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  • 1.  Qualification vs Validation for Biomarker Assays

    Posted 06-12-2025 15:23

    Recently, we had a short survey on the BPMC discussion board asking about how companies handle the classification of Biomarker assays, specifically how they differentiate or define what constitutes qualified versus validated. It has generated some discussion and I wanted to open it up to the wider community to get your feedback.

    Please share with us (anonymously if you prefer) what constitutes a validated biomarker assay at your organization (we are specifically meaning analytical validation). Does it require more runs and experiments than qualified? Does it simply mean that it has been deemed fit-for-purpose based on the context of use? Does the involvement or non-involvement of QA determine classification?

    I would also be interested in knowing / understanding if the Global CRO Consortium (GCC) has had any discussions or offered any consensus on this topic.

    Thanks!



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    Jennifer Vance Ph.D.
    Dir. of Bioanalytical and Biomarker Development
    Recursion Pharmaceuticals
    Salt Lake City UT
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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  • 2.  RE: Qualification vs Validation for Biomarker Assays

    Posted 06-13-2025 06:29

    Hi Jennifer,

    Broadly speaking assay qualifications are experiments that demonstrate what the assay can do, in terms of P & A, linearity and other parameters that may be tested in a validation.  A subsequent validation study includes a set of experiments that has been tested/established  enough to be able to apply acceptance criteria for ongoing use of the assay.  The validation study then 'validates' the expected performance  to enable confidence in the assay performance and allows acceptance or rejection of the analytical runs when analyzing samples.  Often qualification may also be termed assay establishment, especially with biomarkers,  to avoid using the term biomarker qualification, as this has a different application , i.e. qualification of the biomarker as a biological biomarker.

    Context of Use and fit for purpose validations refer to validations based on how the assay data are to be used and to ensue the validation  can demonstrate  required performance of validation  parameters for the intended use. This allows for the fact that not all validations need to keep to PK bioanalysis ICH M10 guidelines and acceptance criteria.

    I hope this helps a little.

    Best wishes,

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



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    David Gordon
    Director Ligand Binding Assay Services
    Alderley Analytical
    MACCLESFIELD
    [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: Qualification vs Validation for Biomarker Assays

    Community Leadership
    Posted 06-14-2025 12:28

    Use of the term qualification for biomarker assays is an artifact of the bioanalytical community and has never been part of the biomarker world where the term qualification is solely used in the clinical sense - qualified biomarkers have demonstrated clinical utility.

    It is important for us to remember that the definition of the term 'method validation' indicates that "the method has been demonstrated to be fit for its intended purpose".  Simplified version being: validation = demonstrated fit-for-purpose.

    For biomarker assays, the purpose is the context of use.  So validation = fit-for-context of use (COU).  Therefore, every biomarker assay needs to be validated for its COU.  Either the assay is valid for the COU, or it is not.  There is no middle ground.  This has been difficult for the bioanalytical community to accept because there is some notion of validations being a predefined set of assessments.  This may be true for PK assays, but that is because they have a singular COU. 

    For biomarker assay validations, the types and extent of assessments performed are dictated by COU and there can be no one-size-fits-all. If the context changes you may need to do additional/different assessments to demonstrate validation (or you may need an entirely different assay).  If you are asked to deliver an assay without knowing COU, then you can analytically characterize the assay, but not claim validation

    Our organization has always operated on these principles.  We never have, and never will, use the term qualification in association with biomarker assays.  We analytically characterize our assays and validate them to COU.  This approach is scientifically driven and has been universally successful for all assays that we have validated in support of a diverse portfolio of drug programs, delivering data that reliably support internal decision-making as well as regulatory approvals

     

     



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    Lauren Stevenson Ph.D.
    Chief Scientific Officer
    Immunologix Laboratories
    Tampa FL
    [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


  • 4.  RE: Qualification vs Validation for Biomarker Assays

    Community Leadership
    Posted 07-02-2025 16:29

    A difference that is applied for vaccine assays that may also be helpful for biomarker assays is that the qualification is only analytical performance without clinical relevance established. The full validation includes the clinical validation for the intended purpose. In that context, you can think of PK assay only being fully validated once shown that they can detect drug from collected rather than spiked samples. I also started another thread on ADA vs vaccine immunogenicity terminology that might be interesting as well.



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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


  • 5.  RE: Qualification vs Validation for Biomarker Assays

    Posted 07-03-2025 10:52
    Hi Joleen et al

    First, I think we should remember that the immune response to the vaccine is a measure of the vaccine efficacy/PD whereas that is not the case for ADA.  So, just because both fields are measuring similar analytes, the ways the data are applied and analyzed are different.   

    I've used the term "analytical validation"  (meaning not "clinical validation") to refer to the series of assessments performed for ADA assay "validation" per regulatory guidance.  I like to retain the term "qualification" to refer to additional studies conducted for expanding the use of the assay i.e. "qualification for new reagent x" "qualification for new manufacturing process material y"  "qualification for new study population z" , although I think "additional validation" or "amended validation" might also be appropriate in some cases.  For nonclinical ADA it seems labs are starting to use "qualification" in part to eliminate or reduce QA auditing requirements.   

    To me, "analytically validated" implies only that the ADA assay has been demonstrated to reliably and reproducibly meet the analytical performance and range requirements for the context in which it would be used per regulatory guidance.  It makes no association with clinical condition, effect or outcome.

    Presumably, "clinically validated" would indicate that a reliable and reproducible association between assay results and some particular clinical condition, endpoint or outcome has been established, although the "clinical validation" might be established only for some assay results (ie only positive result vs a clinically relevant cutpoint, or only a particular titer [or S/N] range, or only a particular specificity [nAb, epitope/domain, isotype], or only positivity above a certain titer range over a certain duration, etc] but not be established for any other assay results.  

    Based on these criteria, IMO currently many or most ADA assays would not be considered "clinically validated".  
      
    My thinking about analytical vs clinical validation evolved when I became involved in trying to convince teams to start applying immunogenicity risk assessment tools (at the time referred to as "predictive assays").  Team members expressed concerns that the assays had not been "validated" and I realized they were really referring to "clinical validation", so I had to remind them that individual product ADA assays are not "clinically validated" either and yet we still apply them to generate useful information.  Another point was that CMC also applies different terms for characterization assays ie. these assays are "qualified" for early clinical development and only "validated" at later stages (? phase 3 usually?).  Therein lies the challenge - aligning with just one other field can result in non-alignment with other fields.

    As a last point - Note that CLSI also uses the terms "analytical validation" and "clinical validation".   

    all the best
    Bonnie Rup



    Original Message


  • 6.  RE: Qualification vs Validation for Biomarker Assays

    Posted 07-04-2025 07:36
    Bonnie, I like your term “analytical validation” because it’s unambiguous what is being validated. Also, you are correct that “qualification” has various meanings in different contexts. You can have a qualified reagent or a qualified analyst, for example.

    I understand what you mean by ADA assays never being truly clinically validated. I could argue the same for PK assays, using that definition. I think we may be overthinking this.

    John Kamerud
    Sent from my iPhone


    Original Message


  • 7.  RE: Qualification vs Validation for Biomarker Assays

    Community Leadership
    Posted 07-09-2025 11:49

    That's definitely the direction I have been going, all those syllables though!



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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