Rabies Vaccines for Human Use: Potency Testing Without Mouse Challenge?

215 Rabies vaccines for human use currently are tested for potency by a mouse challenge assay. this test was developed by the National Institutes of Health (NIH) and is therefore referred to as the NIH test. Its origins go back to the 1950’s, well before good manufacturing practice (GMP) was established. the NIH test soon was recognized to be highly variable, to consume a large number of animals, and to be very distressing to the mice and to the staff performing the test. In the absence of any alternative, it became the mandatory potency test for rabies vaccines worldwide. GMP now is implemented for production of human rabies vaccines, and further tools and tests have been developed that finally will allow the move away from the NIH test. From a regulator’s point of view, potency testing is important to provide reliable information on vaccine batch performance. Therefore, it is in the interest of Public Health to define and apply the most appropriate concept of potency testing. Historically, potency was considered to be assured by a single test on the final-product level. We now understand that a new concept of controlled production and multi-stage testing without the variable NIH test provides more reliability. Better data quality will enable more reliable performance trending. Alternative tests will cause fewer ethical concerns. Alternative tests also are faster and consequently cheaper, especially when the reduced frequency of retesting is considered. Manufacturers have the same objectives for a more reliable testing concept: they want to prevent the loss of production by identifying non-conforming material earlier than the final stage. therefore, they favor the implementation of tools and tests that improve the monitoring to reduce the risk of generating nonconforming batches. In which direction will batch potency testing go? the testing will evolve to demonstrate consistent batch to batch performance. During licensing, the efficacy of the vaccine is assessed on representative batches. Only efficacious products will get access to the market. All batches produced in the same manner as the original representative batches shall have similar performance. Since biological products show intrinsic variability, the production process needs close monitoring to enable consistent production. Testing of the final product is complemented by relevant in-process controls. this concept is expressed by the consistency approach: Not one test but a panel of tests on critical quality aspects will provide more relevant and reliable information on batch performance and consistency. this will be in line with the refinement, reduction, and replacement of animal tests. Rabies Vaccines for Human Use: Potency Testing Without Mouse Challenge?