The US Food and Drug Administration has released long-awaited guidelines to help companies get a handle on nitrosamine impurities in drugs. Drugmakers have been scrambling since 2018 to understand why some of their products contain worrying amounts of nitrosamines, such as N-nitrosodimethylamine (NDMA)—a probable carcinogen. Medications used to treat high blood pressure, diabetes, heartburn, and stomach ulcers have all been recalled because of such impurities.
The recommendations, published Sept. 1, provide industry with acceptable intake limits for six nitrosamine impurities. The FDA’s suggested limit for NDMA is 96 ng/day.
To ensure that their products do not exceed the limits, drug manufacturers should complete a risk assessment within 6 months and test all products considered high risk, the FDA says. If a product exceeds the recommended limit, the FDA advises companies to investigate the cause of the contamination and make changes within 3 years to remedy the situation.
Many factors contribute to the presence of nitrosamine impurities in drugs, including the manufacturing process, ingredients used in manufacturing, chemical structure of the drug, and conditions under which the drug is stored.
The FDA guidelines do not carry the legal force of regulations. The European Medicines Agency and Health Canada issued similar guidelines in 2019.