The recently introduced ICH S1B addendum1 (integrated with the original S1B guideline on 4th August 2022) includes a new weight of evidence (WoE) assessment to determine whether performing a 2-year rat study would add value to the assessment of human carcinogenic risk. The guideline describes six WoE factors –  target biology,  secondary pharmacology,  histopathology chronic studies,  hormonal effects,  genotoxicity, and  immune modulation. An assessment is performed to assess whether carcinogenicity potential in humans is (1) likely, (2) unlikely, or (3) uncertain based on an integrated analysis of the ICH S1B WoE factors.
As discussed in a previous post2, Instem has recently initiated a collaborative working group to develop a pragmatic consensus procedure for performing such an assessment.
At the recent Genetic Toxicology Association3 annual meeting, we presented a poster “Target Carcinogenicity Assessment” (TCA) addressing the WoE factor (#1 Target biology) that investigates whether any biological pathways related to the primary pharmacology are involved in human cancer development and includes: (1) empirical carcinogenicity data on other chemicals within the same primary pharmacological class, (2) the extent to which the biological pathways are well-characterized, and there is no potential involvement in human cancer development and (3) relevant carcinogenicity risks related to the pharmacology of any major human metabolites. This poster was annotated with examples from a TCA performed at Instem.
Please get in touch (Glenn Myatt; email@example.com) if you would like a copy of the poster or would like to talk about ICH S1B.
1. International Council for Harmonisation of technical requirements for pharmaceuticals for human use harmonised guideline, Testing for carcinogenicity of pharmaceuticals – S1B(R1), 4 August 2022 https://database.ich.org/sites/default/files/S1B-R1_FinalGuideline_2022_0719.pdf