Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
We had long done genotoxicity tests on biologics since the first biotherapeutic was approved by FDA in 1982. Ames test on biologics was waived by ICH S6 guideline in 2000. Despite the scientific understanding that Ames test or non-cross reactive rodent tests have no meaning, both industry and regulatory experts sticked to the traditional standard test battery for fear of taking a new step forward without accumulated evidences. The traditional test battery could not detect lethal toxicity, which resulted in the tragedy of TGN1412. We learned a lesson from the history of biologics that scientifically appropriate test battery is important to support human safety with a new modality. Recently, various new modality therapeutics have been emerged. An AAV vector gene therapeutic, BMN307, induced tumors in 6/7 mice. The traditional genotoxicity test battery could not predict cancer risk of this compound. There might be an excuse that insertion of a DNA fragment into random site has a limited impact whereas insertion into a specific site provides high risk. However, many of known genotoxic carcinogens caused mutations at random sites. Here, we discuss how we can make scientifically appropriate assessment for genotoxic potential of middle-sized peptides and gene/nucleotide therapeutics.
