A new draft guideline recently proposed by the International Council for Harmonisation (ICH) outlines a method for manufacturers to determine whether a 2-year rat study adds value in completing a human carcinogenicity risk assessment.
The proposed guideline S1B(R1) is an addendum to S1B on testing for carcinogenicity of pharmaceuticals and is intended to be used in close conjunction with S1A on the need for carcinogenicity studies for pharmaceuticals and S1C(R2) dose selection for carcinogenicity studies.
The addendum introduces a weight of evidence (WoE) approach to determine whether the test compound is either:
- Likely carcinogenic in humans such that the product would be labelled accordingly and any 2-year rat carcinogenicity studies would not add value
- Likely not to be carcinogenic in humans such that a 2-year rat study would not add value (may also not be carcinogenic in rats or carcinogenic in rats through mechanisms known to be irrelevant in humans)
- Potentially carcinogenic to humans and a 2-year rat carcinogenicity study is likely to add value to human risk assessment.
The application of this WoE approach would lead to reduced animal testing in line with the 3Rs principle (reduce/refine/replace). This will allow companies to focus more resources on generating scientific mechanism-based carcinogenicity assessments, maintaining the safety of small molecule pharmaceutical development whilst promoting a more ethical approach.
As of 10 May 2021, the proposed guideline has been signed off as a Step 2 document by the ICH and it has been released to the public for consultation. Concurrently, it has been adopted by the CHMP on 20 May 2021. It is anticipated that the document will be finalised as a Step 4 document in May 2022.
Click here to view the proposed guideline.