Rational arguments for regulatory acceptance of consistency testing benefits of non animal testing over in vivo release testing of vaccines

INTRODUCTION: There are rational arguments to replace existing in vivo potency and safety assays for batch release testing of vaccines with more advanced non-animal techniques to measure critical quality attributes. However, introduction of in vitro alternatives to replace in vivo release assays of authorized vaccines is&nbsp;challenging. AREAS COVERED: This report describes the hurdles encountered in substituting assays and ways to overcome these and provides arguments why more advanced alternatives are superior, not only as tool to monitor the quality of vaccines but also from a practical, economical and ethical point of view. The rational arguments provided for regulatory acceptance can support a strategy to replace/substitute any batch release test if an appropriate non-animal testing strategy is&nbsp;available. EXPERT OPINION: For several vaccines, in vivo release assays have been replaced leading to an optimized control strategy. For other vaccines, new assays are being developed, that can expected to be introduced within 5-10 years. From a scientific, logistical and animal welfare perspective, it would be beneficial to substitute all existing in vivo batch release assays for vaccines. Given the challenges relating to development, validation and acceptance of new methods, and considering the relatively low prices of some legacy vaccines, this cannot be done without government incentives and supportive regulatory authorities from all&nbsp;regions.</p