Abstract:
: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 startup 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 two-fold volumetric productivity increase over the commercial-ready, optimized fed-batch process.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Gagnon M,Nagre S,Wang W,Coffman J,Hiller GWdoi
10.1002/bit.26985subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1946-1958issue
8eissn
0006-3592issn
1097-0290journal_volume
116pub_type
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