Perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes.

Pharmaceutical continuous manufacturing, especially under the context of COVID-19 pandemic, is regarded as an emerging technology that can guarantee the adequate quality assurance and mitigate process risk while guaranteeing the desirable economic performance. Flexibility analysis is one approach to quantitively assess the capability of chemical process to guarantee feasible operation in face of variations on uncertain parameters. The aim of this paper is to provide the perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes. State-of-the-art and progress in the flexibility analysis for chemical processes including concept evolution, mathematical model formulations, solution strategies, and applications are systematically overviewed. Recent achievements on the flexibility/feasibility analysis of the downstream dosage form manufacturing process are also touched upon. Further challenges and developments in the field of flexibility analysis for novel continuous manufacturing processes of active pharmaceutical ingredients along with the integrated continuous manufacturing processes are identified.