Enhancing the Functionality of a Microscale Bioreactor System as an Industrial Process Development Tool for Mammalian Perfusion Culture

Abstract

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging; therefore potentially successful cell lines or perfusion processes are unrealised and their ability untapped. We present here the re-functioning of a high capacity microscale system that is typically employed in fed-batch process development to allow perfusion operation utilising in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0x106 mg/cell/day and 7x107 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilising a cell retention device. Neither specific productivity nor product quality indicated by product aggregation [6%] was significantly different across scales 19 days post inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters relevant to perfusion mode of culturing.