ABSTRACT

Precision/personalized medicine requires the use of biomarkers, but the place of biomarkers in supporting the overall regulatory development effort depends greatly on what one is proposing to support by their use. Another concept that needs to be understood is biomarker “qualification,” which can refer to activities varying from informally justifying the asset-specific use of a biomarker or to a highly formal biomarker qualification procedure under the auspices of the US Food and Drug Administration (FDA) or the European Medicines Agency.

The term “context of use” is an important concept to understand when discussing the regulatory treatment of biomarkers, and examples of various contexts of use are provided, including the following:

Establishment of dose–response and target engagement

Enrichment of a highly responsive population

Elimination of a safety-sensitive population

The special case of surrogate end points

The regulatory process of drug/diagnostic codevelopment is outlined in detail as well as the complexities this raises for both the development of the drug component and the device component.

The section closes with a look toward the future of drug/device codevelopment by addressing the additional regulatory complexities raised by next generation sequencing (NGS), multi-analyte (multiplex) assays, transcriptomics, and proteomics.