Virus retention during constant-flux virus filtration using the Viresolve® Pro membrane including process disruption effects

The growing interest in process intensification and continuous processing has led to concerns regarding the performance of virus removal filters at low permeate fluxes. This paper presents a quantitative analysis of virus retention by the Viresolve® Pro membrane during constant permeate flux filtration and in response to process disruptions using ΦX-174, a bacteriophage, as a model for a mammalian parvovirus. Virus retention by a single layer of Viresolve® Pro membrane was reduced at lower permeate fluxes due to the greater diffusive mobility of phage, although the expected retention for a commercial device employing two layers of membrane remained above 4-logs. The retention data were well correlated with the ΦX-174 Péclet number for filtrate flux from 5 to 100 L/m²/h. Process disruptions caused an immediate transient increase in phage transmission, although this effect was much less pronounced at low permeate flux. The experimental data for phage retention, both with and without process disruptions, were well-described using an internal polarization model with the fraction of virus remaining mobile within the filter scaling as 1/Pe². In contrast, the fraction of previously captured virus that were re-mobilized after a process interruption was independent of the flow rate. Model equations were developed for rapid estimation of virus performance behavior with the Viresolve® Pro membrane, facilitating the design and implementation of virus filtration processes operating at constant filtrate flux.