Using Water Proton NMR to Characterize Aluminum-adjuvanted Vaccines

Abstract

wNMR, which stands for water proton nuclear magnetic resonance, is an emerging noninvasive analytical technology for pharmaceutical manufacturing and product inspection. In wNMR, the NMR signal from water protons is used to assess the physicochemical status of the solutes dissolved or suspended in water. The primary experimental outputs in wNMR are the longitudinal and transverse relaxation rates of water protons, R1(1H2O) and R2(1H2O). Aluminum-adjuvanted vaccines include some of the most commonly used vaccines and contain micron-sized aluminum salt particles, with antigens adsorbed to the particles, and are formulated as whitish aqueous suspensions. This type of suspension vaccine presents a unique challenge for analytical characterization because the sample is very heterogeneous and opaque. Most analytical techniques require significant sample preparations, such as dilution and antigen desorption, which may significantly perturb the sample being analyzed. wNMR offers a simple but effective analytical tool to characterize aluminum-adjuvanted vaccines. In this chapter, the basic principles of wNMR are discussed and specific examples are given of using wNMR to characterize two aluminum adjuvants (ALHYDROGEL® and ADJU-PHOS®) and three marketed aluminum-adjuvanted vaccines (DAPTACEL®, ENGERIX-B®, and VAQTA®). wNMR was used to detect vaccine freeze/thaw and vial-to-vial variability and to monitor vaccine sedimentation kinetics. Analysis is performed on sealed and labelled vials and does not involve any sample preparation. wNMR paves the way for quantitatively inspecting every vial of a finished drug product at the point of release and the point of care.