Global sensitivity, feasibility, and flexibility analysis of continuous pharmaceutical manufacturing processes

Simulation models for continuous pharmaceutical manufacturing processes have been developed and adapted as a powerful computer-aided tool to facilitate the process development. Accordingly, process analysis methods have also been implemented to obtain a more extensive process knowledge. In this book chapter, we gave an overview of the recent advances on two aspects of process analysis methods based on simulations: (1) global sensitivity analysis, and (2) feasibility and flexibility analysis methods. Global sensitivity analysis extracts the process knowledge in a “forward” manner: within certain ranges of the inputs, how these inputs can contribute to the variability in the output. On the other hand, feasibility and flexibility analysis evaluates the process in a “backward” manner: given specified ranges (i.e., process constraints) on the output, what is the design space of the inputs within which a process can always remain feasible. These two process analysis strategies together can strengthen the process understanding in developing a pharmaceutical process.