FDA Science Board

1. FDA Science Board Introduction to Drug Safety April 15, 2005 Rockville, MD RADM Steven Galson, MD, MPH Acting Director, Center for Drug Evaluation and Research Food and Drug Administration

2. Drug Safety Policy Environment has Become More Contentious • Risks of SSRI Antidepressants • Withdrawals of COX-2 analgesics • Allegations – FDA doesn’t care about drug safety • Numerous Congressional oversight investigations and hearings: Drs. Woodcock and Kweder testimony • Press Focus – has evolved towards more nuanced approach FDA SCIENCE BOARD

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4. The Drug Approval Pendulum By Anne Applebaum/Washington Post Wednesday, April 13, 2005; Page A17 "It just breaks my heart when I think of American citizens having to go to Switzerland or Mexico to get the drugs and devices they need to stay alive because the Washington bureaucracy won't approve them." -- Rep. Thomas Bliley (R-Va.), 1995 "When the FDA approves a drug, it should be a Good Housekeeping seal of approval. . . . Consumers shouldn't have to second-guess the safety of what's in their medicine cabinet." -- Sen. Chuck Grassley (R-Iowa), 2005 FDA SCIENCE BOARD

5. Drug Safety Overview • Drug Safety Top Priority Across Regulatory Programs - not just post-marketing surveillance • New drugs • Manufacturing/regulation of drug quality • Generic drugs • Regulation of clinical trials and promotional activities • Pre-market safety evaluation based on mandate of Food, Drug & Cosmetic Act: “All tests reasonably applicable” to safety FDA SCIENCE BOARD

6. Drug Safety Overview cont’d • Implementation- Regulations: Information that “the product is safe…for recommended use.” • Series of FDA & International guidance documents spell out level of evidence needed for safety evaluation: science plus judgment plus policy • Lots of room for disagreement • How safe is safe? • Risk/benefit individual for each drug or class (no formula) • Innovation & new products vs. more assurance of safety FDA SCIENCE BOARD

7. Have user fees modified how we balance benefit and risk? Withdrawal rate and black box warning analyses – NO EVIDENCE

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9. Have Data Requirements Changed? • Yes! More data submitted to support applications than ever before. • Conclusion: Drug Supply safer than ever before, BUT • There are issues: • Science has moved ahead more with efficacy than safety analysis • Bulk of studies conducted have as their main focus efficacy FDA SCIENCE BOARD

10. Safety Issues • Science has moved ahead more with efficacy than safety analysis – doing same tox tests • Size of premarket safety database determined by need of efficacy studies • Rare or time-dependent effects not known at approval • Cannot require additional safety studies after approval. Can only move to take drugs off market FDA SCIENCE BOARD

11. Safety issues – continued • Major additions to pre-approval safety database would be two-edged sword • No national pharmacovigilance system FDA SCIENCE BOARD

12. Plan for this Morning • Pre-Market Drug Safety: Armando Oliva, M.D. • Labeling and Electronic Initiatives: Rachel Behrman, M.D., MPH • Drug Safety Initiatives: Steven Galson, M.D., MPH • Post-Market Drug Safety: Paul Seligman, M.D., MPH • Drug Safety Resources: Theresa Mullin, Ph.D. • Applying New Science to Drug Safety: Janet Woodcock, M.D. • Committee Questions and Discussion FDA SCIENCE BOARD