Hi everybody,
I kindly ask your support to clarify how to calculate the acceptable limits for Nitrosamine drug substance-related impurities (NDSRIs):
According to the formula,
AL= AI /MDD
The MDD to be considered is the MDD of the finished product or the MDD of the API? It seems that there is a bit of confusion in this regard.
Many thanks.
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MDD of the API in the drug product.
Example
MDD for Duloxetine is 120 mg
AI limit for duloxetine is 100 ng/day
N-Nitroso duloxetine limit is 100/120 = 0.83 ppm.
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Just to clarify further:
AI limit is “a level that approximates an increased cancer risk of one additional case in 100,000 people based on a conservative assumption of daily exposure to the impurity over a lifetime (70 years).”
MDD: drug’s maximum daily dose
We have an extensive post on this specific topic with examples
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