Hybrid Modeling for On-Line Fermentation Optimization and Scale-Up: A Review

Modeling is a crucial tool in the biomanufacturing industry, namely in fermentation processes. This work discusses both mechanistic and data-driven models, each with unique benefits and application potential. It discusses semi-parametric hybrid modeling, a growing field that combines these two types of models for more accurate and easy result extrapolation. The characteristics and structure of such hybrid models will be examined. Moreover, its versatility will be highlighted, showing its usefulness in various stages of process development, including real-time monitoring and optimization. Scale-up remains one of the most relevant topics in fermentation processes, as it is important to have reproducible critical quality attributes, such as titer and yield, on larger scales. Furthermore, the process still relies on empirical correlations and iterative optimization. For these reasons, it is important to improve scale-up predictions, through e.g., the use of digital tools. Perspectives will be presented on the potential that hybrid modeling has by predicting performance across different process scales. This could provide more efficient and reliable biomanufacturing processes that require less resource consumption through experimentation.