Bioanalytical Community

 View Only

  • 1.  Immunogenicity Testing | Sample or Subject Status --> Nab

    Posted 01-23-2025 00:40

    Hello immunogenicity experts,

    I am interested in hearing from the community on what the current industry best practice is with regards to progressing samples/subjects to further immunogenicity characterization testing in the neutralizing antibody (NAb) assay.  Since I've joined my current organization, our position is that we only proceed with ADA positive samples from ADA positive subjects to the neutralizing antibody test.  However, this requires that an assessment is made real-time whether the subject is treatment-emergent or treatment-boosted.  And this real-time Subject Status could ultimately change over the duration of a study.  My perception is that most bioanalytical teams are testing ALL positive ADA samples in the neutralizing antibody assay regardless of the Subject Status.  Clearly, there are operational efficiencies to testing all positive ADA samples, but what are the considerations to not performing Nab testing on all ADA positive samples?  Are the considerations for conflicting results (i.e. ADA negative subject with positive Nab results) that outweigh this efficiency?



    ------------------------------
    Kevin Carleton
    Scientific Director
    Johnson & Johnson Innovative Medicine
    Exton PA
    [email protected]

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


  • 2.  RE: Immunogenicity Testing | Sample or Subject Status --> Nab

    Posted 01-24-2025 13:46
    Kevin,
    Personally I've not had an issue determining pre-existing ADA+ (PEA) that do not increase (4x) in titer to become treatment-emergent (TE; I don't like the term "boosted" because it implies that it's the pre-existing response that is giving something akin to an anamnestic response, and there's no good way to know that) in a timely way so that a decision to run in a Nab assay can be made.  Regardless, a PEA (confirmed, of course) is still directed against drug so MAY be impactful including being neutralizing.  Whether it's actually TE or not can be shown in the incidence calculation.  So bottom-line for me is test all confirmed ADA+ whether TE or PEA whose titer remains consistent.



    Original Message


  • 3.  RE: Immunogenicity Testing | Sample or Subject Status --> Nab

    Posted 01-27-2025 09:27

    Kevin,

    The current practice is to include all ADA positive samples, as this aligns with regulatory expectations. If the NAb assay is more sensitive or drug-tolerant than the ADA assay and yields such results, you'll need to determine whether this is due to the cut point or assay variability.

    To address this, include the predose sample for the cut point calculation. This approach should hopefully resolve the issue.

    Good luck!



    ------------------------------
    Ravi Shankar Maurya
    General Manager, Regulated Bioanalysis, Large Molecule
    Lambda Therapeutic Research Ltd
    [email protected]

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

    Original Message


  • 4.  RE: Immunogenicity Testing | Sample or Subject Status --> Nab

    Posted 01-27-2025 12:29

    Hi Kevin, congratulations on your new role! As part of immunogenicity analysis, we determine ADA and NAb status on on both sample and subject level. In CSR TLF's, for the sample level results we have a Table: "Summary of Sample ADA and NAb Status at Each Time Point" and a Listing: "Individual Assay Results and Sample ADA/NAb Status". Of course we also analyze data at the subject level, e.g. determine subject ADA/NAb status and other relevant characteristics such as onset, duration, magnitude (if appropriate). Although subject ADA and NAb status will depend on the subject's ADA and NAb results at the sample level, there is no contradiction between the two types of analysis, and both are needed. And the short answer: we do test all ADA positive samples for NAb. 



    ------------------------------
    Anna Schwartz MS
    Associate Director, Bioanalysis
    Kyowa Kirin, Inc.
    Princeton NJ
    [email protected]

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

    Original Message