The foundation of pharmacokinetics and antidrug antibodies assay robustness relies on the use of high-quality reagents. Over the past decade, there has been increasing interest within the pharmaceutical industry, as well as regulators, on defining best practices and scientific approaches for generation, characterization and handling of critical reagents. In this review, we will discuss current knowledge and practices on critical reagent workflows and state-of-the-art approaches for characterization, generation, stability and storage and how each of these steps can impact ligand-binding assay robustness.
Keywords: ELISA; LBA; LC–MS; biotherapeutics; immunoassay; large molecule; mass spectrometry; method development; proteins; validation.
Lay abstract A critical part of clinical development for new biologic drugs is the use of tests known as ligand-binding assay. These assays must be able to accurately measure drug levels and to assess if the biologic drug interacts with the immune system in patients. In order to support patient efficacy and safety, scientists must use state-of-the-art approaches to develop and identify specific reagents for each new biologic drug. This review aims to cover all key steps that are needed to support the quality and performance of the unique components of ligand-binding assays from the beginning of assay development and throughout the entire life-cycle of the biologic drug.