To speed drug development, ICH proposes reducing rat carcinogenicity testing

Regulatory NewsRegulatory News
| 14 May 2021 | By Joanne S. Eglovitch 

The International Council for Harmonisation (ICH) recently announced a new draft guideline that proposes a “weight of evidence” approach to inform whether a two-year rat study would add value in evaluating a drug’s carcinogenic risks.
The proposed guideline provides more detailed guidance for drug developers who are considering whether rodent studies are needed to assess carcinogenicity. The ICH S1B(R1) addendum, once adopted, should be used in conjunction with the ICH S1A Guideline on the Need for Carcinogenicity Studies for Pharmaceuticals, S1B Testing for Carcinogenicity of Pharmaceuticals, and S1C(R2) Dose Selection for Carcinogenicity Studies.
The ICH Assembly released the addendum as a Step 2 document on 10 May; it is currently available for public consultation.

According to an ICH presentation on the guideline, "these changes to S1 introduce a more comprehensive and integrated approach to addressing the risk of human carcinogenicity of small molecule pharmaceuticals. Under this revised approach, the need for two-year rat studies are not always warranted."
The guideline introduces a three-prong “weight of evidence” approach to assess whether the test compound is either likely carcinogenic and two-year rat studies would not add much value; likely not to be carcinogenic and a 2-year rat study would not add much value; or with uncertain carcinogenic risk and a study is likely to add value to the human risk assessment.
ICH said that “application of this integrative approach would reduce the use of animals in accordance with the 3R (reduce, refine, replace) principles and shift resources to focus onto generating more scientific mechanism-based carcinogenicity assessments, while promising safe and ethnical development of new and small molecules.”
In June 2012, the ICH Steering Committee endorsed a concept paper that supported reducing or eliminating the need for rodent carcinogenicity testing, with the goal of faster and cheaper drug development, mitigating ethical concerns and reducing animal usage (RELATED: Can rodent carcinogenicity testing Be eliminated?, Regulatory Focus 26 June 2012).
The guideline is moving through the formal ICH step-wise procedure; ICH plans to finalize a Step 4 document next May 2022.
ICH S1B(R1) guideline


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