Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product

Abstract

Intravenous (IV) infusion is used for administration of a large proportion of biologic therapeutics, including most monoclonal antibody products. In this study, we determined the subvisible particle levels in IV solutions and after the solutions were processed with an IV administration setup that mimicked the typical clinical method of administration. IV saline in bags manufactured by both Hospira and Baxter contained 1600-8000 microparticles/mL and 4-73 × 10⁶ nanoparticles/mL in solution. When IV immunoglobulin was diluted into the IV saline, 3700-23,000 microparticles/mL and 18-240 × 10⁶ nanoparticles/mL were detected. During processing of the solution through the IV system, in-line filters removed most microparticles. However, there were still 1-21 × 10⁶ nanoparticles/mL in IV saline and 7-83 × 10⁶ nanoparticles/mL in IV immunoglobulin diluted in saline. Finally, in samples processed through in-line filters, we found relatively large microparticles (20-60 μm) that were composed of protein or polycarbonate. These particles resulted from shedding of polycarbonate and sloughing off of protein films downstream from the filter membrane. Overall, the results document that even with in-line filters in place, high levels of subvisible particles are delivered to patients and there is a need for improved, more effective filters and IV solutions with lower particle levels.

Keywords: IgG antibody; adsorption; microparticles; nanoparticles; particle size; protein aggregation; protein delivery.