Integrated upstream and downstream continuous bioprocesses have the potential to revolutionize bioprocessing, leading to significant improvements in cost and process efficiencies.
When converting to continuous processing, the size and volume of the equipment decrease dramatically while volumetric productivity increases. A facility running an integrated continuous process will have a significantly smaller footprint than large-scale batch facilities, resulting in reductions in capital and operational expenses. Such a facility may run small-volume parallel production lines and deploy more portable or single-use equipment.
Perfusion, or upstream continuous processing, has been used in biopharmaceutical manufacturing since the 1980s. The challenge is extending the process to downstream operations where the processes are primarily still operated in batch mode.
To realize maximum benefits, the harvest feedstream from the perfusion bioreactor is loaded continuously on to capture chromatography columns reducing hold times and optimizing cycle times.
A transition from batch to continuous manufacturing may necessitate new equipment and control strategies to establish product equivalency. There are also concerns surrounding process development control, contamination risks, and scale-up potential of traditionally batch-based systems.
Below is a diagram of a typical fed-batch process and the key technologies needed to implement continuous processing and integrate upstream and downstream processes.
The XCell™ ATF System helps meet the upstream needs for rapid cell growth, and high density cell culture to maximize seed train workflow and process productivity. High density (HD) cell banking and N-1 perfusion optimize the upstream workflow, and reduce cycle time to the production bioreactor. High cell density perfusion used in the production bioreactor may eliminate centrifugation and reduce other filtration steps, generating continuous harvests ready for downstream capture chromatography.
Multi-column chromatography can perform high efficiency capture purification in continuous mode, capable of processing the harvest feedstream coming from the upstream bioreactor continuously. Capture chromatography steps occur simultaneously in an array of smaller columns with high process speed and high process capacity.