PsiOxus® platform technology is based on a tumour selective oncolytic adenovirus. Viruses are engineered to express a targeted payload, upon intravenous administration, into a broad range of carcinoma cell lines, but not to replicate, or deliver the payload in normal cells. Adenovirus is manufactured by infecting human embryonic kidney cells (HEK 293) which are grown in suspension, in stirred tank bioreactors.
The aim is to develop a robust manufacturing process for high yield adenovirus production, whilst maintaining high product quality and batch to batch consistency. Therefore, to maximize adenovirus productivity at manufacturing scale, the use of a perfusion system was assessed and compared with standard production in batch mode.
During perfusion mode, cells were separated through tangential flow filtration (TFF) and the medium in the bioreactor was renewed. To avoid high levels of cell lysis, associated with the use of peristaltic pumps in TFF perfusion systems, a low shear centrifugal pump from Levitronix® was evaluated.
Perfusing using Levitronix® centrifugal pump resulted in a 2-fold increase in total virus particles per cell, in comparison to production in batch mode. Furthermore, cell growth and viability were not affected by the continuous cell recirculation during perfusion mode and product quality was maintained.