(262a) Protein Behavior At Pharmaceutically-Relevant Microparticle Interfaces

During shipping, storage and delivery to patients, therapeutic proteins are exposed to a number of interfaces, to which they readily adsorb. These interfaces include fluid-fluid interfaces such as that presented by microdroplets of emulsified silicone oil used to lubricate prefilled syringes, as well a as solid-liquid  interfaces such as those presented by  contaminants such as glass microparticles that slough off vial walls and steel microparticles shed by high-speed filling pumps.  Adsorption to these interfaces may result in conformational changes in the adsorbed proteins, and may also lead to protein aggregation and the formation of large particles that render a product unacceptable for use in humans.   In addition, adsorption to a microparticle may substantially increase that a therapeutic protein will provoke an undesirable immune response.   The adsorption behavior of several therapeutic proteins on a number of these interfaces will be described, along with measurements of tertiary structural changes in the proteins that can be detected by front-face fluorescence quenching measurements.  Finally, the results of tests in murine models to determine the effect of such particles on immune response are described.