Defining the optimal operating conditions and configuration of a single-pass tangential flow filtration (SPTFF) system via CFD modelling

•A three-dimensional CFD model of a UF membrane cassette is developed.•The spatial distribution of pressures, fluxes, and concentrations is simulated.•A systematic comparison of multi-stage filter designs is performed.•Better filtration performance is achieved for mixed multi-stage filters.•Model-based evaluation helps select operating conditions and filter designs. Single-pass tangential flow filtration (SPTFF) is used in biopharmaceutical manufacturing to reduce volumes and concentrate products. The staging of multiple membrane cassettes makes it possible to achieve high concentration factors in one pass, but at the same time increases the system’s complexity. This work aims to provide comprehensive understanding of SPTFF at both membrane cassette level and at equipment level by evaluating the impact of different operating conditions and different filter designs on the filtration performance. An experimentally validated computational fluid dynamics (CFD) model of a commercial ultrafiltration membrane cassette was developed and first used to study the impact of operating conditions on the volumetric concentration factor (VCF). The results show that both the feed flux and the retentate pressure have a substantial impact on the VCF. At low pressures (0.0–0.4 bar) a VCF of 1.2–2.9 is achieved for feed fluxes of 137–394 Lm−2h−1, while at high pressures (0.6–1.0 bar) a VCF of up to 10.5 is achieved. The model was subsequently applied to study concentration-dependent effects and the spatial distribution of relevant physical properties. The simulation results help select suitable operating conditions and evaluate the cassette design with respect to product accumulation. Finally, a systematic comparison of different multi-stage filter designs was performed. The results show clear advantages of mixed filter designs over serial filter designs in terms of TMP and VCF, and serve as a guidance to select a suitable filter design for given concentration targets and pressure limits. An advantage of the presented modelling approach is its applicability to the evaluation of other membrane systems with different geometric dimensions and different membrane properties.