On-line Process Control and Process Analytical Technology: Integration of Chemical Engineering Practice into Semiconductor and Pharmaceutical Industries
چکیده
FDA's PAT Initiative provides an unprecedented opportunity for chemical engineers to play significant roles in the pharmaceutical industry. On-line process control, as an enabling process understanding tool and advanced quality control strategy, has been widely adopted in other industrial sectors. In the present manuscript, the authors will provide their perspectives on the need of chemical engineering principles in pharmaceutical development for a thorough process understanding. From the on-line process control perspective, we will discuss the following topics: (1) how can chemical engineering help meet the challenges from the semiconductor and pharmaceutical industries? (2) how can the chemical engineering practice be integrated 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 will be 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 (Cu ECP, a key process in Cu technology) performance. The concept of Dr.Taguchi's robust engineering design will be briefly discussed with a case study of brake system design. This case study will illustrate how the quality-by-design can be achieved through appropriate experimental design. The third aspect of this manuscript deals with the comparison between a modern chemical plant and a pharmaceutical plant. From the engineering and quality perspectives, the disadvantages of the current pharmaceutical manufacturing mode, the advantages and challenges of Process Analytical Technology (PAT), and the roles of chemical engineering in facilitating and implementing PAT will be discussed. The case study of freeze-dried sodium ethacrynate will be presented to demonstrate the vital importance of controlling the processing factors to achieve the desired product stability. On-line process control and PAT can help the pharmaceutical industry to realize the maximum benefits of the advancements in modern instrumentation, analytical technologies, and robust engineering design, and to achieve process understanding and the desired state of quality-by-design. On-line process control and PAT can maximize the output-to-input ratio at a reasonable cost. Chemical engineers can play a vital role in facilitation and implementation of PAT system in the pharmaceutical industry. Corresponding author: hussaina@cder.fda.gov; 1-301-594-2847; fax: 1-301-827-3689