Nitrosamine control in Metformin /Vildagliptin DP

Limits of Nitrosamines
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Hi Ali and welcome to your Nitrosamine home!..

Here are some key considerations regarding your questions:

  • Confirmatory testing should be based on your Risk Assessment. Do not assume that your product will contain NDSRI (Nitrosamine Drug Substance Related Impurity) or small nitrosamines simply because they have been reported before. For instance, not all Metformin formulations will produce NDMA (N-Nitrosodimethylamine) or NDEA (N-Nitrosodiethylamine). Carefully study the risk of forming any nitrosamines based on your formulation, process, ingredients, and packaging. Do not rely solely on your suppliers’ “declaration letters” for assurance.

  • Generally, excipients (with a few exceptions) are not direct sources of nitrosamines; instead, they often contain precursors, such as nitrites or amines. The quantity of these precursors must be factored into your formulation risk assessment.

  • A fixed nitrite limit traditionally does not apply in this scenario. The risk associated with a particular excipient depends on the formulation and the level at which that excipient is used in the overall process. What may represent a high risk for one formulation might be considered a lower risk for another.

Please refer to this previous post for more context:

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