Mechanistic insights into viral clearance during the chromatography steps in antibody processes by using virus surrogates

Biotechnol Prog. 2020 Nov;36(6):e3057. doi: 10.1002/btpr.3057. Epub 2020 Aug 21.

Abstract

Viral safety is required for biological products to treat human diseases, and the burden of inactivation and or virus removal lies on the downstream purification process. Minute virus of mice (MVM) is a nonenveloped parvovirus commonly used as the worst-case model virus in validation studies because of its small size and high chemical stability. In this study, we investigated the use of MVM-mock virus particle (MVP) and bacteriophage ΦX174 as surrogates for MVM to mimic viral clearance studies, with a focus on chromatography operations. Based on structural models and comparison of log reduction value among MVM, MVP, and ΦX174, it was demonstrated that MVP can be used as a noninfectious surrogate to assess viral clearance during process development in multiple chromatography systems in a biosafety level one (BSL-1) laboratory. Protein A (ProA) chromatography was investigated to strategically assess the impact of the resin, impurities, and the monoclonal antibody product on virus removal.

Keywords: MVM‐mock virus particle (MVP); chromatography; minute virus of mice (MVM); viral clearance; ΦX174.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / therapeutic use
  • Bacteriophages / chemistry
  • Bacteriophages / isolation & purification*
  • Chromatography
  • Humans
  • Mice
  • Minute Virus of Mice / chemistry
  • Minute Virus of Mice / isolation & purification*
  • Virion / chemistry
  • Virion / immunology
  • Virion / isolation & purification*

Substances

  • Antibodies, Monoclonal