1. 1 GOOD MORNING! BONJOUR! GOEDEMORGEN!

2. 2 An Introduction to certain aspects of the US FDA Murray M. Lumpkin, MD Deputy Commissioner International Programs US Food and Drug Administration Belgian Trade Delegation Washington 28 June 2011

3. 3 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm259848.htm

4. 4 http://www.ema.europa.eu /docs/en_GB/document_lib rary/Report/2011/06/WC50 0107900.pdf

5. 5 FDA – Belgium - Europe Long history of interactions Confidentiality arrangements with: Belgian Scientific Institute of Public Health Belgian Federal Agency for Medicines and Health Products Quality of Medicines & HealthCare (EDQM) Health and Consumer Protection Directorate-General (DG SANCO) EMA EFSA

6. 6 Confidentiality Arrangements Legal Framework to share: Commercial confidential information Pre-decisional information Investigative – compliance information Pharmacovigilance data, reports NOT Trade Secret information NO requirement to exchange anything

7. 7 FDA = Federal Drug Administration Food and Drug Administration Part of Department (Ministry) of Health and Human Services Secretary (Minister) part of President’s cabinet (Kathleen Sibelius) Commissioner of Food and Drugs – (Dr Margaret Hamburg) appointed by President, confirmed by Senate, responsible to Secretary – politicals / career CDC, NIH, others also part of DHHS (FDA is the only regulatory body in DHHS) Our secretary & commissioner are not part of our Congress (not a parliamentary system)

8. 8 FDA - Components ~12,000 employees (~7500 in Washington) Office of the Commissioner (OC) Office of Regulatory Affairs (ORA) (inspectorate/enforcement) Center for Devices and Radiologic Health (CDRH) Center for Veterinary Medicine (CVM) Center for Food Safety and Applied Nutrition (CFSAN) National Center for Toxicologic Research (NCTR) Center for Tobacco Products Center for Biologics Evaluation and Research (CBER) Center for Drug Evaluation and Research (CDER)

9. 9 Two medicines laws U.S. Public Health Service Act (1902) Most biologically derived human medicines Biosimilars (2010) Federal Food, Drug, and Cosmetic Act (1938) Most chemically derived human and animal medicines Generic Drugs (1984)

10. 10 NEW MEDICINE DEVELOPMENT Discovery / Screening Synthesis and Purification Animal Testing Pre-clinical Research IND Clinical Studies Short-term Long-term Phase 1 Phase 2 Phase 3 MAA Review Post-authorisation MA “NDA” AP

11. 11 IND PROCESS (IND = Investigational New Drug) Submit IND application before 1 st clinical study in the US (no matter what “phase” the first study is) Regulatory vehicle under which all investigational trials are overseen in the USA All animal data, previous clinical data outside USA (if any), development plan, and first protocol with special emphasis on any safety concerns and manufacturing process for clinical trials supplies Make case for why it is reasonable to proceed into humans at this point and why the plan for safety monitoring is adequate Include IRB (ethics committee) oversight information (name)

12. 12 IND PROCESS After 1 st submission – must wait 30 calendar days. If nothing heard from FDA, may proceed on day 31. Do not need to wait for authorising letter. In fact, there is no “authorising letter” Subsequent submissions are all “notifications”. Do not need to wait to start trial, simply notify.

13. 13 IND PROCESS FDA can place any trial (or part of a trial) on “hold” at any time “Hold” means trial may not proceed and, if started, no further patients may be enrolled If application not complete If FDA does not believe it is reasonably safe to proceed If FDA does not believe company is properly monitoring for potential safety problems If FDA believes trial design puts patients at risk for no scientific purpose (vs not going to answer the question the company wants to have answered)

14. 14 WHY DO WE DO THIS? Promote and Protect Public health – clinical trials are how we initially learn about the safety and efficacy of new products Need independent oversight to help assure that subjects are not put at unreasonable risk and not put into trials from which we cannot reasonably expect to learn something scientifically relevant

15. 15 WHY DO COMPANIES ENGAGE WITH US FDA DURING DEVELOPMENT Submissions are required Essentially all engage much more than minimally required No direct cost for such meetings

16. 16 FDA / SPONSORS DURING DRUG DEVELOPMENT Interact with sponsors to maximise efficiency and scientific robustness of their drug development program

17. 17 VERY IMPORTANT: PRE-IND / END OF PHASE 2 Reach Understanding of Development Goals and Implementation Trial designs / Where to do them Evaluability Criteria Define a “Win” Characterise Product Indications, Dosing Regimen(s) Major Safety Parameters Manufacturing Issues Possible modifications with time

18. 18 SPECIAL PROTOCOLS Carcinogenicity Stability P3 trials that will be primary data for an efficacy claim Performance goal: 45 days Written agreements binding except when science changes

19. 19 When can a product be authorised? When the data show that the demonstrated benefits outweigh the known risks for the intended population when used as directed

20. 20 EARLY ACCESS INITIATIVES Discovery / Screening Synthesis and Purification Animal Testing Pre-clinical Research IND subm Clinical Studies Short-term Long-term Phase 1 Phase 2 Phase 3 MAA Review Post-authorisation AP Subpart E: Submit MA here Accelerated Approval: Priority Review Fast Track- Rolling Review Treatment IND

21. 21 US - EU COMPARISON (Nomenclature) United States Priority Review Accelerated Approval (Subpart H) Subpart E Fast Track European Union Fast Track Conditional Approval Approval under special circumstances No equivalent

22. 22 Thank You / Merci / Dank U Questions? Comments?