Control of Nitrosamine Impurities in Human Drugs | FDA

Control of Nitrosamine Impurities in Human Drugs | FDA

FDA Issues Guidance on Control of N-Nitrosamine Impurities in Human Drugs

FDA is announcing the availability of a guidance for industry, entitled “Control of N-Nitrosamine Impurities in Human Drugs.” This guidance recommends steps manufacturers of active pharmaceutical ingredients and drug products should take to detect and prevent objectionable levels of nitrosamine impurities in pharmaceutical products. The guidance also describes conditions that may introduce nitrosamine impurities. 

Based on the testing results and the agency’s current understanding of the chemistry, FDA has developed this guidance to provide active pharmaceutical ingredients (API) and finished drug manufacturers information on the potential root causes of nitrosamine formation. It recommends ways drug manufacturers conduct risk assessments of their drugs, whether approved, marketed or with pending applications. The guidance also suggests actions they should take to reduce or prevent the presence of nitrosamines in APIs and finished drugs. The recent unexpected finding of nitrosamine impurities, many of which are probable or possible human carcinogens, in drugs such as angiotensin II receptor blockers, ranitidine, nizatidine metformin, rifampin and rifapentine has made clear the need for a risk management strategy to identify and minimize nitrosamines in any pharmaceutical product at risk for their presence.

We are issuing this guidance consistent with our good guidance practices (GGP) regulation (21 CFR 10.115)). We are implementing this guidance without prior public comment because we have determined that prior public participation is not feasible or appropriate (§ 10.115(g)(2)). We made this determination because of the importance of providing timely information to manufacturers regarding risk assessments, testing and other appropriate actions they should take to reduce and mitigate nitrosamine impurities in APIs and finished drugs. Although this guidance document is immediately in effect, it remains subject to comment in accordance with FDA's GGP regulation (§ 10.115(g)(3)(D)).