A model-based framework for integrated process design and flexibility analysis

Process development is typically associated with lengthy wet-lab experiments for the identification of good candidate set ups and operating conditions. In this paper, we present the key features of a model-based framework for the identification and assessment of process design spaces, integrating the analysis of process performance and flexibility. The framework comprises three main steps: (1) model development & problem formulation, (2) design space identification and (3) design space analysis. For the first time, a mathematical representation of the design space boundary is obtained and exploited for the investigation of nominal operating points. We demonstrate how the proposed framework can be used for the identification of acceptable operating spaces, quantification of operational flexibility and assessment of different operating points. The proposed framework is demonstrated on Protein A chromatographic separation of antibody-based therapeutics from cell-derived impurities, used in biopharmaceutical manufacturing.