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.

Accelerating Biomanufacturing by Modeling of Continuous Bioprocessing—Piloting Case Study of Monoclonal Antibody Manufacturing

“…Further emphasis to simplify operation, improve process robustness and reduce handling efforts is; therefore, focused on PAT techniques and process control strategies by advanced process control approaches. This is a logical consequence and straight forward, as those process models are existing and have been experimentally validated [46][47][48]58].…”

“…A continuous filtration/diafiltration method; however, would reduce the problem of handling errors. For this, single-pass tangential flow filtration systems could lead to more consistent results and developments [48].…”

“…In terms of process development, a favorable process design space can be established by introducing risk assessments for each unit operation, supported by process modeling and design of experiments (DoE) [1,38,[45][46][47][48]. The development of control strategies for an advanced process control based on the process analytical technology (PAT) initiative is essential for a robust automatization of each unit operation and; therefore, favorable for a global process optimum.…”

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

“…Further, yield and purity must be included as a function of ionic strength, pH value, PEG content, and dissolution ratio. Thus, a development and validation concept was presented, which has already been successfully implemented for model building of valid physico-chemical models for other unit operations [49,55,56,66,72]. Due to the fact that the model is based on physical principals and laws, less experimental effort for parameter determination is necessary to transfer the model to novel material systems.…”

“…Additionally, a mechanistic model approach for the precipitation curve was presented by Großhans et al [43]. Previous work has already presented a general model development and validation concept, which can be used to construct physico-chemical models of unit operations [66][67][68][69][70][71][72]. The described process is broken down into the individual building blocks and described with physical principles and laws.…”