Digital twin based design and experimental validation of a continuous peptide polishing step

Optimizing or debottlenecking existing production plants is a challenging task. In this case study, an existing reversed phased chromatography polishing step for peptide purification was optimized with the help of a digital twin. The existing batch chromatography was depicted digitally with the general rate model. Model parameter determination and model validation was done with dedicated experiments. The digital twin was then used to identify optimized process variants, especially continuous chromatography steps. MCSGP was found to achieve high purities and yield but at the cost of productivity due to column synchronization. An alternative Continuous Twin Column chromatography process (CTCC) was established that eliminates unnecessary waiting times. Ensuring the same or higher purity compared to the batch process, the continuous process achieved a yield increase of 31% and productivity increase of 27.6%. Experimental long runs confirmed these results.