Alternative Strategies for the Production of an Antibody-Cytokine Fusion Protein from Recombinant BHK Cells

The choice of scale up strategies for production of recombinant proteins from animal cells is often restricted to suspension cultures in stirred tank bioreactors. The primary aim of the work reported here was to identify alternative strategies for scale up of production, from BHK cells, of a recombinant antibody-cytokine fusion protein from BHK cells. We have used a single recombinant BHK clone to address a wide range of scale up options including batch production using aggregates in stirred systems, and attached cells on microcarriers; and continuous production using a fixed bed porous carrier perfusion system. These modalities have been compared with standard and modified (silicone coated) roller bottles. While cell specific production rate and concentration of product in culture supernatant are key factors in the final choice of production method, further comparative assessments of product quality and feasibility and cost at pilot stage are critical to the final selection of scale up technologies for use in production. Key words: Bioreactor, BHK, recombinant fusion protein.