Hi Sujan.
My only caution on this is to ensure that you understand the exact composition of the product final packaging because you don't want to get caught up in whether or not the packaging could potentially pose a risk of nitrosamine generation from your product. If you don't have full information (and confidence that your vendor will not change the packaging manufacturing in any way without your knowledge) then it is potentially risky to remove the test from stability.
Also, in general, I have regularly recommended that if you test a parameter on the finished good at lot release you have determined that the parameter is important in some way to your product overall. If that is the case, it can be a bit difficult to eliminate tests that are continuing to be performed on the release of the lot but then not performed later on stability. To me this adds a layer of complexity that could have you trying to explain your rationale during inspections in the future to someone with less specific knowledge/information than you and your colleagues have and that discussion could move in a very unhappy direction for you and your company.
Just my opinion here but if you believe it is important enough to test the parameter of nitrosamine on release I think you will need to either continue testing through stability or you will need a fairly robust substantiation of the removal of the testing during stability. And I really am not generally a fan of the rationale "we haven't ever found it so it must never be there" especially when a more mature product typically does not include every production lot of finished good being placed into your stability program.
To me this is likely a PAS since you are effectively changing the stability specification if you remove the testing but I think there are arguments that could make this into a different notification category.
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Victor Mencarelli MS
Global Director Regulatory Affairs
New YorkNY
United States
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Original Message:
Sent: 08-Jan-2024 04:21
From: SUJAN BOSE
Subject: Removal of Nitrosamines impurity testing
Hello experts,
Can you please suggest me for a following situation
"we have a ANDA with -sartan group drug product, which we are analyzing for nitrosamine impurities for long time with validated test method."
We want to remove nitrosamine testing from the stability specification as we have -
- API lot nitrosamine test results by vendor for each and every lots
- API lot nitrosamine testing by us on each and every lots
- Nitrosamine testing in each finished products lots before release
- No trace of nitrosamine in all the batches received from vendor.
We will continue to test API and Finished product each and every lots, only stability samples will not be tested.
What should be the supplement filling category, PAS, CBE-30, CBE-0 or AR?
Do you think we should provide any other documents other than test results and justification?
Looking forward for your valuable comments on that.
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SUJAN BOSE
Senior Executive
Global Regulatory Affairs (Drugs)
SPPLC. (Bangladesh)
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