Evolution of FDA Guidelines on Control of Nitrosamine Impurities in Human Drugs – A Comparative Analysis of September 2024 Revisions

Nitrosamine impurities have become a significant concern in the pharmaceutical industry due to their carcinogenic potential. In response, the U.S. Food and Drug Administration (FDA) has continuously updated its guidelines to ensure the safety and efficacy of drug products. This review article provides a comprehensive analysis of the evolution of FDA guidelines on the control of nitrosamine impurities, with a particular focus on the September 2024 revisions. By comparing the latest guidance with previous versions, this article highlights key changes, including the expanded focus on Nitrosamine Drug Substance-Related Impurities (NDSRIs), updated risk assessment strategies, and the introduction of new Acceptable Intake (AI) limits. The analysis underscores the FDA's commitment to enhancing drug safety through rigorous control measures and global harmonization efforts.