Asahi Kasei Unveils Innovative Virus Filtration Model for Bioprocessing

Researchers at Asahi Kasei Bioprocess America have developed a groundbreaking small-scale inline virus spiking and mixing model. This innovation aims to validate viral clearance in continuous bioprocessing, eliminating the need for a surge vessel. The new model connects continuous chromatography and virus filtration systems, a significant advancement for the industry, which is increasingly shifting towards continuous processing.

Ioana Pintescu, a research associate and lead author of a recent study, shared insights on the model, stating that it defines the “viral clearance capabilities of a virus filter undergoing continuous filtration.” This new approach could facilitate fully continuous bioprocessing, potentially saving time and reducing costs while enhancing operational efficiency.

Breakthrough in Continuous Filtration

Pintescu and her colleagues, including Julie Kozaili, PhD, and Daniel Strauss, PhD, connected polishing chromatography and virus filtration steps to create a robust small-scale virus clearance validation model. The model operates in a high-throughput, constant flow environment over a 72-hour period. It achieved a viral limit of detection at 0.73 log TCID50/mL, resulting in complete removal of porcine parvovirus (PPV) and a logarithmic reduction value (LRV) of 5.5 or greater.

The challenge for engineers involved in continuous bioprocessing is that traditional virus filtration validation steps were typically designed for batch processing. Continuous processing introduces unique conditions, such as steady product movement, which can lead to variations in product feed and impact system pressure. This variability can cause filter fouling and fluctuations in pH, conductivity, and product concentration. Although surge tanks have been used to manage these issues, they occupy valuable floor space and may limit operational flexibility.

Optimizing Downstream Processes

To address these challenges, Pintescu and her team focused on worst-case scenarios and developed runs that are more reflective of actual downstream processes for bovine serum albumin (BSA) and monoclonal antibody (mAb) production. The connected chromatography to virus filtration model successfully processed both BSA and mAb protein solutions over the 72-hour period without any disruptions or pressure fluctuations.

Achieving this required careful management of multiple operating parameters. The maximum operating pressure was set at 0.3 megapascals (MPa), determined by the pump, column system, and virus filter design. A flow rate of 0.3 mL/s was established for BSA filtrations, while a rate of 0.165 mL/min was set for mAb filtrations. Throughout the experiment, pressure increased gradually, yet no overpressure or backpressure issues arose.

The system demonstrated consistent performance, responding effectively to both spiked and non-spiked BSA and mAb runs, delivering complete viral clearance starting from virus load titers of either 6.25 or 6.38 log TCID50/mL. Pintescu highlighted the significance of these results, stating, “These findings indicate that extended filtration run times and high throughput volumes posed no problem for the virus filter in this setup.”

The results affirmed that PPV LRV greater than five was achieved across all runs, showcasing the filters’ robustness under the experimental conditions.

Pintescu emphasized the potential for other research and development facilities to replicate this model, provided they have the necessary materials. “More optimization is needed,” she noted, “and new skid systems will have to be designed to accommodate continuous feeds through downstream unit operations without interruption.”

This innovative model represents a significant step forward in the field of bioprocessing, highlighting the potential for enhanced efficiency and reduced costs in viral clearance validation.