Guidelines for Antibiotic group drug substances for the limit of Nitrosamine impurities . (Eg. Azithromycin, Erythromycin )

About Nitrosamines Exchange
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  1. Is any guidelines for Antibiotic group drug substances for the limit of Nitrosamine impurities . (Eg. Azithromycin, Erythromycin )
  2. Specially those drugs are formed by the fermentation is any specific guidance for Nitrosamine Impurities. (Eg. Vancomycin Hydrochloride).
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In Europe, according to EMA requests:
Nitrosamine impurities

Marketing authorisation holders should complete the confirmatory testing and submit their variation applications by:

1 October 2023 for chemical medicines;
1 July 2023 for biological medicines.

No special indications were given for fermentation APIs. So, in my opinion, antibiotics made by fermentation only should be classified as biological medicines.

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@paliog sir , Thanks for your valuable information.

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Anybody dealing with Nitroso-Vancomycin? It is reported in the FDA NDSRIs table as category 4 (1500 ng/da).
I also came across this publication from Preobrazhenskaya et all “SYNTHESIS AND BIOLOGICAL ACTIVITY OF DERIVATIVES OF GLYCOPEPTIDE ANTIBIOTICS EREMOMYCIN AND VANCOMYCIN NITROSATED, ACYLATED OR CARBAMOYLATED AT THE TV-TERMINAL” (1993).

The team showcased the formation of Nitroso-Vancomycin on two typical nitrosating conditions: Isoamyl Nitrite (61% conversion) and Sodium Nitrite (48% conversion).

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Yes my team is working to generate nitrosamine of vancomycin and dalbavensin. We are able to generate, detect and characterized via LC-hrms.
Very soon we are going to publish article.

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