Testing for Glass Flakes in Pharmaceutical Vials

The drug industry has used glass vials for a long time, and most industry professionals assume that these containers are safe. Yet glass vials can pose contamination risks that often are invisible to the naked eye. Glass flaking or delamination, for example, is a serious concern. It can result in a failed quality-assurance test, thus bringing production to a halt and causing substantial revenue loss. More significantly, if glass delamination remains undiscovered, it can pose a serious contamination risk to the drug product and a potential health risk to the public.

What causes glass delamination?
Glass delamination occurs when top layers of a glass surface separate and flake off, typically at a scale invisible to the naked eye. Chemicals from the product solution or manufacturing process can cause the glass surface of the vial to delaminate or discolor. This effect can occur at any point during the vial’s life: during manufacturing, heat treatment, sterilization, or stability testing.

Most pharmaceutical quality-control departments are not equipped to investigate the problem of glass delamination. Instead, they often turn to independent laboratories for their analytical expertise and capabilities.

First method of observation: the stereomicroscope
Laboratories often receive pharmaceutical samples with visible particulates that need to be identified. Some clients may suspect glass delamination as the cause of the particulates, but other clients may not be aware of this phenomenon. Previous experience indicates that manufacturers should submit suspect vials for analysis when they are still filled and intact. The reason is that the fill line often is where glass delamination occurs.

Several steps help determine the presence of glass delamination. A primary technique is using a stereomicroscope with various types of illumination. If the suspect vial was submitted filled, the first observation can be made using fiber-optic oblique lighting against a black background. This illumination may cause a twinkling effect within the vial, which is an indication of glass delamination.

The contents of the vial are then filtered in cleanroom conditions to reduce the risk of contamination from any extraneous particles. When examining the filter that retains the particulate, the best technique for detecting glass flakes is coaxial illumination. Coaxial illumination reflects the interference colors of the flakes, thus revealing their thickness. Thin flakes are a gray-brown color, for example. In some instances, pitting is visible on the filtered particulate and on the vial wall. Pitting on the glass can be an early indicator of glass delamination.

Further analyses
Further chemical and microanalysis can prove definitively whether delamination and pitting have occurred. Examination of the inner vial wall, in addition to the particulate found in solution, reveals qualitative morphological information about the severity of the delamination. This technique also provides clues about where the delamination may have initiated. Common techniques include the following:

• Micro-Fourier transform infrared spectroscopy is used to identify the organic materials present, as well as inorganic materials, including glass.

• Scanning electron microscopy and energy-dispersive X-ray spectrometry analysis can confirm whether a contaminant is glass and can provide clues about the conditions under which delamination most likely occurred.

• X-ray photoelectron spectroscopy (also known as electron spectroscopy for chemical analysis) can help determine the chemical nature of glass delamination.

Potential packing problems can be overlooked easily until late in product development. To ensure product safety and to ensure that the vial is compatible with the drug, pharmaceutical companies should pretest all pharmaceutical packaging, including glass vials. It is important to test a package’s stability and integrity early in the development process to avoid problems later on.

Kristie J. Diebold is cleanroom manager and senior research microscopist at McCrone Associates, the analytical division of the McCrone Group, 850 Pasquinelli Dr., Westmont, IL 60559, tel. 630.887.7100, [email protected].