The US Food and Drug Administration (FDA) on Friday issued a final guidance that outlines a framework for predicting the mutagenic and carcinogenic risk of nitrosamine drug substance-related impurities (NDSRIs) and sets recommended acceptable intake (AI) limits for these compounds that are identified in drug products and active pharmaceutical ingredients (APIs).
FDA calls on manufacturers of approved products to evaluate these NDSRI risks within three months of final guidance’s publication, and recommends these assessments be completed by 1 November 2023. The guidance further specifies that by 1 August 2025, manufacturers and applicants should ensure that any NDSRIs in their drug products meet the FDA-recommended AI limit and its carcinogenic potency category.
Regulators around the globe have raised concerns about the presence of nitrosamine impurities in pharmaceuticals following the discovery of novel nitrosamine impurities in valsartan and other angiotensin II receptor blocker (ARB) drugs in 2018. A more recent case involved novel nitrosamines detected in Merck’s diabetes drug Januvia last year, where traces of Nitroso STG-19 19 (NTTP) were found. (RELATED: Prompted by recent recalls, regulators scramble to address novel nitrosamines, Regulatory Focus 31 October 2022)…
