Glass Flakes in Drug Vials: Longstanding, Vexing Problem

Today's report

that Amgen and JNJ are recalling vials of Epogen and Procrit, respectively, because of internal glass flakes prompts a search at this blog for their causes. The incident appears to be a longstanding plague of storing and delivering parenteral solutions, with Baxter (most recently) recalling glass vials of Hylenex in May for a similar problem.

The phenomenon, known as glass delamination, is an apparently well-described, but not well-understood, event in the industry. In a recently published series of experiments on glass vials, Lilly employees remind us that glass is not an inert substance and that several factors—including sterilization (ie, autoclaving), glass makeup, solution properties (eg, pH changes), and mechanical energy (eg, shaking)—can erode the silica framework and contribute to the instability of glass. The authors emphasize that the generation of visible flakes is not a herald sign of glass instability but a late manifestation. "The stage for delamination is set well before flakes are observed," they write. They further conclude that prevention is problematic.

Because the vial interior is compromised so early in the shelf life of the product, few options exist for the prevention of delamination. The [chemical vapor deposition] coating of SiO2 offers some protection against the formation of visible flakes. Materials substitution using plastic vials is also an alternative; however, there are other challenges incurred with such a change. Lyophilization [ie, freeze drying the liquid drug] is also a viable alternative. Although the liquid does have contact with the glass prior to processing, the time that the liquid resides in the glass vial is much less than would be encountered with a liquid formulation.

Electron micrograph of delamination of internal glass-vial surface from Iacocca et al (2010).