Development and validation of a multiplexed drug level assay in support of combination biologics therapy clinical studies

Publication date: 15 July 2019Source: Journal of Pharmaceutical and Biomedical Analysis, Volume 171Author(s): Huaping Tang, Ketal Shah, Thomas Steinmetz, Anson Abraham, Hans Jensen, Andrew Bouton, Kasia Marullo, Shuangping ShiAbstractClinical development of biotherapeutics for combination therapy requires monitoring the concentrations of both drugs in biological samples. Traditionally, two assays are required to measure drug levels one at a time, which poses challenges in sample management, data reporting, and cost. The Meso Scale Discovery (MSD®) U-PLEX™ platform provides a simple and flexible way to create custom multiplex ligand binding assays (LBAs). We developed and fully validated a two-plex assay on the U-PLEX platform where two therapeutic monoclonal antibodies (mAbs) in Merck’s pipeline, which we call MK-A and MK-B in this manuscript, can be measured simultaneously in one sample. Our results demonstrated that the multiplexed pharmacokinetic (PK) assay has performances, including accuracy, precision, and cross-reactivity, that meet requirements in regulatory guidance. Furthermore, results of MK-A from the multiplex assay are comparable to results from a previously validated MK-A single-plex assay with 80% of samples tested in both assays having concentration differences < 30% relative to the mean of the two measurements. The multiplex assay was used to support a phase I MK-A/MK-B combination therapy clinical study and generated results consistent with histori...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research