Development of a Small‐Scale Continuous Virus Filtration Model That Incorporates Inline Spiking and Mixing

Recent efforts have focused on shifting biomanufacturing from traditional batch mode processing to continuous processing as these technologies have the potential to increase productivity and product quality. However, the lack of a unified methodology for viral clearance validation of virus filtration (VF) in continuous processing has presented a hurdle to its implementation. Through the use of spiking a concentrated virus stock into a continuous filtration system, product flow with a stable virus level can be supplied to the filter over a long duration to allow uninterrupted flow and achieve viral clearance validation conditions comparable to those of traditional batch spiking for batch processing. In this study, we developed a small-scale inline virus spiking and mixing model as a proposed validation strategy for a connected, continuous chromatography and VF system operated in constant flow mode over long durations and with high throughputs. The small-scale model was successfully operated for upwards of 72 h and produced the expected virus-spiked product feed solutions with no deviation in virus, protein and buffer concentrations throughout the runs. In addition, laboratory-scale Planova BioEX filters showed complete removal of porcine parvovirus with a logarithmic reduction value greater than 5.5 when run continuously for 72 h.