ICH M7 Expert Review
Expert assessment is a fundamental part of the evaluation of the mutagenic potential of impurities under the ICH M7 guideline1, and it makes a specific provision for the application of expert knowledge to support or overturn a (Q)SAR prediction. Whilst expert assessment has been successfully applied in this context2,3, the definition of what constitutes expert analysis has been largely left open. Chris Barber et al.4 have recently outlined their views on establishing best practice in the application of expert review under ICH M7.
This section of the website builds on the practices outlined in this paper4 and provides a number of worked examples of performing expert assessment under ICH M7.
ICH M7 Decision Matrix
In reviewing the examples it is important to note the following:
- ICH M7 requires the use of two complementary methodologies (one expert rule-based and the other statistical-based). This exercise uses Derek Nexus which fulfils the requirements of the expert rule-based methodology and Sarah Nexus which fulfils the requirements of the statistical-based methodology.
- For the purpose of this exercise it is assumed that the example compounds do not have any known mutagenicity data (where such data does exists it is ignored). As such all assessments have been made using only the predictions from Derek Nexus and Sarah Nexus, the supporting information they provide and data from similar compounds where applicable (read across).
- All expert calls made on the examples are solely the opinion of experts at Lhasa Limited and are made here for guidance purposes only.
2. Dobo K. L., Greene N., Fred C., Glowienke S., Harvey J. S., Hasselgren C, et al. (2012). ‘In silico methods combined with expert knowledge rule out mutagenic potential of pharmaceutical impurities: an industry survey’. Regul. Toxicol. and Pharmacol. 62(3), 449–55.
3. Sutter A., Amberg A., Boyer S., Brigo A., Contrera J. F., Custer L. L., et al. (2013). ‘Use of in silico systems and expert knowledge for structure-based assessment of potentially mutagenic impurities’. Regul. Toxicol. and Pharmacol. 67(1), 39–52.
4. Barber C., Amberg A., Custer L., Dobo K. L., Glowienke S., van Gompel J., et al. (2015). ‘Establishing best practice in the application of expert review of mutagenicity under ICH M7'. Regul. Toxicol. and Pharmacol.73 367-377