The Effect of Container Surface Passivation on Aggregation of Intravenous Immunoglobulin Induced by Mechanical Shock.

: Aggregation of therapeutic proteins can result from a number of stress conditions encountered during their manufacture, transportation, and storage. This work shows the effects of two interrelated sources of protein aggregation: the chemistry and structure of the surface of the container in which the protein is stored, and mechanical shocks that may result from handling of the formulation. We investigated how different mechanical stress conditions (dropping, tumbling and agitation) and container surface passivation affected the stability of solutions of intravenous immunoglobulin (IVIG). Application of mechanical shock caused cavitation to occur in the protein solution, followed by bubble collapse and the formation of high-velocity fluid microjets that impinged on container surfaces, leading to particle formation. We also observed cavitation following dropping of vials from heights as low as 5 cm and that polyethylene glycol (PEG) grafting could provide temporary protection against drop-induced cavitation. PEG treatment of the vial surface reduced the formation of protein aggregates observed after repeated dropping events, most likely by reducing protein adsorption to container surfaces. These studies enable the development of new coatings and surface chemistries that can reduce the particulate formation induced by surface adsorption or/and mechanical shock. This article is protected by copyright. All rights reserved.