Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Discussions on the revision of ICH S1 are being finalized after the prospective evaluation, drafting of the S1B(R1) addendum and correction based on public comments.
In the prospective evaluation, the carcinogenicity assessment documents (CAD) indicating the predicted results of a 2-year rat carcinogenicity study based on "Weight of Evidence (WoE)" for small molecule pharmaceuticals under development were encouraged to submit, and compared with the views of the five regulatory agencies, along with the actual study results.
With the analysis of collected 45 CADs, more important WoEs for prediction of 2-year rat carcinogenicity outcome were extracted.
This addendum proposes possibility of the waiver of 2-year rat carcinogenicity study, when concern of carcinogenicity can be evaluated comprehensively from WoEs of the drug, the data in the same drug class and literature.
However, since the prospective evaluation is based on the results of rat studies, a carcinogenicity study in mice, either 2-year or a short-term transgenic model as specified in ICH S1B, remains a recommended component of a carcinogenicity assessment plan, even for those compounds where the integrated WoE assessment indicates a 2-year rat study would not contribute significant value.
With the revision, short-term studies using mouse transgenic models, especially rasH2-Tg mice for which background information is being accumulated, might be considered as an option.
At this symposium, for appropriate application, it is expected that information on the characteristics of the tests using rasH2-Tg mice will be shared.
