Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.

No. As long as you are confident that the method has been fully validated, there is no reason that it can't be used. The reason that USP methods exist is so that you don't HAVE to validate a method every time you want to perform a method.

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Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
New York NY
United States
------------------------------

Original Message:
Sent: 03-Feb-2021 11:12
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.

Hi Anon.

I would generally agree with Glen on this.  However, I will caution you that in certain respects, if audited I have seen auditors (especially US FDA inspectors) begin asking about whether the method used provides at least the same level of sensitivity, specificity, etc. as the USP method.  In order to be able to answer that question it is essentially assumed that you (or your vendor) has done some sort of comparative validation of the "in-house" method with the USP methodology.  While you might be able to manage to get the auditor to accept your explanation of what you did and that it is sufficient, it still can cause some issues that might bring additional auditor questions regarding your supplier qualification program.

If you would like to further discuss, please let me know!

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 04-Feb-2021 08:21
From: Glen Park
Subject: Validated method v. USP method

No. As long as you are confident that the method has been fully validated, there is no reason that it can't be used. The reason that USP methods exist is so that you don't HAVE to validate a method every time you want to perform a method.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
New York NY
United States

Original Message:
Sent: 03-Feb-2021 11:12
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.

Original Message:
Sent: 2/4/2021 10:27:00 AM
From: Victor Mencarelli
Subject: RE: Validated method v. USP method

Hi Anon.

I would generally agree with Glen on this.  However, I will caution you that in certain respects, if audited I have seen auditors (especially US FDA inspectors) begin asking about whether the method used provides at least the same level of sensitivity, specificity, etc. as the USP method.  In order to be able to answer that question it is essentially assumed that you (or your vendor) has done some sort of comparative validation of the "in-house" method with the USP methodology.  While you might be able to manage to get the auditor to accept your explanation of what you did and that it is sufficient, it still can cause some issues that might bring additional auditor questions regarding your supplier qualification program.

If you would like to further discuss, please let me know!

------------------------------
Victor Mencarelli
Global Director Regulatory Affairs
MelvilleNY
United States
------------------------------

Original Message:
Sent: 04-Feb-2021 08:21
From: Glen Park
Subject: Validated method v. USP method

No. As long as you are confident that the method has been fully validated, there is no reason that it can't be used. The reason that USP methods exist is so that you don't HAVE to validate a method every time you want to perform a method.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
New York NY
United States

Original Message:
Sent: 03-Feb-2021 11:12
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.

This message was posted by a user wishing to remain anonymous

Is your API a compendial listed substance? If so, yes!
Original Message:
Sent: 03-Feb-2021 11:12
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.

It's unclear whether the subject API is compendial or not.  If the API is compendial (listed in the USP), then the USP test monograph must be followed exactly and the API shown to comply with the monograph.  If the USP method is modified in any way or if an alternate method is used, the "non-USP" method must be shown to yield results equivalent to the USP method and be validated.  The way to demonstrate equivalent results is to test samples from multiple lots of the API using both the USP method and the alternate method, and compare results against pre-established acceptance criteria, generally done through an approved protocol.  This study, along with a proper method validation, would be sufficient to meet FDA requirements.  USP methods do not need to be validated, but labs must demonstrate that the USP method can be properly applied through a method verification protocol.  If the API is not compendial, then a proper method validation would suffice.  I am quite surprised at this discussion since the above has been FDA policy for 40+ years.

War story:  China 1984 - A drug substance (API) manufacturer was using a Chinese Pharmacopeia titrimetric method and the USP method was potentiometric.  Ended the day by telling company that the USP was required.  Overnight, the company borrowed a potentiometer and 2 students from the local university and compared samples from 10 API batches using both methods.  The results were presented first thing in the morning and were comparable showing the USP and CP methods were equivalent.  Note that in 1984 for drug substances, there was little emphasis on instrument qualification and documented analyst training.  

------------------------------
Peter Smith
Principal
Smith GMP Consulting
Narragansett, Rhode Island
USA
------------------------------

Original Message:
Sent: 04-Feb-2021 09:11
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Is your API a compendial listed substance? If so, yes!
Original Message:
Sent: 03-Feb-2021 11:12
From: Anonymous Member
Subject: Validated method v. USP method

This message was posted by a user wishing to remain anonymous

Hello Community,

We have an API supplier who tested for residual solvents with their own validated method for residual solvents.  Do we need to retest using USP's residual solvent method <467>?  Thanks in Advance.