Analytical control strategies for mutagenic impurities: Current challenges and future opportunities?

The last decade has seen continued development and refinement of guidance related to mutagenic impurities (MIs); culminating in June 2014 with the publication of ICH M7. This has seen an introduction of factors such as durationally adjusted limits and emergence of alternative approaches to demonstrate control, such as purge factor calculations, Teasdale et al. This review examines the impact of these changes on the approaches taken to the analysis of MIs. Observed is the emergence of platform approaches; methods that can be applied to a class of MIs rather than simply to individual analytes. Another observation and concern is the continued development of highly specific sensitive methods for analytes, where appropriate knowledge of the status of the analyte (i.e. it is actually non-mutagenic), would have precluded the necessity to do so. This illustrates the need to conduct a thorough review of the available literature before analytical method development is commenced. (C) 2017 Elsevier B.V. All rights reserved.