Prelicensure evaluation of combination vaccines

There is considerable public health interest in licensing safe and effectiv e combination vaccines. Because combination vaccines may progress rapidly f rom phase 1 to a pivotal phase 2 immunogenicity trial, a rigorous approach to address product issues early in development is warranted. Clinical studi es to evaluate the safety, immunogenicity, and (when necessary) clinical en d point efficacy of combination vaccines should be randomized and well cont rolled in most cases. A large phase 3 safety study (i.e., a study that enro lls 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 clinic al trials, or both. For such products, comparative immunogenicity data may be sufficient to support efficacy. When applicable, clinical data to suppor t simultaneous administration with other relevant vaccines should be obtain ed. Given the complexity of combination vaccine development, early consulta tion with United States Food and Drug Administration can be invaluable.