Nitrosamine Impurities: EDQM completes General Monographs 2034 and 2619

At its 174th meeting in November 2022, the European Pharmacopoeia Commission adopted the two revised general monographs Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619). Based on the comments received during the last consultation session in Pharmeuropa, the two monographs were each extended by a section containing requirements with regard to possible contamination by nitrosamines.

According to this, manufacturers of APIs must observe the following requirements:

  • For each API, a risk assessment on possible nitrosamine impurities has to be carried out. This must include the entire manufacturing process as well as the storage of the API.
  • If such a risk is identified, measures must be taken to minimise the risk (e.g. through changes in the manufacturing process).
  • A control strategy must be implemented to reliably detect and monitor nitrosamine contamination.

These core requirements are supplemented in the section of the monograph Pharmaceutical preparations (2619) by the restriction that these requirements do not apply to manufacturers of veterinary medicinal products and unlicensed products ("... manufacturers of medicinal products, except products for veterinary use only and unlicensed pharmaceutical preparations...") and that the risk assessment must consider the entire shelf life of the product as required by the regulatory authorities.

The revised monographs will appear in Supplement 11.3 of the European Pharmacopoeia in July 2023 (see Ph. Eur. Publication schedule) and will apply as of 1 January 2024.

Further information on nitrosamine contamination can be found on the EDQM website in the section entitled N-nitrosamin contamination in brief.

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