title: Characterization of Non-Infectious Virus-Like Particle Surrogates for Viral Clearance Applications.
abstract: Viral clearance is a critical aspect of biopharmaceutical manufacturing process validation. To determine the viral clearance efficacy of downstream chromatography and filtration steps, live viral "spiking" studies are conducted with model mammalian viruses such as minute virus of mice (MVM). However, due to biosafety considerations, spiking studies are costly and typically conducted in specialized facilities. In this work, we introduce the concept of utilizing a non-infectious MVM virus-like particle (MVM-VLP) as an economical surrogate for live MVM during process development and characterization. Through transmission electron microscopy, size exclusion chromatography with multi-angle light scattering, chromatofocusing, and a novel solute surface hydrophobicity assay, we examined and compared the size, surface charge, and hydrophobic properties of MVM and MVM-VLP. The results revealed that MVM and MVM-VLP exhibited nearly identical physicochemical properties, indicating the potential utility of MVM-VLP as an accurate and economical surrogate to live MVM during chromatography and filtration process development and characterization studies.
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Johnson
authors.affiliation: DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Brorson
authors.affiliation: Department of Chemical, Biochemical, and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Frey
authors.affiliation: MockV Solutions, Inc., 22 Baltimore Road, Rockville, MD, 20850, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Dhar
authors.affiliation: MockV Solutions, Inc., 22 Baltimore Road, Rockville, MD, 20850, USA. dcetlin@mockvsolutions.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Cetlin
mesh_terms: D000818:Animals; D051379:Mice; D008915:Minute Virus of Mice / Q000737:chemistry* / Q000302:isolation & purification* / Q000648:ultrastructure
keywords: Bioprocess development; Chromatofocusing; Chromatography; Minute virus of mice; Quality by Design; Viral clearance; Virus filtration; Virus-like particle