Evaluating the impact of in-line PES filters on subvisible particle formation during IV administration of IgG4 monoclonal antibody.

Intravenous (IV) administration is a common delivery route for protein therapeutics, especially when used for oncology indications. Typically, multiple components, including IV bags with diluents and infusion sets, are used for IV administration, where proteins encounter various surfaces and materials, leading to potential physical and chemical degradations. Thus, it is important to evaluate the compatibility of the drug product with IV diluents, and IV administration sets to ensure product quality. In this study, when the compatibility of an IgG4 monoclonal antibody was assessed for two kinds of infusion sets after diluting in IV bags containing 0.9% sodium chloride, an increase in subvisible particles was observed post-infusion through one of the sets. Both infusion sets equipped with in-line PES filters with the same pore size (0.2 µm) and similar nominal filtration area (10 cm2), except for the shape of the filter (rectangular vs cylindrical). To understand the cause of increases in subvisible particles post infusion, a thorough assessment was conducted to evaluate the potential impact of infusion rate, infusion set tubing, in-line filter (particle shedding, location, contact surface area of the filter), and polysorbate 20 concentration in the drug product formulation. The results showed that the pore structure and contact surface area of the filter have an impact on surfactant adsorption which can lead to subvisible particle formation. The results from this study underscores the importance of conducting thorough in-use compatibility studies with different infusion materials during formulation development to identify an appropriate level of surfactant, which can mitigate the risk of subvisible particle formation during IV infusion.