- Is any guidelines for Antibiotic group drug substances for the limit of Nitrosamine impurities . (Eg. Azithromycin, Erythromycin )
- Specially those drugs are formed by the fermentation is any specific guidance for Nitrosamine Impurities. (Eg. Vancomycin Hydrochloride).
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.
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).