Particulate has been the subject of numerous recalls for a variety of drug products. Any drug recall can be a costly and time-consuming issue for pharmaceutical manufacturers. Recalls due to particulate contamination not only affect the outcome of a product, but have the potential to affect patient health. Manufacturers of pharmaceuticals and packaging systems have joined together to identify risks for issues such as delamination and particulate contamination and have developed strategies that could reduce occurrences.

Many elements can contribute to the overall particulate burden, including the container closure system, the drug product itself and the environment. To better understand experiences with glass-particle contamination in drug vials, West Pharmaceutical Services, Inc. sponsored a survey of SERMO’s online physician community. The findings showed that about one-in-two surveyed physicians were aware of recent particle-related drug recalls. However, only two percent of physicians have direct experience with particle-related adverse events. Also, only a subset of physicians are actively addressing particle contamination in their routine practice.

Since human intervention is the most common reason for contamination, manufacturers have been working diligently to eliminate as much of the human element as possible. Proper training of personnel and continued awareness of how easy it is for particulate contamination to occur are important aspects of the manufacturing process. State-of-the-art equipment can further mitigate particulate contamination, but particulates can also be generated from the containment materials or from the drug product interacting with its packaging. Selecting the proper containment materials early in the development process can help mitigate risk of interactions that may cause particulate contamination during the drug product’s lifecycle.

The process for selecting container closure materials compatible with pharmaceutical products and the intended use is an important aspect of delivering safe medicines to patients. The USP recognizes that glass compositions are variable and impact the inner surface durability of glass containers. USP chapter describes several risks associated with glass surfaces including ion exchange between the glass surface and aqueous solutions, which may lower pH and dissolve the silica network; leaching of alkali elements into solutions; and non-homogeneous glass surface chemistry caused by the forming processes. It also provides recommendations on testing glass for compatibility with drug products.

The industry needs to adopt proactive approaches to improved quality by providing innovative solutions. Identifying suitability pitfalls of current and innovative container closure materials may entail greater upfront investment by the pharmaceutical company, but evaluating components and systems early in the development cycle can reduce the risk of failure caused by material incompatibility.

Polyethylenes (PE), polypropylenes (PP) and cyclic olefin polymers (COP), such as Daikyo Crystal Zenith® (CZ), or copolymers (COC) are commonly used materials for injectable containers. The type of polymer selected, as well as the drug product formulations and manufacturing processes, will influence suitability for use. Just as with glass, not all polymer types or formulations behave in the same manner.

In the event that a recall does occur, it is imperative to ensure that life-saving medications reach patients as quickly as possible. Unfortunately, recalls of drugs in high demand or short supply may precipitate a drug shortage.

According to the FDA, once a confirmed drug shortage exists, there are several options that may help mitigate risk to patients.
Tools such as expediting inspections and reviews of submissions, or exercising temporary environment discretion for new sources of medically necessary drugs may help. However, none of these offers immediate relief to existing supplies. When particulate matter results in a drug shortage, the FDA has allowed the contaminated product to be used when distributed with a warning letter advising health care professionals to use a filter when administering the drug product. Use of a filtration system, like a vial adapter, is based on the manufacturer’s ability to demonstrate that the filter did not affect the way the drug works and that the filter also successfully removed the particulate.

Although a temporary means of resolving a particulate issue, filtration has been used for eight important drugs in the past two years, including “life-saving components of IV nutrition for newborns, children and other patients who are unable to eat or drink by mouth.”

To help reduce particulate contamination, pharmaceutical manufacturers should consider traditional glass materials as well as polymeric options for their drug’s container closure system. High-quality polymers, such as cyclic olefin polymers, offer transparent, break-resistant container closure systems that may help eliminate potential for glass lamellae and other particulate contamination due to interaction with the drug product.