Stress testing as a predictive tool for the assessment of potential genotoxic degradants

INTRODUCTION Strategies for dealing with genotoxic impurities (GTIs) or potential genotoxic impurities (PGIs) arising from drug synthesis have received considerable attention in the literature ( 1 –6 ). In contrast to process impurities, genotoxic degradants have received less attention but may require different considerations since there is no opportunity for purifi cation and their presence needs to be considered over the entire shelf-life of the product. This chapter outlines the key considerations that may be involved in understanding the risk to a drug development program of discovering that a degradant may have the potential for genotoxicity.