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  • 1.  Analytical Method Optimization Prior to Approval

    Posted 21-Sep-2022 14:18
    Good Afternoon, 

    I have a question regarding the best practice for updating an analytical method for the analysis of drug product that is currently in review and has not gained final approval.   

    The firm has previously updated this method in response to a deficiency letter from the FDA, however since that time additional optimization work was performed to further strengthen the method.   While the current method is acceptable, validated and meets requirements, the additional work shows that it could be improved. (Tightening of an in-process pH range) The updated method does not contradict the submitted method and only tightens in-process test limits.   

    The current plan is to await approval, submit the optimized method as part of an annual report following approval as a minor change (since it only improves controls).  Unless of course the method is addressed again by the agency prior to that date.  A few stability intervals that remain would be tested using this optimized method at the end of the shelf study.

    Does this sound prudent or are there suggestions for a better route?

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    Kristopher Stavely
    St Petersburg FL
    United States
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  • 2.  RE: Analytical Method Optimization Prior to Approval

    This message was posted by a user wishing to remain anonymous
    Posted 22-Sep-2022 09:17
    This message was posted by a user wishing to remain anonymous

    Hi Kristopher,

    I would even question the need of registering a tighter pH if it's within the registered range. In my experience you can use tighter internal method in-process controls than what's registered (if limits were legitimately derived and not too wide in the first place). This allows for flexibility for lab error for example which will mean if it internally when investigating actually it's still within the registered range but outside the UK internal working limits.