USA – N-Nitrosamine impurities: FDA issues detection, prevention guidance

An immediately effective guidance from the US Food and Drug Administration (FDA) details steps to be taken to detect and prevent the introduction of potentially carcinogenic nitrosamine impurities into finished drug products and active pharmaceutical ingredients.
 
“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,” said FDA in announcing the guidance.
 
The nitrosamine that has been most commonly found at elevated levels in pharmaceutical products is N-nitrosodimethylamine (NDMA), which was first found in valsartan, an angiotensin II receptor blocker, in mid-2018. Elevated levels of NDMA and other nitrosamines have since been found in the drugs and drug classes mentioned by FDA both in the US and globally.  (RELATEDFDA addresses nitrosamines in TB drugs, Regulatory Focus 20 August 2020; FDA recalls some ER metformin for NDMA impurity, Regulatory Focus 29 May 2020)
 
“The FDA and the international scientific community do not expect NDMA to cause harm when ingested at low levels,” said FDA Commissioner Stephen M. Hahn, MD, and Patrizia Cavazzoni, MD, acting director, Center for Drug Evaluation and Research, in a press release announcing the availability of the guidance. “However, given the risk that genotoxic substances such as NDMA may increase the risk of cancer if people are exposed to them above certain levels and over long periods of time, manufacturers have recalled drugs with NDMA levels higher than the FDA’s recommended acceptable intake levels.”…