(1270-C) Development of an Automated Gyrolab® Generic Toxicokinetic Method for the Quantification of Human IgG-based Molecules
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: IgG-based therapeutics account for approximately 90% of antibody therapies marketed in the United States and Europe per the National Institutes of Health. Over the last decade, the drug discovery market has made an increase in the utilization of IgG therapies, translating to a high demand for bioanalytical quantification of these therapeutics. This surge in prevalence has directly impacted organizations supporting this research, including Contract Research Organizations (CROs). A common method used for these applications is plate-based Enzyme-Linked Immunosorbent Assays (ELISA). However, these methods require time intensive preparation, manual dilutions, and incubations, which are prone to user-based errors and increased reagent usage with associated laboratory costs. For these reasons, our laboratory set out to develop an automated high-throughput generic immunoassay targeting human IgG-based therapies under Good Laboratory Practices (GLP) and following regulatory agency-defined parameters and acceptance criteria for a bioanalytical assay (M10 Bioanalytical Method Validation and Study Sample Analysis guidance).
The primary goal was to develop and optimize a method on the Gyrolab® immunoassay system, where this platform has been shown to minimize the hands-on bench time required for users and generate robust data in a highly efficient manner, utilizing fewer materials. Early developmental results were statistically evaluated using Design of Experiment (DOE) through JMP software; objectives of this were to statistically derive optimal predicted assay conditions with respect to targeted outcome desirability. Subsequent method optimizations were made with respect to the required parameters such as range of response, precision and accuracy (inter- and intra-assay), selectivity, carry-over, and dilution linearity.
A secondary goal was to fully automate the workflow by interfacing with Watson, a comprehensive laboratory information management system (LIMS) by Thermo Fisher Scientific, along with a Hamilton Microlab® STAR™ automated liquid handling system to allow for more efficient and precise dilution of samples for analysis and to ease data regression and evaluation. As such, all developmental analyses were performed leveraging the Hamilton ML STAR for all CD control and sample dilutions with data regression performed primarily within the Gyrolab® Evaluator software. Following the completion of development, all future validation analyses will be planned and regressed using Watson LIMS.
In summary, all goals were successfully completed with the implementation of a fully automated high-throughput immunoassay workflow to support delivering accurate, submission-ready data in a highly efficient manner. The availability of the Gyrolab® generic immunoassay for the quantification of human IgG offers a distinct advantage for efficiently completing bioanalytical studies in support of toxicological endpoints in support of the growing demand of IgG-based therapies.