A look at PAT technological developments PAT advances lead to greater knowledge for continuous manufacturing

INTRODUCTION
A high-quality drug is one defined as a product free of contamination and that can reliably deliver the therapeutic benefits promised in its label to the consumer (1). To guide pharmaceutical companies in meeting these requirements when manufacturing medicines and other therapies, the FDA encourages risk-based approaches and the adoption of QbD principles in drug product development, manufacturing, and regulation. The emphasis on QbD from the FDA began with the recognition that increased testing does not necessarily improve quality. This must be built into the product (2). QbD is a pioneering concept first developed by the quality specialist Dr. Joseph M. Juran, who believed that quality should be designed into a product, and that most quality issues relate to the way in which a product is conceived in the first place (3).

The FDA views PAT as an enabling technology for QbD, as it offers a mechanism to design, analyze and control pharmaceutical manufacturing as well as its processes. This is achieved throughout the measurement of critical process parameters (CPPs) that affect the product’s critical quality attributes (CQAs). However, the FDA also suggests that this was not a state-of-the-art endeavor for pharmaceutical manufacturing, compared to other, more future-oriented industries. Improving product quality in pharmaceutical manufacturing without PAT and QbD used to require great effort and cost, with product waste as high as 50%. Scaling up issues as well as concerns over the ability to analyze and understand the reasons for manufacturing failure were also common (4).