Bioanalytical Strategy to Support Clinical Immunogenicity Assessment

Abstract

This chapter focuses on the bioanalytical strategy typically employed for the detection and characterization of antidrug antibodies (ADA) by means of various bioanalytical assays. It discusses the challenges involved and viable solutions that can be implemented in the development of the ADA assays. To ensure patient safety, regulatory agencies mandate that sponsors have robust immunogenicity risk assessments and mitigation plans in place prior to clinical development of investigational biotherapeutics. Currently, the ligand binding format is still the dominant format for ADA detection. The commonly used platforms are enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD). The direct ADA binding assay can be performed using the ELISA or MSD platform. Matrix interference is a common challenge to bioanalytical scientists during immunoassay development. In general, matrix interference can be categorized as nonspecific interferences or specific interferences.