The Application of Multivariate Statistical Analysis and Batch Process Control in Industrial Processes

Abstract

To manufacture safe, effective and affordable medicines with greater efficiency, process analytical technology (PAT) has been introduced by the Food and Drug Agency to encourage the pharmaceutical industry to develop and design well-understood processes. PAT requires chemical imaging techniques to be used to collect process variables for real-time process analysis. Multivariate statistical analysis tools and process control tools are important for implementing PAT in the development and manufacture of pharmaceuticals as they enable information to be extracted from the PAT measurements. Multivariate statistical analysis methods such as principal component analysis (PCA) and independent component analysis (ICA) are applied in this thesis to extract information regarding a pharmaceutical tablet. ICA was found to outperform PCA and was able to identify the presence of five different materials and their spatial distribution around the tablet.Another important area for PAT is in improving the control of processes. In the pharmaceutical industry, many of the processes operate in a batch strategy, which introduces difficult control challenges. Near-infrared (NIR) spectroscopy is a non-destructive analytical technique that has been used extensively to extract chemical and physical information from a product sample based on the scattering effect of light. In this thesis, NIR measurements were incorporated as feedback information into several control strategies. Although these controllers performed reasonably well, they could only regulate the NIR spectrum at a number of wavenumbers, rather than over the full spectrum.In an attempt to regulate the entire NIR spectrum, a novel control algorithm was developed. This controller was found to be superior to the only comparable controller and able to regulate the NIR similarly. The benefits of the proposed controller were demonstrated using a benchmark simulation of a batch reactor.

Date of Award	31 Dec 2010
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Barry Lennox (Supervisor)