Analysis of historical data to accelerate deletion of Abnormal Toxicity Test requirement for biologicals and vaccines

Abstract

Abnormal Toxicity Test (ATT) is performed as quality control test by manufacturers and National Control Laboratory (NCL) to ensure safety of biologicals. However, stakeholders are in general consensus that extraneous toxic contaminations are extremely unlikely where Good Manufacturing Practices (GMPs) and consistent production have been established. This test requiring mice and guinea pigs is still a regulatory requirement for the batch release of biologicals in several countries although it has been deleted by some National Regulatory Authorities (NRAs) and Pharmacopoeias while some are still working on its elimination. Therefore, ten years historic data of ATT performed at National Institute of Biologicals (NIB), India on 4813 batches of biologicals including blood and related products, enzymes, hormones and vaccines by using 33637 animals was analyzed. As per Indian Pharmacopeia (IP), 4783 batches of these biologicals passed the test. The test had to be repeated in 30 batches, all of which were blood products and the repetition rate was 0.62 %. Further, after repeat testing, all these 30 batches also passed the test. This data will help the regulatory authorities of countries where ATT is still a requirement, take appropriate decision regarding its deletion. The elimination of ATT from specific monographs of these biologicals will help save many thousands of animals being used globally for this test.