FDA Publishes Guidance on Control of Nitrosamines

September 2, 2020

The guidance recommends steps to detect and prevent nitrosamine impurities in pharmaceutical products.

On Sept. 1, 2020, FDA announced the publication of Control of N-Nitrosamine Impurities in Human Drugs. The guidance document was developed to help API manufacturers detect and prevent objectionable levels of nitrosamine impurities. The guidance, based on testing results, presents the agency’s recommendations for risk assessments and steps to reduce or prevent nitrosamines. It also describes conditions where nitrosamine impurities may be introduced.

The guidance is being implemented immediately without public comment, “because the Agency has determined that prior public participation is not feasible or appropriate (see Section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2) and (g)(3)). FDA 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 active pharmaceutical ingredients (APIs) and drug products,” FDA states in the document.

Nitrosamines at unacceptable levels may increase the risk of cancer, according to FDA. The impurities have been found in certain drugs, such as angiotensin II receptor blockers, ranitidine, nizatidine metformin, rifampin, and rifapentine. FDA and other regulatory agencies have been working to develop strategies to identify and minimize nitrosamines in drug products.

“Since the outset of our discovery of impurities called nitrosamines in some types of drugs more than two years ago, the US Food and Drug Administration has undertaken a thorough investigation in an effort to protect patients. While nitrosamines are common in water and foods, nitrosamine impurities may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time. For this reason, the discovery of unexpected nitrosamine impurities in some drug products is a serious concern, and the FDA has been working, in collaboration with regulatory counterparts around the world, to find and remove drugs with unacceptable nitrosamine impurities from the US drug supply. As we do so, we’re also taking proactive efforts to help ensure that in the future, drugs can be free from unsafe levels of these impurities from the start of production,” said FDA Commissioner Stephen M. Hahn, M.D., and Patrizia Cavazzoni, M.D., acting director, Center for Drug Evaluation and Research, in a joint statement.

Source: FDA