| dc.description.abstract | The effects of the paradigm shift from batch to continuous manufacturing on pharmaceutical industry, in terms of process safety and product quality, e.g., danger of dust explosions and risk of off-spec products, are of major concerns in the recent research progress in control system design. Specifically, a fault-tolerant control of critical process parameters (CPPs) and critical quality attributes (CQAs) is of paramount importance for the continuous operation with built-in safety and quality. In this study, a systematic framework for fault-tolerant control design, analysis, and evaluation for continuous pharmaceutical solid-dosage manufacturing is proposed, consisting of system identification, control design and analysis (controllability, stability, resilience, etc.), hierarchical three-layer control structures (model predictive control, state estimation, data reconciliation, etc.), risk mapping, assessment and planning (Risk MAP) strategies, and control performance evaluation. The key idea of the proposed framework is to identify the potential risks in the control design, material variance, and process uncertainties, under which the control strategies are evaluated. The framework is applied to a continuous direct compaction process, specifically the feeding-blending system wherein the major source of variance in the process operation and product quality arises. It can be demonstrated that the process operation failures and product quality variances in the feeding-blending system can be mitigated and managed through the proposed systematic fault-tolerant control system design and risk analysis framework. | en |
