Achieving High Productivities through Bioreactor Optimization at Lower than Peak Cell Densities in a Perfusion Process

The demand for producing therapeutic recombinant proteins is generating a renewed interest in perfusion cell culture technologies, leading to the development of cell culture media that can support high cell densities (HCD). However, HCD in bioreactors can generate challenges, due to the requirement to maintain highly productive cells over long periods of time. Implementing a perfusion process utilizing a production bioreactor is costly, requiring small scale models to optimize the process. In this study, BalanCD CHO Perfusion and Perfusion Media Survey Panel was evaluated with perfusion mimic models and a table-top perfusion capable bioreactor featuring an alternating tangential flow filtration unit in both a N-1 perfusion process and a recombinant antibody production process. We demonstrate the optimization of a perfusion process in a table-top perfusion capable bioreactor, scaling-up from small scale perfusion mimic models. We assayed peak cell densities in an N-1 perfusion process demonstrating how productivity is related to various metabolites, glucose, and aeration during a continuous steady-state culture. Our results demonstrate success of achieving high productivities in a continuous steady-state perfusion culture through the optimization of bioreactor parameters, while utilizing an appropriate cell culture medium, without achieving peak cell densities.

Learning Objectives: 

1. The use of perfusion mimic models to assess a perfusion medium

2. Scaling from a micro bioreactor to a table-top perfusion capable bioreactor

3. Optimization of the perfusion process to achieve increased productivity