1. 1 Drug Safety Oversight Board: Recent Activities FDA Science Board Advisory Committee Meeting March 31 st, 2006 Douglas C. Throckmorton, MD Deputy Director Center for Drug Evaluation and Research US Food and Drug Administration

2. 2 Today’s Talk Update Science Board on Drug Safety Oversight Board (DSB) activities and its relationship to other safety activity in CDER. Focus on: Roles of DSB and Advisory Committee (AC) meetings in CDER deliberations on drug safety DSB Activities: Safety Communications Internal CDER process development

3. 3 Drug Safety Oversight Board (DSB) Formed in 2005 as part of CDER response to new needs to communicate and manage product safety Task: provide independent oversight and advice to the CDER Center Director on management of: Important drug safety issues and policies Dissemination of certain safety information through FDA’s website to healthcare professionals and patients

4. 4 DSB Membership Chair – Deputy Director, CDER Executive Director – Dr. Susan Cummins Membership - representatives from CDER offices, CBER, CDRH, NIH, VAH

5. 5 CDER Response to Drug Safety Issues: Complimentary Roles of DSB and AC Meetings

6. 6 DSB does Not Replace AC Meetings or Reduce Public Input DSB Meetings : Review of information on many products at each meeting CDER Process oriented: What steps should CDER take to evaluate, resolve and communicate a complex safety issue? How should CDER track and address emerging safety issues? AC Meetings : Review of information on single drug or class of drugs Regulatory Action oriented: Should a new product be approved for marketing? Is there evidence of a new important risk?

7. 7 DSB does Not Replace AC Meetings or Reduce Public Input (cont) DSB Meetings: Venue for resolving CDER organizational drug safety disputes Venue for discussing need for AC meetings about emerging safety information AC Meetings: Venue for obtaining public input where needed to assist decision-making Discussing safety and efficacy of new products prior to marketing publicly Discussing emerging safety concerns for marketed products Discussing risk management for identified safety concerns both pre- and post-marketing

8. 8 AC Members have Access to Detailed Information Examples: Product developer’s data and analyses CDER efficacy and safety evaluations CDER review from other disciplines: pre-clinical toxicology, clinical pharmacology, statistical CDER reviews of post-marketing Adverse Event reports Summary information on drug use

9. 9 CDER AC Meetings Discuss Drug Safety Issues Drug safety a frequent part of (or sole reason for) AC discussions Examples: Tysabri for Multiple Sclerosis Drugs for ADHD (2 ACs)

10. 10 CDER Outreach for Public Input on Drug Safety Communications beyond AC Meetings December 7 th & 8 th 2005 Part 15 Hearing: FDA’s public communications about drug safety Public supports goals of new FDA communications, but Many types of communications Sometimes confusing Navigating the FDA website: Difficult for various groups to locate documents directed to them: patients, health care providers, regulators

11. 11 Summary DSB and AC Meetings have separate, vital roles in CDER responses to drug safety CDER uses available venues to assure appropriate public input into safety decisions

12. 12 Current Focus of DSB Activities

13. 13 DSB Focus on Emerging Safety Issues Since last Science Board, 11 safety communications discussed with DSB before or after posting. Examples: Nimodipine (Nimotop)— alert about added Black Box warning about cardiovascular risks of inappropriate intravenous use of product approved for oral use Aprotinin (Trasylol)— alert about serious renal toxicity & ischemic events in patients undergoing CABG or cardiac surgery with CP bypass Technetium 99m Tc fanolesomab (NeutroSpec)— market suspension following reports of serious & life-threatening cardiopulmonary adverse events Norlegstromin/ethinyl estradiol (Ortho Evra)— alert about ongoing studies to define clinical consequences of total estrogen levels for users that average 60% higher than oral contraceptives containing 35 micrograms of estrogen

14. 14 DSB Focus on Process Development Work on CDER process for addressing emerging safety issues: Discussion of a CDER-wide tracking system for identified safety issues Work on Guidance for DSB conduct Revision of Proposed Drug Watch Guidance Addressing public comments Revising Guidance where needed Work on Guidance for DSB staff activity Creation of Standard Operating Procedures (MaPP) for: DSB meetings DSB information sheet development Other routine DSB operations

15. 15 DSB Focus on Process Development (from MaPP) Identify, track and oversee management of important drug safety issues Adjudicate organizational disputes concerning management of drug safety issues Select drugs to be placed on Drug Watch and update their status as appropriate Establish policies regarding management of drug safety issues in CDER Oversee the development of patient and professional information sheets in CDER Track important emerging safety issues and ensure they are resolved in a timely manner Ensure CDER decisions about a drug’s safety benefit from the input and perspective or experts within and outside FDA who have not conducted the primary review or served as a deciding official in the ongoing pre-market evaluation or post- market surveillance activities with respect to the drug

16. 16 Summary DSB continues to develop its role in CDER: Continued role in assisting effective safety communication Focus on process development for drug safety tracking and oversight

17. 17 Conclusions DSB does not replace or diminish the importance of AC meetings, or reduce the discussion of safety in public venues DSB continues to be a valued, new voice to assist CDER decision-making on drug safety