Replacement, reduction and refinement alternatives to animal use in vaccine potency measurement.

Models to measure potency in vaccine research and development and preclinical testing are frequently based on an immunization-challenge procedure in laboratory animals. These models have proven to be very instrumental in scientifically underpinning the correlation of protection of selected vaccine antigens and their efficacy. In vivo models in vaccine research and development are, for the time being, irreplaceable, although significant progress has been made in using in vitro prescreening tests to evaluate particular immunological parameters. For a long time, in vivo potency tests have been similarly relevant for routine vaccine lot-release testing. The design of a potency test, defined in most pharmacopeias, relied on a direct or indirect-challenge procedure in laboratory animals. For various reasons, there now is an increased interest in the development of alternatives to the current in vivo potency tests. Animal models have their limitations, with respect to their relevance, reliability, costs and moral acceptability. All alternative approaches have in common that they ultimately result in a refinement, reduction or replacement in the use of animals. The new models range from modifications of the existing in vivo test procedure (e.g., use of humane end points or serology instead of challenge) to in vitro antigen-quantification tests. A new paradigm in quality control of vaccines is the consistency approach. This approach is state-of-the-art in quality control of the new-generation vaccines and it is now finding its way into the quality control of traditional vaccines. The consistency approach implies the use of a set of parameters to constitute a product profile, which is monitored throughout production, and which guarantees that each lot released is similar to a manufacturer-specific vaccine of proven clinical efficacy and safety. Consistency relies heavily on the implementation of quality systems, such as good manufacturing practice and quality assurance, and on the use of in vitro analytical tools, such as immunochemical and physicochemical tests.