On-Line Monitoring of a Continuous Pharmaceutical Process Using Parallel Factor Analysis and Unfolding Multivariate Statistical Process Control Representation

M. Kompany-Zareh

Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731, Iran

On-line high performance liquid chromatography (HPLC) was used to monitor steady state reactions in three reactors (K = 3) over 48.0 h. Different numbers of chromatograms, with J = 1981 retention time points, were recorded for each of the three reactors. Peaks for each chromatogram were baseline corrected and aligned using correlation optimized warping (COW). To make a complete three-way data set of I = 266 chromatograms a cubic Hermite interpolation was performed. The applied bilinear multivariate statistical process control (MSPC) method included the unfolding PCA and the trilinear technique was PARAFAC. Unfolding in reactor (K) mode was the most informative. D-charts and Q-charts were applied to the data to determine samples which were out of control. Confidence limits were then applied to the D and Q-charts and variables with different behaviours from that encapsulated within the reference data set were located. Both bilinear and trilinear methods were found to be useful for process analysis.

Keywords: Multiway on-line continuous process monitoring, Parallel factor analysis, Unfolding multivariate statistical process control, Fault detection, High performance liquid chromatography