NITROSAMINE IMPURITIES

Nitrosamine is a vast group of N-nitroso Compounds (NOCs) with Chemical Structure R2N−N=O, where R is usually an Alkyl Group (CnH2n+1). The NOCs can be divided into two classes: N-nitrosamines and N-nitrosamides and related compounds.
The International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) has recognized Nitrosamines as potentially Carcinogenic and Genotoxic. ICH M7 (R1) Guideline classifies Nitrosamines as Class I Impurities, “known Mutagenic Carcinogens”.

NOCs have been traced to Starting Materials, Intermediates, Solvents, and Reagents in Active Pharmaceutical Ingredient (API) Synthesis. These aside, the possibility of NOC formation during Manufacturing, Storage, and Use of Pharmaceutical Products poses serious risks to Patients leaving Regulators deeply concerned as they are harmful even at very low levels.
FDA has identified Seven Nitrosamine Impurities (NDMA, NDEA, NMBA, NIPEA, NMPA, NDIPA) that could, theoretically be present in Drug Products with the first five being detected in Pharmaceutical Substances/ Products. FDA’s New Regulations that have come into effect from 1st October 2023, require that Companies demonstrate Safe levels of Nitrosamines in all their Drug Products.

EFRAC’s Analytical Capability extends to a wide range of NOCs including Nitrosamine Drug Substance-related Impurities (NDSRIs). It has diligently Developed and Validated Advanced Methods for Analysis of NOCs in Pharmaceuticals.
EFRAC’s Independent Analytical Data Empowers Manufacturers to proactively address Potential Risks and ensure Product Integrity during and after the Development of their Pharmaceutical Products.