1. Advisory Committees Linda Ann Sherman, MD, MPA Advisory Committee Oversight and Management Staff, Director U.S. Food and Drug Administration April 20, 2005

2. Welcome! to the Washington Area!

3. FDA’ s Mission To promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner

4. Most Americans Recognize FDA What is the name of the government agency that conducts the review and approval of new drugs and devices before they can be put on the market in this country? Source: Aggregate Spring 1999 Charleton Research Company

5. U.S. Food and Drug Administration FDA regulates over $1 trillion worth of products, which accounts for 22 cents of every dollar spent annually by American consumers.

6. Public Expectations The Public trusts the FDA, as a public service agency, to safeguard their health and safety by making timely and credible independent scientific judgments on food and health products.

7. FDA Strategies to Address those Expectations Have a Strong Science Base – to support regulatory decisions Exercise Risk Management –before and after products enter the marketplace Provide Effective Risk Communication –to stakeholders

8. FDA’s Responsibilities Remain for the Product’s Entire Lifecycle.

9. Close to 10,000 Persons Work at FDA Physicians & Nurses Microbiologists Chemists Pharmacists Toxicologists Statisticians Biopharmaceutists Engineers Economists Support Staff

10. FDA is composed of six Centers and the Office of the Commissioner and Office of Regulatory Affairs Center for Biologics Evaluation and Research Center for Devices and Radiological Health Center for Drug Evaluation and Research Center for Food Safety and Applied Nutrition Center for Veterinary Medicine National Center for Toxicological Research

11. FDA’s Acting Commissioner Lester Crawford, DVM, PhD Deputy Commissioner of Policy (Acting) –Vacant Deputy Commissioner for Operations (Acting) –Janet Woodcock Deputy Commissioner for Special Programs (Acting) –Murray Lumpkin

12. Commissioner’s Office Office of Management – Kathleen Heuer Office of External Relations –Sheila Dearybury Walcoff Office of Policy –Randall Lutter Office of Legislation –Patrick Ronan Office of Science –Norris Alderson Office of the Chief Counsel –Gerald Masoudi

13. Center Directors CBER – Jesse Goodman, MD CDER – Steve Galson, MD (Acting) CVM - Steve Sundlof, DVM, PhD CFSAN – Robert Brackett, PhD CDRH – Daniel Schultz, MD NCTR - Dan Casciano, PhD ORA – John Taylor, JD

14. What do we really do? Ensure that medical products are safe and effective What do we not do? Dictate medical practice or service

15. FDA Hot Topics Counter-terrorism Ephedra Mercury in Fish Cox-2 Inhibitors Influenza Vaccine Importation of Drugs Breast Implants Obesity

16. The Review Process Original IND, IDE IND, IDE, Submissions Adverse Events Profile NDA, ANDA, PLA, ELA, BLA, PMA, 510K Annual Reports Labeling Changes and Supplements Single Investigator IND

17. Reviewing is a Team Approach

18. Review Team Members Project Manager Biopharmaceutist Microbiologist Chemist Medical Officer Statistician Toxicologist

19. Levels of Review Primary –Detailed data review –Recommends additional information, if needed –Initial recommendation for action Secondary –Works with primary reviewer – edits, challenges –Prepares a secondary review Tertiary –Final action

20. The Value of an Advisory Committee Provides independent expert advice Lends credibility to the product review process Allows for a public discussion of controversial issues Keeps consumers abreast of trends in product development Assists in external review of FDA’s intramural research programs

21. Two Types of Advisory Committees Statutory –Required by law Discretionary –Deemed necessary by the Agency

22. Department Policy on Committee Establishment No Federal advisory committee will be established unless such establishment is specifically authorized by statute, by the President or by the Secretary. Discretionary committees will be established only after the Secretary has determined in consultation with GSA and OMB, where required that the specific functions and duties cannot be adequately performed by existing HHS offices, by informal working relationships within or between departments or agencies of the Federal Government, or by existing Federal advisory committees.

23. Establishment Process FDA can request establishment of a new committee when: –There is a genuine need for advice from an advisory committee and it is in the public interest to establish such a committee and –Agency officials have ensured that adequate authority exists for such establishment and the authority complies with statutory requirements and restrictions.

24. Termination of a Committee For Advisory Committees whose duration is not otherwise fixed by law or Presidential Directive will terminate: –Two years after establishment unless approved for renewal in consultation with General Services Administration or –When its mission has been accomplished even though the expected period of duration has not expired or –When the function can be easily assigned to another committee.

25. Department of Health & Human Services Objectives Limit the number of advisory committees to those that are essential and terminate any committee not fulfilling its purpose Assure adequate opportunities for access by the public to advisory committee meetings Provide clear goals … assure that committees are used solely for advisory functions unless provided otherwise by statute

26. Advisory Committees are Product and/or Center Related There are

27. Center for Biological Evaluation and Research Allergenic Products Cellular, Tissue and Gene Therapies Blood Products Transmissible Spongioform Encephalopathies Vaccines and Related Biological Products

28. Center for Drug Evaluation and Research Anesthetic & Life Support Drugs Anti-Infective Drugs Anti-Viral Drugs Arthritis Drugs Cardiovascular & Renal Drugs Dermatologic & Ophthalmic Drugs Drug Abuse Endocrinologic & Metabolic Drugs Gastrointestinal Drugs Non-Prescription Drugs Oncologic Drugs Peripheral & Central Nervous System Drugs Pharmaceutical Science Psychopharmacologic Drugs Pulmonary-Allergy Drugs Reproductive Health Drugs

29. Center for Devices and Radiological Health National Mammography Quality Assurance* Device Good Manufacturing Practice* Technical Electronic Product Radiation Safety Standards Committee* Medical Devices* *(Statutory Committees)

30. Center for Devices and Radiological Health Medical Devices’ Panels* –Anesthesiology and Respiratory Therapy Devices –Circulatory System Devices –Clinical Chemistry and Clinical Toxicology Devices –Dental Products –Ear, Nose and Throat Devices –Gastroenterology and Urology Devices –General and Plastic Surgery Devices –General Hospital and Personal Use Devices –Hematology and Pathology Devices –Immunology Devices –Microbiology Devices –Neurological Devices –Obstetrics and Gynecology Devices –Ophthalmic Devices –Orthopedic and Rehabilitation Devices –Radiological Devices –Dispute Resolution –Molecular and Clinical Genetics

31. Center for Food Safety and Applied Nutrition Food Advisory Committee

32. Center for Veterinary Medicine Veterinary Medicine Advisory Committee

33. National Center for Toxicological Research Science Advisory Board Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects Phenoxy- Herbicides and Contaminants (Ranch Hand)** ** Chartered and Members appointed by Secretary HHS

34. Office of the Commissioner Science Board of the Pediatrics Advisory Committee* *Statutory

35. Types of Topics Brought Before an Advisory Committee Review of Cutting Edge Scientific Issues Product Approval Issues Adverse Event Problems Labeling Issues Guidance Documents Peer Review of Intramural Research

36. Who Comprises the Membership? Our Stakeholders: –Academicians –Clinicians –Consumers –Industry Representatives –Patients and/or Patient Care Givers

37. FDA Aims for a Diverse Advisory Forum FDA wants to have its Advisory Committee members mirror the population of America with regard to –age –race –sex –ethnicity –geographic location

38. Who Can Recommend a Prospective Member? Referrals come from: –Former/Current Advisory Committee Members –FDA Scientists –Professional Societies and Journals –Academic Institutions –Consumer Groups –Self Nominations –Congressional Staff –Industry

39. Member Selection (Varies Somewhat by Member Type) Public (Federal Register) notice requests Nominations Résumés reviewed by Product Related area within the Agency and recommendation forwarded to the Appointing Official –Screen for Needed Expertise –Preliminary Screen for Conflicts of Interest Consideration is made for Committee Balance A letter of invitation is extended by the Associate Commissioner for External Relations

40. Committee Service Term of Service is usually Four (4) years (service is extended only rarely) Most “standing” Members become special Government employees (SGEs) SGEs are subject to Conflict of Interest (COI) Screening and the Emolument Clause of the U.S. Constitution A Chair is usually selected after experience as a Committee Member

41. Conflicts of Interest Prior to every Meeting each (SGE) member is evaluated for any potential conflicts of interest relative to the meeting topic

42. Conflict of Interest Dilemma Experts by definition are engaged in cutting edge bench science, “clinical trial” research and independent consulting work. By virtue of the above, these individuals are sought out by regulated industry to assist in product development.

43. Meeting Logistics Briefing Packages sent at least 3 weeks in advance to the Advisory Committee Members Redacted Briefing Packages available for review on the Web and as handouts at the time of the Meeting Conflict of Interest Disclosure Statements Read into the Record Chair - Facilitates the Meeting Questions presented to the Committee Discussed and Voted Upon Open Public Hearing (public comment) available at each meeting

44. Who Can Vote? NOT EVERYONE Statute Dependent –COI limitations –Industry Reps –Consumer Reps –Patients

45. An Important Take Home Message Advice from Advisory Committees is thoroughly reviewed by the FDA Scientific Staff However, decisions and votes are NOT binding on the Agency.

46. Finally… Questions(?): Advisory Committee Oversight and Management Staff U.S. Food and Drug Administration 5600 Fishers Lane (HF-4) Rockville, Maryland 20857 301-827-1220 lsherman@oc.fda.gov Or Internet http://www.fda.gov/oc/advisory/default.htm