Chapter 9 - Applications of MVDA and PAT for Drug Product Development and Manufacturing

Abstract

This chapter aims to provide readers with an overview of recent applications of process analytical technology (PAT) and multivariate data analysis (MVDA) in pharmaceutical product development and manufacturing. In-line and at-line PAT tools utilizing spectroscopic techniques, such as near-infrared (NIR) and Raman spectroscopies are discussed. Critical aspects of spectroscopic method design and development, method risk assessment, and validation are described. Calibration design is discussed in detail, including strategies for developing robust partial least squared (PLS) models for active pharmaceutical ingredient prediction in blends and tablets. The chapter highlights two particular applications of PAT and MVDA for two unit operations: blending and tablet compression. An in-line NIR PLS method was implemented to assess blending end-point and homogeneity to support formulation development and scale-up. A second example shows the development and validation of a high-impact at-line NIR method for tablet potency and content uniformity. Implementation and data derived during routine operation are presented to demonstrate the value proposition of applying these tools in commercial manufacturing facilities.