticals are by nature not Article a marketing authorisation under covered by a marketing authorization. Even if these preparations are performed under a 16 - Article 5. manufacturing license and GMP, the starting materials are often not available if the Radiop supplier does not apply for a marketing authorization. There is no scientific reason for the harma link to the marketing authorisation process in this context, as starting materials are to be ceutic processed and not applied directly to patients without full quality control of the final als product. A need for a marketing authorization for starting materials represents a clear overregulation for radiopharmaceutical products that is not existing for any other types of medicinal products! Impact: The supply of a large number of radionuclides that are needed as starting materials for in-house production of commercially not available radiopharmaceuticals is in threat. The  proposed change will ensure that patients will have access to radiopharmaceuticals that need to be prepared locally and lead to a more harmonized regulatory view on this topic. 1.Member States shall take all 1.Member States shall take all Radiopharmaceuticals prepared from kits with marketing authorisation are intended to appropriate measures to ensure appropriate measures to ensure be used within the facility where it is being used (usually the healthcare establishment), that the manufacture of the that the manufacture of the which works under the umbrella of national legislation covering such practices. No medicinal products within their medicinal products within their additional manufacturing authorization requirement should be in place. territory is subject to territory is subject to This would also be in line with Article 61 Nr. 5 b) of the Clinical Trial Regulation, in which authorisation (the “manufacturing authorisation (the “manufacturing the radiopharmaceutical production of an investigational medicinal product does not authorisation”). authorisation”). require a manufacturing authorisation. Article <...> 142 – <...> Impact: Manuf 6. A manufacturing authorisation This clarification would help users in member states, avoid unnecessary bureaucracy and acturi shall not be required for a ensure patient access to locally prepared radiopharmaceuticals, especially in small ng radiopharmaceutical prepared at health care centres providing nuclear medicine services. Autho the time of use by a person or by risatio an establishment authorised, In addition, if this clarification is not added, there will be the contradicting situation, that n according to national legislation, for routine preparations a manufacturing authorization is needed while the preparation to use such radiopharmaceuticals of diagnostic radioactive investigational medicinal products is possible without in an approved healthcare manufacturing authorization. establishment exclusively from authorised radionuclide generators, kits or radionuclide precursors in accordance with the manufacturer's instructions. Saatja: Anne Poksi <[email protected]> Saadetud: 29.08.2024 10:51 Adressaat: <"Eda Lopato">; <"Johanna Liis Udumets">; <[email protected]>; <"Katrin Kiisk">; <[email protected]> Koopia: Ilona Muoni - PERH <[email protected]>; Tiina Kärner <[email protected]> Teema: FW: Your support needed at national level - Revision of the EU Pharma Legislation Lugupeetud Eda Lopato Lugupeetud Katrin Kiisk Eesti Nukleaarmeditsiini seltsile (ENMS) on saabunud märgukiri Euroopa Nukleaarmeditsiini Assotsiatsiooni poliitika ja regulatiivküsimuste nõukogust (EANM Policy &amp; Regulatory Affairs Council (PRAC)). Märgukirjas palutakse pöörata tähelepanu EL farmaatsiaalaste õigusaktide läbivaatamisel ka radiofarmatseutiliste preparaatide arvestatavale tähtsusele ja toetada riigisiseselt EANM muudatusettepanekuid EL ravimiseadustiku radiofarmaatsia osas. EANM muudatusettepanekute eesmärkideks on tagada radiofarmatseutiliste ravimite kättesaadavus patsientidele vaatamata osakonnasisestele, haiglate vahelistele ja riikide vahelistele erisustele; ühtlustada regulatiivseid nõudeid kohapeal valmistatavatele radiofarmatseutilistele preparaatidele; selgitada juriidilisi nõudeid uudseid tehnoloogiaid pakkuvatele tootjatele. Oleme ENMS juhatuses arutanud läbi EANM muudatusettepanekud (artiklites 4, 16 ja 142; lisatud manuses) ning nendega nõus. Meie hinnangul ei muuda EANM muudatusettepanekud Eestis kehtivat radiofarmatseutiliste preparaatide valmistamisega seotud seadusandlust (Ravimiseadus ja sellest tulenevad määrused), vaid üldkokkuvõttes tagavad nukleaarmeditsiiniliste teenuste parema kättesaadavuse patsientidele radiofarmatseutiliste preparaatide valmistamise regulatiivsete nõuete ühtlustamise kaudu. Teeme omalt poolt ettepaneku toetada riiklikul tasemel EANM muudatusettepanekuid EL nõukojas farmaatsiaalaste õigusaktide läbivaatamisel. Oleme nõus vastama tekkivatele küsimustele ja teemat edasi arutama vastastikusel (virtuaalsel)kohtumisel. Lugupidamisega, ENMS juhatuse nimel Anne Poksi Anne Poksi | Keskuse juhataja Diagnostikakliinik | Nukleaarmeditsiinikeskus AS Ida-Tallinna Keskhaigla | Ravi 18, 10138 Tallinn tel &#43;372 620 7940 | mob &#43;372 53 016 767 fax &#43;372 620 7318 From: Amélie de Martini &lt;&gt; Sent: Thursday, August 1, 2024 11:24 AMCc: Silvia Marchetti &lt;&gt;Subject: Your support needed at national level - Revision of the EU Pharma Legislation You don't often get email from . Tähelepanu: E-kiri saadeti väljastpoolt Regionaalhaigla gruppi. Kui sa ei tunne saatjat või kahtled sisu ohutuses, siis ära ava linke ega manuseid! Dear EANM National Delegates, I hope this email finds you well. I am contacting you on behalf of the EANM Policy &amp; Regulatory Affairs Council (PRAC). As you might know, although PRAC has recently achieved great milestones, there was a recent setback on the revision of the EU Pharmaceutical Legislation. Despite the dedicated efforts made by the EANM to advocate for the inclusion of radiopharmaceuticals and their specificities in the legislation, the European Parliament has recently rejected the proposed amendments. Now that the focus has shifted to the Council of the EU (i.e., Member States), PRAC is now increasing its outreaching efforts at the national level, to urge policymakers to reconsider. For more information on the revision of the EU Pharmaceutical Legislation and the EANM views, I invite you to consult the following EANM statements ( and ). To ensure that our efforts at the national level are as effective as possible, we would like to, please, ask for your support. 1. Should you have any relevant contact in your country (Health Ministry, Medicines Agencies or other regulatory bodies), we would very much appreciate if you could contact them to raise awareness on the importance of having radiopharmaceuticals considered within the revision of EU Pharmaceutical Legislation. * To facilitate such an outreach, we have attached to this email a draft email which you could modify based on your needs and approach, as well as the most recent EANM statement and recommendations. 2. In our discussions with national points of contacts, we would like to make sure that we provide Member States´ specific information. Such information could include good practice related to regulation, but also potential impacts of a non-appropriate regulatory framework. Indeed, so far, PRAC has been able to detail the consequences of the current status quo with regards to EU Pharmaceutical Legislation at the European level, but not at the national level. Should you be interested to provide some details on potential consequences in your country, this would be very much appreciated. Thank you very much in advance for your time and consideration. Should you have any questions, please do not hesitate to reach out. Kind regards, Amelie -- Amélie de Martini Head of EU Affairs European Association of Nuclear Medicine (EANM) Schmalzhofgasse 26 1060 Vienna, Austria Phone: &#43;43 1 890 44 27 Fax: &#43;43 1 890 44 27-9 E-Mail: URL: Visit us on social media: , , , , Austrian Register of Associations: no. 063483520 Austrian Data Protection Act: Registration no. 1068431 Please consider the environment before printing this e-mail. To National Authorities We are reaching out on behalf of the European Association of Nuclear Medicine (EANM) to discuss the critical stage of the EU Pharmaceutical Legislation revision, which is now under the Council's review. This legislative update presents a pivotal opportunity to address the rapidly evolving field of radiopharmaceuticals and to ensure that Europe remains at the forefront of medical innovation and patient care. Unfortunately, the changes proposed by the European Commission and the European Parliament regarding radiopharmaceuticals failed to provide sufficient clarity, despite the significant advancements in this field since the last legislative update in 2004. It is with deep regret that we note the exclusion of the Nuclear Medicine community's recommendations from the European Parliament's final position. In this respect, our concern is that the current regulatory framework will not adequately support the continued innovation and application of radiopharmaceuticals in Europe, potentially hindering our continent from leading advancements in this crucial area of healthcare. Nuclear Medicine has become integral to modern healthcare across Europe, with millions of patients benefiting from its diagnostic and therapeutic capabilities annually. From detecting and treating a wide range of diseases to advancing cancer care, Nuclear Medicine is a promising area of medical innovation. The European Union has already recognised its critical role, particularly in cancer care, through priority initiatives such as the SAMIRA Action Plan and Europe's Beating Cancer Plan. These initiatives have acknowledged Nuclear Medicine as an independent medical specialty and supported actions to enhance the supply of medical radioisotopes and improve the quality and safety of medical applications. This recognition should go hands in hands with regulatory support to fully harness its potential for the health of European patients. The recent Council Conclusions on Radioisotopes for medical use, as well as the European Economic and Social Committee opinion on Europe's Beating Cancer Plan: Driving forces for the security of medical radioisotopes supply underscore the current political commitment to facilitate the use of radioisotopes for medical diagnostics and therapy. To ensure that the recommendations are put into action and that healthcare professionals have timely access to relevant medical radioisotopes to treat patients, we wish to share some key suggestions from the Nuclear Medicine community. These suggestions aim to harmonise regulatory views and requirements in the preparation of radiopharmaceuticals and clarify legal requirements for producers. Please find attached the EANM's detailed suggestions. The revision of the EU Pharmaceutical Legislation represents a generational opportunity to secure patient access to radiopharmaceuticals. We hope that, as the proposals are now under the Council's review, specific technical provisions concerning radiopharmaceuticals will be considered. We greatly appreciate your attention to this matter and are available for any questions you may have. We would welcome the opportunity to discuss this issue further in a meeting. Thank you for your consideration. Amélie de Martini Head of EU Affairs European Association of Nuclear Medicine (EANM)