1. Highlights from ExLPharma’s 5th Clinical Data Disclosure Summit January 12-13, 2010 Washington, D.C.

2. Data Disclosure and Transparency European Requirements

4. Italy

5. France

6. Czech Republic

7. Argentina

8. South Africa

9. China Taiwan

10. Brazil

11. India

12. Netherlands

13. Spain

15. Switzerland

17. Germany

18. Japan

19. UK ISRCTN

20. China

21. Latin America

22. Sri LankaSource: Adopted from June 2008 DIA meeting Pamela Rose presentation. Subject to changing legislation

23. For Regulators Eyes OnlyEudraCT: The European Clinical Trial Database Created based on article 11 of Directive 2001/20 (“Clinical Trial Directive”) Allows sharing of information by European health authorities (European Medicines Agency, Commission) on clinical trials Provides for a unique trial identification number Access to regulators and EU Commission only Currently no direct data access by sponsors or investigators EudraCT is currently a document management system

24. How to Enter Information into EudraCT EudraCT Sponsor / investigator completes Trial Application Form and submits to participating NCA´s Sponsor / Investigator requests EudraCT Nr., Other Dbs** NCA´s* *NCA: National Regulatory Authority ** Drug Safety, Investigational Products, Approved Products NCA´s, Commission*

25. EudraCT is ChangingNew features coming up From version 8 EudraCT will be changed from a document storage to a true relational database XML schema publicly accessible Will provide for multi-language fields Version 8 to go public Q2 2010 Public access to protocol information for ongoing and completed clinical trials (adult and paediatric) Will be linked to EudraPharm for marketed products Version 9 release not yet defined (end 2010?) Public access to clinical trial results (adult and pediatric, approved and investigational)

26. Making EudraCT Fit For for the PublicA Challenging Undertaking Public Access Which information: Data fields, protection of confidential data, languages When to release: Before / after trial start, Ethics Committee vote How to access: Search engine, link to other registers and portals Results Which information and how: format, data fields Data Quality: Consistency with other result information (eg FDAAA) Third Country Trials EudraCT number for non-EU trials Link to EudraVigilance and Investigational Products database

27. Some Specific ChallengesTrial Registration Registration in EudraCT is part of the trial application process which is a national process Protocols for the same trial may differ between different countries (“local amendments”) Some EU countries require all or part of the application in local language For Trial Portals (e.g. IFPMA, WHO) and quality assurance: Which protocol version is the reference version?

28. Some Specific ChallengesRelease of Information to the Public Release to information from EudraCT to the public will be triggered automatically once the trial is approved Trial may not start for significant time or not at all Reasons for Ethic Committee rejection will be made public Protocol may undergo numerous amendments before final start Quality and consistency of information between different EU countries and with non-EU registers for global trials For trial designs For result information Creation of a search engine capable of handling multiple languages

29. Some Specific ChallengesThird Country Trials Trials exclusively running outside of the EU do not normally require a EU trial application and no EudraCT number but have to be included in EudraCT when part of a paediatric investigation plan (PIP) Specific process for EudraCT number application Cannot be handled by National authorities Direct access necessary to EudraCT by international sponsors / investigators Adverse drug experience from non-EU trials to be entered into European Pharmacovigilance database Investigational Product database to capture non-EU approved comparators

30. Developing Data Standards The European Medicines Agency joined the CDSC and HL7 consortia Objective is to harmonize electronic data definition standards for health related data on an internationally Study protocols Electronic health data Public health databases Etc Common data definition standards should ease data exchange and maintain data quality

31. Transparency in Clinical TrialsWhat is Different in Europe Compared to US?

32. The Clinical Trials Registry- India (CTRI) New Mandatory Registration: Overcoming the Hurdles and Best Practices for Compliant Registration with India’s Clinical Trials Registry

35. Competent medical professionals

36. Site infrastructure

37. Potential for cost & time savings

38. Likely high growth market in future40 150 34 India has a large patient pool in diabetes, cardiovascular diseaseHIV and Oncology. Source:National Commission on Macroeconomics and Health , Ministry of Health & Family Welfare, Government of India, New Delhi, September 2005

39. India - the highest # of protocols and sites in AsiaBut still relatively limited number…

40. India- 2009 Clinical Study Start Up times * Review time includes Export License approval

41. Key Regulatory milestones No import duty on clinical trial supplies 2003 Exemption from registration requirements for CTS 2003 Amendments to Schedule Y 2005 Export of biological specimens 2005 Exemption from Service Tax on new drug testing 2007 Need for export license (blood products) waived 2009 Mandatory registration of interventional Clinical Trials 2009

42. Clinical Trials Registry - India Set up by ICMR’s NIMS To encourage all registration of clinical trials prior to patient enrolment Full disclosure of all WHO mandated items To improve transparency and accountability Improve internal validity Conform to accepted ethical standards Lead to reporting of all relevant results of all CTs in India and the region

44. To improve internal validity of trials

46. Who is responsible for registering a trial? Principle Investigator (PI) or the Primary Sponsor For Multi-Centric and Multi-Sponsor Trials, it is the lead PI or lead Sponsor should take responsibility for registration. In case of Multi-Country Trials, the Indian PI should also get the trial registered in CTRI quoting any other Registration number as its Secondary ID.

47. Layout of the Registry

48. Still have any questions? For additional information on ExLPharma’s Clinical Data Disclosure Summits, please visit www.exlpharma.com