Does Automation Improve Cell-Based Potency Assay Development?

Hannah Spencer, Labcorp Drug Development Cell based potency assays provide quantitative data about a drugs biological activity (relative potency). The assays are designed and developed bespoke to each drug molecule to reflect its unique mechanism of action and must be able to accurately, precisely and reliably quantify the relative potency for the entire lifetime of the drug molecule. Cell-based potency assays are highly complex multi-step assays, often involving multiple plates, requiring several hours of hands-on time (HoT) and on average 200 liquid transfers per plate. Routine testing in a quality control (QC) environment requires training of these assays to multiple analysts and potentially across multiple sites. All these factors contribute to long and expensive assay development studies which can lead to delays in the drug development process. In this study we investigated if automation using the Hamilton STAR liquid handling robot improved cell-based potency assay development. We developed a manual and semi-automated cellular cytotoxicity assay to quantify the relative potency of Adalimumab using L929 cells and compared the performance of the two methods using 18 samples analysed across 6 independent assays. The semi-automated assay had equivalent assay accuracy to the manual method with a relative bias between -8 to +11 % and for the semi-automated method -6 to + 12%. The assay precision was also comparable, with the manual method having a max % cv of 9.5 ± 3.9% in comparison to 10.2 ± 5.6% for the semi-automated method. While the data quality was comparable implementation of automation reduced the number of liquid handling steps by 78% and the overall HoT by 30 minutes. Furthermore, the semi-automated method had improved traceability as a log is produced for all liquid handling steps.