PAT implementation for advanced process control in solid dosage manufacturing - A practical guide.

The implementation of continuous pharmaceutical manufacturing requires advanced control strategies rather than traditional end product testing or an operation within a small range of controlled parameters. A high level of automation based on process models and hierarchical control concepts is desired. The relevant tools that have been developed and successfully tested in academic and industrial environments in recent years are now ready for utilization on the commercial scale. To date, the focus in Process Analytical Technology (PAT) has mainly been on achieving process understanding and quality control with the ultimate goal of real-time release testing (RTRT). This work describes the workflow for the development of an in-line monitoring strategy to support PAT-based real-time control actions and its integration into solid dosage manufacturing. All stages are discussed in this paper, from process analysis and definition of the monitoring task to technology assessment and selection, its process integration and the development of data acquisition.