An empirical single‐breakthrough curve workflow for rapid early‐phase development of continuous capture chromatography for monoclonal antibodies and mAb ‐derived proteins

Abstract

Continuous chromatography for Protein A capture of monoclonal antibodies (mAbs) and related biotherapeutics is gaining popularity for higher throughput and reduced costs but introduces challenges for development and modeling. We present a streamlined, single‐breakthrough‐curve approach that predicts maximum and operating binding capacities (MBC and OBC, respectively) for continuous Protein A chromatography of monoclonal antibodies and derivatives. Our empirically‐calibrated model—intended for early‐stage, material‐limited process development—enables accurate OBC prediction (root mean squared error [RMSE]≤ 5% for four distinct proteins) using less than 1 g of protein. This approach reduces the experimental timeline by ~2 weeks and is best suited for rapid screening and initial process optimization, not full design‐space determination. Results confirm the model's accuracy across molecules, with clear practical advantages for accelerating preclinical pipeline advancement.