Digital Twin for Centrifugal Extractors Exemplified for pDNA Clarification Process after Lysis

Plasmid DNA is an important substance for the pharmaceutical industry. A major challenge in its production is the clarification of the lysate after harvesting. In this work, a novel process for this is demonstrated in an annular centrifugal contactor (ACC) with an aqueous two-phase extraction. The ACC can increase the space-time yield of the clarification step by at least a factor of 2 compared to the horizontal continuous separator. A model for describing and predicting the conditions in the rotor is created for the ACC and calibrated with an accuracy of R2 = 0.94, which is sufficient for prediction in process design and operation. A digital twin (DT), which determines the purity of the phases at the outlet of the ACC, is calibrated with an accuracy of 95% for the light phase and 97% for the heavy phase, which defines in manufacturing operation the safety margin for both phases below the theoretical optimal operation point. By using the DT, an additional increase in productivity of 25% can be achieved in the ACC with model-predictive control.