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Practical Implementation of (Q)SAR and Expert Review for Compliance with ICH M7 Guidelines

pdf fileBercu J;

Streamlining Drug Discovery and Development: Leveraging Data Analysis and Modelling for Design - San Francisco 

Dr. Joel Bercu, Associate Director, Gilead

The ICH M7 Guidelines on assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals was written in June 2014 with implementation starting in 2016.  As such, the guideline states that pharmaceutical sponsors should evaluate all actual and potential impurities and degradation products for bacterial mutagenicity.  The use of (Q)SAR has facilitated the review of a large number of structures to determine which compounds should be tested for mutagenicity or controlled below the threshold of toxicological concern.  The guideline recommends the use of two (Q)SAR methodologies, one that is statistically-based and the other that is rules-based.  While there are many (Q)SAR methodologies for the prediction of bacterial mutagenicity, using off-the-shelf models can facilitate submissions with regulatory agencies because of published validations and their familiarity with the software.   Expert-knowledge can be used to provide additional supporting evidence of any positive, negative, conflicting or inconclusive prediction to provide a rationale for the final conclusion.  This session will provide an overview of this process and practical examples to demonstrate its implementation.  


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