The role of intermolecular interactions on monoclonal antibody filtration through virus removal membranes

Matthew Billups1, Mirko Minervini1, Melissa Holstein2

  • 1Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.

Biotechnology Journal
|August 29, 2023
PubMed

Insights

Monoclonal antibody (mAb) filtration flux is limited by reversible self-association, not just size. Understanding mAb hydrophobicity and interactions aids virus removal process design.

Area of Science:

  • Biopharmaceutical manufacturing
  • Filtration science
  • Protein aggregation

Background:

  • Virus removal filtration is essential for monoclonal antibody (mAb) product safety.
  • Low filtrate flux during mAb filtration presents challenges, with unclear underlying mechanisms.
  • Antibody properties influencing filtration behavior require further investigation.

Purpose of the Study:

  • To investigate the mechanisms behind flux decline during virus removal filtration of mAbs.
  • To identify antibody characteristics that correlate with filtration performance.
  • To provide insights for optimizing mAb virus filtration processes.

Main Methods:

  • Filtration experiments using three distinct mAbs and three commercial virus filters.
  • Measurement of filtrate flux and flux decline under varying conditions.
  • Characterization of mAb properties including hydrodynamic diameter (via dynamic light scattering) and hydrophobicity (via hydrophobic interaction chromatography).

Main Results:

  • Flux decline during mAb filtration was predominantly reversible.
  • Filtrate flux strongly correlated with the hydrodynamic diameter of the mAbs.
  • mAbs exhibiting the lowest flux showed increased attractive intermolecular interactions and hydrophobicity.

Conclusions:

  • Reversible self-association of mAbs is a primary driver of filtration flux behavior.
  • mAb hydrodynamic diameter and intermolecular interactions significantly impact virus removal filtration efficiency.
  • These findings support improved design of virus filtration strategies and early identification of problematic mAbs.

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