Glass delamination(1) has become a bit of a hot topic in the area of parenterals over the past several years. Glass delamination is, indeed, a serious issue which can not only cause pharmaceutical companies millions of dollars in recalls, but also stands as a safety hazard to end users. Delamination is essentially the flaking off of the top layers of a glass surface into the liquid contents of a pharmaceutical vial, syringe, or other container. Numerous companies have experienced this issue, and have had to open investigations(2) to address the issue. The question is, how can we be proactive, rather than reactive, in addressing concerns with glass delamination? How can we minimize the risk of experiencing a delamination issue, in order to protect the welfare of end-users and uphold the quality of our products?
USP <1660> (3) details the testing requirements for the assessing the durability of glass container surfaces. The purpose of this document is to recommend “approaches to predict the potential of a drug product to cause formation of glass particles and delamination and to detect their occurrence.” These methods are not only applicable to the common vials we encounter, but also to syringes, ampules, and other glass containers that house drug products. USP <1660> describes the various types of glass encountered, how molded/tubing glass containers are manufactured, and glass surface chemistry. After discussing the variables that affect the durability of the inner surface of glass containers, both predictive and aggressive screening suggestions are outlined.
These screening methods include utilization of technologies to test the degree of pitting/chemical composition on the glass surface, the conductivity/pH and extractables of elements in solutions, and the size/number/morphology/composition of glass particles (visible and subvisible) in solutions. Techniques include microscopy (DIC, SEM, etc.), pH meters, ICP spectroscopy, and particle size analyzers.
Both pharmaceutical companies and glass manufacturers alike are in a position to benefit from performing screening studies on glass containers used to hold drug products. The benefits and necessity for the pharmaceutical companies are quite obvious (increased safety and quality, decreased risk of costly recalls). Glass container manufacturers also can benefit from such screening as well…predictive and aggressive durability screening of their glass container products can be included as a selling point to their customers. As always, it does not come as a surprise that a focus on quality is key in successful drug product manufacturing.
References:
- http://rx-360.org/en-us/Alerts-News/Alerts/Glass-Delamination
- https://gatewayanalytical.com/resources/webinars/evaluation-pharmaceutical-vials-glass-delamination
- http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/c1660.pdf
- USP <1660> Evaluation of the Inner Surface Durability of Glass Containers, www.usp.org