The plastic alternative
Growth in the market for plastic prefilled systems is expected to result from a rise in new biotechnology products and vaccines.
This growth will be associated with significant challenges in the formulation development of proteins and monoclonal antibodies,
which are typically administered in high doses. High-concentration proteins tend to interact with each other and with the
packaging components, thus causing protein instability, especially when the volume of delivery is approximately 1 mL. Glass
prefilled syringes typically face the additional challenges of breakage, the presence of particulates, the glass's reactivity
to the drug product, and potential leachables such as silicone, tungsten, and adhesive.
Plastic prefilled syringes provide a way to solve such problems (7, 8). Cyclic olefin polymer resins such as CZ possess many
advantageous properties, including glasslike transparency, which permits the visual inspection of the manufactured components
and of the parenteral products that are delivered to the end user. The polymers exhibit high impact resistance and break resistance
and form an excellent moisture barrier (9, 10).
A plastic prefilled syringe can eliminate the need for silicone, tungsten, and adhesive, depending on the quality attributes
of the entire prefilled system. For instance, the CZ 1-mL insert needle (IN) system uses no silicone to improve syringe functionality,
no tungsten (which is often required to form glass syringes), and requires no adhesive to hold the needle in place.
Tungsten has been identified as a leachable in glass prefilled syringes. Reports describe tungsten-based particulate matter
that leached into and interacted with the protein drug product (11). Tungsten pins typically are used to keep the fluid path
open at the nozzle end of the syringe during the glass-syringe formation process. Upon cooling, a needle is staked in with
adhesive to make a glass prefilled syringe with a staked needle (SN). Residual tungsten can migrate into the drug product
and cause the protein to form protein–tungsten aggregates. Although this phenomenon appears to occur only with specific proteins,
it is important to test for protein–tungsten interaction at an early stage of drug development. Concerns about aggregation
may be mitigated by plastic SN syringes.
Silicone-oil-free syringes have been shown to have consistent travel forces over time and at various temperatures. The tighter
dimensional tolerance of plastic syringes and the consistency of syringe functionality make autoinjectors' operation predictable.
The break resistance of the finger flange for plastic syringes is likely to be significantly higher than that of glass syringes.
Because of their higher dimensional tolerances, plastic 1-mL IN syringes are likely to have much less residual volume than
glass 1-mL SN syringes. This difference means that less drug product is wasted or left behind in the barrel, and it could
yield significant savings for drug manufacturers.
Limitations on glass autoinjectors' performance may begin with their material of construction. Glass is a formed product that
must be heated. Mandrels form glass syringes' overall length, nose or tip, and flanges. This process can create dimensional
variability. During manual operation, a glass syringe's variability usually is mitigated by the human user. However, dimensional
tolerances may vary so much that an autoinjector system may be subject to failures such as incomplete injections.
The majority of today's autoinjector delivery systems include glass prefilled syringes that are inserted by the pharmaceutical
manufacturer. The products are sold as single-dose, disposable injection systems.
Glass creates the possibility of breakage, which is a safety concern. Upon activation, the system's spring places all of its
pressure on the syringe's glass flange. The flange is the weakest point of a syringe; it snaps off if subjected to enough
pressure. In autoinjectors, a strong spring is required to overcome variability in the sustaining force or inconsistent siliconization
in a glass prefilled syringe. Viscous drugs require more pressure for a complete injection. This pressure can lead to breakage
or an incomplete injection. A change in the place where pressure is applied, or registered, can greatly affect the safety
of the delivery system.
Overcoming autoinjectors' limitations
The simple technique of registering the force of the injection on the syringe's shoulder or nose instead of the flange creates
two benefits for glass and plastic syringes. First, it places the pressure of the spring on the strongest part of the syringe,
which reduces the risk of glass breakage.
Second, registering force on the nose or shoulder compensates for the dimensional variability associated with glass syringes.
For example, if the overall length of the syringe is too great, registering the pressure at the flange could affect the performance
of the injection. In contrast, registering force at the shoulder makes it easier to know precisely where the end of the syringe
is during needle insertion and dose delivery. The depth of needle insertion is much more consistent with this technique than
it is when the syringe is supported at the flange.
The ConfiDose autoinjector system from West (Lionville, PA) is an example of this change in design, which is meant to facilitate
injections. The ConfiDose system is registered on the shoulder. The system also eliminates some steps of the injection process,
which can be beneficial to patients. The three-step operation of ConfiDose automatically inserts the needle, delivers the
complete dose, and retracts the needle from the injection site, thus leaving the delivery system safe for disposal. The autoretraction
technology may help alleviate pain for those with poor dexterity, as opposed to manually removing the needle.
Syringes made of cyclic olefin polymers have advantages for autoinjector systems such as tighter dimensional tolerances, increased
resistance to breakage, and consistency of the travel forces over time. The combination of an autoinjector delivery system
with a plastic syringe can help ensure a level of drug stability for manufacturers and provide end users with reliable product