RTD modeling of a continuous dry granulation process for process control and materials diversion

Area of Science:

• Chemical Engineering
• Pharmaceutical Manufacturing
• Process Systems Engineering

Background:

• Continuous manufacturing processes require robust monitoring to predict and mitigate disturbance propagation.
• Residence Time Distribution (RTD) is a key parameter for understanding material flow and variability in unit operations.

Purpose of the Study:

• To develop and apply RTD models for a dry granulation process in continuous manufacturing.
• To assess the impact of feeding events on disturbance propagation and waste generation.
• To provide a foundation for a control concept in pharmaceutical manufacturing.

Main Methods:

• Impulse-response measurements using color tracers to characterize feeders.
• Development of RTD models for the blender and roller compactor units.
• Simulation of four feeding event scenarios to analyze disturbance propagation.
• Definition of out-of-specification material based on active pharmaceutical ingredient (API) concentration.

Main Results:

• RTD models were successfully developed for key unit operations in dry granulation.
• Simulations quantified waste material under various process upset scenarios.
• The study demonstrated the capability of RTD models for material tracking and contaminant spread analysis.
• Effective identification of waste material at diversion points was achieved.

Conclusions:

• RTD modeling is a valuable tool for pharmaceutical continuous manufacturing process development and design.
• RTD models facilitate effective process monitoring and material tracking.
• The developed approach aids in minimizing waste and ensuring product quality by predicting disturbance propagation.