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?
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.
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.