GOOD MORNING! BONJOUR! GOEDEMORGEN!

1. GOOD MORNING!BONJOUR!GOEDEMORGEN!

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

4. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/06/WC500107900.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/06/WC500107900.pdf

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

11. IND PROCESS(IND = Investigational New Drug) • Submit IND application before 1st 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. IND PROCESS • After 1st 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. 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. 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. 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. FDA / SPONSORS DURING DRUG DEVELOPMENT • Interact with sponsors to maximise efficiency and scientific robustness of their drug development program

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

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

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