(623b) Application of Advanced Process Control Tools in Continuous Processing

Continuous manufacturing is now widely discussed in the pharmaceutical industry. The availability of turn-key lines offered by various suppliers allows the transfer of established and new products to the continuous manufacturing approach. At the moment the focus is mainly on solid oral dosage forms including the common routes via wet and dry granulation or direct compaction. From a processing point-of-view the shift to continuous mode is supported by the fact that most common unit operations are continuous machinery by design, such as feeding, tableting or granulation. One challenge is the integration of all units into a single line, which needs implementation of interfaces, transport units and buffers. The remaining challenge is the establishment of control concepts that enable a fully automated, yet still flexible process, capable of handling start-up and shut down, as well as of out-of-spec events. Tools for in-line monitoring of critical quality attributes and real-time acquisition of process data have been widely demonstrated. Process models, fast enough for design of controllers, have been developed recently. However, most continuous processes filed by pharmaceutical industry still remain on a level 2 control strategy based on in-process controls without control loops.

 

In this work different tools for advanced process control were developed and investigated and their implementation in processes or unit operations will be shown. This includes novel process analytical technologies enabling real-time data acquisition of statistical representative numbers or even each single dosage form, concepts for out of spec material handling based on modelling of residence time distribution or model predictive control. The latter approach was developed for a feeding and blending unit. The rotation speed of the blender is manipulated to control the mass hold-up and the outlet mass flow rate in order to mitigate fluctuations of homogeneity caused by feeder events. Another example deals with the discharge of out-of-spec material, in combination with an operating concept for a tablet press based on different pre-defined set points of the turret speed. Recent developments in the field of PAT will complete the presentation.