Technical and economic considerations of cell culture harvest and clarification technologies

Abstract Bioprocessing for biopharmaceutical production has made significant technological strides in the past decades, both in upstream and downstream processing. Intensification of upstream cell culture processes has led to higher cell densities, enabling smaller bioreactors to provide equivalent or higher throughput than larger, lower titer systems. These high-intensity cultures increase the burden on the process between upstream and downstream processes: specifically, harvest separations, which increased burden may shift some of the technical and economic benefits and drawbacks of a given harvest technology. With these changes in mind, here we review the basics of operations for highlighted harvest technologies and discuss potential factors the bioprocess engineer might consider in selecting an appropriate technology for their intensifying processes. This review summarizes the specific challenges faced by aging technologies in context of upstream intensification, as well as the path forward for implementing new strategies and nascent technology. Leveraging bioprocessing economics modelling tools, we examine the economics of two well-accepted technologies: disc-stack centrifugation and single-use depth filtration and discuss how bioprocessing trends will impact economics of these harvest methods. Considering the changing and diverse landscape of bioprocessing, there is likely no one-size-fits-all solution and many factors must be carefully weighed for appropriate harvest separations selection.