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Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material.
Journal article

Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material.

  • Allmendinger A Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, 4070, Switzerland.
  • Mueller R Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, 4070, Switzerland.
  • Huwyler J Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, 4056, Switzerland.
  • Mahler HC Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, 4070, Switzerland.
  • Fischer S Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, 4070, Switzerland.
  • 2015-07-08
Published in:
  • Journal of pharmaceutical sciences. - 2015
PES filter
PVDF filter
excipients
highly concentrated monoclonal antibody formulation
polysorbate
protein formulation
proteins
sterilizing-grade filter
surfactant
viscosity
Antibodies, Monoclonal
Biological Products
Chemistry, Pharmaceutical
Excipients
Filtration
Membranes, Artificial
Polymers
Polyvinyls
Porosity
Proteins
Rheology
Sterilization
Sulfones
Viscosity
English Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/246712
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