Dear team,
I have tested 2 batches on shelf life for nitrosamine impurity and the obtained results are less than 10% of the limit specified in EMA. do I need to take any further actions?
Appreciate your help
If testing is performed to justify omission from the specification, it has to be demonstrated that the levels of the respective nitrosamines are consistently at or below 10 % of the acceptable limit.
And for marketed products, test results from 10% of annual batches, or 3 per year, whichever is highest, should be submitted. If fewer than 3 batches are manufactured annually, then test results from all manufactured batches should be submitted.
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No action is required as longer as the LoQ of the analytical method employed is ≤ 10% of the acceptable limit based on the AI.
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@sbasaleh would you mind sharing bit more information on the case? are you testing any specific nitrosamines or NDSRIs, what’s the condition on the stability samples? … more context information always help understand the big picture.
Thanks
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good question…but more data are required
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Dear Naiffer,
Thank you for your response. We tested for the presence of n-nitroso pseudoephedrine. Testing has been performed on two reference batches (Room temperature). Our thinking was that we will test two batches on shelf life. If the limit is high, we will go for further action. However, the obtained results were less than 10% of the limit (1500ng/day).i am doubting if further action is required?
Hi @sbasaleh,
Can you justify that the increase of nitrosamines is consistently acceptable through shelf-life of the product? Further data such as accelerated tests or additional batches support the theory. It’s the same as ICH Q1. I do not know details of your data, but it sounds enough for me in many cases.
If you can justify both initial amounts of nitrosamines and the increase of nitrosamines through storage are acceptable or negligible, further data will not be needed. Then you can consider availability of batches, as @Ankit_Gangani said.
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For me this could well depend on the format of your product, and the risk that can then be associated as to whether the batches tested to date reflect what is “the common” level (based on nitrites within raw materials, manufacturing conditions etc.) and also what the potential is for increase in nitrosamine levels upon stability.
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This added detail makes a lot of sense. Do you have a reference for it?
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That’s great! Thanks for sharing. I had been looking for this for a long time, but had not seen this detail in a formal document.
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