Development and authorization of cell-based therapies in Europe

Transkriptio

1 Development and authorization of cell-based therapies in Europe ISCT Auckland, 25 th April 2013 Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 1

2 TEPs sctmps GTMPs Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 2

3 Somatic Cell Therapy Medicinal Products (SCTMP) contains or consists of cells or tissues that have been subject to substantial manipulation so that biological characteristics, physiological functions or structural properties relevant for the intended clinical use have been altered, or of cells or tissues that are not intended to be used for the same essential function(s) in the recipient and the donor; is presented as having properties for, or is used in or administered to human beings with a view to treating, preventing or diagnosing a disease through the pharmacological, immunological or metabolic action of its cells or tissues. Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 3

4 Cancer immunotherapy Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 4

5 Tissue engineered product (TEP) Contains or consist of engineered cells or tissues Presented as having properties for, or is used in or administered to humans with a view of regenerating, repair or replacing a human tissue Definition of engineered cells/tissue Substantial manipulation; or Not intended to have the same function in donor / recipient Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 5

6 Cartilage repair Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 6

7 Combination products in EU Regulation 1394/2007/EC: Combined ATMP means a product that fulfils the following conditions: - must incorporate, as an integral part of the product one or more medical devices (93/42/EEC) or active implantable medical devices (90/385/EEC) its cellular or tissue part must contain viable cells or tissues or the non-viable cellular/tissue part must have action that is primary to that of the device(s) Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 7

8 Number of ATMP clinical trials / EU IMPs * GTMP sctmp TEP Multinational CTs 2012: GTMP 7/28, TEPs 10/19, SCTMPs 5/65 Main indications: - Cancer immunotherapy (sctmp and GTMP) - cardio-vascular - TEPs for repair of skin/eye/liver/bone/cartilage - vaccines (GTMPs for HIV, HPV, HCV etc.) * Cumulative number of new applications (report is suggestive and should not be considered exhaustive). This report has been generated from the information in EudraCT Data Warehouse.. Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 8

9 The EU legal / regulatory framework Blood 2002/98/EC Clinical Trials 2001/20/EC Paediatrics 1901/2006 Annex I 2003/63/EC 2009/120/EC Tissues / Cells 2004/23/EC Medicinal Products Community Code Dir. 2001/83/EC Advanced Therapy 1394/2007 PhVig legislation Dir. 2010/84/EU Reg. 1235/2010 Medicinal Products Centralised procedure Reg. 726/2004 Falsified Med. Dir. 2011/62/EU Other starting materials Medical Devices 93/42/EC, 90/385/EC GMP 2003/94/EC Orphans 141/2000 Variations 1084(5)/ /2008 Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 9

10 EMA Committees for ATMPs CHMP Chair: Dr. T.Salmonsson CAT Chair: Dr. C.Schneider 5 double members Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 10

11 MA applications Submitted Total Approved (forecast) GTMP SCTMP TEP Approved: ChondroCelect, Glybera At the moment 3 cell-based products under evaluation (2 near opinion, 1 at D120) 3 new CBMP submissions verified for 2013 (one SCTMP, two TEPs) Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 11

12 Scientific advice Total Gene therapy Cell therapy TEP Total Total new only % of scientific advice on cellbased products Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 12

13 Classifications Total Gene therapy Gene therapy, combined ATMP Cell therapy Cell therapy, combined ATMP TEP TEP, combined ATMP ATMP (not subclassified) not ATMP Total Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 13

14 Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 14

15 Drug development of ATMPs in EU Scientific advice (national and/or EMA), certification Development Preclinical Clinical trials PhI PhII PhIII MAA Review Post Marketing GMO application GMP CT application (national authorities) Pre MAA PSUR Meetings cycle (Rapp & Co-Rapp) CE marking/ Evaluation of structural Component(s) by Notified Body Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 15

16 MAA procedure for ATMPs RAPPORTEUR TEAM CHMP Co-ordinator (at CHMP level) + CAT Rapporteur (at CAT level) incl. Q/S/E Experts CO-RAPPORTEUR TEAM CHMP Co-ordinator (at CHMP level) + CAT Co-Rapporteur (at CAT level) incl. Q/S/E Experts CHMP Peer review by 1 CHMP member 1 (or more) CAT member(s) CHMP Co-ordinator responsible for flow of information between CAT & CHMP + discussion/adoption of opinion at CHMP CAT (Co)Rapp coordinate procedure & discussions at CAT + prepare draft opinions and assessment reports CAT Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 16

17 Available EU guidance for CBMPs Guideline on cell-based medicinal products (2008) Potency testing of cell-based immunotherapy MPs for treatment of cancer (2007) Reflection paper on stem-cell based MPs Reflection paper on Chondrocyte containing MPs for cartilage repair (2009) Reflection paper on combined CBMPs Guideline on Xenogeneic CBMPs (2009) Guideline on MPs containing genetically modified cells Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 17 17

18 Other applicable guidance Available disease specific guidance GMP Guideline Annex 2 Ph.Eur. monographs Guideline on Safety and Efficacy Follow-up Risk Management of ATMPs EMA / ICH guidelines Q, S, E traceability guidance GCP guidance Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 18 18

19 Risks vs. limitations of ATMPs infections (microbial contamination of starting materials or during processing) tumourigenicity (cell transformation, integration to genome) dedifferentation / loss of function of the cells immunogenicity, rejection ectopic engraftment of cells to non-target tissues shedding (genet. modif. CBMPs; germ line, environment) small sample sizes, short shelf-lives, availability of proper animal models, applicability of analytical methods etc. Risk-based approach for all ATMPs Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 19

20 Framework Reg. 1394/2007/EC Products legally on national markets via GMP certificate Hospital exemption Article 28, 1394/2007/EC Transitional period ATMPs, other than TEP Tissue engineered products, Marketing stopped Centralised MAA Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 20

21 Article 28, 1394/2007/EC: Hospital exemption Any ATMP,, which is prepared - on a non-routine basis - according to specific quality standards, and - used within the same Member State - in a hospital - under the exclusive professional responsibility of a medical practitioner in order to comply with an individual medical prescription for a custom-made product for an individual patient Manufacturing to be authorised by the MS competent authorities National traceability and pharmacovigilance requirements Specific quality standards as on the community level Currently under Commission evaluation (consultation and report) Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 21

22 Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 22

23 In conclusion A lot of new products in the pipeline; most still in phase II and developed by academia / hospitals /SMEs first products: sctmps for cancer immunotherapy and cardiac repair, TEPs for cartilage/eye/skin/bone repair Regulation 1394/2007/EC has clarified authorisation and use of novel cell therapy products in Europe; problems with grey zone products CAT/EMA assistance available: classification, certification of Q/NC data, informal ITF meetings, scientific advice, guidance Risk-based approach for all ATMPs hospital exemption dedicated for non-routine production of CBMPs for individual patients under a national manufacturing lisence Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 23

24 Thank you for your attention! Lääkealan turvallisuus- ja kehittämiskeskus Paula Salmikangas 24