1. Advanced Therapy Regulation Hearing, Brussels May 11, 2006 Dr.Andreas Reimann CEO, Mukoviszidose e.V. (German Cystic Fibrosis Association) Vice-Chairman, ACHSE e.V. (German Alliance for Rare Diseases) Member of the Board of Directors, European Organisation for Rare Diseases (EURORDIS)

2. 2 Statement on potential Conflicts of Interest Mukoviszidose e.V. (Bonn) -Financed up to 4% in total by funds provided by approx. 25 pharmaceutical companies -Mainly financed by private donors not related to health industry ACHSE e.V. (Berlin) -Financed mainly (approx.90%) by funds provided by institutional or corporate donors not related to the health industry EURORDIS (Paris) -Financed up to 16% by funds provided by the members of the EURORDIS Round Table of Companies and 37% provided as an unrestricted grant from the French Muscular Dystrophy (AFM) association. Remainder mainly financed through EC-project grants (31 %) and members (3 %).

3. 3 Disclaimer Unless mentioned specifically, the views expressed in that presentation represent the authors personal opinion and may or may not represent the views of Mukoviszidose e.V., ACHSE or EURORDIS. EURORDIS has commented on a previous draft in 2005 and this contribution is included in that presentation, where applicable. Neither of the organisations has issued a consensus document on the use of human embryonic stem cells. This disclaimer should, however, not be understood in a way that the views expressed in that presentation are reflecting an isolated position only.

4. 4 Why patients with rare diseases hope for Advanced Therapies (AT) 30 mio citizens of Europe affected by one of the 5-6000 rare diseases 80% are of genetic background, most affect children For the majority of rare diseases, no cure is available today Patients put therefore considerable hope on new therapies including but not limited to ATs We realize that nobody can for sure say when and whether these therapies will be helpful for specific diseases

5. 5 General positive comments Because patients put considerable hope on Advanced Therapies, the scope and content of the EC proposal is very much welcomed Central Evaluation and composition of CAT (patient representation, expertise) is welcomed because of the need to evaluate and to monitor both safety and efficacy of ATs Incentives for applicants are appropriate The need for sufficient flexibility is well recognized

6. 6 Critical issues - general No support for the commercialisation of unmodified human tissues and cells, therefore donation of tissues and cells must (rather than should) be unpaid and voluntary It is fine to exclude tailor-made products for single patients from need for registration, however, this must not become an easy way to evade the central registration

7. 7 Critical issues – role of CAT Who provides the scientific advice to the applicants, the CAT or the CHMP/SAWP or both? (re: art.17.1) Can the CAT provide scientific advice to the applicant on its own right or only by request of CHMP? What happens if CAT scientific advice on development is not in accordance with CHMP? What happens if CAT and CHMP are in disagreement with regard to MA? Is the CAT a scientific body only or will it have the opportunity to appeal to the EC? (re: art.9.4)

8. 8 Critical issues – traceability and post- authorisation follow-up Long-term follow up of both safety and efficacy must be mandatory to establish a learning system. Provisions needs to be in place to ensure so. Therefore, relevant data (clinical trials, observational studies, registries, spontaneous reporting) on PM-surveillance (safety and efficacy) must be reported systematically to the EMEA, where a public risk management system needs to be established. Traceability to the end-user must be established independent of the MA-holder. Art.16 should therefore be amended accordingly

9. 9 Because of its skills, and of its harmonised procedures, this structure would allow for a better follow-up of these products and the constitution of a precious public registry on safety and efficacy of advanced therapies products. This long term follow-up and data collection would certainly benefit the development of the whole sector and would enhance public support and confidence towards advanced therapies. Central Data Base

10. 10 Points to consider Concept of rec.6 and art.28 is welcome, i.e. central evaluation but opt-out option for MS if there exists a conflict with their national legislation or policy in using certain types of cells (e.g. human embryonic stem cells) That principle must be legally water- tight

11. 11 Points to consider (cont) However, there is no need to include animal cells in that exceptional provision for ethical reasons The regulation should specifically exclude the evaluation and marketing- authorisation of techniques using genetic manipulation of germ-cells, reproductive cloning or human/animal chimaeras

12. 12 German Cystic Fibrosis Association www.muko.info European Organisation for Rare Diseases www.eurordis.org German Rare Disease Alliance: Allianz Chronischer Seltener Erkrankungen www.achse-online.de