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Arne Staby

and 10 more

The fifth modeling workshop (5MW) was held in June 2023 in Favrholm, Denmark and sponsored by Recovery of Biological Products Conference Series. The goal of the workshop was to assemble modeling practitioners to review and discuss the current state, progress since the last fourth mini modeling workshop (4MMW), gaps and opportunities for development, deployment and maintenance of models in bioprocess applications. Areas of focus were four categories: biophysics and molecular modeling, mechanistic modeling, computational fluid dynamics (CFD) and plant modeling. Highlights of the workshop included significant advancements in biophysical/molecular modeling to novel protein constructs, mechanistic models for filtration and initial forays into modeling of multi-phase systems using CFD for a bioreactor and mapped strategically to cell line selection/facility fit. A significant impediment to more fully quantitative and calibrated models for biophysics is the lack of large, anonymized data sets. A potential solution would be the use of specific descriptors (ex. patch sizes and types mapped to a homology model) in a database that would allow for detailed analyses without sharing proprietary information. Another gap identified was the lack of a consistent framework for use of models that are included or support a regulatory filing beyond the high-level guidance in ICHQ8-Q11. One perspective is that modeling can be viewed as a component or precursor of machine learning (ML) and Artificial Intelligence (AI). Recent requests for feedback from health authorities on use of ML and AI may provide an opportunity for more clarity regarding expectations for use and deployment. Two specific additional outcomes of the workshop were alignment on a key definition for “mechanistic modeling” and the acknowledgement/realization that modeling can have a significant impact on improving sustainability of bioprocessing through elimination of experiments both during development and manufacturing. Feedback from the participants was that there was progression in all of the fields of modeling within scope of the conference. Some areas (e.g. biophysics and molecular modeling) have opportunities for significant research investment to realize full impact. However, the need for ongoing research and development for all model types does not preclude the application to support process development, manufacturing and use in regulatory filings. Analogous to ML and AI, given the current state of the four modeling types, a prospective investment in educating inter-disciplinary subject matter experts (SMEs) (e.g. data science, chromatography) is essential to advancing and maintaining the modeling community.