Intramodule pressure profiles and protein accumulation during tangential flow filtration

Area of Science:

• Biotechnology
• Chemical Engineering
• Membrane Science

Background:

• Tangential flow filtration (TFF) using 30 kDa ultrafiltration membranes is standard for concentrating monoclonal antibodies (mAbs).
• High protein concentrations during TFF lead to a significant decline in filtration rate (flux), hindering biopharmaceutical manufacturing.
• Monoclonal antibodies (mAbs), often IgG type proteins (140-160 kDa), require high concentrations (≥200 mg/mL) for formulation.

Purpose of the Study:

• To directly measure local transmembrane pressure drops during TFF of high concentration proteins.
• To visualize protein accumulation on membrane surfaces using confocal imaging.
• To understand the mechanisms limiting ultrafiltration rates in mAb purification processes.

Main Methods:

• Utilized a modified membrane system for direct measurement of local transmembrane pressure drops.
• Employed off-line confocal laser scanning microscopy to image protein accumulation.
• Conducted experiments using 150 kDa bovine IgG at concentrations exceeding 200 mg/mL.

Main Results:

• Measured a constant transmembrane pressure drop of approximately 1.2 psi/cm along the membrane length.
• Observed a uniformly deposited protein layer, 50 μm thick, on the membrane surface at high protein concentrations.
• Confirmed that axial pressure decreased by 58 psi across the membrane cassette.

Conclusions:

• Protein deposition is a primary factor limiting ultrafiltration rates in TFF of concentrated mAbs.
• Localized measurements provide critical insights into membrane performance limitations.
• Findings suggest potential targets for improving TFF membrane performance in biopharmaceutical manufacturing.