Conclusion
This study evaluated the impact of co-current filtrate flow on product
retention during steady-state perfusion processes using hollow fiber
modules as cell retention devices. Whereas Starling recirculation in TFF
and alternating crossflow TFF is dependent on crossflow velocity and
filter module characteristics, co-current filtrate flow enabled
independent control of Starling recirculation. Pressure characterization
studies performed by inserting additional pressure sensors along the
filter module length revealed detailed insights into the filtrate
pressure gradient and confirmed the theoretical concept of altering TMP
by co-current filtrate flow. Further, control of Starling flow was not
only demonstrated at lab-scale, but also successfully applied to a
manufacturing scale filtration module. The benefits of HPTFF operation
or precisely controlling the direction and intensity of Starling
recirculation in scTFF operation was further demonstrated in
steady-state perfusion cell culture processes which showed much higher
product sieving compared to standard TFF operation. Starling flow
control enabled by co-current filtrate flow operation represents an
effective tool not only to study filter fouling, but also to reduce
product retention in steady-perfusion cell culture processes as well as
other operations such as dynamic perfusion or N-1 perfusion.