A spate of drug recalls earlier this year has renewed attention on their cause: glass delamination. Glass vials have been long considered safe because of their longevity in the industry.
|Kristie Diebold, Cleanroom Manager and Senior Research Microscopist, McCrone Associates|
Senior research microscopist Kristie J. Diebold of McCrone Associates, the analytical division of The McCrone Group, answers some questions frequently posed to the group about how to better understand glass delamination and determine potential causes. The McCrone Group, a microscopy, microanalysis, and materials characterization company, has developed methods that drug manufacturers can use to pretest glass vials to ensure product-packaging compatibility as an alternative to reactive quality testing.
Q: What is glass delamination?
Diebold: Glass delamination occurs when top layers of a glass surface separate and flake off, typically at a scale invisible to the naked eye. Delamination is often correlated with pitting, a form of extremely localized corrosion that leads to the creation of small holes in the surface of the glass.
Q. What can cause glass delamination to occur?
Diebold: Some examples of how glass delamination can occur are (1) during manufacture when the vials are fused at the neck or base; (2) chemical reaction with the vial contents (e.g., etching due to an acidic or basic solution, or one with a high sodium or salt content); (3) heat treatment; and/or (4) sterilization.
Q. Where does glass delamination most frequently occur?
Diebold: An indicator of adverse reactions is observed frequently at the fill line, so if a filled vial is stored inverted, the delamination may be seen near the base of the vial instead of near the neck when stored upright. A vial that is submitted filled can be examined for this phenomenon.
Q. If glass delamination is suspected, what should be done?
Diebold: To ensure product safety and drug compatibility, pharmaceutical companies should install a program to proactively pretest all pharmaceutical packaging, including glass vials. Many of our clients are stability testing their products with several types of vials to find the proper combination to prevent glass delamination. Some manufacturers are using surface-
treated vials to improve chemical resistance, and others are investigating the performance of these vials with their products.
Companies that don’t have a laboratory with the equipment and expertise to test for glass delamination can send their samples to an independent laboratory for analysis. Clients that suspect it should send their vials filled, so we can determine if the fill line is a factor.
Q. How do you identify glass delamination?
Diebold: Quite often glass delamination flakes are invisible to the naked eye. Our laboratory uses several methods to detect glass delamination.
A primary technique is using a stereomicroscope with different types of illumination. If the suspect vial was filled when submitted, then the first observation is made using fiber-optic lighting against a black background. This illumination causes what is referred to as a “twinkling” effect within the vial, which is an indication of glass delamination.
The filled vial can also be filtered and broken to reveal the inner walls to find further evidence of delamination using coaxial illumination.
Further techniques to identify glass delamination include:
• Infrared spectroscopy (FTIR) analysis. Used to identify the organic materials present as well as some inorganic materials, including glass.
• Scanning electron microscopy (SEM) and energy dispersive X-ray (EDS). Analyses that can confirm whether a contaminant is glass and can provide clues to the conditions under which delamination is most likely to have occurred.
• X-ray photoelectron spectroscopy (XPS, also known as electron spectroscopy for chemical analysis or ESCA). Used to help determine the chemical nature of glass delamination.
Q. What should a QA/QC department be equipped with to investigate glass delamination themselves?
Diebold: Many quality control departments do not have all of the analytical techniques available, but most can acquire the equipment and training to perform basic examination of glass vials for glass delamination. The most useful and economical piece of equipment is a stereomicroscope equipped with coaxial and oblique illumination.
Q. Where can I learn more about how to detect glass delamination?
Diebold: There are plenty of opportunities to learn more about how to detect glass delamination. Hooke College of Applied Sciences offers a Microscopical Particle Handling course and a course focused on the identification of Pharmaceutical Materials and Contaminants that includes glass delamination. In addition, organizations like the American Association of Pharmaceutical Scientists and The Analysis of Pharmaceutical Quality have been known to conduct informational and instructional sessions.
Kristie J. Diebold is cleanroom manager and senior research microscopist at McCrone Associates, the analytical division of The McCrone Group. She also assists in teaching an Infrared Microscopy course at Hooke College of Applied Sciences that briefly touches on glass delamination. HCAS also offers a Pharmaceutical and Sample prep class that explores glass delamination.