Translational and Clinical Science Community

Dear Translation & Clinical Science and Discovery & Preclinical Research Communities (Formerly Biomarkers and Precision Medicine),

With multi-parameter biomarker platforms such as NULISA and Olink becoming increasingly mainstream, questions regarding the appropriate level of validation are becoming more relevant. We currently apply ICH M10 parameters to "validate" endogenous or target biomarkers and other novel modalities. As these RUO panels become more routinely used, I can foresee a time when data generated from these assays-whether standard or custom panels-may be incorporated into inclusion criteria, treatment decisions, and/or regulated bioanalytical applications and may expect a similar "validation" approach.

Has anyone else encountered similar considerations? We have a few initial ideas and would be very interested in hearing others' perspectives. @Hiroshi Sugimoto would it make sense to consider this as a future focus topic, potentially with the goal of developing a white paper or similar publication?

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Wendy Adamowicz, M.S.
Principal Scientist
PPD Clinical Research, ThermoFisher Scientific
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Hi @Wendy Adamowicz,

Thank you for bringing this to our attention. Emerging and multiplexing bioanalytical and biomarker technologies, such as NULISA, Olink, and SPEAR Bio technologies are gaining increasing interest across the field. A similar topic was also discussed at the 2023 WRIB meeting, where I served as a session chair, and the key insights were captured in a white paper. "It is important to distinguish between the semi-quantitative vs. quantitative analysis for high-plex proteomics technologies. For QCs, start with the system suitability and assay controls for the large panel followed by applying QC samples for specific decision-making quantitative protein biomarker analysis." (Kholmanskikh et al, 2023 Bioanalysis, https://www.tandfonline.com/doi/full/10.1080/17576180.2024.2340961).

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Hiroshi Sugimoto
Director
Takeda
Cambridge MA
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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I think it is important to avoid "level of validation" conceptually as every biomarker assay should be validated to context of use.  It is either valid for intended use or it is not.  Unfortunately our industry seems to have conflated analytical assay validation parameters, number of runs, etc. to 'level of validation'.  This risks inappropriate assumptions about true fitness for COU.  A simple reframing of the question would be what extent of analytical characterization can be done outside knowledge of COU and then as a particular COU arises, determine whether or not the assay is suitable.

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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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I agree with the comments emphasizing context of use as the primary driver, but I wonder if part of the challenge is that we are often discussing two separate questions simultaneously.

1. Can the platform reliably measure thousands of analytes?
   • This is an analytical characterization question (system suitability, reproducibility, lot-to-lot consistency, matrix effects, etc.).
2. Can the resulting data be used to make a specific decision?
   • This is a context-of-use (COU) question.

For platforms such as NULISA and Olink, the first question is often where much of the value lies. These technologies provide the ability to identify biological patterns, pathways, patient subgroups, and candidate biomarkers across hundreds or thousands of proteins simultaneously. In many discovery and translational settings, the objective is less about establishing definitive quantitative measurements for every analyte and more about generating robust biological insights and identifying meaningful trends.

The second question is where context of use becomes critical. The evidentiary requirements should increase with the consequence of the decision being made. If a biomarker identified through a high-plex platform is ultimately intended to support patient selection, treatment decisions, or regulated applications, then additional targeted analytical validation may be appropriate for that specific biomarker and use case.

From this perspective, I am not sure a single validation paradigm applied uniformly across all analytes on a high-plex platform is the most useful framework. A fit-for-purpose approach may be more appropriate: analytically characterize the platform sufficiently to establish confidence in the biological signals and trends it generates, then apply additional validation to the smaller set of biomarkers that ultimately become decision-enabling.

In my view, the discussion may be less about defining a universal level of validation for multiplex platforms and more about distinguishing platform performance from decision-specific evidentiary requirements.

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Saloumeh Fischer Ph.D.
Sr. Fellow / Sr.Director
Genentech Inc
South San Francisco 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:
Sent: 06-04-2026 09:00
From: Lauren Stevenson
Subject: Multi Parameter Biomarker Platforms

I think it is important to avoid "level of validation" conceptually as every biomarker assay should be validated to context of use.  It is either valid for intended use or it is not.  Unfortunately our industry seems to have conflated analytical assay validation parameters, number of runs, etc. to 'level of validation'.  This risks inappropriate assumptions about true fitness for COU.  A simple reframing of the question would be what extent of analytical characterization can be done outside knowledge of COU and then as a particular COU arises, determine whether or not the assay is suitable.

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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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Dear Wendy, dear all,

I fully agree that a clearer and more harmonized framework for validating emerging multi-parameter biomarker platforms would be highly valuable for the field. Such a framework would greatly support end users in making more informed assay-selection decisions and would strengthen confidence in cross-platform comparisons.

At the same time, I believe it would be very helpful for the industry to define more precisely what we mean by “validated” in each specific context of use. This includes the relevant performance criteria, intended application, sample type, and decision-making purpose. Greater clarity here would help avoid ambiguity and ensure that the term is used consistently, transparently, and constructively.

I also very much appreciate why technology providers would welcome broader industry recognition of their platforms. A shared, well-defined validation framework could create meaningful value for both vendors and users by providing a more objective basis for trust, adoption, and scientific comparability.

AAPS, through its meetings, internal expert discussions, and interactions with regulators, could serve as an excellent forum for discussing fit-for-purpose validation strategies. I am confident that AAPS would warmly welcome and support efforts by vendors to rigorously validate their platforms and to ensure that future claims are supported by robust, transparent, and reproducible data.

Kind regards, Jan

Jan Detmers is a biomarker veteran. The views expressed here are his own and do not necessarily reflect those of his former employers, companies in which he has invested, affiliated organizations, or professional societies.

This is a good conversation; however, I would emphasize that the Context of Use (COU) needs to remain the central driver when considering validation expectations, particularly for multi-parameter biomarker platforms. Given the wide range of potential applications; from early discovery and hypothesis generation to decision-enabling biomarkers for clinical development, there is no single validation strategy or approach that can adequately address all of the use cases. Instead, the level of analytical rigor and degree of characterization have to be aligned with how the data will ultimately be used. Multiplex biomarker analysis has been part of the AAPS discussions for quite some time and generated a strong foundational reference (Jani D, et al Recommendations for use and fit-for-purpose validation of biomarker multiplex ligand binding assays in drug development. AAPS J. 2015). As platforms move toward higher levels of multiplexing, more complex and flexible standards will be required based on the specific context of use, since treating every analyte with uniform rigor is often impractical and a prioritization based on the impact of each biomarker and the decision risk is essential. This concept is further highlighted by the qualification of multi-marker panels such as the C-Path kidney safety biomarker panel, where a clearly defined COU underpins the level of evidence and validation required for the application in early clinical development. (KSP-Composite COU-User Guide) Ultimately, aligning validation expectations with context of use will be critical to enabling broader and more confident adoption of these technologies. I'd be interested to hear how others are approaching COU-driven validation strategies for high-plex platforms?

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Robert Neely Ph.D.
Scientific Director-Translational Sciences
Immunologix Laboratories
Mount Laurel NJ
[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: 06-04-2026 11:58
From: Jan Detmers
Subject: Multi Parameter Biomarker Platforms

Dear Wendy, dear all,

I fully agree that a clearer and more harmonized framework for validating emerging multi-parameter biomarker platforms would be highly valuable for the field. Such a framework would greatly support end users in making more informed assay-selection decisions and would strengthen confidence in cross-platform comparisons.

At the same time, I believe it would be very helpful for the industry to define more precisely what we mean by "validated" in each specific context of use. This includes the relevant performance criteria, intended application, sample type, and decision-making purpose. Greater clarity here would help avoid ambiguity and ensure that the term is used consistently, transparently, and constructively.

I also very much appreciate why technology providers would welcome broader industry recognition of their platforms. A shared, well-defined validation framework could create meaningful value for both vendors and users by providing a more objective basis for trust, adoption, and scientific comparability.

AAPS, through its meetings, internal expert discussions, and interactions with regulators, could serve as an excellent forum for discussing fit-for-purpose validation strategies. I am confident that AAPS would warmly welcome and support efforts by vendors to rigorously validate their platforms and to ensure that future claims are supported by robust, transparent, and reproducible data.

Kind regards, Jan

Jan Detmers is a biomarker veteran. The views expressed here are his own and do not necessarily reflect those of his former employers, companies in which he has invested, affiliated organizations, or professional societies.