Recent work by our guest presenter, Dr. John Carpenter (University of Colorado Anschutz Medical Center), discovered that nanoparticles present in solutions of intravenous immunoglobulin (IVIG) serve as precursors for microparticles during pharmaceutically-relevant stresses such as freeze-thawing or agitation. Depletion of nanoparticles (e.g. by ultracentrifugation) prior to stress greatly reduces the rate of microparticle formation. However new nanoparticles can form during the stress.

Also, therapeutic proteins can adsorb to foreign nanoparticles, resulting in particles containing both protein and foreign material. Sources of nanoparticles of foreign materials include filters, filling and transfer pumps, and chromatography columns.

Importantly, nanoparticles of therapeutic proteins (with either protein alone or with foreign materials) can induce adverse immunogenicity. Our recent study of mouse growth hormone in mice documented that samples containing only protein monomers and trace amounts of nanoparticles were highly immunogenic when administered subcutaneously or intravenously.

Taken together, current data show that nanoparticles play important roles in protein aggregation pathways and in adverse immunogenicity. Thus, regulatory agencies are now viewing quantitation and sizing of nanoparticles as important parts of product quality assessment.