As of August 2022, the ICH S1B(R1) Guideline integrates a new Addendum with the original S1B Guideline which was finalised under Step 4 in July 1997. This Addendum expands the evaluation process for assessing human carcinogenic risk of pharmaceuticals by introducing an additional approach that is not described in the original S1B Guideline. Application of this integrative approach reduces the use of animals in accordance with the 3R (reduce/refine/replace) principles and shifts resources to focus on generating more scientific mechanism-based carcinogenicity assessments, while continuing to promote safe and ethical development of new pharmaceuticals.

Since publication of the S1B Guideline, scientific advances toward elucidation of mechanisms of carcinogenicity, greater understanding of the limitations of rodent models, and several retrospective analyses of pharmaceutical datasets indicate that 2-year rat carcinogenicity studies might not add value to human carcinogenicity risk assessment in some cases and the carcinogenic potential could have been assessed adequately based on a comprehensive assessment of all available pharmacological, biological, and toxicological data.

To determine whether the conclusions from these retrospective analyses could be confirmed in a real-world setting (i.e., prior to knowledge of the 2-year rat carcinogenicity study outcomes), a subsequent international prospective study was conducted under ICH S1(R1) Proposed Change to Rodent Carcinogenicity Testing of Pharmaceuticals – Regulatory Notice Document. The process and several status updates reporting results are posted and available on this page.