  We demonstrate the use of holographic video microscopy to detect individual
subvisible particles dispersed in biopharmaceutical formulations and to
differentiate them based on material characteristics measured from their
holograms. The result of holographic analysis is a precise and accurate
measurement of the concentrations and size distributions of multiple classes of
subvisible contaminants dispersed in the same product simultaneously. We
demonstrate this analytical technique through measurements on model systems
consisting of human IgG aggregates in the presence of common contaminants such
as silicone oil emulsion droplets and fatty acids. Holographic video microscopy
also clearly identifies metal particles and air bubbles. Being able to
differentiate and characterize the individual components of such heterogeneous
dispersions provides a basis for tracking other factors that influence the
stability of protein formulations including handling and degradation of
surfactant and other excipients.
