Abel Hastings, Director, Process Sciences, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: UFDF lacks standardization and controls to enable comparison across multiple scales and to provide meaningful PAT to minimize risk. We spend a lot of effort de-risking this step when changing scales because there is so much variability and so little solid PAT.
Timothy Hill, Director, Upstream Process Development, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: Separation of cells from protein supernatant at the end of cell culture processes is time-consuming and expensive at higher production scales and can introduce product variation. New technology is needed to rapidly remove cells, in order to move the product to downstream capture chromatography where protease and other impurities are removed and the protein is stabilized in defined chemical buffers. Pall’s Cadence Acoustic Separator holds promise for this purpose.
Andrew Bulpin, Head of Process Solutions Strategic, Marketing & Innovation, MilliporeSigma
A: Improving bioreactor and cell retention setup used in perfusion processes could be a major improvement area for biologic manufacturers. Although substantial benefits can be achieved using perfusion, current approaches are complex and require that the biologic manufacturers complete the integration of the bioreactor and cell retention device. By enabling the simple integration of the cell retention device and bioreactor, along with all the necessary control requirements, complexity can be reduced to achieve better and more consistent results within a robust process operation.
Michael Murray, Downstream Process Development, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: Continuous processing is the ultimate goal, which has the promise of reducing time, footprint and cost. Systems are currently in development, but issues such as control strategies and regulatory approaches still need to be determined. A shorter-term goal would be a cost- effective means of automated buffer preparation, coupled with thoughtful process design and cycling strategies, and preparation of buffers from concentrated stocks will have a dramatic impact on the footprint of a process, eliminating the need for storage of large volumes of buffers. The associated cost with the current buffer preparation systems prevents their use as a point-of-use device as multiple systems are required for this approach.