An improved abnormal toxicity test by using reference vaccine-specific body weight curves and histopathological data for monitoring vaccine quality and safety in Japan.

Vaccines differ from other pharmaceutical products. The quality and safety of batches are regulated to high standards by national regulatory authorities. Various quality control and safety tests have been developed, including the abnormal toxicity test (ATT), which is described in the World Health Organization (WHO) guidelines and in each country's pharmacopoeia. However, the criteria for abnormal results are not well defined in these guidelines. In addition, the animal grade to be used in ATT, classified on the basis of microbial colonization, was not designated in either guideline. In this study, we report a new and improved method of performing ATT, including statistical, histopathological analysis and hematological findings. It is based on the observation that there are body weight changes characteristic to each vaccine, and such standardized changes can be used as references for evaluating test vaccines. In addition, histopathological data are useful for determining vaccine quality and safety. Combined with histopathological examination, the improved ATT will be of great use for evaluating the consistency, quality and safety of different batches of vaccine. The results of these analyses were similar using either 'clean' or specific pathogen-free guinea pigs.