Increasing CHO cell harvest efficiency with cyclical cake filtration

Efficient clarification of bioreactor harvests remains a critical bottleneck in biomanufacturing, directly impacting throughput, product yield, and operational costs. Current industry practice typically relies on depth filtration due to its effective removal of particulates and impurities; however, depth filters are prone to clogging, require oversized filter areas, and can reduce product yield through non-specific adsorption. Alluvial filtration addresses some of these limitations by using a diatomaceous earth (DE) filter cake to protect the underlying media and extend filtration capacity. Cyclical cake filtration further leverages the advantages of diatomaceous earth (DE) cake filtration through multi-cycle cloth regeneration. This study examines cyclical cake filtration and compares it with traditional and alluvial depth filtration regarding performance and scalability. Cyclical cake filtration maintained higher flow rates than depth filtration and exhibited no clogging under the tested conditions. With the addition of DE and various ion-exchange resins, cyclical cake filtration achieved filtrate turbidities as low as 2.8 NTU while maintaining product yields of 91–94%. DNA and host cell protein concentrations were reduced by up to 95% and 62%, respectively, approaching levels achieved by conventional two-stage clarification processes. Scale-up studies demonstrated comparable flow rate behavior and filtrate quality across three filtration scales spanning an 18-fold increase in filter area. Product yield remained consistent across scales, while impurity levels and turbidity exhibited minor variation. A commercial scale assessment for processing 2000 L of Chinese hamster ovary (CHO) culture estimated a primary clarification filter area requirement of 0.88 m 2 for cyclical cake filtration, compared with 16.8 m 2 and 28.5 m 2 for alluvial and depth filtration, respectively. When processing time and filter area were combined into a proposed efficiency parameter, cyclical cake filtration demonstrated the most favorable performance. These results demonstrate that cyclical cake filtration is a scalable and efficient clarification technology capable of reducing process risk and consumable requirements while maintaining high product recovery and consistent filtration performance, and offers options for competitive impurity removal. Key points • Cyclical cake filtration offers an alternative to depth and alluvial filtration. • More efficient cell harvest if combined filter area and processing time are considered. • Lower process risk, filter area requirement, waste, and cost.