title: Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures.
abstract: Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost-effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale-down (USD) mimics requiring 25-110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost-effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario.
authors.affiliation: Department of Biochemical Engineering, University College London, London, UK.
authors.forename: Daria
authors.initials: D
authors.lastname: Popova
authors.affiliation: Lonza Biologics plc, Slough, Berkshire, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Stonier
authors.affiliation: Lonza Biologics plc, Slough, Berkshire, UK.
authors.forename: David
authors.initials: D
authors.lastname: Pain
authors.affiliation: Department of Biochemical Engineering, University College London, London, UK.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Titchener-Hooker
authors.affiliation: Department of Biochemical Engineering, University College London, London, UK. s.farid@ucl.ac.uk.
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Farid
mesh_terms: D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods*; D001709:Biotechnology / Q000379:methods; D016466:CHO Cells / Q000166:cytology*; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D002498:Centrifugation; D006224:Cricetinae; D003412:Cricetulus; D005374:Filtration / Q000379:methods
keywords: Bioseparation; High cell density; Mammalian cell culture; Primary recovery; Tangential flow filtration