Effects of a pressure release on virus retention with the Ultipor DV20 membrane

Abstract

Recent data have shown that a temporary release in the transmembrane pressure can cause a significant increase in virus transmission through a number of commercial virus filters. The objective of this work was to study the effect of a pressure release on retention of the bacteriophage ΦX174 by the Ultipor DV20 membrane, with phage capture within the membrane visualized by confocal microscopy. Phage challenge tests showed a significant transient increase in phage transmission (typically by an order of magnitude) immediately after a pressure release. This transient increase was not due to any damage to the filter or to the presence of a back-flow (from permeate to feed). Confocal images demonstrated that the pressure release caused the migration of previously captured bacteriophage further into the depth of the filter. Data were analyzed using a modified internal polarization model, with the results providing important insights into the factors controlling virus retention during virus filtration.

Probing effects of pressure release on virus capture during virus filtration using confocal microscopy

“…The results with the DV20 (Fig. a) are similar to those reported previously by Woods and Zydney (). There is a slight increase in phage concentration during the first portion of the experiment, with a 2‐log (100‐fold) increase in phage transmission immediately after the pressure release followed by a more gradual decline.…”

“…There is a slight increase in phage concentration during the first portion of the experiment, with a 2‐log (100‐fold) increase in phage transmission immediately after the pressure release followed by a more gradual decline. Woods and Zydney () observed a much more rapid decline in phage concentration after the pressure release, with the permeate concentration returning to approximately the value obtained before the pressure release after about 9.5 L/m 2 . The filtrate flux during filtration of φX174 through the DV20 membrane (data not shown) remained nearly constant during the initial stage of the filtration at a value of 8.0 × 10 −6 m/s (30 L/m 2 /h) but increased by approximately 30% immediately after the pressure release and then remained constant.…”

“…Woods and Zydney () saw similar capture profiles for the DV20 membrane after a pressure release experiment, although the images were obtained using only green‐labeled phage, making it impossible to distinguish between the phage that were in the challenge before versus after the pressure release. They hypothesized that the captured phage were able to diffuse out of the retentive pores during the pressure release, migrating laterally within the filter and then moving deeper into the filter (with some phage passing all the way into the filtrate) when the pressure was re‐applied.…”

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

“…An industry‐wide evaluation of small virus retentive filters also found that large enveloped viruses were reduced below the limit of detection in all 198 cases examined, providing additional rationale that viral testing only needs to be performed with smaller virus as a worst case scenario . It has been shown that virus breakthrough can occur with small virus retentive filters during long processing times . However, proper evaluation and control of process parameters and solution properties can maintain high filter flux and mitigate this risk .…”

Viral clearance for biopharmaceutical downstream processes

“…Data for virus retentive filters have been summarized in a publication by Miesegaes et al [34]. Process operating ranges and depressurization have been reported to impact virus bleed through for virus-retentive filters designed to remove parvoviruses [35]. Sustained pressure excursions had a greater impact on log reduction values than the pressure differential (dP).…”