Continuous viral filtration for the production of monoclonal antibodies

Abstract Continuous processing is the future manufacturing method for monoclonal antibodies (mAb). Consequently, also continuous viral clearance has to be investigated. Viral filtration is one of the two standard methods for viral clearance within mAb production processes. This work investigates key differences in operation of batch and continuous viral filtration and provides first data on the performance of four different filters under continuous mAb production conditions. The scenario applied shows that continuous viral filtration for mAb production has to be operated under fundamentally different conditions than batch filtration, operating at low pressure conditions of 0.3 L/m²/h instead 30-60 L/m²/h. Consequently, no data from filter validation or application notes exist which answer the question whether or not the existing filters can be used for continuous viral filtration. Two first-generation filters and two second-generation filters were tested. Continuous filtration for 72 h at 0.3 L/m²/h as well as start-stop scenarios were investigated, identifying the filter types that are possible candidates for the continuous production of mAb. The two first generation filters (Pall SV4 and Sartorius Virosart CPV), did not achieve a LRV > 4 under the conditions tested. The two tested second-generation filters, Pall Pegasus Prime and Sartorius Virosart HF were able to maintain a LRV > 4 for at least 20 L/m² or the entire filtration time, respectively. All filters tested showed a state of constant LRV after an initial decrease. Additional experiments with short and long-term stops with the Pall Pegasus Prime filter revealed that the steady state observed before is reached earlier with stops, independently of the stop duration.