Rachel, great questions! I am sharing some thoughts on each below.
1. Currently, my team adds a context of use (COU) statement in the validation plan/report providing background as to the type of biomarker and the intended use of the data from the biomarker assay. We also add the matrix, the population under study and expected changes in the biomarker. This statement contextualizes the validation parameters and approach chosen. However, we do not routinely include the details of how drug assays differ from biomarker assays generally. I am curious to hear how many others add a COU statement or what others include in their plans/reports as background/justification for the validation approach.
2. The biology of the biomarker is a key consideration. The acceptance criteria should be appropriate for the biomarker's context of use. For example, if subtle changes need to be detected in the biomarker assay, precision may need to be tighter; and in contrast, if larger changes are anticipated, it could be acceptable to validate an assay with larger precision CVs. In the case of stability, inaccurate measurements will be obtained if that parameter isn't well defined. Widening criteria may not be appropriate in some cases, rather more characterization (including pre-analytical requirements) will inform on the timelines and conditions within which the measurements will be accurate.
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Karen Quadrini, PhD
Director, Clinical Biomarkers
Prothena Biosciences
Brisbane, 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: 03-28-2025 12:23
From: Rui Wang
Subject: OSD on 2025 FDA Biomarker Guidance (Level 2)
Thanks for organizing the webinar, Karen. It was a informative discussion.
I have some follow up questions,
- about "concept of use" for the biomarker assay. I wonder how people in the community make the statement of the concept of use for their assay and justify that it can be done differently from a PK assay, such as no nominal concentration available, no real reference material or the purpose of the assay etc.
- A big difference between a endogenous marker versus a drug molecule is that biomarkers aren't always as stable and in a single form. It's very difficult to meet the PK acceptance criteria in some cases. Is it acceptable to widen the biomarker assay criteria because of these natures?
Regards,
Rachel
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Rachel Wang, Ph.D.
Bioanalytical assay development lead
Spark Therapeutics
Philadelphia, PA.
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
Original Message:
Sent: 03-26-2025 09:00
From: Karen Quadrini
Subject: OSD on 2025 FDA Biomarker Guidance (Level 2)
Thanks to everyone that joined in the discussion on the 2025 FDA BMVB Guidance yesterday. We were at capacity for the dial-ins (>260 people), and we are thankful for everyone's patience with time delays and audio glitches as we truly challenged the GoToMeeting platform. The recording of the presentation and a PDF of the slide deck can be accessed through the link below for those who were unable to join the live discussion.
24Mar2025 OSD on 2025 FDA BMV for Biomarkers Guidance
We look forward to continuing discussion around this guidance, the differences in validation of drug assays vs. biomarker assays, and how Context of Use (CoU) principles are fundamental to biomarker method validation. We welcome the community to share any additional thoughts here on the board to further that conversation.
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Karen Quadrini, PhD
Director, Clinical Biomarkers
Prothena Biosciences
Brisbane, 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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