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  • 1.  Partial/Full Validation requirement of higher sensitive PK assay

    This message was posted by a user wishing to remain anonymous
    Posted 07-28-2025 09:27
    This message was posted by a user wishing to remain anonymous

    We have a validated clinical PK assay with an LLOQ of 10 ng/mL but require higher sensitivity (LLOQ ~2 ng/mL) to support lower doses. Using the original method, we can now achieve this sensitivity, with changes in LLOQ, LQC, and MQC. Do we need a full validation for the more sensitive PK assay?  



  • 2.  RE: Partial/Full Validation requirement of higher sensitive PK assay

    Community Leadership
    Posted 07-28-2025 09:58

    You can theoretically do a partial validation, but given how many assessments are performed at the now lower LLOQ and LQC, it's basically a full validation.



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    Joleen White Ph.D.
    AAPS 2024 Global Health Community Chair
    Bioanalytical 101 Course Development
    Senior Advisor
    BioData Solutions LLC
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 3.  RE: Partial/Full Validation requirement of higher sensitive PK assay

    Posted 08-05-2025 08:57

    Agree it's pretty much a full validation as many parameters are tested in LLOQ and LQC levels.  

    @Joleen White I also have a question for matrix stability (short term, F/T and LTS). The stability is established at LQC and HQC. If either LQC or HQC concentration is changed but still within the validated calibration range, should the stability be repeated at the new concentration, or the original stability can be accepted? Also, if later during sample analysis, another level of QC (eg. a LMQC between L and M) is added, will additional stability data of the LMQC be required, or not necessary as it is covered by LQC and HQC? Thanks!



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    Jason (Hao) Wang, Ph.D.
    Resolian Bioanaytics,
    Brisbane, Australia
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    Original Message


  • 4.  RE: Partial/Full Validation requirement of higher sensitive PK assay

    Community Leadership
    Posted 08-05-2025 10:50

    I will find the exact citation, but when you are adding QCs within the previously validated range, you are not required to do a partial validation, only qualify the accuracy and precision of the new QC level prior to implementing. Since the QC performance is extrapolated to the full quantitative range in the original validation, I would also not redo stability. The exception, of course, is if the reason you are moving the QC is that it poorly represented the full quantitative range. An example could be if the old QC was on top of a calibrator so had artificially low variance. In that case, you would not be able to rely on the prior data for extrapolation.



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    Joleen White Ph.D.
    AAPS 2026 National Biotechnology Conference Track Chair
    Bioanalytical 101 Course Development
    Senior Advisor
    BioData Solutions LLC
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
    ------------------------------

    Original Message


  • 5.  RE: Partial/Full Validation requirement of higher sensitive PK assay

    Posted 07-29-2025 12:41
    Seems to me IF the method remains unchanged (including the standard values), but presumably only a lower LLOQ (which already has a standard point associated with it??) was tested and found acceptable, then a full validation isn't necessary.  If the LOQ is still within 3x LLOQ (probably not) it doesn't need to change, but if it is changed then a few runs to establish intra-/inter-assay precision would be good at the new (spiked) LLOQ and LQC (and if one or more low end standards were incorporated for the new LLOQ then as well the standards which of course are run at the same time).  I doubt if the MQC needs to change give the modest LLOQ change.



    Original Message


  • 6.  RE: Partial/Full Validation requirement of higher sensitive PK assay

    Community Leadership
    Posted 07-31-2025 10:06

    The key consideration is what reassessments are necessary and, whether a partial validation makes sense compare to a full revalidation. At a minimum, you will need to repeat your core runs, selectivity assessments, and certain stability evaluations. If you plan to use both methods concurrently, it may be more efficient to proceed with a full revalidation under the new method so you can pull whichever method you need to use.



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    Jim Shen Ph.D.
    Executive Director, Head of Regulated Bioanalysis & Mass Spectrometry
    Bristol-Myers Squibb
    Princeton NJ
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message