As mammalian cell culture has become more productive, there has been a drive to scale down manufacturing processes into a smaller footprint and shift to single-use technologies. The high cell densities that drive this productivity create significant harvest challenges that must be overcome in order to enable a scaled-down, disposable process. Beyond direct depth filtration (DF) and early prototype single-use centrifugation systems, there are few options for single-use harvest technologies that are commercially available. Acoustic wave separation (AWS) is a novel technology that clarifies cell culture in a continuous manner utilizing 3D standing acoustic waves. Acoustic forces generated by the standing waves trap cells and cell debris, which agglomerate to form large cell particles that settle out of solution. As the primary harvest step, this technology has the potential to reduce high cell density cultures to levels that can be managed by the secondary DF step using significantly less filter area.
In this presentation, the results of an evaluation of AWS technology for a range of cell culture processes will be reviewed. Parameters affecting AWS performance were explored, including: feed packed cell mass, feed and solids stream flow rate, voltage, and number of stages. Optimized process conditions delivered greater than 95% reduction in normalized turbidity, 92% in total cell density and 80% in packed cell mass, while maintaining a step yield of greater than 85%. In comparison to a platform direct DF harvest, pre-processing with AWS was able to reduce the DF area requirements by approximately 6x, providing an estimated 6.7x cost savings. Based on these results, AWS provides a promising alternative to current single-use harvest technologies.
