Regulation of genotoxic and carcinogenic impurities in drug substances and products

While the use of pharmaceuticals is always a balance of risks and benefits, the same is not true for impurities in pharmaceuticals; impurities carry only risk. A number of international guidelines and regional guidance documents instruct drug developers and regulatory agencies on how to evaluate and to control impurities in drug substances and drug products. These guidelines explicitly identify triggers for reporting, identifying and qualifying impurities. In addition, the guidelines provide direction on the assays that should be used to determine if impurities are genotoxic. However, the guidelines fail to provide direction on how levels of genotoxic impurities should be controlled. This article discusses practical and theoretical methods for controlling levels of genotoxic impurities in drug substances and drug products.