Hi Olga.
First, start the process looking at what you would need to do to "validate" your methodology against the USP method. When you start there, your answer might become more simplistic.
In regard to whether you are required to "first" prove the method in USP is insufficient, the answer technically is "no." However, recognizing that the FDA is likely to look at the USP as the starting point methodology, you probably need to show something about the USP method is providing something less than what is expected or where you have a potential issue that causes you problems with integration or separation in the analysis. If you are trying to use the non-USP method you will need to show that your method provides "at least equivalent" results as the USP method. In doing this analysis you might be able to show that the USP method is less effective than your method.
The other question, as has been previously pointed out, is whether or not your product is under an NDA. If so, it is likely that FDA will be expecting to see your methodology for the analysis of residual solvent levels in your NDA package as part of your specifications. You will definitely need to convince FDA that your method is valid and is producing at least equivalent results to the USP during that review. If you have already submitted and have an approved NDA on this product, you will need to run the analysis against USP, any other method that might have been approved through your original submission package and then submit a supplement to the NDA for approval for the new method for residual solvents.
No matter how you run it, you will need to validate the non-USP method against the USP method itself and prove that your new method is more useful for this product. Otherwise you are not likely to get approval for any changes to the USP. Also, remember, just because a method is "equivalent" it doesn't mean that the FDA would be required to accept/approve the method for use.
Hope some of this helps!
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Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
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Original Message:
Sent: 21-Feb-2021 18:50
From: Olga Figueroa Brito
Subject: Residual Solvents Alternative Methods
Hello community,
I am looking for input/exchange specifically from the USP statements below (in bold), they are from the USP's FAQ page "Residual Solvent" Alternative Methods.
USP allows the use of alternative methods, are drug product manufacturers required to FIRST prove (with data) that the USP method is inadequate and not suitable (for our products) before selecting/validating/using their own method?
"26-The USP methods still have many drawbacks and may not be able to detect or quantitate certain solvents. How can the industry comply with the requirements if an alternative method has not been developed or validated?"
"27-Can USP add a statement to <467> that will provide companies the flexibility to use the USP method or their own validated procedure?"
The General Notices also allow for the use of other validated methods. Does this mean without having to FIRST prove that the USP method is not working out?
Thanks in advance,
Olga
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Olga Figueroa Brito
Santa Ana CA
United States
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