Therapeutic Product Immunogenicity Community

Dear all,

Based on a recent Bioanalytical Community thread about biomarker validation versus qualification, I wanted to discuss how we talk about immunogenicity assays for ADA versus vaccines. For ADA, we use the term validation for the pre-study assay performance, and only use qualification for an incomplete assessment of performance (which per the biomarker discussion is really just a difference context of use so still technically a validation with different use conditions).

For vaccines, however, the pre-study assay performance assessment is called a qualification because it is limited to the assay performance, and validation is when there is clinical data to demonstrate utility. With all the discussion around alternate paradigms and adjusting thresholds to reflect clinical impact rather than a statistical cut point based on false positive rates, would shifting to this terminology make sense for ADA as well? Then the method performance characteristics would be qualification, while the subsequent validation reflects clinical impact?

One challenge I already see with this is that a key experimental difference for vaccine studies is that the validation uses a positive control pooled across vaccinated individuals (an endogenous positive control), while that isn't typically possible for ADA methods. Although the thought of a reference standard for ADA with clinical impact is honestly quite compelling as a step towards monitoring patients for high risk consequences.

I'd love to have this conversation here on the community with pros/cons/what abouts/you're nuts rather than side emails. So if you aren't interested in commenting publicly but have something to add, please do post anonymously rather than by private chat or email.

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Joleen White Ph.D.
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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Thanks for bringing up this interesting discussion point, Joleen.

I'm going to throw out one of my favorite concepts of 'it's all biomarkers',  ADA are biological responses to a therapeutic intervention = biomarker.  Immune responses to vaccines - biomarker of successful vaccine administration and use of endogenous control also a biomarker approach.  Lastly, drug concentrations (PK) is also a biomarker of successful drug administration.  If you find yourself tempted to dispute this, consider how many times you've used this 'biomarker' to determine that a patient or animal was misdosed!

So, why don't we try to harmonize across all since it's all biomarkers?

As you pointed out, everything depends on context of use.  For PK assays we are in relatively good shape since the way the data are used is quite standardized and we can work under the premise of a single context of use.  Therefore, guidance for analytical assay validation is often conflated wit validated for context of use.  That said, we all do 'in-study validation' as we monitor data throughout ongoing trials and may even investigate our assay's appropriateness when things look anomalous. 

For immunogenicity and what we traditionally think of as biomarkers, it is more complex, with widely varied contexts of use and potentially changing contexts of use over time.

Perhaps instead of using different words like qualification vs validation, we consider adding clear modifiers or more descriptive words so there is clarity.  We currently use the following terminology in our biomarker lab:

• Analytically characterized - demonstrates assay performance characteristics only when no clearly articulated context of use is available
• Validated for context of use x - analytical assay validation for specific context of use
• Qualified is reserved for a qualified biomarker - the biomarker (not the assay) is clinically proven for context of use

I can see how this might feel unwieldy to some, but the descriptors are a more accurate representation of the state of the assay and datasets.  But, aligning the use of qualification across all domains would limit future confusion.

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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:
Sent: 07-01-2025 14:41
From: Joleen White
Subject: Terminology clarification for ADA versus vaccine

Dear all,

Based on a recent Bioanalytical Community thread about biomarker validation versus qualification, I wanted to discuss how we talk about immunogenicity assays for ADA versus vaccines. For ADA, we use the term validation for the pre-study assay performance, and only use qualification for an incomplete assessment of performance (which per the biomarker discussion is really just a difference context of use so still technically a validation with different use conditions).

For vaccines, however, the pre-study assay performance assessment is called a qualification because it is limited to the assay performance, and validation is when there is clinical data to demonstrate utility. With all the discussion around alternate paradigms and adjusting thresholds to reflect clinical impact rather than a statistical cut point based on false positive rates, would shifting to this terminology make sense for ADA as well? Then the method performance characteristics would be qualification, while the subsequent validation reflects clinical impact?

One challenge I already see with this is that a key experimental difference for vaccine studies is that the validation uses a positive control pooled across vaccinated individuals (an endogenous positive control), while that isn't typically possible for ADA methods. Although the thought of a reference standard for ADA with clinical impact is honestly quite compelling as a step towards monitoring patients for high risk consequences.

I'd love to have this conversation here on the community with pros/cons/what abouts/you're nuts rather than side emails. So if you aren't interested in commenting publicly but have something to add, please do post anonymously rather than by private chat or email.

------------------------------
Joleen White Ph.D.
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:
Sent: 7/1/2025 2:42:00 PM
From: Joleen White
Subject: Terminology clarification for ADA versus vaccine

Dear all,

Based on a recent Bioanalytical Community thread about biomarker validation versus qualification, I wanted to discuss how we talk about immunogenicity assays for ADA versus vaccines. For ADA, we use the term validation for the pre-study assay performance, and only use qualification for an incomplete assessment of performance (which per the biomarker discussion is really just a difference context of use so still technically a validation with different use conditions).

For vaccines, however, the pre-study assay performance assessment is called a qualification because it is limited to the assay performance, and validation is when there is clinical data to demonstrate utility. With all the discussion around alternate paradigms and adjusting thresholds to reflect clinical impact rather than a statistical cut point based on false positive rates, would shifting to this terminology make sense for ADA as well? Then the method performance characteristics would be qualification, while the subsequent validation reflects clinical impact?

One challenge I already see with this is that a key experimental difference for vaccine studies is that the validation uses a positive control pooled across vaccinated individuals (an endogenous positive control), while that isn't typically possible for ADA methods. Although the thought of a reference standard for ADA with clinical impact is honestly quite compelling as a step towards monitoring patients for high risk consequences.

I'd love to have this conversation here on the community with pros/cons/what abouts/you're nuts rather than side emails. So if you aren't interested in commenting publicly but have something to add, please do post anonymously rather than by private chat or email.

------------------------------
Joleen White Ph.D.
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.
------------------------------