Acceptable intake for an impurity in a new anticancer drug

Client

A pharmaceutical company.

Background

A possible impurity was identified in the development of a new anticancer drug.

Project goals

Bibra was asked to conduct Leadscope analyses on this impurity to assess its genotoxic/mutagenic potential and to subsequently classify it in line with ICH guideline M7 on the control of DNA-reactive impurities. If the impurity fell into Classes 1, 2 or 3, bibra was requested to estimate an acceptable exposure level.

Approach

The potential genotoxicity of the impurity was analysed using Leadscope and the key findings were summarised and interpreted by bibra. Additionally, various literature searches for genotoxicity and carcinogenicity data were conducted and the relevant papers were evaluated. Following an assessment of all the available data, bibra proposed an acceptable intake for the impurity in line with ICH M7 guidance.

Project outcome

The information obtained through Leadscope analyses and experimental evidence indicated that the impurity should be assigned to ICH Class 2 and a lifetime acceptable intake of 1.5 μg/day was proposed.

Bibra project team

Daniel Threlfall
James Hopkins

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