Challenges in the nonclinical safety evaluation of biotechnology-derived pharmaceuticals and perspectives for revision of the ICH S6 guideline based on analysis of approved products in Japan

抄録

This article outlines current challenges in the nonclinical safety evaluation of biotechnology-derived pharmaceuticals and discusses future directions for revising the ICH S6 guideline. Analysis of products approved in Japan showed that, despite the frequent use of nonhuman primates for antibody therapeutics, novel and unexpected toxicities are rarely detected in long-term toxicity studies. We also summarize the potential utility and challenges of using homologous proteins, transgenic animals, and new approach methodologies. Based on these findings, we propose that the nonclinical safety evaluation process should transition to a flexible, scientifically sound framework based on the weight of evidence, rather than regarding standardized animal testing as the default approach.