ERNIE HILLIER
Scientific Consultant Optimal Industrial Technologies, USA

Abstract

As we look back at 2004 when the U.S. Food and Drug Administration (FDA) first released its Guidance for Industry PAT – Framework for Innovative Pharmaceutical Development and Quality Assurance, it is clear to see how much Process Analytical Technology (PAT) and its applications have progressed over the last 19 years.
In particular, there are four elements that this article considers: sampling, chemistry, sensors, and software programs. The latter are an integral part of the other elements and include specialized software platforms that have been developed to optimize PAT applications.
The article explores the development of these core aspects to support Quality by Design (QbD), PAT, and continuous manufacturing as well as their impact on pharmaceutical 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 ...