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Should we include a Drug Tolerance section in the Bioanalytical Quality Summary (BQS) for ADA and NAb sample analysis?

  • 1.  Should we include a Drug Tolerance section in the Bioanalytical Quality Summary (BQS) for ADA and NAb sample analysis?

    Posted 11-04-2023 23:53

    Dear AAPS Therapeutic Product Immunogenicity Community Members, 

    For the BQS of ADA and NAb sample analysis, should we include a Drug Tolerance section to assess how many samples may be impacted by the interference of circulating drug? If so, would it be reasonable to incorporate the validated drug tolerance level that is above but closest to the drug trough concentration?

    Thank you in advance for your feedback!

    All the best,

    Bonnie

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    Bonnie Wu Ph.D.
    Associate Scientific Director
    Johnson&Johnson Innovative Medicine
    Spring House PA
    [email protected]
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  • 2.  RE: Should we include a Drug Tolerance section in the Bioanalytical Quality Summary (BQS) for ADA and NAb sample analysis?

    Posted 11-06-2023 12:44

    Hi Bonnie,

    yes, definitely. The FDA has been asking for that information. In order to understand if the assays were adequate, they need to know if circulating drug was likely to affect the detection. So the bionalytical (immunogenicity) report should include the validated drug tolerance and the concentrations at the time of ADA/NAb testing, so they have all the information in one place.



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    Francesca Civoli
    Principal
    Francesca Civoli Consulting LLC
    Half Moon Bay CA
    [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: Should we include a Drug Tolerance section in the Bioanalytical Quality Summary (BQS) for ADA and NAb sample analysis?

    Posted 11-06-2023 22:53

    Hi Francesca,

    Thanks for the comments. I understand the agency would need the drug tolerance (DT) information to help assess whether the DT is adequate to support reliable ADA/NAb assessment. Some sponsors don't include the validated drug tolerance information in BQS since they consider the validation report already provides the information. On the other hand, the drug tolerance (DT) is assessed based on a surrogate PC. It serves as a benchmark to estimate the DT level of the method but does not reflect the actual DT in clinical samples. Some samples may have circulating drug concentration above the DT level but still test positive in sample bioanalysis.

    If the DT section is included in BQS, should we estimate how many samples may be under the inference of circulating drug even if this is not likely an accurate assessment?

    Thank you!

    Best,

    Bonnie



    ------------------------------
    Bonnie Wu Ph.D.
    Associate Scientific Director
    Janssen Research & Development LLC
    Spring House PA
    [email protected]

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

    Original Message