1. © Safeguarding public health Meet the Regulators MHRA, London 13 April, 2011 LRMN/ MHRA MEETING

2. © ATMPs - the regulatory setting Marketing Authorisation centralised licence (MA) (CAT) EMA Commercial Clinical Trials Phase I, II, III Pre- clinical Safety Clinical Trials national licence (CTA) NCA EUTCD or Blood Directive Donation, procurement & testing (processing) Unlicensed (Hospital Exemption / Specials) Cert. of Quality & non-clinical data EMA GP GMP MIA(IMP) GMP MIA GLP Dossier Transplants or Transfusions Processing, preservation, storage, distribution GP Borderline – classification of product: medicinal product? Dossier Advice and guidance NCA / EMA

3. © Presentation Outline Abbreviation glossary ATMPs – the regulatory setting Useful links

4. © Abbreviation Glossary ATMP- Advanced Therapy Medicinal Product (GT, SCT, TEP) CAT- Committee for Advanced Therapy EMA- European Medicines Agency EUTCD- EU Tissue and Cells Directive (2004/23/EC) GP- Good Practice (Quality System under Blood & EUTCD) GT- Gene Therapy NCA- National Competent Authority (e.g. MHRA) SCT- Somatic Cell Therapy TEP- Tissue Engineered Products

5. © Inspectorate contact with ATMP Industry Regulatory advice on manufacturing : -Verbal -Written -Meetings – GMP only / with CTU / with Licensing Division Inspections: -Hospital Exemption - Manufacturer’s Specials -CT - MIA(IMP)- Full - MIA

6. © Inspectorate contact with ATMP Industry Formal classification advice: -Available from EMA and via MHRA website -MHRA’s centralised process been in place for 3 years: Year No. ·08/09: 8 ·09/10: 24 ·10/11: 13 -System been well received -Advice requests received on a broad range of product types

7. © Inspectorate contact with ATMP Industry DH initiatives -Stem Cell Tool Kit Commission / ATMP Regulation : -Article 5 (Annex 2) -Article 25 (Report and review)

8. © Useful links EMA – What’s new in Inspections: -http://www.emea.europa.eu/Inspections/WhatsNew.html Commission ‘Latest News on Pharmaceuticals’: -http://ec.europa.eu/health/documents/new_en.htm GMP Volume 4: -http://ec.europa.eu/health/documents/eudralex/index_en.htm

9. © Scientific Advice (National) for ATMP 2009 - present Safeguarding public healthCTMPGTMP200953 201051 2011 (to Mar) 20

10. © 1. Characterisation and Impurities 2. Mechanism of Action and Potency Testing 3. Demarcation of Drug Substance and Drug Product Recurring issues for CTMP:

11. © Safeguarding public health Advanced Therapy Medicinal Products: EU procedures LRMN 13 April 2011 Patrick Celis, PhD CAT Secretariat, EMA, London

12. © CLASSIFICATION EVALUATION CERTIFICATION Tasks of the CAT Tasks of the Committee for Advanced Therapies (CAT) Scientific Advice Support to PDCO Support to CHMP / COMP Interaction with stakeholders Publications, Guidelines

13. © ATMP Evaluation procedure ATMPs will follow the Centralised procedure (mandatory scope)  single MA (marketing authorisation) for entire EU: 210 Day procedure Evaluation by two independent (Rapp/CoRapp) teams from CAT All scientific discussion and adoption of key documents at CAT ATMP evaluation procedure builds on full transparancy between CAT and CHMP to avoid divergent views. * CHMP = Committee for Human Medicinal products. Responsible for opinion on centralised MAA + post-authorisation follow-up / Pharmacovigilance

14. © Classification procedure Incentive Open to all applicants Scientific Recommendation from CAT on the Regulatory Classification of their ATMP 60-day procedure (often shorter) Publication of summary information on classification Procedure reviewed (simplified) following experience in 2009

15. © Classification procedure 44 applications received so far 42 finalised Within 60 days 4 out of 42: 1 month clock stop for clarifications (Status April 2011) GTMP Not ATMP ATMP TEP CTMP

16. © Certification procedure Only for SMEs Scientific evaluation by CAT of -(early) quality / development data (Module 3) -(early) non-clinical data (Module 4) 90 day procedure Evaluation to the scientific standards of a MAA -The SME applicant will always received the evaluation report (and List of issue for future consideration) -If positive evaluation: Certificate by EMA 1 Certification procedure finalised (May 2010)

17. © Source: CAT monthly report March 2011

18. © Thank you for your attention Dr Patrick Celis (CAT Secretariat) Patrick.celis@ema.europa.eu +44 207 418 8656 Queries: AdvancedTherapies@ema.europa.euAdvancedTherapies@ema.europa.eu ATMP Microsite: www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/ge neral/general_content_000294.jsp&murl=menus/regulations/r egulations.jsp&mid=WC0b01ac05800241e0 www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/ge neral/general_content_000294.jsp&murl=menus/regulations/r egulations.jsp&mid=WC0b01ac05800241e0

19. © CAT workprogramme 2010-2015 19 Useful links Developers CAT MHRA information on ATMPs http://www.mhra.gov.uk/Howweregulate/Advancedtherapym edicinalproducts/index.htm EMA information on Advanced Therapies http://www.ema.europa.eu/ema/index.jsp?curl=pages/regul ation/general/general_content_000294.jsp&murl=menus/reg ulations/regulations.jsp&mid=WC0b01ac05800241e0&jsenabl ed=true European Commission’s Directorate for public health and risk assessment http://ec.europa.eu/health/human-use/advanced- therapies/index_en.htm

20. © Useful links Developers CAT CAT Work programme 2010-2011 http://www.ema.europa.eu/docs/en_GB/document_library/W ork_programme/2010/11/WC500099029.pdf CAT Interested Parties and Focus Group Non-Clinical development http://www.ema.europa.eu/ema/index.jsp?curl=pages/regul ation/general/general_content_000309.jsp&murl=menus/reg ulations/regulations.jsp&mid=WC0b01ac058009a23d&jsenabl ed=true

21. © Contacts for further information MHRA Dr Gopalan Narayanan - gopalan.narayanan@mhra.gsi.gov.uk Mr Ian Rees - ian.rees@mhra.gsi.gov.uk Dr Elaine Godfrey - elaine.godfrey@mhra.gsi.gov.uk EMA CAT Secretariat Dr Lucia D’Apote - lucia.dapote@ema.europa.eu