437479 Ultra High Density Perfusion for Enabling Automated Cell Banking

Wednesday, November 11, 2015: 2:30 PM
150D/E (Salt Palace Convention Center)
James Lambropoulos1, Christopher Ta2, Alan Gilbert1, Rashmi Kshirsagar3 and Thomas Ryll3, (1)Cell Culture Development, Biogen, Cambridge, MA, (2)Biogen, Cambridge, MA, (3)Cell Culture Development, Biogen, Morrisville, NC

The typical process for manufacturing biologics begins with the thaw of a cell bank and the expansion of inoculum culture. Current technologies for the generation of these cell banks can be labor intensive, and include several steps that introduce a significant risk of contamination or operator error. We describe here the development of an ultra-high-density, controlled cell culture process that mitigates these risks, and can be used for the production of both standard- and high-density cell banks. Alternating tangential flow perfusion technology was implemented and challenges of oxygen delivery and carbon dioxide accumulation were addressed. The final process supported high-viability cultures with ultra-high cell densities. These cultures were subjected to a revised banking protocol, which involved in situ addition of DMSO and direct vialing, eliminating the need for pooling cultures, centrifugation, or re-suspension, and increasing process consistency. Cell banks generated in this manner showed comparable recovery from thaw as traditional cell banks, and were considered suitable replacements for the standard-density banks. High-density, large volume cell banks generated using this process can be thawed directly into a seed train bioreactor, thus avoiding shake flask culture, reducing the time required for inoculum expansion by up to two weeks, and lowering the cost of production.

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