ICH M7 guidance on mutagenic impurities (MIs) supports the control of potential MIs based on a sufficient understanding of the manufacturing process. This strategy would reduce the need to perform testing on MIs predicted to be purged during synthesis of an active ingredient.<br/>A concept was brought forward in which semi-quantitative “purge factors” are calculated, based on physicochemical properties such as reactivity, solubility and volatility, to give confidence that a MI is likely to be absent in an end-product. This approach is used by several organisations within the pharmaceutical industry to support regulatory submission for e.g. late phase development. Our goal is to expand its use and standardise the approach through a consortium in order to establish a framework which would estimate “purge factors” and provide sufficient support for regulatory submissions. The key aims are to 1) standardise how calculations are performed throughout industry, 2) collate existing data and promote cross-industry data sharing to facilitate supported and accurate decision making, and 3) provide an automated in silico system which predicts purge factors based on experimental data and expert knowledge.<br/>A successful international collaboration has been established, with a number of pharmaceutical companies guiding the development of the software and models for the prediction of physicochemical properties. This work has the potential to save both time and money in regards to analytical testing and also to ensure effort is focussed correctly on those impurities that present a substantive risk. This communication describes our scientific approach and recent progress.

Using physicochemical data and predictions in the risk assessment of mutagenic impurities

251st National Meeting (2016)

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