Computer simulations are now indispensable in many industries, enabling boosts in productivity and faster innovation cycles. In biopharmaceutical processes, mechanistic modeling has drawn increasing attention over the past decade, but adoption has lagged — in part because of a lack of simple and straightforward modeling workflows. To help develop a unified and simple modeling workflow, we present recent work in fundamental adsorption modeling, system characterization, and accompanying software-implemented workflows.<br/>Our proposed description of protein adsorption and desorption is based, whenever possible, on non-stoichiometric modeling approaches and on modeling of the surface coverage as a key factor for adsorption. This mechanistic approach means that all model parameters are based on known physical properties of the materials and molecules, which reduces the number of calibration experiments required.<br/>These methods go hand in hand with the use of pre-calibrated equipment such as chromatography systems, columns, or resin lots. The fact that the effects of system and material properties on the chromatogram can be distinguished from the interaction of retained sample components means that the model parameters are more accurate, and the time needed for finalizing the model is shorter.<br/>Our aim for the software is to provide reliable, reusable guidance. Systems, columns, resins, buffers, and molecules or feed materials, as well as the chromatographic method, are all considered as determining factors in the outcome of a chromatographic experiment. The software supports process developers by providing an overview of the status of the modeling project, performing “sanity checks” of imported experimental results, and offering data analytical methods to quickly finalize a model based on experimental data. The process understanding improves as development progresses, making it possible to use simulations to predict the results of experiments on other pre-calibrated hardware — enabling significant reductions in time and costs.

Software-implemented workflows for model-based downstream process development

ACS Spring 2022

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