5 - Quality by Design and the Importance of PAT in QbD

Abstract

This chapter clearly describes the modern philosophy for pharmaceutical drug product development and manufacturing beginning with the identification of core regulatory documents that define cGMPs for the twenty-first century, process analytical technology (PAT) and quality by design (QbD). The critical role of PAT in a successful QbD environment is documented, providing an overview of important multivariate mathematical techniques and modern analytical technologies for process monitoring that facilitate process understanding and ultimately process control. The concept of design space is considered, describing the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs). A discussion of control models provides a perspective on how such models function to ensure that CPPs and other process variables are maintained in a state of control within the working range that corresponds to the desired set of CQAs. Finally, the chapter provides considerations regarding how the pharmaceutical industry may achieve return-on-investment (ROI) while achieving advanced process control and real-time release (RTR) by capitalizing on manufacturing efficiencies.