title: Modeling industrial centrifugation of mammalian cell culture using a capillary based scale-down system.
abstract: Continuous-flow centrifugation is widely utilized as the primary clarification step in the recovery of biopharmaceuticals from cell culture. However, it is a challenging operation to develop and characterize due to the lack of easy to use, small-scale, systems that can be used to model industrial processes. As a result, pilot-scale continuous centrifugation is typically employed to model large-scale systems requiring a significant amount of resources. In an effort to reduce resource requirements and create a system which is easy to construct and utilize, a capillary shear device, capable of producing energy dissipation rates equivalent to those present in the feed zones of industrial disk stack centrifuges, was developed and evaluated. When coupled to a bench-top, batch centrifuge, the capillary device reduced centrate turbidity prediction error from 37% to 4% compared to using a bench-top centrifuge alone. Laboratory-scale parameters that are analogous to those routinely varied during industrial-scale continuous centrifugation were identified and evaluated for their utility in emulating disk stack centrifuge performance. The resulting relationships enable bench-scale process modeling of continuous disk stack centrifuges using an easily constructed, scalable, capillary shear device coupled to a typical bench-top centrifuge.
authors.affiliation: Process Biochemistry, Biopharmaceutical Development, Biogen Idec, Inc., San Diego, CA 92122, USA. matthew.westoby@biogenidec.com
authors.forename: Matthew
authors.initials: M
authors.lastname: Westoby
authors.forename: Jameson K
authors.initials: JK
authors.lastname: Rogers
authors.forename: Ryan
authors.initials: R
authors.lastname: Haverstock
authors.forename: Jonathan
authors.initials: J
authors.lastname: Romero
authors.forename: John
authors.initials: J
authors.lastname: Pieracci
mesh_terms: D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques; D002498:Centrifugation / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D010316:Particle Size