Opportunities and challenges for model utilization in the biopharmaceutical industry: current versus future state

Processes and manufacturing in the biopharmaceutical industry are mainly based on experimental data and statistical approaches, however, regulatory expectations of increasing understanding and insights into methods behind medicinal products have paved the way for employment of more mechanistic and first principle modeling tools and concepts. Current, advanced modeling tools can basically be divided into four groups: biophysical modeling, mechanistic modeling, computational fluid dynamics, and plant modeling. Although very useful in themselves, the first three modeling concepts may also be used to establish better plant models, where digital twins of manufacturing plants are pursued broadly in the industry. This review presents the current development stage, opportunities, and challenges of the four modeling tools, and activities needed to reach future state of modeling or 'in silico CMC' (Chemistry, Manufacturing and Controls), a state where modeling, based either on first principles or hybrid approaches combining both empirical and mechanistic approaches, can be routinely employed in lieu of solely empirical or experimental approaches. It builds largely on presentations and discussions at the recent 4th Mini Modeling Workshop from May 25, 2021.