Role of Automatic Process Control in Quality by Design

Successful Quality by Design (QbD) requires good comprehension and implementation of robust automatic process control. This chapter discusses the role and application of control in QbD, with a primary emphasis on the crystallization of pharmaceuticals. Some successful industrial applications of automatic process control strategies are reviewed, as well as alternative control strategies that have been proposed for providing various tradeoffs between model fidelity, sensor inaccuracies, and robust performance. These strategies include feedback controllers based on solution concentration measurement via ATR-FTIR spectroscopy as well as measurements of particles in crystallizers based on in-process laser backscattering. The use of models for crystallization kinetics to improve crystallizer designs, increase product quality, and reduce scale-up risk is also discussed. This is followed by simulation and experimental results that demonstrate how a target crystal size distribution can be obtained by combining continuous seeding with controlled crystal growth.