Continuous downstream processing for high value biological products: A Review

Abstract

There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations.

Production Rate‐Dependent Key Performance Indicators for a Systematic Design of Biochemical Downstream Processes

“…The abbreviation MoBiDiK means modular bioproduction, being disposable and continuous. For further information, the reader is recommended to overviews of the availability of continuous bioprocessing technology [29,30] and current opinions on the future of bioprocessing [31,32]. Case studies for the applicability of the SPI cont might, therefore, arise soon.…”

Using Computational Modeling To Optimize the Design of Antibodies That Trap Viruses in Mucus

“…Much effort has been spent on reducing the costs of antibody production, such as the production of antibodies in plants, 14 as well as cheaper and more efficient methods of purifying antibodies. 15 Here, we introduce a novel and completely distinct approach—based on tuning IgG–mucin interactions—that could markedly reduce the dose of bnAbs needed to block vaginal HIV transmission. The majority of bnAbs against HIV appear to possess k on in the range of 10 4 M s −1 , which we previously estimated may require concentrations in excess of 5–10 µg/mL to facilitate effective protection.…”

Perspectives on integrated continuous bioprocessing—opportunities and challenges

“…UF/DF processes are currently performed as batch operations. Continuous versions of these membrane processes could potentially be developed based on membrane cascades [35] and/or single pass tangential flow filtration [36], although additional work will be needed to demonstrate the effectiveness of these methods, particularly for highly concentrated monoclonal antibody formulations [16 ]. Alternatively, product formulation could be achieved using lyophilization or crystallization in continuous tubular reactor systems [37].…”