Model-based risk assessment on dynamic control of twin-column continuous capture under feedstock variations

Dynamic control is essential to guarantee the stable performance of continuous chromatography. AutoMAb dynamic control strategy has been developed to ensure a consistent protein load in twin-column CaptureSMB continuous capture by integrating the UV signal of breakthrough. In this study, the process risk of CaptureSMB continuous capture under AutoMAb control towards the feedstock variations was assessed by a mechanistic model developed by us. The effects of target protein and impurities under the variation range of ±10 mAU·min−1on load amount, protein loss, process productivity, and resin capacity utilization were investigated. The results showed that the CaptureSMB process could be successfully controlled by AutoMAb towards increased or slightly decreased concentration of feedstock. However, the load process would be out of control with drastically decreased target protein or impurities, and the decreased impurities would lead to protein loss. It was found that AutoMAb control would cause 44.7% non-operational areas and 18.3% protein loss areas in the variation range of ±10 mAU·min−1. To improve the stability of the CaptureSMB process, a modified AutoMAb control that would stop the load procedure when the absolute value of the integral area reached the preset value, was proposed to reduce the risk of protein loss and the non-operational area.