Virus removal filtration of chemically defined Chinese Hamster Ovary cells medium with nanocellulose-based size exclusion filter

Biologicals. 2019 May:59:62-67. doi: 10.1016/j.biologicals.2019.03.001. Epub 2019 Mar 12.

Abstract

Sterility of bioreactors in biotherapeutic processing remains a significant challenge. Virus removal size-exclusion filtration is a robust and highly efficient approach to remove viruses. This article investigates the virus removal capacity of nanocellulose-based filter for upstream bioprocessing of chemically defined Chinese hamster ovary (CHO) cells medium containing Pluronic F-68 (PowerCHO™, Lonza) and supplemented with insulin-transferrin-selenium (ITS) at varying process parameters. Virus retention was assessed by spiking ITS-supplemented PowerCHO™ medium with small-size ΦX174 phage (28 nm) as a surrogate for mammalian parvoviruses. The nanocellulose-based size exclusion filter showed high virus retention capacity (over 4 log10) and high flow rates (around 180 L m-2 h-1). The filter had no impact on ITS supplements during filtration. It was further shown that the filtered PowerCHO™ medium supported cell culture growth with no impact on cell viability, morphology, and confluence. The results of this work show new opportunities in developing cost-efficient virus removal filters for upstream bioprocessing.

Keywords: Cell culture media; Mille-feuille filter paper; Steam sterilization; Upstream bioprocessing; Viral safety.

MeSH terms

  • Animals
  • CHO Cells
  • Cellulose / chemistry*
  • Cricetinae
  • Cricetulus
  • Culture Media, Conditioned / chemistry*
  • Filtration / methods*
  • Nanocomposites / chemistry*
  • Particle Size
  • Parvovirus / isolation & purification*
  • Reproducibility of Results
  • Viruses / isolation & purification*

Substances

  • Culture Media, Conditioned
  • Cellulose