title: Prelicensure evaluation of combination vaccines.
abstract: There is considerable public health interest in licensing safe and effective combination vaccines. Because combination vaccines may progress rapidly from phase 1 to a pivotal phase 2 immunogenicity trial, a rigorous approach to address product issues early in development is warranted. Clinical studies to evaluate the safety, immunogenicity, and (when necessary) clinical end point efficacy of combination vaccines should be randomized and well controlled in most cases. A large phase 3 safety study (i.e., a study that enrolls thousands of vaccinees) should be included in the development plan if a phase 3 (clinical end point) efficacy trial will not be conducted. Often, the new combination vaccine under development contains immunogens that have all been previously licensed, have demonstrated efficacy in earlier clinical trials, or both. For such products, comparative immunogenicity data may be sufficient to support efficacy. When applicable, clinical data to support simultaneous administration with other relevant vaccines should be obtained. Given the complexity of combination vaccine development, early consultation with United States Food and Drug Administration can be invaluable.
authors.affiliation: Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. Goldenthal@cber.fda.gov
authors.forename: K L
authors.initials: KL
authors.lastname: Goldenthal
authors.forename: L A
authors.initials: LA
authors.lastname: Falk
authors.forename: L
authors.initials: L
authors.lastname: Ball
authors.forename: A
authors.initials: A
authors.lastname: Geber
mesh_terms: D002986:Clinical Trials as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D023381:Endpoint Determination; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016032:Randomized Controlled Trials as Topic; D013678:Technology, Pharmaceutical; D014481:United States; D014486:United States Food and Drug Administration; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000592:standards
chemical_list: D007136:Immunoglobulins; D017778:Vaccines, Combined