Effect of the Tubing Material Used in Peristaltic Pumping in Tangential Flow Filtration Processes of Biopharmaceutics on Particle Formation and Flux

Abstract

Tangential flow filtration (TFF) is a central step in manufacturing of biopharmaceutics. Membrane clogging leads to decreased permeate flux, longer process time and potentially complete failure of the process. The effect of peristaltic pumping with tubings made of three different materials on protein particle formation during TFF was monitored via micro flow imaging, turbidity and photo documentation. At low protein concentrations, pumping with a membrane pump resulted in a stable flux with low protein particle concentration. Using a peristaltic pump led to markedly higher protein particle formation dependent on tubing type. With increasing protein particle formation propensity of the tubing, the permeate flux rate became lower and the process took longer. The protein particles formed in the pump were captured in the cassette and accumulated on the membrane leading to blocking. Using tubing with a hydrophilic copolymer modification counteracted membrane clogging and flux decrease by reducing protein particle formation. In ultrafiltration mode the permeate flux decrease was governed by the viscosity increase rather than by the protein aggregation; but using modified tubing is still beneficial due to a lower particle burden of the product. In summary, using tubing material for peristaltic pumping in TFF processes which leads a less protein particle formation, especially tubing material with hydrophilic modification, is highly beneficial for membrane flux and particle burden of the product.

Keywords: Diafiltration; Interface; Membrane fouling; Protein adsorption; Protein aggregation; Protein particles; Pumping; Tangential flow filtration; Tubing; Ultrafiltration.