Mechanism of Protein-PDMS Visible Particles Formation in Liquid Vial Monoclonal Antibody Formulation

Visible particles (VPs) formation in liquid monoclonal antibody formulations is a critical quality issue. Formulations that include poloxamer 188 (PX188) as a surfactant are prone to the formation of VPs comprising aggregated complexes of protein and polydimethylsiloxane (PDMS; silicone oil) derived from primary containers. However, the mechanisms through which these VPs form are complicated and remain to be fully elucidated. This study demonstrates for the first time the dominant spot and pathway of protein-PDMS VP formation in a particular liquid vial formulation. Specifically, when a vial sealed with a PDMS-coated stopper is stored in an upright position under conditions whereby the antibody solution has become well-adhered to the stopper and an air phase exists in the vicinity, protein-PDMS aggregates form on the stopper and are then desorbed into the drug solution to be detected as VPs. Here, we evaluated the effects of several factors on VP formation: adhesion of the drug solution to the stopper, storage orientation, silicone coating on the stopper, vial material, and hydrophobicity of PX188. Remarkably, we found that changing any one of the factors could significantly affect VP formation. Our findings are instructive for better understanding the mechanisms of VP formation in vial products and can provide strategies for VP mitigation in biotherapeutics. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

The formation of visible particles (VPs) in liquid monoclonal antibody formulations is a significant quality concern. This study investigates the mechanisms of protein-polydimethylsiloxane (PDMS) VP formation and identifies the dominant spot and pathway in a specific vial formulation. Factors such as drug solution adhesion, storage orientation, silicone coating, vial material, and surfactant hydrophobicity have a notable impact on VP formation. The findings contribute to a better understanding of VP formation mechanisms and provide strategies for mitigating VPs in biotherapeutics.