EMA/CAT support to ATMP developers

Transcription

1 EMA/CAT support to ATMP developers CAT-ISCT Workshop: Challenge and opportunities for the successful development and approval of Advanced Therapy Medicinal Products. Presented by Patrick Celis on 25 September 2015 CAT Secretariat An agency of the European Union

2 Content Support to all developers Scientific advice, ITF, SME ATMP Specific incentives ATMP classification and ATMP certification Early access mechanism Types of marketing authorisations How to make best use of the existing regulatory tools Adaptive Pathway Pilot 1

3 Looking for the best way forward to develop an ATMP? Other EMA / CAT activities Scientific advice from CHMP and CAT at the EMA via SAWP 2

4 Support to developers of medicines: Scientific Advice (1) Incentive: early late / scientific certainty Open to all applicants Fee reduction for SMEs Fee reduction for ATMP developers (non-smes) Protocol assistance (free) for Orphan medicinal products Scientific advice is given from the SAWP of the CHMP in collaboration with the CAT (+ other committees & working parties) Fast procedure: 40 or 70 days (if face to face meeting with the Applicant) Possibility for parallel SA with FDA SA also used in the frame of DG Research Horizon2020 projects 3

5 Support to developers of medicines: Scientific Advice (2) The forum to agree on the methodological approach and scientific rationale in quality, non-clinical and clinical aspects / prospective Frequently asked questions for ATMPs: Quality: comparability and potency assays Non-clinical: relevance of animal models for pharmacology and toxicology studies Clinical: milestones of study design, including e.g. non-feasibility to conduct a comparative trial; small populations The scientific advice letter contains the consolidated view of the CHMP, SAWP, CAT, et al 4

6 Scientific Advice for ATMPs CAT involved in all SA s for ATMPs 157 SA procedures discussed Increase in SA s for ATMPs (especially for GTMP) SA requests until July

7 Parallel scientific advice with Health Technology Assessment (HTA) bodies - Aim: bringing together stakeholders for early dialogue in medicines development - EMA pilot project since 2010, in total 34 procedures - The same time schedule as in regular scientific advice procedure - Evaluation of the project on-going - 4 ATMPs included 6

8 Additional Support to developers of medicines Innovation task forces (ITF) - Agency-wide coordination - Support of CHMP for borderline discussions - Briefing meetings - Forum for early dialogue between Developers and Regulators - Regulatory/procedural advice + (non-binding) scientific feedback - Involvement of Committee/Working Party members if needed 7

9 Additional Support to SME developers of medicines Micro-, small- and medium-sized enterprise (SME) office -specific provisions on 15 Dec 2005 by the EC EMA s SME office to promote innovation and the development of new medicines -dedicated personnel support: responds to practical or procedural follow-up of product development -SME specific incentives SME online survey deadline 25 September 2015 See: Human Regulatory SME office 8

10 Additional Support to SME developers of medicines Incentives Administrative/procedural assistance Fee reduction of scientific advice, post-authorisation activities Fee deferral for marketing authorisation applications (MAA) (fee exemption where SA was followed but MAA not successful) Translation of product information for MAA Fee exemption / reduction for pharmacovigilance activities 9

11 ATMP specific incentives: ATMP classification (1) Incentives: Early / Regulatory certainty Open to all applicants Free of charge Simple procedure: submit (high level) briefing note: Product and product development (manufacturing, quality, non-clinical, clinical) Your views how the product fulfills the definition of medicinal product / ATMP Scientific recommendation from CAT on the regulatory classification of their ATMP 60-day procedure (often shorter) 10

12 ATMP specific incentives: ATMP classification (2) All classification outcomes are published (summary) 134 procedures finalised Stepping stone for first contacts with Regulators (CAT/EMA) ATMP 1 Not-ATMP 16 ATMP Classification GTMP 25 GTMP CTMP TEP ATMP l=pages/regulation/general/general_conte nt_ jsp&mid=wc0b01ac058007f4b c TEP 49 CTMP 43 Not-ATMP (Status July 2015) 11

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14 ATMP specific incentives: ATMP certification Incentive: early-late / scientific certainty Only for SMEs Scientific evaluation by CAT of (early) quality / development data (Module 3) (early) non-clinical data (Module 4) 90 day procedure The applicant will always received the evaluation report and List of issue for future consideration If positive evaluation: Certificate by EMA 6 Certification procedures finalised, 1 ongoing 13

15 Type of Marketing authorisations 1. Standard (full) marketing authorisation (if eligible to centralised procedure): no conditions Positive Benefit Risk (B/R) demonstrated on basis of comprehensive data package (i.e. full clinical development, including completed pivotal trials) Renewal after 5 years Post marketing measures (PAM) following assessment (optional) For ATMPs: (Art 14 of ATMP Regulation) possibility for a full approval with commitment for a post-authorisation study to follow-up safety/efficacy (PASS-PAES). Used e.g for ChondroCelect approval 14

16 Type of Marketing authorisations (2) 2. MA under exceptional circumstances Conditions apply: the applicant cannot provide comprehensive data on Safety/ Efficacy because: (1) rarity of disease; (2) present state of scientific knowledge; (3) not ethical Conditions to be justified by applicant, to be agreed by CHMP/CAT MA valid for 5 years, with specific obligations (e.g. post marketing surveillance, registry study ) Annual re-assessment of the B/R profile based on data for specific obligations 15

17 Type of Marketing authorisations (3) 3. Conditional MA Scope: MP for seriously debilitating/life-treatening diseases; for use in emergency situations; for orphan MP Criteria: B/R positive + comprehensive data can be provided + unmet medical need + immediate availability outweighs risk due to missing data. On request of applicant or proposed by CAT/CHMP MA with specific obligations (e.g. finalisation of Ph3 trial), valid 1 year Annual renewals based on assessment of responses to Specific Obligations (SO) Switch to full MA after fulfilment of all SO 16

18 Approved ATMPs ChondroCelect: Cell suspension for cartilage defects of the knee (full MA) Glybera: Gene therapy for lipoprotein lipase deficiency (MA under except circumstances) MACI: Implant for cartilage defects of the knee (full MA) Provenge: Cancer vaccine for prostate cancer (full MA) Holoclar: Limbal SC deficiency (Conditional MA) 4 ATMPs currently under review (2 GTMP, 1 sctmp, 1 TEP) 17

19 EMA activities to improve early access of products to the EU public health needs ATMPs are included Conditional approval Accelerated assessment Making better use of existing regulatory tools Adaptive pathways initiative (previously Adaptive licensing ) New initiative 18

20 Conditional marketing authorisation Revised Guideline for public consultation Emphasis on importance of planning CMA prospectively to ensure swift assessment procedure, advantages of early dialogue with EMA on the development programme (including joint scientific advice with HTA bodies) Clarification of how a positive benefit-risk balance should be substantiated when less complete data Further guidance on the level of evidence to be provided at the time of authorisation and data that can be provided post-cma type rocedural_guideline/2015/07/wc pdf 19

21 Accelerated assessment (AA) Medicinal products of major public health interest and in particular from the viewpoint of therapeutic innovation Applicant to proactively initiate a dialogue at the EMA Revised Guideline for public consultation Clarification of the justifications by the applicant that their product would fulfil the criteria for AA. 20

22 Accelerated assessment (AA) Procedure for applying for AA: Step 1: Early presubmission dialogue (6-7 months prior MAA) mutual understanding that the data package is mature Step 2: a) formal request for an AA 2-3 months before MAA submission EMA Rapporteurs assessment CHMP/CAT decision in 40 d (Y/N) b) AA procedure of MAA 150 d procedure with 1 month clock stop by default WC pdf 21

23 Adaptive pathways initiative project since March 2014 [Q&A published Sept 2014] to guide the pathway of product development with a lifespan outlook possibly earlier access to market Stage I pilot part closed Febr 2015 after receiving 34 applications 10 product selected to a discussion contact (2 ATMPs, 5 orphans, 4 from SMEs) based on 2 scenario: a) indication possible to be widened to a larger population b) prospective for conditional MA, eg. surrogate endpoints further supported by post CMA data full MA For both a+b: development programs addressing HTA needs 22

24 Adaptive pathways initiative Stage II 6 products selected for in-depth 2-4 h discussion with participation of several stakeholders (incl. HTA) 1 ATMP -Pilot closed but new applications will be considered provided there is a well-developed plan / proposal for - Iterative development - Involvement of HTAs and other stakeholders (e.g. patients, prescribers) - Monitoring/collecting real-world post-authorisation data (e.g. registries) to supplement the clinical trials. 23

25 Adaptive pathways initiative Contact - Q&A (Sept 2014) - Report on initial experience of the pilot project (Dec 2014) 24

26 New initiative: watch our website Accelerated assessment criteria also being considered for a new scheme under development Aim: to reinforce scientific and regulatory support to optimise development and enable accelerated assessment of new medicines addressing major public health needs Details for the scheme under discussion Finalisation and launch planned for the end of

27 European Commission (EC) expert group: STAMP (Safe and Timely Access to Medicines for Patients) Temporary working group, created on advice of the Pharmaceutical Committee Set up to provide advice and expertise to the EC in relation to the implementation of the EU Pharmaceutical legislation, as well as programmes and policies Is to exchange experience of Member States, examine national initiatives and identify ways to use more effectively the existing EU regulatory tools Main goal: to further improve safe, timely access and availability of medicines Not mandated to provide advice with the aim to revise the basic acts Directive 2001/83 and Regulation 726/

28 Thank you for your attention Further information EMA Website / human regulatory Patrick Celis Patrick.Celis@ema.europa.eu European Medicines Agency 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0) Facsimile +44 (0) Send a question via our website Follow us