Monitoring, Design and Optimization of Bioprocesses
With new cell lines designed for vaccine production, various options for establishment of advanced process strategies are available. For ease of scale-up, suspension cell lines are used, whenever available, that grow in chemically defined media. Ideally, these cells can be used for more than 100 passages and grow in batch culture easily to 5-10 x 106 cells/mL.
For recombinant protein production, perfusion and fed-batch strategies using suspension CHO cells are state-of-the-art. The corresponding processes are running over several weeks leading to (semi-)continuous manufacturing with high product yields. To further support process intensification, optimized perfusion media and special feeding schemes have been developed.
For the cell lines used in viral vaccine manufacturing, however, such media are not readily available. Typically, at cell densities exceeding 4 x 106 cells/mL), the so-called “high cell density effect” often leads to a significant drop in cell-specific yield. Accordingly, better substrate formulations and process strategies need to be developed and tested comprehensively to overcome this crucial limitation. Additionally, alternative process options, especially towards disposable, single-use bioreactors and fully continuous processes need to be explored for future high-yield vaccine manufacturing.