Effect of filtrate flux and process disruptions on virus retention by a relatively homogeneous virus removal membrane

Recent studies have shown that virus retention by specific virus filters can be reduced at low flow rates and after process disruptions; however, the magnitude of these changes in virus retention and the underlying mechanisms controlling this behavior are still not well understood. The objective of this study was to develop a quantitative understanding of the factors controlling the virus retention behavior of a relatively homogeneous polyvinylidene fluoride virus removal filter. Data were obtained with the bacteriophage phi X174 as a model virus. Virus retention decreased as the filtrate flux was reduced and also declined slightly over the course of the virus filtration. Virus retention immediately after a process disruption decreased by as much as a factor of 1000 (3-logs) depending on the duration and timing of the disruption. The experimental results were well-described using an internal polarization model that accounts for accumulation and release of virus during the filtration / disruption, with the key model parameters dependent on the filtrate flux. These results provide important insights into the factors controlling the virus retention behavior as well as guidelines for the effective use of virus removal filters in bioprocessing.