During the past two years, the growing problem of glass particles in injectable medications has led to a number of product recalls. The crux of the problem is the durability of glass containers. Specifically, the inner surfaces of some glass containers are less durable and thus more susceptible to delamination (i.e., the shedding of glass flakes from the vial's interior walls) than others. Numerous factors may affect glass durability. Although the impact of glass delamination on patient safety remains a point of debate, the presence of these particles is at the very least a serious quality problem that must be addressed.
In a March 2011 FDA advisory to drug manufacturers on the formation of "glass lamellae" in certain injectable drugs, the agency noted that, although no adverse events had been reported at that time, there is the potential for drugs administered intravenously that contain these fragments to cause embolic, thrombotic, and other vascular events; and when administered subcutaneously, to lead to development of foreign body granuloma, local injection site reactions, and increased immunogenicity. Several conditions have been associated with a higher incidence of lamellae formation, including glass vials manufactured by the tubing process (and thus produced under higher heat); drug solutions formulated with certain buffers; drugs formulated at high pH; and drug products that undergo terminal sterilization. Based on the sudden increase in this occurrence and subsequent recalls, the US Pharmacopeial Convention (USP) Packaging, Storage, and Distribution Expert Committee developed a new general chapter that recommends approaches to predict potential formation of glass particles and delamination. The new informational chapter, General Chapter <1660> Evaluation of the Inner Surface Durability of Glass Containers, will be proposed in the July–August 2012 Pharmacopeial Forum (PF) and was posted in advance of its publication on the USP website in May 2012.
For the purposes of pharmaceutical packaging, three types of glass are defined by USP General Chapter <660> Containers—Glass. Type I (borosilicate glass) is suitable for most products for injectable and noninjectable use. Type II is treated soda-lime glass, and Type III is soda-lime glass on the basis of the hydrolytic resistance of the glass. Glass, in the form of ampuls, bottles, cartridges, vials and prefillable syringes, is the container material of choice for injectable products, particularly biopharmaceuticals.Recent recalls underscore the fact that not all Type I glass is equal in terms of quality. Glass delamination, which ultimately results in the appearance of lamellae, is a lagging indicator of structural instability of a container. Although delamination is the most obvious visual indicator of instability, it represents the final stage of a seriously weakened glass surface structure, and can be observed only at a point where prevention is no longer an option. As such, proper evaluation of the quality of glass containers is crucial.