Maria Sanna -

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 entered into force on 16 March 2023 (EMA/774371/2022), implementing 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.

Regulatory Pharma Net (RPN) has successfully supported companies to optimize drug development strategies.

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