Applied Biochemistry and Biotechnology

, Volume 183, Issue 1, pp 318–331 | Cite as

Characterization of Non-Infectious Virus-Like Particle Surrogates for Viral Clearance Applications

  • Sarah Johnson
  • Kurt A. Brorson
  • Douglas D. Frey
  • Arun K. Dhar
  • David A. Cetlin


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.


Viral clearance Bioprocess development Quality by Design Minute virus of mice Virus-like particle Chromatofocusing Chromatography Virus filtration 



This project was supported in part by an appointment to the Research Participation Program at FDA/CDER/OBP administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the DOE and FDA. Funding was also provided by the Regulatory Science and Review Enhancement Program (RSR) 15-14 and the Research Review Coordinating Committee (RRCC).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Sarah Johnson
    • 1
  • Kurt A. Brorson
    • 1
  • Douglas D. Frey
    • 2
  • Arun K. Dhar
    • 3
  • David A. Cetlin
    • 3
  1. 1.DBRRII, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  2. 2.Department of Chemical, Biochemical, and Environmental EngineeringUniversity of Maryland Baltimore CountyBaltimoreUSA
  3. 3.MockV Solutions, Inc.RockvilleUSA

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