Annex 1: Enhancing Pharmaceutical Safety Through Advanced Glass Vial Technologies

Instead of simply testing and monitoring to detect contamination, manufacturers must now consider every step in which contamination could occur and put preventive measures in place. Matt Hall, Technical Affairs Director for Corning Pharmaceutical Technologies (CPT), explained, "You're taking a holistic, science-based, risk mitigation-based approach to looking at your people, your facility, your product, and your process to see how you can reduce contamination."

According to Annex 1, a CCS can include controls related to the active substance and the components of the pharmaceutical product, manufacturing facilities and equipment, operating conditions, in-process controls, and monitoring methods. The CCS should not be static; it should be reviewed and updated as needed to drive continual process improvement.

Risk Mitigation-Based Approach to Pharmaceutical Safety 

Another notable change is that the updated regulation takes a risk mitigation-centric approach, as opposed to the more regulatory-based approach of the prior version.

What does this risk mitigation-based approach entail? "The guidelines assume that, as the end manufacturer, you should know best how to conduct your manufacturing process," Hall said. "There is a lot of flexibility in how to accomplish an end goal based on your knowledge of your product, process, and risk management needs."

While the updated regulation does include specific requirements for things like clean room grades, it doesn't dictate exactly what manufacturers must do in all instances. For example, section 8.2 states: "Primary packaging containers and components should be cleaned using validated processes to ensure that particle, endotoxin/pyrogen, and bioburden contamination is appropriately controlled," but it does not specify exactly how this should be done.

As such, manufacturers must use the provided guidance and their own knowledge and testing to determine how to meet these requirements.

Preventing contamination and damage during the fill and finish process is essential to the success of contamination control efforts. Section 8 of the updated regulation is titled, "Production and Specific Technologies," and covers the fill and finish process and different sterilization techniques. It also includes new guidance on packaging.

One potential source of contamination in the packaging of sterile products is the container closure system (e.g., a glass vial, a rubber stopper, and an aluminum seal that crimps and presses on the stopper, creating a seal and keeping the interior sterile). Some end users purchase vials that must be cleaned and sterilized; however, this is an intensive process due to the energy, time, and equipment required.

To avoid these costs, an increasing number of manufacturers are choosing to outsource this cleaning and sterilization process by purchasing ready-to-use (RTU) containers. RTU containers are pre-cleaned and sterilized and can simply be brought into the facility and filled. In addition to helping to reduce risk, RTU vials can also lower total cost of ownership, while increasing speed and flexibility in the production process.

While many suppliers offer RTU containers, there are some differences to consider amongst the various options.

"With Corning pharmaceutical glass vials, it's the vial surface treatment that's different," Hall said. Corning's glass vials have an external coating that reduces the risk of contamination in multiple ways.

With traditional, uncoated vials, Hall explains, "When the surfaces of vials come into contact or rub against each other, it can lead to multiple risk factors. One possible threat is the formation of glass particulates, which are a potential contaminant. Our proprietary low-friction vial coating can reduce this risk by up to 96%."

Another concern is vial damage during the production process, including cracks and breakage. "Let's say the vial cracks, so there is a continuous pathway from the interior to the exterior of the vial. The vial is not broken, but microbial ingress can occur." By reducing the risk of cracks, Corning's external coating helps reduce risk of microbial contamination. "The strength of a glass container is controlled by the level of damage it's seen across its lifetime. The external coating on Corning's vials reduces this damage, which supports Annex 1 compliance."

In addition to a reduced risk of microbial ingress due to cracks, stronger vials are also less likely to break during the fill and finish process. A broken vial in the manufacturing line would require intervention by a human operator. Another such incident could be vials jamming or tipping over in the line during the fill and finish process.

"Any time there's a glass incident that requires a human operator to intervene, that presents a risk of contamination," Hall said. "Annex 1 tries to limit (product) contact with humans because we're major sources of contamination, including microbial and particulate matter."

The exterior coating on Corning's glass vials targets each of these concerns: reducing glass particulates, preventing cracks and breakage, and ensuring smooth flow by reducing friction as vials move through the filling line, boosting fill and finish efficiency by 20-50%.

As regulations applying to pharmaceutical manufacturers continue to get more stringent, stakeholders in the industry must work together at every step of the process to optimize safety and quality. Corning is dedicated to helping pharmaceutical customers meet efficiency goals, comply with Annex 1 and other regulations while keeping costs down.

Corning's portfolio of pharmaceutical vials includes options that support high performance, more environmentally friendly packaging options, with glass and glass surface coatings that resist cracks, breakage and cosmetic rejects - all to protect valuable drug pipelines. Each glass vial solution, including Corning Velocity® Vials, Corning Viridian® Vials, and Corning® Valor® Glass, feature Corning's proprietary external low-friction coating and high quality assurances, all available in RTU formats.