Pre-Stage Perfusion and Ultra-High Seeding Cell Density in CHO Fed-Batch Culture: A Case Study for Process Intensification Guided by Systems Biotechnology



Process intensification strategies are needed in the field of therapeutic protein production for higher productivities, lower cost of goods and improved facility utilization. This work describes an intensification approach, which connects a tangential-flow- filtration (TFF) based pre-stage perfusion process with a concentrated fed-batch production culture inoculated with an ultra- high seeding density (uHSD). This strategy shifted biomass production towards the pre-stage, reaching up to 45 × 106 cells/ mL in perfusion mode. Subsequently, production in the intensified fed-batch started immediately and the product titer was almost doubled (1.9-fold) in an equivalent runtime and with comparable product quality compared to low-seeded cultures. Learn More