Biomarker validation, qualification, and companion diagnostics are related but often confused topics. However, an accurate understanding of these concepts is vital for the development of new drugs. To cut through the confusion, Stephanie Traub, Associate Director at UCB, presented on understanding the difference between the terms.
An important factor in the drug development process is the qualification of biomarkers. That mean that the biomarker in question has been demonstrated to reliably support a specific manner of interpretation. Only once a biomarker has been qualified can it be made publicly available and used in drug development programmes.
In support of generating more useful biomarkers for drug development, the FDA has its own Biomarker Qualification Program. Critically, the programme focuses on qualification of the biomarker itself rather than qualification of the assay that tests for the biomarker. This means that a qualified biomarker is not necessarily acceptable for clinical practice or as an in vitro diagnostic.
Traub then introduced the concept of validation as distinct from qualification. While qualification establishes the scientific basis for the biomarker’s relationship to a biological process or clinical endpoint, validation refers to the process of confirming the accuracy, reliability and safety of the assay itself. Traub noted that while these concepts are related, they are nonetheless discrete, as such they are often confused.
Central to biomarker validation is fit for purpose categorisation which tailors the burden and stringency of proof required for the assay based on its intended use. Here, assays are given a score (often 0, 1, 2 or bronze, silver, and gold), which indicates stringency. This depends on whether the assay is used for internal decision making, exploratory biomarkers, or regulated purposes.
Finally, Traub shared the definition of companion diagnostics. These are medical devices that help healthcare professionals assess the risk-benefit of a treatment, often involving a more stringent development pathway compared to fit for purpose assays. Regulatory considerations for companion diagnostics include FDA IVD regulations and EMA regulations, which differ from those for biomarker assays used in clinical trials.
