Ready and Sealed: The RTU Advantage for Optimal Vial Sealing
For small-batch, high-value drug products, the aseptic advantages of pre-sterilized ready-to-use vials are clear. To realize the full scope of benefits that RTU vials can provide, integration with traditional processes and equipment must be carefully considered. Modern and flexible technologies such as robotics are key to seamlessly integrating RTU vials into aseptic fill/finish processes. The benefits of this approach include:
- Enhanced sterility assurance
- Faster qualification and process validation
- Significant savings on equipment, facility, & operations
- Increased speed to market maximizes patent utility
Robotics and automation are a natural ally of the RTU approach, creating a low-risk, holistic approach to the vial capping process.
Vial Sealing Considerations
Vial sealing, or “capping” as commonly referred to, is the final process required to fully close a parenteral vial. Simply described, this process entails placing a cap or over-seal atop a filled and stoppered vial, compressing the stopper with the cap, and then forming the cap’s aluminum skirt around the neck of the vial. The end result is a vial with a properly compressed rubber stopper and an optimal seal around the vial opening, maintaining the sterility and integrity of the drug product within. Given that this process is vital to ensuring long term sterility and quality of the drug product, having a reliable and repeatable vial sealing process has considerable regulatory significance, and is vital to achieving production milestones.
There are several technical variables that must be optimized and maintained in the vial sealing process. Critical variables such as stopper compression must be monitored and controlled on a per-vial basis to ensure that the cap applies the correct amount of stopper compression prior to forming the cap skirt around the vial neck.
Crucial to Annex I regulatory compliance, visual inspection must also be performed to ensure proper placement of the stopper onto the vial prior to application of the cap. This inspection process is typically performed with machine vision or laser micrometer systems that are sensitive enough to detect minute gap distances between the vial top and the sealing surface of the rubber stopper.
Approaches to Vial Sealing
The traditional cap forming process generally uses one of two processes for vial sealing. The first and most common for small-scale applications is a jaw-style crimper and the second is a rail design that may be fixed or rotating. The jaw crimper has the advantage of generating very little aluminum particles during operation, but over time aluminum builds up on the jaws which can degrade the quality of the vial seal. The rail design is well suited for higher-speed production, provides better stopper compression control and forms a pharmaceutically aesthetic crimp. Unfortunately, this process can generate higher particulate levels which can present a contamination risk to uncapped vials if not properly contained.
With this in mind, AST has been leveraging an innovative low particle approach: a crimping process that uses a gentle and precise free-spinning disk design. This approach forms a pharmaceutically aesthetic seal and provides scratch-free capping for polymer and glass vials.
Another modern approach is utilizing press-fit caps. With the plastic cap approach, the cap can be pressed firmly onto the vial, fully seating the rubber stopper, while generating little to no contaminating particles during the process. For lyophilization applications the cap can be applied and then pressed onto the vial by the lyophilizer shelves before exiting the lyophilizer.
The advantages of the plastic cap are obvious; by minimizing or eliminating particles, contamination risk is reduced. By sealing the vial immediately after filling, the overall exposure to the environment is minimized thereby also reducing contamination risk. Press-capping also offers an operational alternative to a crimping station, which is a cost savings up front by eliminating equipment and throughout the fill-finish process with less sterile space required for operation. Having one less module also saves significant time in equipment setup and decontamination protocols.
There are, however, a few technical challenges that require mitigation before full implementation. The primary obstacle is the ability of a press-fit cap to provide a consistent high-integrity seal, which can be challenging when one understands the amount of dimensional variation vials, rubber stoppers and plastic caps have. This is further complicated by the fact that various rubber materials compress differently than others. These issues can be resolved by employing an automated solution that accurately and repeatedly seats the stopper and uses seal pressure monitoring to ensure a consistent pharmaceutical-grade seal.
Lastly, having a final confirmation that each vial’s press-fit cap is fully seated is paramount to ensuring every vial is properly sealed. The right aseptic system will provide instrumental feedback to ensure a seamless, high-efficiency fill-finish operation.
Advanced vial closing solutions that fully capture the benefits of ready-to-use vials require a combination of industry-proven closing methods integrated with technologies that provide flexibility and improve overall product quality. AST’s Vial Sealing Module (VSM) available across our product line, does just this. Learn how these innovative systems can provide your organization with the highest quality vial sealing solutions – contact our experts today.