A model-based approach towards accelerated process development: A case study on chromatography

TL;DR

This paper introduces a model-based methodology for accelerating process development in chromatography, focusing on identifying and analyzing process design space to improve efficiency and flexibility in biopharmaceutical manufacturing.

Contribution

It presents a structured approach combining modeling, design space identification, and analysis, applied to Protein A chromatography for antibody therapeutics.

Findings

Effective identification of acceptable operating spaces

Quantification of process flexibility

Application to biopharmaceutical chromatography

Abstract

Process development is typically associated with lengthy wet-lab experiments for the identification of good candidate setups and operating conditions. In this paper, we present the key features of a model-based approach for the identification and assessment of process design space (DSp), integrating the analysis of process performance and flexibility. The presented approach comprises three main steps: (1) model development & problem formulation, (2) DSp identification, and (3) DSp analysis. We demonstrate how such an approach can be used for the identification of acceptable operating spaces that enable the assessment of different operating points and quantification of process flexibility. The above steps are demonstrated on Protein A chromatographic purification of antibody-based therapeutics used in biopharmaceutical manufacturing.