【优质】ApproachestoVaccineDevelopment.pptVIP

Approaches to Vaccine Development - Miller Approaches to Vaccine Development Nancy Miller, M.D. Medical Officer CBER/OVRR/DVRPA/VCTB Spend Tax Day with the FDA 4/15/05 Vaccine Development Complex process Goal is licensure of a safe, immunogenic and effective product The product is manufactured in a consistent way Stages of Review and Regulation Phase 1 - Safety, immunogenicity (prelim) Phase 2 – Immunogenicity, Safety, Dose Ranging Phase 3 – Efficacy, Safety, Immunogenicity BLA – Pre-clinical and clinical data to support approval, inspection Phase 4 – Inspection, Safety, Efficacy, Lot Release BLA-Supplement (post-approval changes) Vaccine Efficacy There are 3 options for showing vaccine efficacy: Clinical endpoint Immune response endpoints, if accepted by FDA (e.g., Hib vaccines, Hepatitis B vaccines) “Animal Rule”, if certain criteria are met Assessment of Efficacy Guidance for Industry – Providing Clinical Evidence of Effectiveness for Human Drugs and Biological Products (May 1998) Two efficacy trials are the “standard” One trial can be adequate if result is compelling, which is often the case for vaccine efficacy trials Robust data, e.g., multicenter Correlate(s) of Protection Interest in determining if particular type and quantity of immune response(s) is associated with protection from disease or infection caused by fully virulent pathogen(s) Make an assessment for an individual Correlate(s) of Protection Example: HIV preventive vaccines Try to identify immune correlate in efficacy trial Need vaccine efficacy to find a correlate Insight into what may prove to be correlate(s) in an efficacy trial might be gained from e.g.: In vitro Animal challenge protection trials Characteristics of long-time survivors Multiply exposed but uninfected persons Phase 2 clinical data Studies with passive products (Mab, HIVIG) Correlate(s) of Protection Immune correlate(s) useful for interpreting immune response endpoints, e.g., bridging studies However, identification of co