A novel high-throughput process development screening tool for virus filtration

Abstract

Virus filtration is used extensively in mammalian cell culture derived biopharmaceutical manufacturing processes. This processing step relies on bench scale models that require large volumes of filter load to demonstrate throughput, as well as expensive virus clearance studies to demonstrate clearance of virus spiked into load. A lack of adequate process knowledge about the virus clearance step can result in oversized virus filters and costly reprocessing steps. High throughput process development (HTPD) integrates parallel processing and automated scale-down models to minimize load volumes and process development timelines while maximizing process knowledge. Although a high throughput filter device would be useful for maximizing process knowledge on virus filtration step, a virus filter micro-scale HTPD model is not available. We designed a 96-well filter plate with a single layer of Viresolve® Pro filter media that was produced by MilliporeSigma (Burlington, MA USA). We tested the 96 well filter plate to assess its suitability to be a novel micro-scale HTPD scale-down model. In combination with an automated liquid handling robot, a Tecan EVO, our scale-down model generated flux decay curves for water, buffers and multiple different monoclonal antibodies (mAbs). The experimental setup demonstrated reproducibility and scale-up predictability. Virus filtration optimization is now a viable option using our HTPD scale-down model, enabling rapid process development using a fraction of the load material required for bench scale models while gaining a broader understanding of robustness of this important manufacturing step.