The Japan Agency for Medical Research and Development (AMED)'s initiative for regulatory harmonization and evaluation has conducted collaborative research projects spanning industry, government, and academia. This initiative focuses on “Research for the quality and process control for pharmaceutical continuous manufacturing.” A notable project under this initiative has investigated “A feasibility research for Multivariate Statistical Process Control (MSPC) in continuous manufacturing of solid dosage formulation” since 2021. To ensure “State of Control” in continuous manufacturing, one approach is to continuously monitor and control Critical Quality Attributes (CQA) and/or Critical Material Attributes (CMA) using Process Analytical Technology (PAT) such as near-infrared spectroscopy. However, challenges, including low API content and technical hurdles in high-frequency real-time monitoring, sometimes make PAT-based control impractical. This study has examined the feasibility of MSPC, which enables simultaneous monitoring of multiple factors of the manufacturing process, as an alternative tool for anomaly detection within the control strategy for continuous manufacturing. The investigation has identified both technical and regulatory challenges. To clarify the way for strategic integration of MSPC into control strategy and description in CTD, the research team developed “CTD mock-up document of the case study for the implementation of the Multivariate Statistical Process Control (MSPC) in the continuous manufacturing process for oral solid dosage form.” The control strategy presented in this mock-up document is just one example, and it should be noted that other approaches are also feasible.
