During the last years, in silico process optimization and characterization have become a key technology in early and late stage development and the focus is turning more and more to mechanistic models for chromatography processes. Nevertheless, the complex and time-consuming model calibration inhibits the implementation of mechanistic modeling workflows in current development strategies. Quantitative structure-property relationship (QSPR) models have the potential to mitigate the risks related to parameter estimation by inverse curve fitting to experimental data. Here, we will present our multi-dimensional modeling pipeline, leading to the digital twin of a cation exchange (CEX) chromatography process from the primary sequence of the monoclonal antibody (mAb). Starting with the primary sequence, homology models were built for 21 IgG1, IgG4, and complex antibody-formats. Protein surface analysis resulted in &gt;1000 structural descriptors per molecule, including shape-, patch-, and region-specific descriptors. Multiple high-throughput and lab-scale experiments were conducted for all mAbs. The comprehensive dataset enabled the calibration of a transport-dispersive model and the steric-mass action isotherm. QSPR models correlated structural properties to mechanistic chromatography model parameters. The established models were then used for the prediction of isotherm parameters and entire chromatograms of mAbs not involved in the training data set. Further, the correlations found between certain descriptors and isotherm parameters increased the understanding of the binding-mechanism in CEX chromatography. Feature selection revealed which subdomains of the mAb contribute to the adsorption process. Our work demonstrates a bottom-up approach for building mechanistic chromatography models for therapeutic antibodies.

From sequence to process: In silico DSP development based on quantitative structure-property relationships

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.