Enhancing Patient Safety through the Use of a Pharmaceutical Glass Designed To Prevent Cracked Containers

Abstract

An essential role of packaging material for the storage and delivery of drug products is to provide adequate protection against contamination and loss of sterility. This is especially important for parenteral containers, as lack of sterility or contamination can result in serious adverse events including death. Nonetheless, cracked parenteral containers are an important source of container integrity failures for injectable drugs and pose a serious risk for patients. Despite significant investments in inspection technology, each year many injectable drugs are investigated and recalled for sterility risks associated with cracked borosilicate containers. Multiple studies and the many difficulties in detection of cracked containers suggest that the magnitude of the public health risk is even larger than the recall rate would suggest. Here we show that the root cause of cracked parenteral containers (low internal energy following annealing) is inherent to the glasses currently used for primary packaging of the majority of injectable drugs. We also describe a strengthened aluminosilicate glass that has been designed to prevent cracks in parenteral containers through the use of an engineered stress profile in the glass. Laboratory tests that simulate common filling line damage events show that the strengthened aluminosilicate glass is highly effective at preventing cracks. Significant safety benefits have been demonstrated in other industries from the use of special stress profiles in glass components to mitigate failure modes that may result in harm to humans. Those examples combined with the results described here suggest that a significant improvement in patient safety can be achieved through the use of strengthened aluminosilicate glass for parenteral containers.LAY ABSTRACT: Cracks are small cuts or gaps in a container which provide a pathway for liquid, gas, or microbes through a glass container. When these defects are introduced to conventional glass containers holding injectable medicines, the affected drug can pose serious risks to the patient receiving that medication. Specifically, the drug product may become less effective or even non-sterile, which could lead to bloodstream infections and, in some cases, death. This article presents a review of some previously documented cases of cracked glass containers that led to patient infections and deaths. Following a survey of common crack locations in glass vials, lab-based methods for replicating these cracks are presented. These methods are then used to compare the fracture response of vials made from conventional borosilicate glass and strengthened aluminosilicate glass. The results show that stable cracks are essentially prevented (at least 31 times less likely to occur) in the strengthened aluminosilicate glass containers (relative to conventional borosilicate glass). This improvement in safety is similar to improvements already engineered into other glass product designs by utilizing stored strain energy to mitigate certain failure modes.

Glass: The best material for pharmaceutical packaging

“…The efforts made by both glass and pharmaceutical companies have greatly reduced the risk of breakage, and the reported number of recalls of borosilicate containers due to cracks and breakage in the last years is limited compared to the estimated production of vials containing injectable drugs 29,30 …”

Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

“…Several new glass surfaces have been developed [75,76]. Alkali aluminosilicate glasses or aluminosilicate glasses have been introduced as possible alternatives to alkali borosilicate glasses.…”

High-throughput injection molding of transparent fused silica glass

“…Many components are made in polymers rather than glasses because IM allows polymer components to be mass-market manufactured quickly, cost-efficiently, and at high precision (9,10). One consequence of the lack of scalable manufacturing processes for glass is that key components for mass-market optical systems, such as microlenses, are made from polymers, in spite of glass having superior optical properties to those of the polymer-based components (11)(12)(13).…”

“…The optical, thermal, mechanical, and chemical properties of silicate glasses make them the material of choice for many applications in optics, miniaturized chemical synthesis, and packaging (12)(13)(14)(15). In contrast to thermoplastic polymers, which are accessible through IM at relatively moderate temperatures of ~200°t o 250°C, glasses are still mostly processed by melting at temperatures of ~2000°C for fused silica and of 1500°C for other silicate glasses (16,17).…”