1. Polio Eradication -- Global Progress and Development of Post-Eradication Strategies: Implications for U.S. Stockpile and Outbreak Response Preparations National Vaccine Advisory Committee February 8-9, 2005

2. Objectives of Session To provide update on polio eradication progress & plans for post-eradication era To provide update on U.S. success in eliminating all forms of paralytic polio & status of U.S. polio vaccine stockpile To elicit committee discussion re: key actions for U.S. stockpile

3. (III) Elimination of Paralytic Poliomyelitis in U.S.A.

4. Epidemiology of Polio – U.S.A. (I) Routine childhood immunization program –IPV (1950s) & OPV (1960s) –Elimination of indigenous wild polio (1979) & imported wild polio (1993) Adverse effects of oral polio vaccine –VAPP: average 9 cases / year –Accepted as necessary consequence of OPV use, to reduce risk of imported wild polio

5. Paralytic Poliomyelitis and OPV licensing United States, 1960-1969 YEAR No. of Cases tOPV VAPP Cases type 3 mOPV type 1 mOPV type 2 OPV

6. Paralytic Poliomyelitis, United States, 1980-1989 YEAR No. of Cases

7. Epidemiology of Polio – U.S.A. (II) Cessation of OPV in U.S. –Global polio eradication progress in 1990s: Lower risk of imported wild poliovirus in USA Changing benefit / risk ratio for OPV VAPP = unacceptable risk –Transition to IPV: Sequential IPV-OPV schedule (1997) All IPV schedule (2000) –Last VAPP cases occurred in 1999

8. Paralytic Polio Cases and OPV Doses Distributed United States, 1990-2003 Year VAPP cases OPV doses in millions IPV-OPV All-IPV

9. Epidemiology of Polio – U.S.A. (III) Post-OPV Cessation Era –High vaccination coverage maintained (2002 NIS) –High seroimmunity to all 3 serotypes after IPV-OPV or all-OPV schedules (urban areas) (Prevots et al.) Paralytic Polio: Current & future risks –Source: Imported wild virus (primary) –Risk groups: Under-vaccinated children in urban areas Vaccine refusers in religious communities –Magnitude: very low but not zero

10. Epidemiology of Polio – U.S.A. (Conclusion) The U.S. has reached an important milestone – elimination of VAPP, through OPV cessation & transition to IPV. A low risk of polio cases or outbreaks in the U.S. remains until the world is polio-free. A polio vaccine stockpile, as approved, will help ensure an effective control of future outbreaks.

11. (IV) U.S. Polio Vaccine Stockpile & Outbreak Response: Status, Issues & Future Directions

12. Outline Topics: –IPV stockpile –OPV stockpile –Global collaboration –State & local collaboration –Sabin IPV –Antiviral drug Order of presentation: –NVAC/ACIP Report –Current Status & Issues –Future Directions –Points for Discussion

13. U.S. Polio Vaccine Stockpile: IPV (I) NVAC/ACIP report: –Projected / recommended = 8 million doses –Used alone / with OPV for outbreak control –Need for licensed, uncombined IPV Current status & issues: –Current = ~4 million doses & holding –Might be difficult to get 8 million doses of uncombined IPV under current mechanism

14. U.S. Polio Vaccine Stockpile: IPV (II) Future directions –Continue efforts to develop uncombined IPV stockpile through Pediatric Vaccine Stockpile –Consider other options for IPV stockpile Discussion points –How to maintain target supply of uncombined IPV long-term? –IPV stockpile: U.S. issue only or global one?

15. U.S. Polio Vaccine Stockpile: OPV (I) NVAC/ACIP report: –Access to & effective use of OPV in outbreak –Needed = 8 million doses (tOPV or each mOPV serotype) –Preferred type = mOPV, if available –Need to develop mechanism for use (IND vs other) Current status & issues: –IND for OPV –Need to identify vaccine manufacturer and specific OPV product to continue

16. U.S. Polio Vaccine Stockpile: OPV (II) Future directions –Discuss regulatory options with FDA –Work with WHO & vaccine manufacturers re: mOPV –Develop IND & explore other emergency response use mechanisms Discussion points –Proceed to mOPV stockpile without tOPV? –Are there other emergency response mechanisms to use?

17. U.S. Polio Vaccine Stockpile: Global Collaboration (I) NVAC/ACIP report: –CDC, FDA, WHO & other int’l partners –Finance, create & maintain global PVS –Guaranteed & immediate U.S. access Current status & issues: –CDC & WHO staff – ongoing collaboration on stockpile & outbreak response –CDC will collaborate with FDA & other agencies – regulatory issues & mechanisms for use of vaccines

18. U.S. Polio Vaccine Stockpile: Global Collaboration (II) Future directions –Support WHO efforts to… License mOPV & develop mOPV stockpile Evaluate the safety of Sabin IPV (sIPV) Assess potential use of antiviral drug Determine appropriate global stockpile size, composition & regulation Discussion points (sIPV & antiviral drug)

19. U.S. Polio Vaccine Stockpile: State & Local Collaboration NVAC/ACIP report: –Develop polio outbreak response plans Current status & issues: –Outbreak response plan being drafted Future directions / discussion –Involve CSTE, NACCHO & others in outbreak response plan development

20. U.S. Polio Vaccine Stockpile: Sabin IPV Global developments –Well outlined in Dr. Cochi’s presentation Discussion points –Efficacy? Safety? Source? –Issues for potential licensure of sIPV in US for stockpile use? –Emergency use only (IND and/or other)?

21. U.S. Polio Vaccine Stockpile: Antiviral Drug Developments & issues –Outlined in Dr. Cochi’s talk –WHO-CDC-Private collaborative group –Exploring potential candidate antiviral drugs –Wider consideration: proposed NAS meeting Discussion points –Support for NAS-sponsored meeting? –Potential to add as component of stockpile?

22. U.S. Polio Vaccine Stockpile: Conclusions U.S. stockpile: not yet a reality -- optimal size, composition & use IPV stockpile: affected by economic issues OPV stockpile: direction pending –Global developments re: mOPV –Regulatory issues / emergency use options Potential products: evaluation / development –Sabin IPV, Antiviral Drug

23. Acknowledgements WHO –David Heymann –Bruce Aylward –Roland Sutter –Anna-Lea Jenny Harvard SPH & other –Kim Thompson –Rad Tebbens –Marc Collett CDC –Hamid Jafari –Denise Johnson –Linda Venczel –Margie Watkins –Nalinee Sangrujee –Mark Pallansch –Jane Seward –Lorraine Alexander –Kristin Kenyan

24. Thanks!

25. U.S. Polio Vaccine Stockpile: Discussion (I) IPV Stockpile: –How to maintain target supply of uncombined long-term? –IPV stockpile: U.S. issue only or global one? OPV stockpile: –Proceed to mOPV stockpile without tOPV?

26. U.S. Polio Vaccine Stockpile: Discussion (II) Sabin IPV: –Efficacy? Safety? Source? –Issues for potential licensure of sIPV in US for stockpile use? –Emergency use only (IND or other)? Antiviral drug: –Support for NAS-sponsored meeting? –Potential to add as component of stockpile?

27. Extra slides

28. Paralytic Poliomyelitis United States, 1951-1959 IPV licensed YEAR Poliomyelitis Cases *

29. Paralytic Poliomyelitis United States, 1970-1979 YEAR No. of Cases