A platform immunoassay for the quantification of biotherapeutics with glycine-serine linkers.

Assessing the pharmacokinetics of biotherapeutics is essential across all phases of drug development to understand drug exposure. At early stages, platform drug quantification immunoassays offer a versatile method for evaluating exposure for diverse biotherapeutics when specific reagents are not yet available, providing fast data for molecules with common structural features. To ensure clearly defined bioanalytical data, it is essential to conduct interference testing for anti-drug antibodies (ADA) or soluble target (starget), although these assays measure total exposure. In this study, a novel platform immunoassay has been developed that detects a variety of multi-domain drugs with the common structural feature of glycine-serine (G/S) linkers. The assay was successfully qualified and is suitable for early total drug exposure analysis of compounds with G/S linkers. Qualification parameters, including accuracy and precision, were successfully determined, and interference from ADAs and starget was assessed. ADA and starget interference tests showed no impact for one compound, but may affect total drug detection for another. Therefore, it remains recommended to assess the impact of ADAs and starget on assay performance. Overall, the platform G/S linker assay provides a rapid alternative for total exposure analysis in early development when specific assays are unavailable.