Deterministic mathematical modeling, sensitivity analysis, and dynamic optimization of cross-flow ultrafiltration systems for concentration of monoclonal antibody solutions

Abstract

This manuscript proposes a general new framework for mathematical modeling, extended sensitivity analysis and dynamic optimization of tangential flow filtration (TFF) systems for concentration of monoclonal antibody (mAb) products and, potentially, other biologics. This framework is comprised of four major components: (I) a new first-principles-inspired TFF model; (II) dedicated parameter estimation strategies for automated model training; (III) new extended sensitivity analysis techniques for enhancing TFF phenomenological understanding and providing general guidance on TFF process development; and (IV) novel mono-objective and multi-objective dynamic optimization strategies for optimal TFF design and operation. The application of this framework to Bovine immunoglobulin γ (IgG) – a mAb analog in terms of physicochemical properties – shows the potential benefits it may offer in terms of overall TFF performance and rapid TFF development for new mAb candidates, compared to the current state of the art.