Biomarker Development: validate and qualify (or is it the other way around)

Biomarker development is fundamentally the parallel processes of developing a technically reliable biomarker measurement method and establishing the significance of a biomarker relationship with a specific biological process. The former process is generally referred to as "validation" or more precisely "method validation" while the FDA suggested that the latter be referred to as "qualification".

The problem is that the term "qualification" means something quite different to my PK bioanalytical colleagues. Indeed, it refers to the process of testing the performance of an assay under stringent conditions to record the its variability without setting "pass/fail" criteria as it would be done for a validation process. 


To make matter worse, the FDA itself seems to struggle with the term"qualification" in its proposed three stages of biomarker qualification:

• Exploratory: fit for internal decision only
• Assay development à assay qualification
• Limited or no clinical data
• Probable valid: fit for regulatory decision applied to early clinical development
• Well established assay performance
• Initial significance of clinical test result
• Known valid: fit for regulatory decision applied to late clinical development
• Measurement independently reproduced
• Agreement by scientific community.

In other words, when a biomarker is qualified it becomes valid. Confusing isn't it?

In my mind, the only practical way to resolve this semantic issue is to simply be more precise by specifying whether we are referring to a process related to a method:

• Method qualification
• Method validation

Or, referring to a process related to the scientific relevance of a biomarker:

• Scientific qualification

Thierry Sornasse for Integrated Biomarker Strategy