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Once potential impurities have been identified, the next step is an assessment of their mutagenic potential. The relationship between structure and mutagenicity is discussed in detail in Chapter 4. Such an assessment is typically made through the use of in silico SAR systems. ICH M7 [8] defines the need to apply two (Q)SAR methodologies. One methodology should be expert rule‐based and the second methodology should be statistical‐based; however, the guidance does not define which software packages are preferable; this decision is left to the end user. Importantly, it also highlights the need for an expert evaluation of the results. Again this concept is examined in depth in Chapter 4.

The use of the described methodologies provides numerous permutations, which range from confirmatory, likely to be mutagenic or not, to the in silico tools being unable to provide a prediction with varying levels of certainty/uncertainty in between.

It is typical that through the application of in silico screening the number of potential impurities that remain of concern will have been drastically reduced, perhaps by close to 90% of those initially part of the assessment.