The intensification of industrial biopharmaceutical production and the integration of process steps pave the way for patients to access affordable treatments. The predominantly batchwise biomanufacturing of established cell clarification technologies, stainless steel disc stack centrifugation (DSC) and single-use (SU) depth filtration (DF), pose technological and economical bottlenecks, that include low biomass loading capacities and low product recoveries. Therefore, a novel SU-based clarification platform was developed combining fluidized bed centrifugation (FBC) with integrated filtration. The feasibility of this approach was investigated for high cell concentration with more than 100E6 cells/mL. Furthermore, scalability to 200 L bioreactor scale was tested for moderate cell concentrations. In both trials, low harvest turbidities (4 NTU) and superior antibody recoveries (95%) were achieved. The impact on the overall economics of industrial SU biomanufacturing using an up-scaled FBC approach was compared with DSC and DF technologies for different process parameters. As a result, the FBC showed to be the most cost-effective alternative for annual mAb production below 500 kg. In addition, the FBC clarification of increasing cell concentrations was found to have minimal impact on overall process costs, in contrast to established technologies, demonstrating that the FBC approach is particularly suitable for intensified processes.
Keywords: cell removal; clarification; cost analysis; fluidized bed centrifuge; high cell density; monoclonal antibody.
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