Digital Twin Based Design and Experimental Validation of a Continuous Peptide Polishing Step

Abstract

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.

Multivariate Parameter Determination of Multi-Component Isotherms for Chromatography Digital Twins

“…The chromatography model used throughout this work, namely the general rate model, as well as the general modelling approach, is described in detail in Zobel-Roos et al [24]. The model was used and parametrized in Zobel-Roos et al [25].…”

“…All necessary parameters for fluid dynamic (D ax , ε s and ε p,i ), mass transfer (k f ,i ) and adsorption equilibrium were measured in a previous work [25]. The Langmuir isotherm was measured for the modifier, a short-chain aliphatic alcohol.…”

“…In previous work [25], the isotherm dependency on the modifier concentration was implemented with 4 factors for each component, a 1,i , a 2,1 , b 1,i and b 2,i . These factors influence the Langmuir parameters Henry coefficient H i and maximum loading capacity q max,I depending on the modifier concentration:…”