1. VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE USPHS INFLUENZA VIRUS VACCINE STRAIN SELECTION 2001-2002

2. QUESTION FOR COMMITTEE WHAT STRAINS SHOULD BE RECOMMENDED FOR INCLUSION IN THE INACTIVATED INFLUENZA VIRUS VACCINES FOR 2001-2002 ?

3. RATIONALE FOR INFLUENZA VACCINE STRAIN CHANGES Production of antibodies to hemagglutinin (HA) and neuraminidase (NA) is the main action of current vaccines Antigenic match of vaccine HA and NA with new strains is main predictor of vaccine effectiveness Influenza viruses are constantly evolving to escape immune control

4. CONSIDERATIONS FOR RECOMMENDATIONS Are there new antigenic variants? Are new variants spreading? Are current vaccines able to induce antibodies to the new variants? Are any new variants useful for vaccine production?

6. Causes of Delay in Vaccine Distribution Production delay at 3 of the 4 manufacturers licensed to produce influenza vaccine in 2000 Correction of deviations from good manufacturing practices Low yield of A/Panama/2007/99 strain

7. Review of Vaccine Distribution Delay in 2000 FDA= Vaccine production CDC= Use of vaccines NIH= Clinical studies

8. VACCINE PRODUCTION CYCLE

9. VACCINE RECOMMENDATIONS H3N2 A/MOSCOW/10/99-LIKE (A/PANAMA/2007/99) H1N1 A/NEW CALEDONIA/20/99-LIKE (A/NEW CALEDONIA/20/99) B B/BEIJING/184/93-LIKE (B/YAMANASHI/166/98) H3N2 A/MOSCOW/10/99-LIKE (A/PANAMA/2007/99) H1N1 A/NEW CALEDONIA/20/99-LIKE (A/NEW CALEDONIA/20/99) B B/SICHUAN/379/99-LIKE (B/JOHANNESBURG/5/99 OR B/VICTORIA/504/2000) USPHS / WHO 2000-2001WHO S. HEMIS. 2001

10. TIME OF DISTRIBUTION OF STRAINS AND REAGENTS SEPSEP OCTOCT NOVNOV DECDEC JANJAN FEBFEB MARMAR APRAPR MAYMAY JUNJUN JULJUL AUGAUG SEPSEP A/PANAMA/2007/99 A/New CALEDONIA/20/99 B/YAMANASHI/166/98 A/BEIJING/262/95 A/SYDNEY/5/97 = REFERENCE VIRUSES = POTENCY REAGENTS

12. MONOVALENT VACCINES SUBMITTED FOR RELEASE PER CENT OF TOTAL MONOVALENT LOTS H1N1H3N2B NEW STRAIN 199838%25%37% A/BEIJING A/SYDNEY 199928%18%54% B/YAMANASHI 200047%29%24% A/NEW CALEDONIA A/PANAMA

14. Summary Distribution delays or shortages can be expected if production is delayed at multiple manufacturing facilities Production of vaccine was delayed by temporary difficulties with a new vaccine strain and by need to correct manufacturing practices One manufacturer (Parkedale) did not complete corrections and withdrew from production In other ways, the experience in 2000 was typical of influenza vaccine production in most years