Dear Community,
in the latest EMA update of the Q&A paper 23 June 2022, in the section 4 of risk factors related to the manufacture of the active substance the introduced under bulletpoint 3 the topic of disinfected water, which i did not found in all nitrosamine statements from vendors well evaluated and i wanted to know your interpretation and experience.
According to the refferences given by EMA i understood mayor issues are resudual amounts of monochloramine or dichloramine which could be introduced into the manufacturing process and act as nitrosating agent.
Are such compounds controlled in general or will be decomposed in the purifications procedures like disillation or reverse osmosis?
An additional risk was citied in relation to Chlorination of nitrite-containing water which could lead to the formation of nitrosating species and consequently result in the formation of nitrosamines during disinfection which i would assume to be at lower risk since nitrite levels should be controlled.
(J. Org. Chem. 2021, 86, 2037−2057)
EMA Q&A Paper 06/22EMA/409815/2020 Rev.10
Hi, @JohannesReiner.
I found the Comparison Chart of Drinking Water Guidelines, Regulations, and Directives from around the World. The limit of total chloramines is 3, 4 mg/L, or no limit.
And chlorine and chloramine are mainly used to disinfect water, according to the CDC page. Water Disinfection with Chlorine and Chloramine | Public Water Systems | Drinking Water | Healthy Water | CDC
As far as I know, a typical example of nitrosamine formation is the recycling of wastewater. Some wastewater includes amines and causes nitrosation through UDMH(unsymmetrical dimethylhydrazine) with disinfection.
Most communities use either chlorine or chloramines. The limit of total chloramines is for communities using chloramine for water disinfection. However, the reaction between ammonia and chlorine seems to lead to chloramine formation.
That is why I recommend you check the quality standards of drinking water and how to disinfect water in your country.
Please correct me if I am wrong.
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Dear Yosukemino,
thank you for your fast advice and feedback which i found really helpful. Regarding the FP production i really agree here are several procedures in place but i was thinking at the API production where maybe TAP water is used and i am not aware of the typical purification modalities for the drug substance manufacturing process related to water in case water is used during the process.
Thank you and have a joyful weekend.
All the best
Johannes
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Thank you for your kind message. I’m happy to help you. And carbon filtration is effective in reducing the amount of chloramine.
All the best
Yosuke
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