Regulatory Experiences with Root Causes and Risk Factors for Nitrosamine Impurities in Pharmaceuticals

N-Nitrosamines (also referred to as nitrosamines) are a class of substances, many of which are highly potent mutagenic agents which have been classified as probable human carcinogens. Nitrosamine impurities have been a concern within the pharmaceutical industry and by regulatory authorities worldwide since June 2018, when regulators were informed of the presence of N-nitrosodimethylamine (NDMA) in the angioten-sin-II receptor blocker (ARB) medicine, valsartan. Since that time, regulatory authorities have collaborated to share information and knowledge on issues related to nitrosamines with a goal of promoting convergence on technical issues and reducing and mitigating patient exposure to harmful nitrosamine impurities in human drug products. This paper shares current scientific information from a quality perspective on risk fac-tors and potential root causes for nitrosamine impurities, as well as recommendations for risk mitigation and control strategies.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

N-Nitrosamines are a class of substances that are highly potent mutagenic agents and probable human carcinogens. Since the presence of N-nitrosodimethylamine (NDMA) in valsartan was discovered in 2018, nitrosamine impurities have been a concern for the pharmaceutical industry and regulatory authorities. This paper shares current scientific information on risk factors, root causes, and strategies for risk mitigation and control of nitrosamine impurities.