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This section (Section 5 of the guideline) is essentially the start point for the overall risk assessment process itself. Critically, in practical terms, this essentially advocates the same approach as previous guidelines. The emphasis remains focused on actual impurities and potential impurities likely to be present in the API/DP. Another important aspect of this section of the guideline is that it also looks to link the ICH M7 [1] to ICH Q3A [5]/Q3B [6] reporting and identification requirements. Actual impurities are defined as those observed in the DS above the ICH Q3A reporting thresholds. Identification of actual impurities is expected when the levels exceed the identification thresholds outlined by ICH Q3A [6]. This confirms the primacy of ICH Q3A in terms of identification thresholds.

In practical terms this means that there is no formal requirement to attempt to identify every possible impurity at a TTC‐like level. Such an attempt would be in reality, impractical. Instead, the guideline tacitly accepts the finite but low risk of a mutagenic impurity existing, unidentified, at level below the ICH Q3A identification threshold. This is considered to be an acceptably low risk provided a comprehensive risk assessment is made of the synthetic process, its related impurities, DP manufacturing process, and associated degradants.