Design and characterization of a novel perfusion reactor for biopharmaceuticals production

Abstract

The demand for commercially valuable biopharmaceuticals able to treat different immunopathological diseases has accelerated in the last few decades. In recent years the industry has shifted the preferred mode of operation towards continuous strategies and has favoured the adoption of perfusion approaches for the cell culture step. In this mode successful perfusion process examples have reached up to 10-fold higher cell densities and product titres than fed-batch, while maintaining product quality at reduced costs. Perfusion processes are operated at high cell densities where cells are retained, while product and waste are continuously removed. This leads to different requirements in flow and mixing in comparison to lower cell density operations, potentially influencing the cellular production performance and therefore product quality. As the pharmaceutical industry is highly regulated, ensuring homogeneity in the bulk throughout the process is critical, while oxygen and mixing requirements of high cell density cultures must be continuously met. This paper presents the design and characterization of a novel 250 mL stirred tank reactor (STR) developed to work in perfusion mode. The results presented include the experimental measurement of the power consumption, the mixing analysis of the flow within the bioreactor which informs design consideration and scaling efforts and the biological data of the perfusion stage with an industrially relevant cell line producing an IgG monoclonal antibody. The characterization allows the operating window of the reactor to be established, resulting in increased productivity of intensified cultures.