Industry Perspective on Clinical Trial Issues for Combination Vaccines

Abstract

The development and production of vaccines remains complicated, largely because of the complexity of the vaccines, which are virtually always manufactured in a biological system; the nature of most vaccines precludes the use of the detailed chemical analysis that is possible for simple chemical entities. Therefore, approval and release of vaccines is dependent upon careful view of the manufacturing processes, the analytical data that are available, and data from clinical trials of consistency lots. The makeup of consistency lots from combinations, the purpose and utility of such lots, and the timing of their production depend not only on the maturity of the manufacturing process but also upon mutual agreement between the sponsor and the regulators. Consistency of application of regulations and precedent are important in the sponsor's ability to carry out successful development programs. The science of adjuvants is still in its infancy, but opportunities for it to mature are legion. Aluminum salts remain the mainstay of contemporary adjuvants but will no doubt be supplanted in the near future. The ethics of doing efficacy studies in infants who could be protected by safe and well-tolerated vaccines must be debated openly. Closely related to efficacy studies are the use of surrogates, which should be developed, recognized, and utilized. Finally, the potential utility of M-M-R IIV was shown by studies of the individual attenuated virus components in vaccines.