Manufacturing of Proteins and Antibodies: Chapter Downstream Processing Technologies

Abstract

Cell harvesting is the separation or retention of cells and cellular debris from the supernatant containing the target molecule Selection of harvest method strongly depends on the type of cells, mode of bioreactor operation, process scale, and characteristics of the product and cell culture fluid. Most traditional harvesting methods use some form of filtration, centrifugation, or a combination of both for cell separation and/or retention. Filtration methods include normal flow depth filtration and tangential flow microfiltration. The ability to scale down predictably the selected harvest method helps to ensure successful production and is critical for conducting small-scale characterization studies for confirming parameter targets and ranges. In this chapter we describe centrifugation and depth filtration harvesting methods, share strategies for harvest optimization, present recent developments in centrifugation scale-down models, and review alternative harvesting technologies.

Keywords: Capillary shear; Centrifugation; Continuous centrifugation; Depth filter; Disk-stack centrifuge; Filter capacity; Harvest; Mammalian cell; Primary recovery; Scale-down; Sigma factor; Single-use centrifuge; Tangential flow filtration.