loading page

An innovative fixed bed bioreactor platform for linearly scalable, biomass predictable, single-use adherent cell biomanufacturing
  • +15
  • Vasiliy Goral,
  • Yulong Hong,
  • Jeffery Scibek,
  • Yujian Sun,
  • Lori Romeo,
  • Abhijit Rao,
  • Daniel Manning,
  • Yue Zhou,
  • Joel Schultes,
  • Vinalia Tjong,
  • Dragan Pikula,
  • Kathleen Krebs,
  • Ann Ferrie,
  • Stefan Kramel,
  • Jennifer Weber,
  • Zara Melkoumian,
  • Todd Upton,
  • Ye Fang
Vasiliy Goral
Corning Incorporated
Author Profile
Yulong Hong
Corning Incorporated
Author Profile
Jeffery Scibek
Corning Development Inc
Author Profile
Yujian Sun
Corning Incorporated
Author Profile
Lori Romeo
Corning Incorporated
Author Profile
Abhijit Rao
Corning Incorporated
Author Profile
Daniel Manning
Corning Incorporated
Author Profile
Yue Zhou
Corning Development Inc
Author Profile
Joel Schultes
Corning Incorporated
Author Profile
Vinalia Tjong
Corning Incorporated
Author Profile
Dragan Pikula
Corning Incorporated
Author Profile
Kathleen Krebs
Corning Development Inc
Author Profile
Ann Ferrie
Corning Incorporated
Author Profile
Stefan Kramel
Corning Incorporated
Author Profile
Jennifer Weber
Corning Incorporated
Author Profile
Zara Melkoumian
Corning Incorporated
Author Profile
Todd Upton
Corning Development Inc
Author Profile
Ye Fang
Corning Incorporated

Corresponding Author:fangy2@corning.com

Author Profile

Abstract

Scalable single use adherent cell-based biomanufacturing platforms are part of solutions to realize the full potential of cell and gene therapies. Here, we reported the development of an innovative fixed bed bioreactor platform for the scale-up of adherent cell culture. The bioreactor platform is centered on a packed bed of woven polyethylene terephthalate mesh discs that are vertically stacked and sandwiched between two fluid guide plates. Computational fluid dynamics modeling was used to direct the design and development of bioreactor series, targeting uniform flow with minimal shear stress. Residence time distribution measurements revealed that a pulse injected dye tracer solution passed through the bioreactors with great uniformity and narrow distribution of residence time, mimicking plug flow. Periodic media sampling with an offline analyzer showed that there was minimal gradient of four important metabolites (glucose, glutamine, lactate, and ammonia) across the bioreactor throughout cell growth. The bioreactor platform was further validated in automated cell harvesting with ~96% efficiency and ~98% viability, as well as linear scalability, in terms of both operational parameters and performance, for cell culture and adeno-associated virus vector production. Finally, mathematic models based on oxygen uptake rates were developed and proven effective to model cell growth curves and estimate biomass in real-time. This study shows that this innovative fixed bed bioreactor platform enables linearly scalable adherent cell-based biomanufacturing with high productivity.
15 Nov 2023Submitted to Biotechnology Journal
16 Nov 2023Submission Checks Completed
16 Nov 2023Assigned to Editor
18 Nov 2023Review(s) Completed, Editorial Evaluation Pending
19 Nov 2023Reviewer(s) Assigned
01 Jun 2024Reviewer(s) Assigned
07 Jun 2024Review(s) Completed, Editorial Evaluation Pending