Recent process intensification has enabled manufacturers to achieve increased product output, pushing titers past 10 g/L in some cases. These output achievements require increased production efficiency and input, pushing many bioreactor systems past their limits. Quality requirements, robustness, and functional performance of traditional S.U.B.s can all become constraints, especially up to 2,000 L. For example, as oxygen transfer rate (OTR) becomes a limiting factor, most traditional S.U.B.s rely primarily on increased sparging flow to raise oxygen mass transfer.
Maintaining a dissolved oxygen (DO) target in high-demand cell cultures can be difficult due to limitations in the amount of mixing power that can be distributed effectively through the drive train of traditional S.U.B.s. Sparging through a microsparger has become a widely used strategy to improve OTR in traditional S.U.B.s and typically requires a secondary sparger to facilitate removal or stripping of dissolved CO2 (measured as partial pressure of CO2 or pCO2). Some cell lines, however, are sensitive to the higher shear produced by micro-sparging, and process scale-up cannot depend on this method alone to ensure sufficient O2 delivery or pCO2 removal.
The goal of this study was to evaluate the performance of the DynaDrive S.U.B. across 50–5,000 L scales using two different cell lines together with previously developed processes specific to those cell lines for manufacturing up to 2,000 L scale. These experiments were designed to demonstrate that the DynaDrive S.U.B. could be successfully implemented for use with multiple, high-demand CHO cell lines across scales with standard scale-up criteria. Both cell lines were subjected to a 14-day fed-batch run at full working volume for each scale.
If this topic interests you, please view Part 1 and Part 3 of this series as well.