A fundamental challenge during scale-up of cell culture processes is the need to reproduce a large number of environmental conditions using a limited number of control parameters. In particular, aeration strategies are typically designed to maintain similar oxygen transfer rates (kLa) or power inputs (P/V) across scales, often at the expense of replicating dissolved carbon dioxide levels. In this work, the sparge configuration in lab-scale 2L bioreactors was modified to enable decoupling of oxygen and carbon dioxide control in order to better match profiles seen at 12kL manufacturing scale. By modulating air, oxygen, and nitrogen flows through three inlets – an overlay, a microsparger, and an open-pipe sparger, respectively – dissolved oxygen and carbon dioxide profiles could be adjusted independently to match those observed at large scale. Using this approach, significant differences in cross-scale performance were resolved, including improved replication of cell viability, lactate, and titer profiles. In particular, differences of up to 40% in harvest titer were eliminated through use of this 2L model.

Matching dissolved carbon dioxide profiles to achieve comparable cell culture performance across scales

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.