Hi everyone,
Hope you’re well.
We have a question here.
A manufacturer controls DMF in final API as 880 ppm.
The maximum daily dose is 500 mg/day and we have a risk of nitrosamines formation (pH 3,5, nitrite in excipients and liquid formulation)
How would you calculate the NDMA limit for the finished product?
Can I consider this 880 ppm from DMF ((96/500)/0,088 = 2 ppm), or do I need to consider the entire API (96/500 = 0,2 ppm) since the risk is only from the DMF?
Thank you!
Hi,
I recommend checking out the following link for better understanding of the calculation:
Moreover, if there’s any known Nitrosamine impurity, it should be calculated as AI ng per day / MDD mg per day.
Eexample: NDMA= 96/500= 0.192 or 0.2 ppm. This limit also applies to DS and DP.
You may raise your question to DS team how they calculate NDMA limit is 880 ppm ?
Regards,
Dr. Dinkar
Hi,
Although the DMF control limit in API is 880ppm as per ICH Q3C, considering the limit of 0.2ppm for the corresponding NDMA impurity by the formula ** AI ng per day / MDD mg per day** based on maximum daily dose of the drug is a better choice for control in DS and DP.
Regards,
Maximum daily dose of the drug product is considered irrespective of the controls established in the final API. The limit for NDMA in drug product would be 0.19 ppm (rounded to 0.2 ppm). Hope this helps and happy nitrosamine assessment/mitigation.
Inspired by @krishmnt !!
@romnaiffer Thank you
