The ICH S1B(R1) Guideline provides international regulatory guidance on approaches for evaluating the carcinogenic potential of small molecule pharmaceuticals. An addendum to this Guideline implements several key updates to the original 1997 guidance, which are supported by significant scientific advances, retrospective analyses, and an independent, international prospective study.

The updated guidance introduces an integrative, mechanism-based method for assessing human carcinogenic risk using a Weight of Evidence (WoE) approach. While a mouse carcinogenicity study (either 2-year standard mouse study or 6-month transgenic rasH2-Tg study) is still required in most cases, a 2-year rat study is now only required when the WoE approach cannot adequately assess human carcinogenic risk without it. This new approach reduces the use of animals in accordance with the 3Rs principles and without compromising patient safety. The addendum also clarifies high dose identification for rasH2-Tg studies, with a plasma exposure ratio-based option now acceptable.

This updated guidance is a major step forward, both in reducing the use of animal studies and in answering open questions related to test article dose selection for rasH2-Tg studies. But what could it mean for your drug development program?

The updated guidance encourages a shift towards mechanism-based carcinogenicity risk assessment starting earlier in drug development.

What does that look like from a practical standpoint?

If a 2-year rat study is not required, how could that change the timeline for safety assessment and marketing approval.

Does it change the calculus regarding use of a 2-year standard mouse study versus a 6-month rasH2™ study?

Watch this virtual presentation as Dr. Frank Sistare, Rapporteur of the ICH S1 Carcinogenicity Expert Working Group, provides an overview of the changes made through this Addendum to ICH S1B and a discussion of the anticipated real-world impact on pharmaceutical drug development.

Learning Objectives:

1. How the weight-of-evidence criteria are expected to be applied for evaluating the potential value and need for conducting a 2-year rat carcinogenicity study.

2. The expanded practical role and value of the rasH2-Tg study to pharmaceutical carcinogenicity testing.

3. The impact on animal use, on pharmaceutical drug development, and on the evolution of new carcinogenicity tool development to bolster future WoE based decision making.