title: A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration.
abstract: In the production of biopharmaceuticals disk-stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot-scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale-down approach based upon the use of a shear device and a bench-top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large-scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited. Biotechnol. Bioeng. 2016;113: 1934-1941. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
authors.affiliation: The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, London, WC1E 6BT, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Joseph
authors.affiliation: MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Kenty
authors.affiliation: MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Mollet
authors.affiliation: MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hwang
authors.affiliation: MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Steven
authors.initials: S
authors.lastname: Rose
authors.affiliation: The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, London, WC1E 6BT, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Goldrick
authors.affiliation: MedImmune LLC Gaithersburg Headquarters, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Jean
authors.initials: J
authors.lastname: Bender
authors.affiliation: The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, London, WC1E 6BT, United Kingdom.
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Farid
authors.affiliation: The Advanced Centre of Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, London, WC1E 6BT, United Kingdom. nigelth@ucl.ac.uk.
authors.forename: Nigel
authors.initials: N
authors.lastname: Titchener-Hooker
mesh_terms: D000818:Animals; D016466:CHO Cells; D002452:Cell Count; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000502:physiology; D002498:Centrifugation / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D005374:Filtration / Q000379:methods*; D008962:Models, Theoretical; D033081:Shear Strength
keywords: capillary shear; centrifugation; continuous centrifugation; depth filter; disk-stack centrifuge; filter capacity; mammalian cell; primary recovery; scale-down