Singlicate Ligand Binding Assay Using an Automated Microfluidic System: a Clinical Case Study

Abstract

The bioanalytical strategy for monoclonal antibody therapeutics, intended for multiple oncology indications, includes multiple integrated measurements of pharmacologically relevant therapeutics from discovery through development. Three ligand binding assays were cohesively developed and validated, as applicable, using the Gyrolab microfluidic system for the measurement of a free monoclonal antibody BMS-986207. Accuracy and precision demonstrate %bias from −6.3 to 4.4%, percent coefficient of variation (%CV) from 2.6 to 9.8%, and total error from 4.2 to 13.4% in the nonclinical assay; %bias from −0.3 to 3.3%, %CV from 3.5 to 18.2%, and total error from 6.1 to 19.7% in the clinical assay; and >97% of the sample meeting incurred sample reanalysis criteria. The clinical assay was validated using singlicate wells after gaining significant data in the early phase studies to support this cost-effective and efficient strategy. Each assay met fit-for-purpose and/or regulated bioanalytical method validation criteria including stability, selectivity, dilutional linearity, carryover, and specificity criteria with no interference from co-administered monoclonal antibody.