Analytical Validation Strategies for DBS Biomarker Assays

Abstract

In recent years biomarker assays have gained precedence both in the clinical and pharmaceutical laboratory. In the pharmaceutical arena biomarkers play multifaceted roles in the safety and efficacy studies of drug development. Alternatively, in the clinic, biomarker assays are useful in screening, diagnosis, detection, prognosis and prediction of diseases and disorders. The bio analytical validation of biomarker assays has been a topic of wide interest. The major bottle neck in this area is the paucity of a fixed regulatory guidance. The various phases in the development of new biomarker assays are pre-analytical considerations, analytical considerations and biomarker assay implementation. The focus of this review has been to address in detail the pre-analytical and analytical considerations in the development of new biomarker assays in a well-known matrix like dried blood spots both in the pharmaceutical and clinical laboratory. The validation parameters discussed include specificity, sensitivity, matrix effect, precision, accuracy, linearity, dilution linearity, parallelism, carry over, proficiency testing and reference intervals. Additional parameters for dried blood spot assays include hematocrit, blood spot volume, chromatographic effect, spot to spot carry over and DBS vs whole blood/plasma concentration.