[Is the abnormal toxicity test still relevant for the safety of vaccines, sera and immunoglobulins? A retrospective analysis of data on the relevance of the pharmacopoiea requirement V.2.1.5] [Article in German]

Abstract

The German Pharmacopoeia (DAB) requires the abnormal toxicity test (ATT) using mice and guinea pigs as a non-specific safety test for vaccines, sera and immuno-globulines. The purpose of this project was to investigate the relevance of ATT after the introduction of GMP- and GLP-principles in the manufacturing of biological products. A great variability in the test performance became evident for the different test laboratories, involving the animal number as well as the vaccine dosage administration and test duration. The retrospective analysis of ATT results reveals reasons for the incompatibility of particular preparation groups, vaccine components or additives with the animal species used. There were highly significant differences between the manufacturers and the PEI regarding the frequency of deviating test results for identical test batches. Positive ATTs never resulted from the insufficient quality of a batch. On the other hand vaccines causing adverse reactions in the target species were not identified by the ATT. For these reasons the abnormal toxicity test is unsuitable to detect harmful batches. The results of the analysis of data show that finally the ATT has always been passed, i.e. there was no retention by the vaccine manufacturers and no refusal by the controlling authorities due to the ATT-results. Considering the present animal model and the questionable transferability of the test results to the target species only a poor reliability is evident. Taking into account aspects of drug safety and animal welfare it is recommended to the DAB to omit the ATT.