is there any template that could be used in risk assessment report for nitrosamine impurities in finished product? how we can check the conditions of the manufacturing process of FP to exclude the risk of NDSRI formation, if the API include a secondary amine in its structure and we can’t exclude the present of Nitrite in excipients, so how to exclude the risk by referring to manufacturing conditions instead of conformity testing? if anyone can provide a template for such cases
Dear heba-1994
there is no specific template to be used in RAR for nitrosamines.
The risk assessment methodology follows ICH Q9 principles.
As for your case, where the API include a secondary amine in its structure and we can’t exclude the present of Nitrite in excipients, ad based on previous experience, confirmatory testing is expected.
However, for a theoretical approach you may refer to publications:
https://jpharmsci.org/article/S0022-3549(25)00034-6/abstract
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At first, a risk assessment should be carried out, according to EMA or FDA guidelines, see below links:
As a result of the risk assessment, you will discover which potential nitrosamine impurities will be formed from your manufacturing process, API, excipients, air.
There is also risk of formation of low molecular weight nitrosamine impurities and risk of formation of NDSRI in your product.
At the end, you should provided the results of the analysis (low molecular weight and high molecular weight nitrosamine impurities (NDSRIs) ( lower than FDA and EMA acceptance intake limits).
If the NDSRIs acceptance intake doesn’t include in FDA or EMA list, you should to carry out CPCA analysis.