Genotoxic Impurities : A Quantitative Approach

Abstract Starting materials, intermediates and by-products are often found as impurities in active pharmaceutical ingredients (APIs). Some of these known impurities are potential mutagens or carcinogens but can be difficult or impossible to eliminate completely from the synthetic scheme. Based on current regulatory guidances for genotoxic impurities, analytical methods should be developed to meet the required limit of 1.5 µg/day daily intake of each individual impurity for new drug substances. During the early clinical development stages the Pharma Task group proposed a staged TTC concept, where greater daily intake can be allowed. The allowable daily intake thus calculated would then provide a basis for estimating the quantitation limit (QL) required for the development of an analytical method for determining genotoxic impurity levels. The approach for choosing an analytical technique will depend on many factors including availability of the instrumentation and physical and chemical properties of the ana...