Perfusion And Single-Use Bioreactors: A Partnership For Scale Up

Perfusion has emerged as a viable technology for the commercial production of biopharmaceuticals. Perfusion solutions can offer very cost-efficient scale up solutions, driving down operating costs due to the smaller equipment and facilities needed as compared to batch or fed-batch systems. Alternating Tangential Flow Filtration devices from Refine Technology, PBS Biotech’s partner in perfusion have produced a record-high titer of 1.5g/L/day in a concentrated perfusion process and 24 g/L for an antibody grown in concentrated fed-batch culture. The ability to continuously harvest product is a unique advantage of perfusion systems that can be of utmost importance for labile products.

PBS bioreactors feature very efficient, low shear mixing and high mass transfer rates due to the patented AirWheel™ mixing mechanism. For perfusion processes, the bioreactors are easily and conveniently coupled to Refine Technology ATF™ System perfusion devices with the aid of aseptic connectors and very short tubing lengths.

A Refine Technology ATF-4 System was fitted with a 0.22 µm membrane device and a GE ready-mate connector on the main line, then sterilized by autoclaving according to manufacturer’s directions. After autoclaving, a connection was made to the PBS 15 bag using a bottom entry port. The bioreactor was batched to 10L, equilibrated and inoculated, and the cells were grown to a density of nearly 7 M c/mL before the perfusion was started on day 3. The glucose concentration at the beginning of perfusion was approximately 1 g/L.