The validation of potency tests: hurdles identified by EMA/CVMP/IWP.

Abstract

The biological nature of IVMPs leads to some unavoidable batch to batch variation in production. The potency test is part of the quality control of the finished product intended to confirm consistency of production and that each batch is formulated equivalent to batches that have been demonstrated to be efficacious. Adequate validation of potency tests is essential to ensure that the results of the assays accurately reflect the amount, titre, or potency of the active substance measured and to indicate the limitations on the accuracy of the measurements to be expected from the test used. The CVMP/IWP published their conclusions concerning validation of potency tests in a Reflection Paper in March 2010. The test validation must demonstrate a dose response and the precision of the result should enable reliable detection of a sub-standard batch. However, the inherent variability in experimental animals often leads to unacceptably wide confidence intervals for in vivo tests which limits their ability to detect slight changes of the antigen amount. The development of in vitro methods as alternatives to in vivo potency tests is encouraged.