Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
ICH S5 was revised for the first time in approximately 20 years. The main changes from ICH S5 (R2) are about the timing for conducting EFD studies, the utilization of preliminary studies, the high dose selection based on exposure, the use of alternative assays, and other items related to risk assessment. The revised guideline also shows the concept of safety margin in risk assessment based on published literature. Given the background of ICH S5 guideline, we surveyed drugs approved in 2017 to 2021 to deeply understand the interpretation of the reproductive and developmental toxicity studies results. We summarized the interpretation of reproductive and developmental toxicity studies results in review reports and the safety margin between the exposure of NOAEL in EFD studies and the exposure of MRHD. The Guideline for Package Inserts (PI) of Prescription Drugs has also been revised in approximately 20 years. It is required to provide the specified precautions for pregnant women in consideration of amount and duration of exposure during pregnancy and clinical experience as well as placental transfer and teratogenicity. Similarly, the precautions for women with reproductive potential and breastfeeding should be defined based on the results of nonclinical and clinical studies. Based on these, we also investigated and summarized the contents of the package insert. In this presentation, we will show the analysis and discussion of the rationale for drug approval and the reflection of the results in the PI from the viewpoint of the indication diseases and modalities.
