A Mechanistic Model-Based Digitalisation Framework for Continuous Manufacturing Processes

Due to the improvement of manufacturing technologies and publicised industrial cases realising the potential value of adopting continuous manufacturing in pharmaceutical production, much of the research focus has been realigned to the understanding of integrating batch-wise operations into a single production line. However, there is little regulatory instruction and good model-based principles to follow. From a modelling point of view there is a lack of coherence in approach due to the profound lack of understanding of the process dynamics. Despite a significant adoption of particulate system modelling approaches, it is apparent that very few existing, science-based models from academia are fully explored and implemented for industrial practice. Furthermore, while a generic modelling platform for integrated modelling of an industrial process could be an enabling technology, it can be formidable for an industrial practitioner to apply such digital tools.

This paper aims to develop a systematic framework for approaching digital design of a continuous manufacturing process by transferring state-of-the-art innovations from the modelling world into industrial practice through a mechanistic model-based digitalisation platform. The digitalisation framework is built upon gPROMS using a defined case explored in the DiPP (Diamond Pilot Plant), a continuous powder processing in the University of Sheffield, to demonstrate the usability and expandability of the mechanistic model approach. The DiPP of a Consigma^TM-25 manufacturing line from powder to tablet consists of twin screw granulation, fluid bed dryer, cone mill, vertical blender and tableting compaction. Global System Analysis of the DiPP with sound engineering principles defined in underlying mechanistic models is carried out to enable a comprehensive exploration of the systematic responses and the development of a robust operating space. The systematic modelling framework will enable the pharmaceutical industry to effectively and efficiently design and implement continuous pharmaceutical manufacturing processes, leading to safer and faster design and operating decisions.