Nitrosamine impurities even in small amounts are known to be mutagenic and carcinogenic. Numerous recalls and enhanced regulatory scrutiny of drug substances and high-profile drug product batches contaminated with nitrosamines have recently been carried out by several national authorities including FDA, EU, Canada, Australia, Switzerland, and Singapore. The pharmaceutical industry has witnessed recalls of several drugs, including those used to treat elevated blood pressure (such as valsartan, losartan, and irbesartan), heartburn, and acid reflux (such as ranitidine and nizatidine), resulting in heavy loss of revenue for manufacturers and the temporary withdrawal of treatment for many patients worldwide. Regarding the control of these contaminants with interim limits, various regulatory authorities have released press releases and notices. It is imperative that drug product manufacturers identify and understand the probable sources of nitrosamine formation in their manufacturing process and apply mitigation strategies with proper controls to reduce the formation of nitrosamine carcinogenic impurities. This review covers a variety of aspects that are essential to successful control measures against current and upcoming nitrosamine issues, as accumulated knowledge of toxicity concerns and potential root causes of nitrosamine contamination, accurate risk assessment, and various mitigation strategies are explained in depth.

Dr. Harsha Kathpalia*; Ms. Swapnali Patil; Mr. Rohan Choudhary

Nitrosamine, carcinogenicity, varenicline, ascorbic acid