title: Mechanistic failure mode investigation and resolution of parvovirus retentive filters.
abstract: Virus retentive filters are a key product safety measure for biopharmaceuticals. A simplistic perception is that they function solely based on a size-based particle removal mechanism of mechanical sieving and retention of particles based on their hydrodynamic size. Recent observations have revealed a more nuanced picture, indicating that changes in viral particle retention can result from process pressure and/or flow interruptions. In this study, a mechanistic investigation was performed to help identify a potential mechanism leading to the reported reduced particle retention in small virus filters. Permeate flow rate or permeate driving force were varied and analyzed for their impact on particle retention in three commercially available small virus retentive filters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:959-970, 2016.
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Daniel
authors.initials: D
authors.lastname: LaCasse
authors.affiliation: U.S. FDA CDER/OPS/DMA, 10903 New Hampshire Ave, Bldg 72 RM 2220, Silver Spring, MD, 20903.
authors.forename: Scott
authors.initials: S
authors.lastname: Lute
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fiadeiro
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Jonida
authors.initials: J
authors.lastname: Basha
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Matthew
authors.initials: M
authors.lastname: Stork
authors.affiliation: U.S. FDA CDER/OPS/DMA, 10903 New Hampshire Ave, Bldg 72 RM 2220, Silver Spring, MD, 20903.
authors.forename: Kurt
authors.initials: K
authors.lastname: Brorson
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Ranga
authors.initials: R
authors.lastname: Godavarti
authors.affiliation: Pfizer Biopharmaceuticals, 1 Burtt Road, Andover, MA, 01810.
authors.forename: Chris
authors.initials: C
authors.lastname: Gallo
mesh_terms: D005374:Filtration; D057446:Hydrodynamics; D010316:Particle Size; D017992:Parvovirus / Q000302:isolation & purification*; D014771:Virion / Q000737:chemistry / Q000302:isolation & purification*
keywords: bacteriophage; convective flow; depth filtration; in membrane diffusion; monoclonal antibody; parvovirus; purification; viral clearance; virus retentive filtration