Regulation of Advanced Therapy Medicinal Products: Insights from the European Medicines Agency (EMEA)

1. The Advanced Therapy Medicinal Products Regulation from the European Medicines Agency (EMEA)'s perspective Nathalie Rampal Olmedo EMEA – Directorate – Legal Sector British Institute of International and Comparative Law 25th September 2008

2. ADVANCED THERAPY MEDICINAL PRODUCTS (ATMP) • Medicinal products based on • genes (gene therapy) • cells (cell therapy) • tissues (tissue engineering) • Revolutionary treatments of a number of diseases or injuries, such as skin in burn victims, Alzheimer, cancer or muscular dystrophy • Huge potential for patients and industry

3. REGULATION (EC) No 1394/2007

4. KEY ELEMENTS • Centralized marketing authorization (Single scientific evaluation) • New Committee for Advanced Therapies (CAT) • Specific rules on authorisation, supervision and pharmacovigilance • Specific technical requirements (SPC, labelling and package leaflet) • Combined ATMP evaluated by EMEA • Post-authorisation requirements (follow-up of efficacy/adverse reactions, risk management, traceability) • Special incentives (SMEs)

5. CAT • EvaluationProcedure • Incentives • Application/ImplementationPlan

6. COMMITTEE FOR ADVANCED THERAPIES (CAT) • New EMEA Committee(Article 20(1)) • A CAT shall be established within the EMEA • Composition (Recital 11 and Article 21) • EU best available expertise on ATMP (gene therapy, cell therapy, tissue engineering, medical devices, pharmacovigilance, ethics) • 5 CHMP members (co-opted or not), 1/MS and alternates from same MS or, in the case of co-opted CHMP members, identified by CHMP + 22 from MS not represented through CHMP and alternates + 2 representing clinicians and alternates+2 representing patients and alternates • Tasks (Article 23) • Draft opinion on the Q/S/E of each ATMP for final approval by the CHMP • Advice on ATMP classification • Advice on any question related to ATMP • Assist scientifically in the elaboration of any documents related to the objectives of ATMP Regulation • Scientific expertise and advice for any Community IMI and therapies • Scientific advice procedures • Interaction(Recital 12 and Article 20(3)) • EMEA shouldensure the coordination between the CAT and its other Committees, advisory groups and working parties, notably the CHMP, the COMP and the SAWP

7. EVALUATION PROCEDURE Article 8 1. The Committee for Medicinal Products for Human Useshall consult the Committee for Advanced Therapies on any scientific assessment of advanced therapy medicinal productsnecessary todraw up the scientific opinionsreferred to in Article 5(2) and (3) of Regulation (EC) No 726/2004[1]. The Committee for Advanced Therapies shall also be consulted in the event of re-examination of the opinion pursuant to Article 9(2) of Regulation (EC) No 726/2004[2]. 2. When preparing a draft opinion for final approval by the Committee for Medicinal Products for Human Use, the Committee for Advanced Therapies shall endeavour to reach a scientific consensus. If such consensus cannot be reached, the Committee for Advanced Therapies shall adopt the position of the majority of its members. The draft opinion shall mention the divergent positions and the grounds on which they are based. 3. Thedraft opinion given by the Committee for Advanced Therapies under paragraph 1 shallbe sentto theChairman of the Committee for Medicinal Products for Human Use in a timely mannerso as to ensure that the deadline laid down in Article 6(3)[3] or Article 9(2) of Regulation (EC) No 726/2004 can be met. 4. Where the scientific opinion on an advanced therapy medicinal product drawn up by the Committee for Medicinal Products for Human Use under Article 5(2) and (3) of Regulation (EC) No 726/2004is not in accordancewith the draft opinion of the Committee for Advanced Therapies,the Committee for Medicinal Products for Human Use shall annex to its opinion a detailed explanation of the scientific grounds for the differences. 5. The Agency shall draw up specific procedures for the application of paragraphs 1 to 4.

8. EVALUATION PROCEDURE (2) • [1] Article 5(2) and (3) of Regulation (EC) No 726/2004: • 2. Without prejudice to Article 56 or to other tasks which Community law may confer on it, theCommittee for Medicinal Products for Human Use shall be responsible for drawing up the opinion of the Agency on any matter concerning the admissibility of the files submitted in accordance with the centralised procedure, the granting, variation, suspension or revocation of an authorisation to place a medicinal product for human use on the market in accordance with the provisions of this Title, and pharmacovigilance. • 3. At the request of the Executive Director of the Agency or the Commission representative, the Committee for Medicinal Products for Human Use shall also draw up an opinion on any scientific matter concerning the evaluation of medicinal products for human use. The Committee shall take due account of any requests by Member States for an opinion. The Committee shall also formulate an opinion whenever there is disagreement in the evaluation of medicinal products through the mutual recognition procedure. The opinion of the Committee shall be made publicly accessible. • [2] Article 9(2) of Regulation (EC) No 726/2004: • Within 15 days after receipt of the opinion referred to in paragraph 1,the applicant may give writtennotice to the Agency that he wishes torequest a re-examination of the opinion.In that case, the applicant shall forward to the Agency the detailed grounds for the request within 60 days after receipt of the opinion. • Within 60 days following receipt of the grounds for the request, the said Committee shall re-examine its opinion in accordance with the conditions laid down in the fourth subparagraph of Article 62(1). The reasons for the conclusion reached shall be annexed to the final opinion.

9. EVALUATION PROCEDURE (3) • CHMP shall consult the CAT on any scientific assessment of ATPM including re-examination of opinions(Article 8(1)) • CAT prepares/is responsible for a draft opinion on the Q/S/E of each ATMP for final adoption by the CHMP(Recital 10 and Article 8(2)) • CHMP adopts the final opinion by 210 days(Article 8(3)) • EMEA to draw up specific procedures (Article 8(5))

10. INCENTIVES • Scientific Advice on the design and conduct of pharmacovigilance and risk management (Article 16) • 90% fee reduction for SMEs, 65% for others • Scientific Recommendation on ATMP classification(Article 17) • SMEs: Certification of quality and non-clinical data (Article 18) • Additional fee reduction for SME or hospital proving there is a particular public health interest in the Community (Article 19) • 50% reduction on Marketing Authorisation fees • 50% reduction on post-authorisation activities during 1 year • Applies during transitional period referred to in Article 29

11. APPLICATION ATMP Regulation will apply from 30/12/2008(Article 30) • Transitional period for ATMP «legally on the Community market» (Article 29) • 3 years (SCT and GT) => no later than 30/12/2011 • 4 years (TEP) => no later than 30/12/2012

12. 30th December 2008 !

13. Commission has made public its priorities for theimplementation of the ATMP Regulation The implementation plan has been developed and agreed with the EMEA http://ec.europa.eu/enterprise/pharmaceuticals/advtherapies/index.htm http://www.emea.europa.eu/htms/human/mes/advancedtherapies.htm

14. IMPLEMENTATION PLAN • Commission: • GCP guidelines (Article 4) • GMP guidelines (Article 5) • Amend Annex I to Directive 2001/83/EC (Article 7) • Traceability guidelines (Article 15(7)) • Implementing provisions on certification of quality/non-clinical data (Article 18) • Appoint CAT patients/clinicians representatives (Article 21(c)(d)) • EMEA: • Specific procedures for evaluation (Article 8) • Guidelines on Post-authorisation follow up/Risk management (Article 14) • Establishment of CAT (Articles 20 and 21) • CAT’s Rules of Procedure (Article 61(8) Regulation (EC) No 726/2004)

17. Thank you for your attention Any questions ?