1. European Parliament Advanced Therapies Hearing May 11, 2006 Advanced Therapies The proposed EU regulation from the viewpoint of a Pharmaceutical company with experience in the field of Tissue Engineering Priv.Doz.Dr,med.Detlef Niese Novartis Pharma AG, Basel CH European Biopharmaceutical Enterprises (EBE) Member of EuropaBio Advanced Therapies Working Group

2. European Parliament Advanced Therapies Hearing May 11, 2006 About EBE  EBE – European Biopharmaceutical Enterprises is a specialised group of EFPIA created in 2000  EBE has 65 corporate members engaged in research in Europe involving the application of emerging bioscience technologies with the aim of launching new healthcare products

3. European Parliament Advanced Therapies Hearing May 11, 2006 Advanced Therapy Products and Pharmaceutical Companies  Academic institutions, small biotech companies and some large pharmaceutical companies have been involved and are still involved in research and development of cell therapy, tissue engineering and gene therapy products.  Regulatory uncertainty and development risks associated with these products prove to be significant hurdles  As a pharmaceutical company, Novartis has gathered development experience in all sectors of „advanced therapies“

4. European Parliament Advanced Therapies Hearing May 11, 2006 A Real Life Case: Apligraf What it looks like Histology Apligraf Normal Skin

5. European Parliament Advanced Therapies Hearing May 11, 2006 Apligraf ® A Long Clinical & Regulatory Path 1979 E. Bell M.I.T. 1985 Organogenesisformed 1995199820002003 VSU-001 DUS-001 FDAApproval Venous Leg Ulcers 2004 FDAApproval Diabetic Foot Ulcers 19921996 FDA Designated as device class III interactive wound dressing I.D.E.submitted E.M.E.A.Submission E.M.E.A.Withdrawal

6. European Parliament Advanced Therapies Hearing May 11, 2006 A Diverse Regulatory Environment Initial Regulatory Classifications Eventual Regulatory Classification Medicinal Product ApligrafRegulatory DeviceMedicinal OtherReg Unregulated USA Finland Germany Sweden Norway Spain Portugal Denmark France (Cell Therapy) Belgium(Tissue Bank) Greece Switzerland (Transplant) UK Italy Ireland Austria Netherlands Canada Apligraf DeviceMedicinalUnregulated USA Finland Germany Sweden Norway Spain Portugal Denmark France (Cell Therapy) Belgium(Tissue Bank) Greece Switzerland (Transplant) UK Italy Ireland Austria Netherlands Canada

7. European Parliament Advanced Therapies Hearing May 11, 2006 Lessons Learned  A harmonized regulatory framework for all cell based products in Europe is urgently needed to address  Quality assurance  Development and Marketing authorisation  Address unique safety & efficacy issues  Include efficacy assessments based on trial designs that address ethical and practical aspects of surgical research  Benefits of harmonised regulations  Protection of patient safety  Encourage investment by industry and successful global commercialisation through “level playing field”  Provide patients access to innovative & valuable therapies

8. European Parliament Advanced Therapies Hearing May 11, 2006 How We See the Proposed Regulation – What We Welcome  A single, harmonised regulatory framework for all advanced therapy products  Use of the Centralised Procedure through EMEA ensuring harmonised efficacy, quality and safety requirements for all products  The creation of a Committee for Advanced Therapies consisting of experts in the field  The use of subsidiarity for ethical aspects such as embryonic stem cells

9. European Parliament Advanced Therapies Hearing May 11, 2006 How We See the Proposed Regulation – Our Concerns  To ensure safety and effectiveness of AT products the regulation should apply to all products produced following a standardised process (no exemptions)  Instead of exemptions from the regulation, consider providing administrative support or regulatory expertise as an additional incentive for all manufacturers who may require it

10. European Parliament Advanced Therapies Hearing May 11, 2006 How We See the Proposed Regulation – Our Concerns  The formation of a specialised committee (CAT) at EMEA is welcomed but  Expertise of members should reflect the broad spectrum of products and technologies  Expertise of members should prevail over national representation (which is provided by CHMP)  Existing legislation needs adaptation to (e.g. 2001/20, GMP)

11. European Parliament Advanced Therapies Hearing May 11, 2006 Conclusion  The new regulation is principally welcome  Assurance of safety and efficacy through review by regulatory authorities supported by an expertise based CAT should drive development of high quality products and support access for patients  Instead of excluding specific products from the regulation, administrative hurdles for hospital based products or SMEs should be minimised and may require additional incentives  Careful adaptation of all affected existing legislation (like Directive 2001/20 EC) is a crucial success factor