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Radhika Jayakar, Cytiva: Process Intensification with Xcellerex™ APS

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The Cytiva Xcellerex™ APS (Automated Perfusion System) enables mammalian cell culture customers to enhance existing batch seed, fed-batch production, and existing perfusion processes.

This technology has been tested using a traditional final seed stage(N-1) process controlled in perfusion mode using tangential flow filters for cell retention. This process was compared to the same process cultivated in a ReadyToProcess WAVE™ 25 bioreactor. The intensified N-1 seed perfusion process was seeded from an N-2 culture of Chinese hamster ovary (CHO) cells expanded in HyClone™ ActiPro™ medium and was fed in perfusion mode using HyClone™ CellBoost™ Supplements 7a and 7b. The seed process achieved a final concentration of 179 million cells/ml. Seed viability and cell density growth trends were comparable to 5L and 25L N-1 perfusion seed cultures grown in a WAVE™ 25 bioreactor. All three seed cultures were expanded into a fed-batch flask process, all providing similar profiles for cell density, culture viability, protein productivity, and target protein product functional chemistry.

The fully automated control loops built into the Cytiva APS system empower customers to plug-and-play a fluid control system. This system is designed to pair with the current Xcellerex™ XDR-50, XDR-200, and XDR-500 using a standard perfusion bioreactor consumable. The APS maintains culture flow rates over and through a tangential flow filtration (TFF) ReadyToProcess™ hollow fibre filter, while monitoring for filter fouling by changes in filter pressure differentials using in situ pressure sensors. By offering automatic filter and media/permeate collection switching,  the system reduces manual check-in and in-process manual manipulations to sustain a perfusion process relative to manual systems. Additional automated fluid controls ensure sustained media levels in the bioreactor and cell bleed functions via gravimetric and flow rate control. The form factor for the system allows for standardization of an operation foot-print for perfusion operations
for culture volumes from 28L to 500L.

Company Cytiva