Artificial Neural Network for Fast and Versatile Model Parameter Adjustment Utilizing PAT Signals of Chromatography Processes for Process Control under Production Conditions

Abstract

Preparative chromatography is a well-established operation in chemical and biotechnology manufacturing. Chromatography achieves high separation performances, but often has to deal with the yield versus purity trade-off as the optimization criterium regarding through-put. The initial trade-off is often disturbed by the well-known phenomenon of chromatogram shifts over process lifetime, and has to be corrected by operators via adjustment of peak fraction cutting. Nevertheless, with regard to autonomous operation and batch to continuous processing modes, an advanced process control strategy is needed to identify and correct shifts from the optimal operation point automatically. Previous studies have already presented solutions for batch-to-batch variance and process control options with the aid of rigorous physico-chemical process modeling. These models can be implemented as distinct digital twins as well as statistical process operation data analyzers. In order to utilize such models for advanced process control (APC), the model parameters have to be updated with the aid of inline Process Analytical Technology (PAT) data to describe the actual operational status. This updating process also includes any operational change phenomena that occur, and its relation to their physico-chemical root cause. Typical phenomena are fluid dynamic changes due to packing breakage, channelling or compression as well as mass transfer and phase equilibrium-related separation performance decrease due to adsorbent aging or feed and buffer composition changes. In order to track these changes, an Artificial Neural Network (ANN) is trained in this work. The ANN training is in this first step, based on the simulation results of a distinct and previously experimentally validated process model. The model is implemented in the open source tool CasADi for Python. This allows the implementation of interfaces to process control systems, among others, with relatively low effort. Therefore, PAT signals can easily be incorporated for sufficient adjustment of the process model for appropriate process control. Further steps would be the implementation of optimization routines based on PAT and ANN predictions to derive optimal operation points with the model.