Overview of Currently Approved Serological Methods with a Focus On Diphtheria and Tetanus Toxoid Potency Testing

AbstractVaccines are biological products made from living organisms. The natural complexity of biological molecules along with the inherent uncertainties of product manufacturing introduces the likelihood that random alterations can impact the quality of the vaccine each time it is made. The factors that can affect the final product are often unknown. Testing for potency of vaccine bulk or product dispensed into final containers was designed with the hope of ensuring that a vaccine is effective when used during its approved dating period and that its protective activity was not inadvertently altered during any phase of production. Ideally, potency testing measures a biological or biochemical property of the vaccine that is related to its ability to elicit protective immunity in the target population and provide some assurance that consistent clinical benefit is derived from each lot of product. Potency methods vary depending on the nature and composition of the vaccine. In vivo potency testing might entail immunizing groups of laboratory animals and then challenging them directly to measure survival, or involve serological potency assays in which sera from immunized laboratory animals are tested for the ability to neutralize pathogens or toxins. In the U.S., diphtheria toxoid and tetanus toxoid potency tests have customarily involved a serological method. This approach uses fewer animals than would have been required using a direct challenge method, while providing satisfactory evidence that each toxoid lot could induce protective immunity. This paper will discuss the details of the original U.S. test method for diphtheria and tetanus toxoid potency and present issues that must be considered when developing and validating non-animal-based approaches to refine or replace these tests