Characterizing the impact of pressure on virus filtration processes and establishing design spaces to ensure effective parvovirus removal

Abstract

Virus filtration provides robust removal of potential viral contaminants and is a critical step during the manufacture of biotherapeutic products. However, recent studies have shown that small virus removal can be impacted by low operating pressure and depressurization. To better understand the impact of these conditions and to define robust virus filtration design spaces, we conducted multivariate analyses to evaluate parvovirus removal over wide ranges of operating pressure, solution pH, and conductivity for three mAb products on Planova TM BioEX and 20N filters. Pressure ranges from 0.69 to 3.43 bar (10.0-49.7 psi) for Planova BioEX filters and from 0.50 to 1.10 bar (7.3 to 16.0 psi) for Planova 20N filters were identified as ranges over which effective removal of parvovirus is achieved for different products over wide ranges of pH and conductivity. Viral clearance at operating pressure below the robust pressure range suggests that effective parvovirus removal can be achieved at low pressure but that Minute virus of mice (MVM) logarithmic reduction value (LRV) results may be impacted by product and solution conditions. These results establish robust design spaces for Planova BioEX and 20N filters where high parvovirus clearance can be expected for most antibody products and provide further understanding of viral clearance mechanisms.

Microscopic visualization of virus removal by dedicated filters used in biopharmaceutical processing: Impact of membrane structure and localization of captured virus particles

“…Roush et al reported that the impurity in the virus spike source affects virus removal capacity. Additionally, using three different monoclonal antibodies in comprehensive design space experiments, Strauss et al, demonstrated that solution conditions, as well as filtration pressure, could impact minute virus of mice LRV. Virus spike volume, filter area, protein concentration, and transmembrane pressure should all be covered in further experimental studies.…”

Use of a noninfectious surrogate to predict minute virus of mice removal during nanofiltration

“…The utility of any viral clearance spiking agent relies on the sensitivity and dynamic range in which the agent can be accurately measured. MVM studies typically employ infectivity assays (e.g., TCID 50 ) which can measure the titer of infectious particles over an 8 log 10 range to as little as <1.0 log 10 TCID 50 /mL . qPCR techniques have also been established which indiscriminately measure infectious and noninfectious MVM over a 6 log 10 dynamic range to as little as 2 MVM copies .…”

Interactions between protein molecules and the virus removal membrane surface: Effects of immunoglobulin G adsorption and conformational changes on filter performance

“…Recent virus filtration studies have focused on the effects of process parameters on throughput and viral retention. Operating pressure and solution conditions have been identified as crucial parameters for virus retention. Dishari et al indicated that solution pH and ionic strength can alter the electrostatic interactions between viruses and membranes, affecting virus retention .…”