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  • 1.  Validated assay

    Posted 17-May-2019 16:33
    Edited by Michael Bui 17-May-2019 17:36

    Hi,

     

           Does an assay have to be validated in Phase 1 study ? Does a clinical trial assay (CTA) have to be validated ?

     

     





  • 2.  RE: Validated assay

    Posted 19-May-2019 16:44
    It depends on what you mean by "validated". Assays used for testing of clinical supplies do not have to undergo full ICH validation before commercial manufacture, but you should do some sort of evaluation of the method so that you can be confident of the results. The earlier in development, the looser it can be. European authorities in particular expect to see some kind of "validation data" in the IMPD at least at Ph2. It was highlighted at a CASSS CMC Strategy Forum in Jan 2018 that strictly speaking the assays don't have to be validated until BLA/MAA, but it is STRONGLY RECOMMENDED that the sponsor does so before Ph3/PPQ batches, just because it is a pretty big risk to go through your PPQ and then find out that one or more methods cannot pass validation.

    (Speaking for biologicals & biotech products, anyway)​

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    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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    Original Message


  • 3.  RE: Validated assay

    Posted 20-May-2019 08:38
    ​Speaking about biologics, I strongly agree with Rachel.  At Phase 1, typically assays are "qualified" rather than validated - ie., some initial work has been done to demonstrate that the method is suitable for the intended purpose.  Validation typically is performed at or during Phase 2, to be ready for Phase 3, because of the much more intensive effort required. 

    However, it is important to validate the assay early enough in development - if it fails validation, a new method may need to be identified/developed, and samples from Phase 1 and Phase 2 clinical trial material tested to ensure the material is comparable.  Getting the timing right can be especially challenging if you are working on a product that may go from Phase 2 directly to BLA - you'll need to balance the financial and time investment with the potential for delays or additional queries/commitments during review.  Risk assessments can help here - it is unlikely that your pH test will fail, for example, but a complex biological potency assay may warrant either earlier validation, or an orthogonal method to test the same characteristic.

    Best of luck!

    Cathy

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    Catherine Anderson PhD, RAC
    Associate Director - Regulatory CMC
    Hillsborough NC
    United States
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    Original Message


  • 4.  RE: Validated assay

    Posted 20-May-2019 09:23
    There is no need to fully validate an analytical method according to ICH Q2 for clinical phases (1/2/3) from regulatory perspective. Some companies adopt a more conservative approach to ensure analytical method validation completed before phase 3 starts as there is some risk that maybe unreliable data might be obtained by unvalidated methods and it could render repeat of some of the studies using the validated methods. This conservative approach however, faces several challenges, such as 1) more and more developments are accelerated and BLAs/NDAs submitted based on only phase 2 data, 2) analytical methods tends to evolve as the development progresses and the state of acceleration changes, 3) scientifically sound methods applied in early phases development infrequently resulted in a significant risk that cannot be bridged later by an analytical comparability exercise, 4) the business risk may or may not be fully justified to validate all analytical methods at development phases as like saying you should invest more early to derisk when no one is even sure that the clinical evidence is proven.

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    Gene Zhu
    Independent Consultant
    Basking Ridge NJ
    USA
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    Original Message


  • 5.  RE: Validated assay

    This message was posted by a user wishing to remain anonymous
    Posted 20-May-2019 09:24
    This message was posted by a user wishing to remain anonymous

    No, an assay method doesn't have to be validated for a phase 1 study as it understood that the product and method may still be in development.
    Original Message


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