Purification of an Fc-fusion biologic: clearance of multiple product related impurities by hydrophobic interaction chromatography

J Chromatogr A. 2008 Jan 11;1177(2):265-71. doi: 10.1016/j.chroma.2007.07.049. Epub 2007 Jul 28.

Abstract

An hydrophobic interaction chromatography step was developed for the large-scale production of an Fc-fusion biologic. Two abundant product-related impurities were separated from the active monomer using a Butyl resin and a simple step-wash and step-elution strategy. Capacity and resolution of the HIC step was optimal when sodium sulfate was employed as the lyotropic salt and pore size of the Butyl resin was 750A. Factorial analysis identified critical parameters for the Butyl chromatography and an operating window capable of delivering high product quality and yield over a broad column loading range.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • CHO Cells / metabolism
  • Chromatography, Affinity / methods
  • Chromatography, Liquid / instrumentation
  • Chromatography, Liquid / methods*
  • Cricetinae
  • Cricetulus
  • Culture Media, Conditioned / chemistry
  • Hydrophobic and Hydrophilic Interactions*
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin Fc Fragments / isolation & purification*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sepharose / analogs & derivatives
  • Sepharose / chemistry
  • Staphylococcal Protein A / chemistry

Substances

  • Culture Media, Conditioned
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Staphylococcal Protein A
  • phenyl-sepharose
  • butylagarose
  • Sepharose