PROCESS CONTROL PERSPECTIVE FOR PROCESS ANALYTICAL TECHNOLOGY: INTEGRATION OF CHEMICAL ENGINEERING PRACTICE INTO SEMICONDUCTOR AND PHARMACEUTICAL INDUSTRIES

Abstract

FDA's Process Analytical Technology (PAT) initiative provides an unprecedented opportunity for chemical engineers to play significant roles in the pharmaceutical industry. In this article, the authors provide their perspectives on (1) the need for chemical engineering principles in pharmaceutical development for a thorough process understanding; (2) applications of chemical engineering principles to meet the challenges from the semiconductor and pharmaceutical industries; and (3) the integration of chemical engineering practice into the semiconductor and pharmaceutical industries to achieve process understanding and the desired state of quality-by-design. A real-world case study from the semiconductor industry is presented to demonstrate how a classic chemical engineering concept, mixing homogeneity, can be implemented by inducing forced flow to ensure an excellent copper electrochemical plating process performance and to improve product quality substantially. Further, a case study of brake system design is discussed with the concept of Dr. Taguchi's robust engineering design to illustrate how quality-by-design can be achieved through appropriate experimental design, in conjunction with the discussion on the concept of quality-by-design in pharmaceuticals. Third, a case study of freeze-dried sodium ethacrynate is presented to demonstrate the vital importance of controlling the processing factors to achieve the desired product stability. Finally, the problems of the current pharmaceutical manufacturing mode, the opportunities and engineering challenges during implementation of PAT in the pharmaceutical industry, and the role of chemical engineering in implementation of PAT is discussed in detail.

Keywords:

• Chemical engineering principles
• On-line process control
• Process Analytical Technology (PAT)
• Quality-by-design
• Taguchi robust engineering design

Acknowledgments

The following persons and organizations are appreciated for their permissions to use the table and figures in the original publications: Prof. Tim Anderson at the School of Engineering, University of Florida (part of Table I); McGraw-Hill Education (Figures 10 and 11); Prof. John Collett at the School of Pharmacy and Pharmaceutical Sciences, University of Manchester (UK) (Figures 13 and 14). The early discussion between Huiquan Wu and Dr. Down Downey (currently with Patheon) on pharmaceutical manufacturing is acknowledged. The invaluable suggestions of two unanimous reviewers of our manuscript are greatly appreciated. Dr. Vincent Lee at the Office of Pharmaceutical Science and Dr. Lucinda Buhse as the Acting Director for the Office of Testing and Research, CDER of FDA, are acknowledged for the internal review.

Disclaimer: The views and opinions expressed in this paper are only those of the authors and do not necessarily reflect the views or policies of the FDA.

Notes

Adopted from TABLE 1 in Anderson (1990). Courtesy of Professor Tim Anderson of the University of Florida.

Additional information

Notes on contributors

Ajaz S. Hussain

Current address: Global Biopharmaceutical Development, Sandoz, Princeton, New Jersey.