Near Infrared Spectroscopy - A Real-Time Method to Measure Aluminum Content and Protein Concentration in Adsorbed Vaccines

Abstract

Development of analytical methods to streamline real-time measurements during process development is a priority for the evolution of bioprocess manufacturing. Current methods to measure downstream processes are limited, therefore, in this study, NIR and NMR spectroscopies have been successfully applied for the quantitation of aluminum content in the vaccine drug substance and drug product. In addition, NIR capabilities were demonstrated to measure concentration of adsorbed protein inline. Statistical methods, such as Multivariate (PLS) Partial Least Squares and Principal Component Analyses (PCA) provided quantitative information about various components of vaccine drug substances that could be further developed to monitor downstream formulation processes. Samples of various protein antigens, such as Tetanus Toxoid, recombinant Neuraminidase, Pertactin and genetically detoxified Pertussis Toxin drug substance were shown to closely conform to modeled calibration data. 27Al NMR spectroscopy was also applied as an orthogonal method to independently quantify aluminum content. This analytical technique tandem is shown to provide rapid determination of aluminum content in adsorbed drug substance.