Novel, Linked Bioreactor System for Continuous Production of Biologics.

Authors:
Matthew Gagnon
Matthew Gagnon
Department of Family Medicine
Shashikant Nagre
Shashikant Nagre
100 Cummings Center
Wenge Wang
Wenge Wang
University of Pennsylvania School of Medicine
United States
Jon Coffman
Jon Coffman
University College London
United Kingdom
Gregory W Hiller
Gregory W Hiller
Pfizer
Groton | United States

Biotechnol Bioeng 2019 Apr 5. Epub 2019 Apr 5.

Culture Process Development, Pfizer Inc., 1 Burtt Road, Andover, Massachusetts.

A novel, alternative intensified cell culture process comprised of a linked bioreactor system is presented. An N-1 perfusion bioreactor maintained cells in a highly proliferative state and provided a continuous inoculum source to a second bioreactor operating as a continuous-flow stirred-tank reactor (CSTR). An initial study evaluated multiple system steady-states by varying N-1 steady-state viable cell densities, N-1 to CSTR working volume ratios, and CSTR dilution rates. After identifying near optimum system steady-state parameters yielding a relatively high volumetric productivity while efficiently consuming media, a subsequent lab scale experiment demonstrated the start-up and long-term operation of the envisioned manufacturing process for 83 days. Additionally, to compensate for the cell-specific productivity loss over time due to cell line instability, the N-1 culture was also replaced with younger generation cells, without disturbing the steady-state of the system. Using the model cell line, the system demonstrated a 2-fold volumetric productivity increase over the commercial-ready, optimized fed-batch process. This article is protected by copyright. All rights reserved.

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http://dx.doi.org/10.1002/bit.26985DOI Listing
April 2019
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