Alternative approach for carcinogenicity testing of pharmaceuticals implemented as ICH S1B(R1) addendum

The International Council for Harmonisation (ICH) has integrated an addendum to the carcinogenicity testing guideline (ICH S1B) that describes an integrative weight of evidence approach as an alternative to conducting a two-year rat carcinogenicity study for assessing the human carcinogenic risk of pharmaceuticals. Application of this mechanism-based approach reduces the use of animals in the development of new pharmaceuticals. The development of the addendum was motivated by an improved understanding of the mechanisms of carcinogenicity, the limitations of rodent models, and retrospective analyses of pharmaceutical datasets on the value of the 2-year rat carcinogenicity study on risk assessment. These lead to an international prospective study under ICH S1(R1) Proposed Change to Rodent Carcinogenicity Testing of Pharmaceuticals – Regulatory Notice Document. The full process is described on the ICH website.

The new version of the guideline was implemented by Swissmedic, Switzerland on August 4, 2022; by FDA, US on November 2, 2022 (Federal Register Vol. 87, No. 211, p. 66195-66197) and by the EMA, EU on March 16, 2023 (EMA/774371/2022).