title: Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale-down model for biologics process development.
abstract: Demands for development of biological therapies is rapidly increasing, as is the drive to reduce time to patient. In order to speed up development, the disposable Automated Microscale Bioreactor (Ambr 250) system is increasingly gaining interest due to its advantages, including highly automated control, high throughput capacity, and short turnaround time. Traditional early stage upstream process development conducted in 2 - 5 L bench-top bioreactors requires high foot-print, and running cost. The establishment of the Ambr 250 as a scale-down model leads to many benefits in process development. In this study, a comprehensive characterization of mass transfer coefficient (kLa) in the Ambr 250 was conducted to define optimal operational conditions. Scale-down approaches, including dimensionless volumetric flow rate (vvm), power per unit volume (P/V) and kLa have been evaluated using different cell lines. This study demonstrates that the Ambr 250 generated comparable profiles of cell growth and protein production, as seen at 5-L and 1000-L bioreactor scales, when using kLa as a scale-down parameter. In addition to mimicking processes at large scales, the suitability of the Ambr 250 as a tool for clone selection, which is traditionally conducted in bench-top bioreactors, was investigated. Data show that cell growth, productivity, metabolite profiles, and product qualities of material generated using the Ambr 250 were comparable to those from 5-L bioreactors. Therefore, Ambr 250 can be used for clone selection and process development as a replacement for traditional bench-top bioreactors minimizing resource utilization during the early stages of development in the biopharmaceutical industry. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:478-489, 2017.
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Colleen
authors.initials: C
authors.lastname: Clark
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Todd
authors.initials: T
authors.lastname: Ryder
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Colleen
authors.initials: C
authors.lastname: Sparks
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Michelle
authors.initials: M
authors.lastname: Wang
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Reb
authors.initials: R
authors.lastname: Russell
authors.affiliation: Global Manufacturing and Supply, Bristol-Myers Squibb, Bloomsbury, NJ, 08804.
authors.forename: Charo
authors.initials: C
authors.lastname: Scott
mesh_terms: D000818:Animals; D061249:Batch Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D019149:Bioreactors; D016466:CHO Cells; D049109:Cell Proliferation / Q000502:physiology*; D017076:Computer-Aided Design; D003412:Cricetulus; D004209:Disposable Equipment; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008904:Miniaturization
keywords: TAP Ambr; automated microscale bioreactor; clone selection; oxygen transfer coefficient; scale-down model; upstream process development