Anion exchange membrane adsorbers for flow-through polishing steps: Part I. clearance of minute virus of mice

Authors

  • Justin Weaver,

    1. Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523
    Search for more papers by this author
  • Scott M. Husson,

    1. Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC
    Search for more papers by this author
  • Louise Murphy,

    1. Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523
    Search for more papers by this author
  • S. Ranil Wickramasinghe

    Corresponding author
    1. Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523
    2. Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR; telephone: +1-479-575-8475; fax: +1-479-575-4937
    • Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523.
    Search for more papers by this author

Abstract

Membrane adsorbers may be a viable alternative to the packed-bed chromatography for clearance of virus, host cell proteins, DNA, and other trace impurities. However, incorporation of membrane adsorbers into manufacturing processes has been slow due to the significant cost associated with obtaining regulatory approval for changes to a manufacturing process. This study has investigated clearance of minute virus of mice (MVM), an 18–22 nm parvovirus recognized by the FDA as a model viral impurity. Virus clearance was obtained using three commercially available anion exchange membrane adsorbers: Sartobind Q®, Mustang Q®, and ChromaSorb®. Unlike earlier studies that have focused on a single or few operating conditions, the aim here was to determine the level of virus clearance under a range of operating conditions that could be encountered in industry. The effects of varying pH, NaCl concentration, flow rate, and other competing anionic species present in the feed were determined. The removal capacity of the Sartobind Q and Mustang Q products, which contain quaternary ammonium based ligands, is sensitive to feed conductivity and pH. At conductivities above about 20 mS/cm, a significant decrease in capacity is observed. The capacity of the ChromaSorb product, which contains primary amine based ligands, is much less affected by ionic strength. However the capacity for binding MVM is significantly reduced in the presence of phosphate ions. These differences may be explained in terms of secondary hydrogen bonding interactions that could occur with primary amine based ligands. Biotechnol. Bioeng. 2013; 110: 491–499. © 2012 Wiley Periodicals, Inc.

Ancillary