Nitrosamine in DS and DP specifications

I want to ask if the detected nitrosamine is consistently below 30% of AI, should it be added the COA of the DS or DP. In other words, how the “skipping” should be reflected in the regulatory documents.
Also, what is the regulatory criteria for the term “consistently”, is there certain number of batches to be tested?


I cannot help you with how it should be reflected in the CoA, but it regarding what consistently means, according to ICH M7 all batches have to be below that value. As soon as 1 batch is above 30%, all batches should be tested until an investigation has been carried out, correction actions applied if applicable and you are able to demonstrate that the manufacturing process is capable again to keep results below 30%.
Regarind number of batches to be tested, the guideline is quite clear, 3 batches or 10% of annual batches, whichever is higher.
Please note that this number of batches should be multiplied per API source for example, if you have more than 1 API supplier, and that this amount of batches should be tested for each year of the product’s shelf-life, meaning that if your product has a 3 year shelf-life, you should test 3 batches or 10% of the batches manufactured of each annual production.



Clearly explained Javier, Gracias!