Shelf life of pharma glass vials

There are multiple reasons why glass is often considered an ideal material for pharmaceutical packaging, one of which is its chemical durability.  Assuming that a suitable glass composition is selected, a vial can often withstand the corrosive effects of liquid drug products for many years (see Footnote 1).  What about an empty glass vial?  How long can we expect its properties to remain intact?  As is often the case, the answer is “it depends”.  I would generally expect the shelf life of a bulk glass vial to be effectively indefinite assuming that it is stored under reasonably constant environmental conditions.

Environmental conditions of interest include temperature and relative humidity (RH).  In particular, I’m interested in the possibility of fluctuating temperature and/or RH conditions that lead to the condensation of static water droplets on the surfaces of the glass vial.  Emphasis is on the word “static”, a condition in which the same water droplet remains in contact with the glass surface for an extended period of time.  This is contrast to a dynamic environment in which water that initially contacts the glass surface is displaced by gravity, freshly introduced water, etc. Static water droplets create a localized environment in which alkali ions such as sodium (Na⁺) are extracted from the glass surface over time.  This alkali extraction is accompanied by a pH increase of the liquid droplet, which in turn accelerates corrosion of the glass surface in contact with the droplet (refer to Figure 1).  This localized attack can lead to visible haze, pitting, or even the spallation of corroded flakes from the affected glass surface.

The extent to which these static corrosion processes may be observed is strongly dependent on glass composition.  For example, a 1975 study by Walters and Adams considered the corrosive effects of static and cyclically varying humidity conditions under accelerated conditions (i.e., elevated temperature) on a variety of glass compositions (see Footnote 2).  Not surprisingly, they found that borosilicate glasses (see Footnote 3) were among the most resistant to attack under high humidity conditions.  Furthermore, this sort of attack is not automatically the result of a one-off event.  For example, static corrosion is often included under a broader category known as “weathering” of glass surfaces.  Weathering processes are generally observed as the result of repeated exposure occurring over an extended period of time (see Footnote 4).  All of this is to say that I wouldn’t necessarily toss a batch of pharmaceutical glass vials that experienced a short-term exposure to water condensation (see Footnote 5).  I might become more suspicious of a long-term storage facility for vials where this occurred on a frequent basis, although I’m admittedly not aware of any studies that have actually looked at this issue.

To reiterate then, I would expect the shelf life of a bulk glass vial to effectively be indefinite.  I’m being careful here to use the word “bulk” as a qualifier, meaning a vial that must be washed and depyrogenated prior to being filled with a parenteral drug product.  A ready to use (RTU) vial is an entirely different matter.  Specification sheets for RTU vials will often include a shelf life statement, but this has nothing to do with the longevity of the glass vial.  It is instead measuring the ability of the secondary packaging around the vial to maintain a clean, sterile environment that allows the container to be immediately filled without additional processing.  The shelf life that appears in a product specification can be the result of accelerated and/or long-term stability testing.  However, let’s be clear – a quoted shelf life of 5 years (for example) doesn’t necessarily mean that the RTU supplier detected a failure at 5 years during stability testing.  The shelf life statement may simply be based on the last time point that the supplier chose to evaluate.  I’m also not suggesting that it’s safe to use RTU product past its expired shelf life – just that it may be worthwhile to discuss the basis for shelf life statements with your supplier.

Questions or comments? – please leave them below of feel free to directly contact me.

Footnotes

1.       Chemical resistance tests are frequently used to initially screen the durability of glass containers.  Just remember that achieving a high durability rating (e.g., Type I according to compendial methods outlined in USP <660>/EP (3.2.1)) does not automatically mean that the glass container will be compatible with a given drug product.  Also note that I used the phrase “withstand the corrosive effects”.  This does not mean that the container is fully impervious to corrosion.  All glass types will react to some extent with liquids.

2.       Reference: Walters HV and Adams PB (1975).  Effects of humidity on the weathering of glass. In Glass Surfaces, pp. 183-199, Elsevier.

3.       The exact compositions of the borosilicate glasses evaluated in the study by Walters and Adams were not specified, and so I can’t be certain if any of them are equivalent to what might be considered a modern formulation suitable for parenteral glass packaging.

4.       Considering the potential for weathering of glass surfaces is definitely relevant in some contexts, including but not limited to: architectural windows, cover glass used on solar panels, cultural heritage artifacts (e.g., medieval stained glass windows and ancient glass vases), etc.

5.       One example might be liquid drug products requiring refrigeration.  It’s not uncommon for recently filled vials to go into cold storage prior inspection and labeling (so called “brite stock”).  Pulling those cool, refrigerated vials back out into ambient conditions for labeling can lead to water condensation, but I don’t regard this short-lived process to be relevant for static corrosion of the glass vial surface.

About the Author

Matthew Hall is Technical Affairs Director for @Corning P, a manufacturer of primary glass packaging for parenteral drug products.  Based in upstate New York, Dr. Hall serves as a technical expert supporting business operations, sales, and marketing and educating customers on pharmaceutical glass packaging.  He is a member of the Parenteral Drug Association and the International Society of Pharmaceutical Engineering.