Biomarkers in drug discovery and development: Pre-analytical and analytical considerations

Abstract

Today biomarkers are used widely across the drug development continuum to improve the success rate and cost-effectiveness of rational drug development [1, 2]. These include diagnostic indicators of disease, assessments for biological pathways for new therapeutics, confirmation of target engagement or mechanism-of-action, safety indicators, and as pharmacodynamic (PD) measures of therapeutic efficacy [1, 2]. The application of biomarkers is now commonplace in drug development and has helped usher in a new era of predictive, preventative, and personalized medicine, where therapeutics can be tailored to a patient’s unique biology. However, prior to being used for these purposes, there are several practical aspects of biomarker utilization that need to be taken into account. These include biomarker validation and qualification. Analytical validation is the formal process of evaluating an assay to ensure it provides reliable data [1, 2], whereas qualification (also known as clinical validation) is the evidentiary process of linking a biomarker with biology, pharmacology, or clinical endpoint [1, 2]. Analytical validation is important, as issues of quality herein can limit the utility of biomarker data. Moreover, a lack of proper analytical validation can potentially undermine successful demonstration of a biomarker-related pharmacodynamic effect during clinical investigation [1, 2]. Not surprisingly, successful biomarker testing in drug development requires careful consideration of pre-analytical factors that may impact reliable biomarker quantification in biological matrices. Most often, pre-analytical factors include activities associated involving collection, shipment, tracking, storage, and distribution of test samples. Analytical considerations include the use of kits versus custom assays, reference standard sourcing, sample preparation strategies [3, 4], instrumentation and the removal of matrix interferences. This chapter will discuss some of the various factors that need to be taken into account when preparing for biomarker analysis.