Genotoxic impurities in pharmaceutical products
Several organisations have developed guidelines that specifically address genotoxic impurities in pharmaceutical products. Here, Dr Sol Bobst and Gowri Sukumar discuss the regulatory landscape, testing requirements and calculation methods for occupational exposure limits.
The recall of Valsartan containing NDMA by several companies in 2018 has refocused interest in the regulatory and testing requirements for genotoxic impurities in pharmaceutical products.1 This includes occupational and consumer safety protection. Over the past decade, industry standards and best practices have been developed in order to address the risks posed by impurities and to help regulatory managers manage these risks appropriately. This article provides an overview of the current resources available to quality and safety professionals to safely and effectively manage these risks.
The levels of impurities in drugs must be reduced to acceptable safety limits to protect patients. Additionally, reliable and accurate data measured in pharmaceutical laboratories are key to ensure product safety. Several organisations from industry and regulatory authorities have developed guidelines specifically addressing genotoxic impurities. Per the International Council for Harmonization (ICH) S2 (R1) Guideline, genotoxic impurities can be broadly defined as impurities that have been demonstrated to cause deleterious changes in the genetic material regardless of the mechanism. Presence of genotoxic impurities can be confirmed when tested via an appropriate genotoxicity test model (eg, bacterial gene mutation – Ames).2