Feasibility studies to confirm Nitrosamine (NDSRI) formation / Nitrosamine Failure Report

Nitrosamine including NDSRI impurities are formed in Drug substance and drug products due to the presence of amine functionalities in API molecules or its impurity molecule which reacts with nitrosating agents like nitrites which are contaminants in reagents and excipients.

Many amine-containing compounds may not undergo the expected N-nitrosation reaction when exposed to nitrosating conditions. Taking this into account the EMA suggests  that “If, despite extensive efforts, it becomes apparent that the relevant nitrosamine impurity cannot be synthesized, then this could be an indication that the nitrosamine either does not exist or that there is no risk of it being formed

We can perform a standard set of a few orthogonal forced nitrosation reactions that can be used to investigate the potential for the generation of novel N-nitrosamines by nitrosation of complex amines.

These complementary condition are considered to provide a thorough evaluation of the potential for N-nitrosamine formation from complex amines with respect to risk factors within pharmaceutical manufacturing.

The chemical understanding gained from the lack of formation of an N-nitrosamine

when using stoichiometric amounts of nitrosating agents can be used to justify the absence of an N-nitrosamine risk in the drug substance and/or drug product.

We can submit such failure reports to health authorities as part of nitrosamine risk assessment..

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