Review on identification and quantification of genotoxic impurities

Abstract

Genotoxic impurities can be broadly defined as those impurities that have been demonstrated to cause harmful changes in genetic material regardless of the mechanism. Globally people suffer from various health complications due to genotoxic impurities. Recent recommendations from European and United States (USA) drug regulatory bodies mandate the management of genotoxic and possibly genotoxic contaminants in pharmaceutical ingredients at per million levels. The purpose of this review is to make a critical analysis of the techniques used to comply with the prevailing rules and regulations and very strict limits on genotoxic impurities. Possible strategies to further expand the scope of currently available technologies and regulations are also to be discussed. These strategies include redesigning the synthesis of the drug substance to avoid introducing problematic impurities; modifying relevant process parameters to eliminate or reduce such impurities to negligible levels; Using process understanding to demonstrate that a particular genotoxic impurity cannot be formed or removed efficiently and by conducting toxicity studies to demonstrate that a suspected impurity is not harmful to it at low levels.