Model-based design and process optimization of continuous single pass tangential flow filtration focusing on continuous bioprocessing

Abstract

In this study the Single-Pass-Tangential-Flow-Filtration (SPTFF) concept for continuous ultrafiltration in bioprocessing is investigated. Based on a previously validated physico-chemical model for a single ultrafiltration cassette, the transfer to a multistage SPTFF is predicted and validated experimentally by concentration steps for bovine serum albumin (BSA) and the monoclonal antibody immunoglobulin G (IgG) are compared. The model applied for the ultrafiltration membrane contains the Stagnant Film Model (SFM) for concentration polarization, as well as the Osmotic Pressure Model (OPM) and the Boundary Layer Model (BLM) for the mass transfer through the membrane. In addition, pressure drop correlations as a function of the Reynolds number are included to describe the development of the transmembrane pressure over the length of the module. The outcome of this study shows the potential to improve this multi-parameter dependent unit operation by a model-based optimization allowing significant reduction of experimental efforts and applying the Quality by Design (QbD) approach consistently. Consequently, a versatile tool for conceptual process design is presented and further application is discussed.