Advantages of closed-vial technology
Closed vials can offer three main advantages compared with traditional glass vials.
Increased patient safety.
In glass vial technology, the vial stays open for more than 30 minutes between exiting the depyrogenation tunnel and stoppering.
Stoppers may remain in a stopper bowl for several hours, in which direct contact with surfaces increases the risk of transferring
a contaminant to the vial. A closed vial, however, remains permanently closed except during needle penetration, thereby reducing
the risk of contaminant entering the vial by two logs (5).
Simplified manufacturing process.
The closed vial is delivered clean and sterile, allowing the pharmaceutical manufacturer to eliminate container-component
preparation, including water for injection (WFI) washing, steam sterilization, and hot-air depyrogenation. High speed stoppering
and aluminum cap crimping are also eliminated. The break-resistant polymer material reduces vial breakage inside the filling
area and during the supply chain.
Easier handling for healthcare professionals.
The closed vial's cap can be easily opened by breaking small polyethylene bridges. Piercing is facilitated by a large piercing
area. Liquid collection is complete due to the absence of recess areas in the stopper design. Finally, the vial does not break
if dropped. A market study performed for Aseptic Technologies in 2007 found that among 246 professionals (i.e., medical doctors,
nurses and hospital pharmacists), 87% preferred the closed vial (Crystal Closed Vial, Aseptic Technologies) and 7% preferred
the glass vial. The most often cited reason for preferring the closed vial, as shown in Figure 2, was that it is easy to handle.
Figure 2: Results of market survey of healthcare practitioners showing the reason for their preference of closed over glass
Closed vial container design
The following sections describe a typical closed-vial container and the manufacturing and filling process. These sections
also explain how the container design and the manufacturing process provide a solution for challenges in aseptic filling.
In this closed-vial system, cyclo-olefin copolymer (COC) (Topas, Topas Advanced Polymer) was selected for the vial body because
it does not create high particle levels during molding. Low particle generation is a requirement for avoiding WFI washing
after manufacturing in an ISO5 clean room. COC is already used in some injectable products (Metalyse, Boehringer-Ingelheim),
and is widely used in blister packaging. COC is a clear, transparent polymer that allows good light transmission and has a
high barrier to water vapor. In addition, it can be gamma-irradiated without degradation or a visible change of color at
standard irradiation doses. COC is shock resistant, which reduces the risk of loss during production and transportation.
Polymer molding has greater design flexibility compared to glass forming. Several features are shown in Figure 3. In particular,
the tightness of the vial is ensured under all conditions, even under the low temperatures of liquid nitrogen.
Figure 3: Detail of closed vial container design showing features not available in glass vials.
The stopper should reseal when heated by the laser to ensure reclosing of the puncture trace. The stopper must be able to
absorb the laser energy with a good profile of heat distribution. Second, the stopper should be highly flexible and easy to
pierce with a large needle without generating particles of significant size or amount and without material loss. Third, to
ensure optimal resealing process after liquid fill and after lyophilization, the stopper should have good elastic memory.
It is crucial to have both sides of the piercing trace in tight contact to ensure optimal laser resealing. Finally, the stopper
material used should not release deleterious leachables. A thermoplastic elastomer (TPE) has these features, and the polymer
can be engineered using a color pigment to ensure optimal absorption of laser energy.
The vial head is equipped with a top ring to secure the assembly of the vial body and the stopper, as shown in Figure 3.
In this design, the vial head has also been equipped with a snap-fit, high density polyethylene (HDPE) cap. This design eliminates
the complex and particle-generating crimping process necessary with an aluminum cap. A small rib on the internal surface of
the cap adds closure integrity by isolating the central part of the stopper from the environment until use by the doctor.