1. Counter-terrorism at FDA Andrea Meyerhoff MD Director, Office of Counter-terrorism US Food and Drug Administration

2. Overview FDA mandate in counter-terrorism (CT) CT Strategic Plan Organization of CT activities Scientific issues in CT

3. FDA mandate: counter-terrorism Law Enforcement –To prevent, investigate and respond to tampering with food and animal feed, blood, radiation-emitting instruments, drugs, vaccines, medical devices Public Health –To facilitate the availability of safe and effective medical countermeasures-drugs, vaccines, medical devices -for individuals exposed to a biological, chemical, or nuclear agent

4. FDA mandate: counter-terrorism Civilian –generally operate in areas of lower risk –special populations, e.g., children, elderly –public health actions in counter-terrorism likely to follow sentinel event Military –potential to operate in areas of highest risk –generally healthy adults –public health actions may precede event

5. FDA Counter-terrorism Strategic Plan

6. Pre September 11 CT Budget $8.2 million Bioterrorism: Adequate supply of drugs, vaccines, biologicals CDER & CBER FDA’s CT activities pre/post September 11, 2001 Post September 11 CT Budget > $159 million Counter-terrorism: Full range of FDA products Total agency involvement

7. Counterterrorism Strategic Plan Goal 1: Safety and security of regulated products (deterrence, detection, investigation and interdiction) Goal 2: Medical countermeasures Goal 3: Emergency preparedness and response Goal 4: Radiation safety

8. Goal 1: Deterrence, detection, investigation and interdiction: safety and security of FDA regulated products

9. Goal 2: Medical countermeasures

10. Goal 3: Emergency preparedness and response

11. Goal 4: Radiation safety

12. Organization of FDA Counter- terrorism activities

13. Office of the Commissioner: Office of Crisis Management Office of Security Operations, Policy and Planning Office of Emergency Operations Office of Counter-terrorism

14. Organization from the outside: CT queries to FDA Sources –Industry, academic investigator, foreign government, other federal agency, state/local governments, concerned private citizen Portal of entry FDA –Office of CT, Office of the Commissioner Queries –FDA jurisdiction? –Funding? –Where/What in FDA?

15. Organization from the inside: CT Steering Committee 5 Centers –CFSAN (foods and cosmetics) –CVM (veterinary medicine) –CDER (drugs) –CBER (vaccines and other biologics) –CDRH (medical devices and radiation- emitting instruments) Office of Regulatory Affairs (field operations) NCTR (toxicology labs) Press, congressional, legal, international affairs, budget, planning and evaluation

16. FDA scientific issues in Counter-terrorism New standards development building on regulatory precedent

17. FDA: Scientific issues in CT Medical countermeasures –Drugs and biologics –Diagnostic devices Food security Radiation safety

18. OrganismDisease Variola majorSmallpox Bacillus anthracisAnthrax Yersinia pestisPlague C. botulinum toxinBotulism Francisella tularensisTularemia Filo-/ArenavirusesHem fever Biological Agents: Category A US CDC, 1999

19. Medical countermeasures: drugs and biologics Rare diseases: indications with little regulatory precedent Efficacy endpoints for animal models Availability of non-human primates Availability of laboratory space

20. Medical countermeasures: ciprofloxacin for anthrax Accelerated approval –Surrogate= human serum levels Cipro –Reached or exceeded monkey serum levels –Consistently higher than MIC B. anthracis –Associated with improved survival in animals exposed to aerosolized B. anthracis spores compared with those animals receiving placebo –Database of human pathology permitting direct comparison with animal model (Sverdlovsk, 1979) –Database of US industrial exposure

21. Ciprofloxacin Trough Concentrations - All

22. Challenge (from Friedlander et al 1993) Survival TOC End of treatment

23. Ciprofloxacin safety Approved 1987, used > 250 million >1000 patients > 60 days (clinical trials) Compared with patients Cipro® short course and active controls GI most common, generally similar rates across all 3 groups Abdominal pain (3.5%), rash (3.9%) more common > 60 days Cipro® group No previously unidentified AEs

24. Medical countermeasures: diagnostic devices New range of biological agents to assay First step in identifying an outbreak or intentional release of biologic agent Public health, infrastructure, economic consequences linked to performance of assays Need for sensitivity and specificity standards Need to validate the assays

25. Food security: test methods development Detection of biological agents in various food matrices Questions –Survival of pathogen in matrix? –Can pathogen cause human disease following oral ingestion? –Relevant inoculum causing clinical disease?

26. Radiation safety Decades of experience Expertise in –radiological public health –population dosimetry studies from medical x-ray –emergency response Science credentials and on-the-job training Need for inventory in training and expertise

27. Conclusion: FDA counter- terrorism programs FDA mandate –Regulated products meet a standard of purity, safety and effectiveness and are available Public health emergency –Rapid availability of regulated products for large- scale use FDA role in counter-terrorism –Availability of pure, safe and effective products consistent with the legal responsibilities of regulatory agency