(605b) Development of a Control Strategy for Continuous Manufacturing of Solid Dosage Forms

During the last years the advantages of continuous manufacturing have been increasingly demonstrated (and publicized) by academia, industry and regulators. Slowly, this is leading to a paradigm shift in pharmaceutical manufacturing, away from batch towards advanced continuous processing based on real-time quality assurance. As a result, different equipment suppliers are providing turn-key solutions for continuous manufacturing systems, ranging from powder feeding, to blending, granulation, tableting and/or coating. While several systems have been reported and studied in the literature, open questions still remain, especially with respect to system robustness, online measurement and process control.

In this work a control strategy for a novel industrial-scale production line for oral-dosage forms was developed. The objective of the control strategy is to consider all possible variability in raw material properties, process-settings, equipment design and environmental conditions. Constant product quality is maintained by proper equipment design and integration of unit operations, utilization of process understanding, a risk-based PAT strategy and appropriate control actions.

The presentation will highlight a successful implementation of an in-line monitoring system for critical quality attributes. In order to enable Real Time Release, PAT tools were selected with appropriate data acquisition systems to support control actions. This includes chemometric models for start-up and steady state. Out-of-spec materials are detected and eliminated at different stages of the process. All sensors are embedded in a PAT data management system to treat and register process data. Additionally, a concept for 100 % quality control of final tablets will be presented.