The European Pharmacopoeia (Ph. Eur.) Commission (EPC) adopted the revised general monographs 2034 and 2619, at its 174th session in November 2022, which now includes a paragraph explaining the Ph. Eur. approach to the control of N-nitrosamine impurities.

A paragraph on N-nitrosamines has been added to Substances for pharmaceutical use (2034) under ‘Production’:

“N-Nitrosamines. As many N-nitrosamines are classified as probable human carcinogens, manufacturers of active substances for human use are expected to evaluate the potential risk of N-nitrosamine formation and contamination occurring throughout their manufacturing process and during storage. If the risk is confirmed, manufacturers should mitigate as much as possible the presence of N-nitrosamines – for example by modifying the manufacturing process – and a control strategy should be implemented to detect and control these impurities. General chapter 2.5.42 N-Nitrosamines in active substances is available to assist manufacturers.”

A similar paragraph on N-nitrosamines has been added to the same section in Pharmaceutical preparations (2619):

“N-Nitrosamines. As many N-nitrosamines are classified as probable human carcinogens, manufacturers of medicinal products, except products for veterinary use only and unlicensed pharmaceutical preparations, are expected to evaluate the potential risk of N-nitrosamine formation and contamination occurring throughout their manufacturing process and throughout their shelf-life, according to the requirements of the relevant competent authorities. If the risk is confirmed, manufacturers should mitigate as much as possible the presence of N-nitrosamines – for example by modifying the manufacturing process – and a control strategy must be implemented to detect and control these impurities. General chapter 2.5.42. N-Nitrosamines in active substances is available to assist manufacturers.” [EDQM _ EPR]