Integrated operation of continuous crystallization and filtration is critical in pharmaceutical continuous manufacturing of drug substances. A proprietary rotary plate filter was implemented in an end-to-end integrated continuous manufacturing pilot plant. In this work, an initial design-of-experiment (DoE) was conducted to analyze the sensitivity of filtration performance to process parameters. The QbD approach also includes the development of a dynamic mathematical model for the rotary plate filter to simulate the effects of cake wash flowrate and its distribution on the impurity levels in the wet cake. The increased product and process understanding contributed to the determination of the design space for the integrated operation, e.g., a minimum ratio of cake wash flowrate to the slurry. This minimum ratio was used in the feedback and feedforward control strategy implemented on the DeltaV control system. Process analytical technology tools were also developed to predict the impurity level in the final dried product.
Learning Objectives:
To understand the importance of mathematical modeling in process understanding
To learn the application of design space in a real pilot plant practice
To learn the pathway from process development to engineering and manufacturing
