Prospects for multivariate classification of a pharmaceutical intermediate with near-infrared spectroscopy as a process analytical technology (PAT) production control supplement. 2010

Julia Märk, and Max Andre, and Martin Karner, and Christian W Huck
Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 52a, 6020 Innsbruck, Austria; Sandoz GmbH, 6250 Kundl, Austria.

NIR spectroscopy was applied to develop a fast and reliable quality control system for a pharmaceutical substance to support information obtained through PAT surveillance of its manufacturing process. After calculating different quantitative calibrations of the substance's key quality parameters, a general classification model has been derived to capture the over-all product grade. The final spectral quality conformity model consisting of 96 representative batches - covering high process variability - was sensibilized toward five important quality parameters by their incorporation as PLS responses. The model characteristics were extensively investigated and interpreted to derive a reasonable limit for the reduced chemometric summary quality measure (Hotteling's T(2)). Through this parameter new batches can be assessed easily by their NIR spectra, using versatile test batches for confirmation. Different sets of good quality batches, bad production batches beyond the respective chemical quality limit and synthetic batches exactly at the limit could be accurately assigned through their multivariate evaluation to a large extend. However, high model sensitivity to non-relevant product properties can lead to limited applicability of the model. This may be caused by restricted bandwidth of quality parameters in production environment for calibration, repack effects and high process instability.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D011786 Quality Control A system for verifying and maintaining a desired level of quality in a product or process by careful planning, use of proper equipment, continued inspection, and corrective action as required. (Random House Unabridged Dictionary, 2d ed) Control, Quality,Controls, Quality,Quality Controls
D002138 Calibration Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency or other output. Calibrations
D002511 Cephalosporins A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D013678 Technology, Pharmaceutical The application of scientific knowledge or technology to pharmacy and the pharmaceutical industry. It includes methods, techniques, and instrumentation in the manufacture, preparation, compounding, dispensing, packaging, and storing of drugs and other preparations used in diagnostic and determinative procedures, and in the treatment of patients. Technology, Pharmacy,Pharmaceutic Technology,Pharmaceutical Technology,Pharmacy Technology,Technology, Pharmaceutic
D015999 Multivariate Analysis A set of techniques used when variation in several variables are studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. Analysis, Multivariate,Multivariate Analyses
D019265 Spectroscopy, Near-Infrared A noninvasive technique that uses the differential absorption properties of hemoglobin and myoglobin to evaluate tissue oxygenation and indirectly can measure regional hemodynamics and blood flow. Near-infrared light (NIR) can propagate through tissues and at particular wavelengths is differentially absorbed by oxygenated vs. deoxygenated forms of hemoglobin and myoglobin. Illumination of intact tissue with NIR allows qualitative assessment of changes in the tissue concentration of these molecules. The analysis is also used to determine body composition. NIR Spectroscopy,Spectrometry, Near-Infrared,NIR Spectroscopies,Near-Infrared Spectrometries,Near-Infrared Spectrometry,Near-Infrared Spectroscopies,Near-Infrared Spectroscopy,Spectrometries, Near-Infrared,Spectrometry, Near Infrared,Spectroscopies, NIR,Spectroscopies, Near-Infrared,Spectroscopy, NIR,Spectroscopy, Near Infrared

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