vaccinesandrelatedbiologicalproductsadvisorycommit.docVIP

Vaccines and Related Biological Products Advisory Committee Meeting Date: December 17, 2002 FDA Clinical Briefing Document for MedImmune Vaccines Inc. Cold Adapted Influenza Vaccine, Trivalent - FluMist( ChrisAnna Marie Mink, M.D. Antonia Geber, M.D. Douglas Pratt, M.D. Table of Contents INTRODUCTION Description of the Product Indication Sought Regulatory History UNRESOLVED SAFETY ISSUES Number of Subjects Exposed Summary of Newly Submitted, Finalized Trials Specific Adverse Events Asthma and Wheezing Pneumonia, Bronchitis and Bronchiolitis Abdominal Pain CNS Events Data for Re-Vaccination of Older Children and Adults Data for Concurrent Immunization Shedding and Transmission of Vaccine Virus Shedding of Vaccine Virus Transmission of Vaccine Virus Phenotype and Genotype Stability EFFICACY SUMMARY APPENDIX Table 4.1 Nucleotide Changes in Attenuating Genes of Viruses Shed After Vaccine Administration INTRODUCTION 1.1 Description of Product FluMist( Influenza Virus Vaccine, Trivalent A B Live, Cold Adapted (FluMist) is an intranasal vaccine for active immunization for the prevention of influenza. FluMist contains three strains of live, attenuated, cold-adapted, temperature-sensitive influenza virus: two Type A (H1N1 and H3N2) and one Type B. Each 0.5 ml dose contains approximately 107 TCID50 of each of the three strains of influenza in normal allantoic fluid (NAF) containing sucrose-phosphate-glutamate (SPG). 1.2 Indication Sought The sponsor has proposed the following label indication, “FluMist( is indicated for active immunization for the prevention of disease caused by influenza A and B viruses in healthy children, adolescents and adults, 5 years through 64 years of age.” The requested dosing regimens: for the first use in children 60 months through 8 years, two 0.5 ml doses given at least one month apart should be administered. For those previously immunized against influenza and for individuals 9 yea