(400b) Development of a Continuous Production Line for Solid Dosage Forms Via Dry Granulation

During the last years, academia, industry and regulators have increasingly demonstrated and addressed the advantages of continuous manufacturing. More and more, this is leading to a shift in paradigm for pharmaceutical manufacturing, towards advanced continuous processing based on real-time quality assurance and away from batch processing. As a result, turn-key solutions of continuous manufacturing systems are provided by various equipment suppliers. The available equipment is ranging from raw material feeding, to blending, granulation as well as tableting and coating. Even though several systems have been studied and discussed in the literature there are still some remaining questions open. Now with the first continuous plants being implemented for continuous production of solid oral dosage forms, interest is shifting towards system robustness, integration of unit operations, in-line measurement and process control. Such �advanced� turn-key solutions are required to fulfill a wide variety of demands, when processing different raw materials with varying properties.

In this talk we will highlight a control strategy that was validated by system tests of the integrated plant. The objective of the control strategy was to consider all possible process settings and raw material properties, thereby guaranteeing constant product quality. The described manufacturing line is dedicated to the continuous and automated production of solid-oral-dosage forms via a dry granulation route. In order to enable continuous process control and real-time-release, several PAT instruments were implemented. Proper control actions are based on actual process information from the in-line monitoring systems. Process parameters were screened for utilization as soft sensors, to enable even better process understanding and control. Out-of-spec material is detected and removed from the process at different stages. The control strategy enables continuous production even if out-of-spec material has to be removed. By setting the proper process parameters the mass flow can be modified, while still producing in-spec products. A concept will be presented, which allows variation of the mass flow of single unit operations to keep the entire production line within specified limits.