CREATEDATE \@ "d MMMM yyyy" \* MERGEFORMAT 27 October 2022 IF DOCPROPERTY "DM_emea_doc_ref_id" \* MERGEFORMAT EMA/858436/2022 <> "Error*" DOCPROPERTY "DM_emea_doc_ref_id" \* MERGEFORMAT EMA/858436/2022 \* MERGEFORMAT EMA/858436/2022 Inspection of third country leukapheresis centre – Summary Agreed EC position (following CTX-0001 request for advice) It can be confirmed that there is no legal basis to conduct an inspection of a third country leukapheresis centre by an EEA Competent Authority either within the ATMP nor BTC legal framework in cases where the starting material is not directly imported into the EU. However there are international standards that such centres would be expected to comply with, and the Agen cy/ rapporteurs are entitled to confirm with the ATMP manufacturer whether this is the case in the context of marketing authorisation applications; In addition, as part of the application, the applicant/MAH should confirm whether the compliance to these in ternational standards is equivalent to compliance to the EU BTC requirements. Overall, EC also concurs with the Agency that (as per the GMP for ATMP), compliance with those standards should be supervised by the third country ATMP manufacturer/MAH; and whi lst during the GMP inspection of a third country ATMP manufacturer, the compliance of the starting material (supplier) is usually verified, this can also be stressed as a point of particular interest to the GMP inspectors during the assessment. Finally, t he EC highlighted the importance of confirming that a quality management system by the ATMP manufacturer is in place that cover written procedures for all activities, health donor information, test results, traceability data and internal and external audit s, as an additional element that could be considered to verify compliance. In addition, we understand that the EC considers point 7.23 from the GMP for ATMP not to be restricted to established cell lines/cell banks but to be also applicable to all blood cells/blood components used for the manufacture of ATMPs including cases where cells used as starting material are collected repeatedly during the life cycle of the product (e.g. autologous or allogeneic cell/gene therapies where apheresis material from do nors/patients are used starting material). Additionally, it is our understanding that the same above principles apply in the case of plasma and blood starting materials for the manufacturing of blood-derivative products. Scenarios developed by CAT members and updated based on EMA interpretation of the BTC legislative framework BTC starting material (SM) obtained within the EU ( for manufacturing in the EU ) If the BTC material is obtained from an EU site for manufacturing of an ATMP at an EU-based manufacturing site, the BTC site ( s ) should comply with the EU BTC legislation for donation, procurement and testing and therefore be accredited, designated, authorized or licensed in accordance with Directive 2004/23/EC on safety and quality of human tissues and cells (or Directive 2002/98/EC on safety and quality of human blood and blood components) . NB: An i nspection is required for EU BTC sites in the framework of Blood-Tissue-Cell ( BTC ) legislation . BTC SM obtained from third-country site for manufacturing in a third country This is the only scenario brought to the attention of the EC and covered by the positi on a bove. If the BTC material is obtained from a third-country site for manufacturing at the same or another third-country-based manufacturing site, both the supplier and manufacturing sites fall outside the scope of EC/2004/23. There is therefore no legal basis to conduct an inspection of the supplier sites by an EEA Competent Authority either within the MP or BTC legal framework since the starting material is not directly imported into the EU. However (as per the GMP for ATMP), compliance with standards equivalent to Directive 2004/23/EC should be supervised by the third country ATMP manufacturer/MAH and during the GMP inspection of the third country ATMP manufacturer inspecto r s can verify the GMP requirements established in the ATMP GMP guideline for starting materials (paragraph 7.3) . In summary, only BTC material obtained from supplier and/or importing sites meeting as a minimum equivalent standard to Directive 2004/23/EC would be deemed acceptable for approval. BTC SM obtained from third-country site imported for manufacturing in the EU If the BTC material is obtained from a third-country site and imported for manufacturing at an EU-based manufacturing site, the importing site should be accredited, designated, authorized or licensed as importing tissue establishment in accordance with Directive 2004/23/EC, to be allowed to import such material from a third-country. In this scenario, inspection in the framework of BTC-legislation is required for the importing site (per Article 7 of the Directive 2004/23/EC) and where appropriate of the third country supplier, as per Article 4 of Directive 2015/566/EC ( for cell and tissues ) to ensure the equivalency of the quality and safety standards of the tissues and cells to be imported with the standards laid down in Directive 2004/23/EC (the same principles apply for blood products). It is within the remit of the national BTC competent authority to decide if the third-country BTC sites from which starting material is imported, is in accordance with Directive 2004/23/EC. For blood-derived cells, compliance with Directive 2002/98/EC regarding donation, procurement and testing is likewise acceptable.
Saatja: <
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Saadetud: 24.11.2022 10:39
Adressaat: <
[email protected]>
Koopia: Pothet Caroline <
[email protected]>; Brusselmans Tom
<
[email protected]>; <
[email protected]>;
KOUFOKOTSIOU Paschalia <
[email protected]>; FEHILY
Deirdre <
[email protected]>; VAN DER SPIEGEL Stefaan
<
[email protected]>
Teema: Verification of safety and quality of SoHO starting materials for
ATMP
Dear colleagues, dear competent authorities for safety of blood and blood
components and for tissues and cells
We herewith provide you with a summary, and a set of explanatory slides,
from EMA/CAT so called CAT learning- regarding their interpretation of
the key principles in the existing framework associated with blood,
tissue and/or cells serving as starting materials for ATMP.
In short, this document summarizes 3 situations:
1. BTC starting material (SM) obtained within the EU (for
manufacturing in the EU): this fall under the BTC provisions and under
the oversight of BTC authorities
2. BTC SM obtained from third-country site for manufacturing in a
third country (of ATMPs for eventual use in the EU): while there is no
legal basis for inspections in these 3rd countries, these BTC are to be
compliant with standards equivalent to Directive 2004/23/EC. GMP
inspectors can verify the GMP requirements established in the ATMP GMP
guideline for starting materials during the GMP inspection of the ATMP
finished product manufacturer.
3. BTC SM obtained from third-country site imported for
manufacturing in the EU: import of these BTC is to be organised by an
importing tissue establishment according to provisions and oversight of
the import directive 2015/566.
DG SANTE has been involved in the preparation of this statement with EMA
colleagues, and we believe the enclosed summary and CAT slides correctly
reflects our understanding.
Nevertheless, we feel it is important that you are timely informed, and
have an opportunity to provide possible comments.
As CAT plans to finalise these documents during the next meeting of CAT
on 7-9 December, we would kindly ask you to send us possible comments by
30 November to .
After that, colleagues will proceed with the further finalisation of
these documents.
With kind regards,
On behalf of the EMA colleagues and the SoHO team
European Commission DG SANTE (Health and Food Safety)
Unit D2 Medical Products: quality, safety, innovationOffice address: Rue
Breydel 2, 06/004, B-1049 Brussels/Belgium