Tangential flow filtration systems are widely used cell retention devices in perfusion cultures, but significant challenges occur with prolonged operation. A well-known and common issue includes membrane fouling, which leads to low efficiency and increased product retention.
In this work, different process set ups and conditions were tested using magnetic levitation pumps for low shear TFF systems in small-scale perfusion bioreactors (200 ml). Process parameters such as cell growth, cell specific productivities and product sieving were compared with ATF systems. A novel concept based on the application of reverse flow across the hollow fiber using two magnetically levitating pumps was validated with a CHO cell line producing a recombinant monoclonal antibody (IgG). This approach makes it a valuable alternative to conventional ATF systems and can be used in various scales.
Moreover, a correlation between the passage of high molecular weight species (HMWS) to the harvest stream of the perfusion process and the mode of operation as well as the degree of product sieving was found. This results in important aspects in terms of product quality in integrated continuous bioprocesses.