Efficiency and scalability in harvesting mammalian cell cultures: A scale-down approach to continuous centrifugation

Continuous centrifugation is a well-established method for clarifying mammalian cell cultures, but traditional batch-based approaches often fall short of modern biomanufacturing's scalability and flexibility demands. Increasing variability in product volumes and manufacturing setups calls for adaptable, scalable solutions. To address this, we developed a scaled-down continuous centrifuge ("Mini") based on a commercial disc-stack centrifuge, facilitating efficient early-stage development and improving technology transfer and scale-up. This study demonstrates the Mini's potential to bridge the gap between small-scale optimization and industrial-scale centrifugation. Proof-of-concept experiments with Chinese hamster ovary cell culture confirmed its separation efficiency, achieving low turbidity, high product recovery (up to 98.5%), and minimal cell stress. Lactate dehydrogenase activity remained low, with a maximum increase in host cell proteins of 11.9% across various operating conditions. Validation experiments against the pilot-scale Culture One™ Primo showed comparable or superior turbidity reduction and lower lactate dehydrogenase activity, highlighting the Mini's gentle cell handling. The Mini enables continuous small-scale centrifugation while replicating key performance parameters of the pilot-scale system, ensuring accurate performance predictions and reliable scale-up. It provides a scalable, flexible solution that meets the evolving needs of modern biomanufacturing for efficient and adaptable clarification processes.