A consortium-driven framework to guide the implementation of ICH M7 Option 4 control strategies

- ICH M7 Option 4 permits the use of predicted purges in lieu of analytical testing of mutagenic impurities.
- Predicted purge factors derived from expert knowledge or experimental data can be derived for stages in a synthesis.
- Thresholds of the predicted purge over the required purges can ensure a negligible risk from a mutagenic impurity.
- The level of scientific support needed to defend a purge estimate has been proposed.

The ICH M7 Option 4 control of (potentially) mutagenic impurities is based on the use of scientific principles in lieu of routine analytical testing. This approach can reduce the burden of analytical testing without compromising patient safety, provided a scientifically rigorous approach is taken which is backed up by sufficient theoretical and/or analytical data. This paper introduces a consortium-led initiative and offers a proposal on the supporting evidence that could be presented in regulatory submissions.

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