Establishing best practise in the application of expert review of mutagenicity under ICH M7.

Abstract The ICH M7 guidelines for the assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals allows for the consideration of in silico predictions in place of in vitro studies. This represents a significant advance in the acceptance of (Q)SAR models and has resulted from positive interactions between modellers, regulatory agencies and industry with a shared purpose of developing effective processes to minimise risk. This paper discusses key scientific principles that should be applied when evaluating in silico predictions with a focus on accuracy and scientific rigour that will support a consistent and practical route to regulatory submission.