Nov 2020

Helium Leak Detection for Prefilled Syringes -Inherent Integrity

Helium Leak Detection for Prefilled Syringes – Inherent Integrity

In two recent blogs, we’ve discussed the practical applications of helium leak detection to vial and cartridge package systems. A vial, with its single compression-based seal, can be readily tested by helium leak detection in cases to optimize sealing parameters, validate assembly, routinely test production samples, etc. On a cartridge, the compression-based crimp seal can be similarly tested and optimized. On the opposing end, an elastomeric plunger relies on a compression fit against the syringe barrel based on the dimensional overlap of the two components. This seal can be similarly assessed by helium at dimensional extremes to further demonstrate inherent integrity and robust understanding of the package assembly process.

While cartridge-based and specifically vial-based systems represent the majority of pharmaceutical and biotech industry package formats, the rate of one group’s growth far exceeds its peers: prefilled syringes (PFS). From a human factors and dose-delivery perspective, the benefits of a prefilled syringe format over a traditional vial-based injection can be myriad. Not the least is their ability to be incorporated into single-use autoinjection and safety systems. However, the PFS, and autoinjection systems in particular, present unique challenges from a CCI testing standpoint.

In a combination product autoinjection system, most frequently the syringe is fully housed inside of a device. This limits direct access to the product-containing portion of the package, preventing some technologies from being feasible from an analytical standpoint. Further, the product inside is liquid, contributing to increased challenges when testing using a vacuum-based technology. Frequently, this means that testing a fully-assembled injection system for CCI is infeasible or not sensitive enough to provide meaningful assurance. It is in these cases especially that fully characterizing the inherent integrity of the primary package, the syringe, is critical for reducing risk downstream with respect to package integrity.

Much like its application to vial and cartridge systems, helium leak detection is well suited for inherent integrity evaluations of prefilled syringes, regardless of whether their final destination is housed inside of a device body. Similar to cartridge systems, the plunger seal of a PFS system relies on a compression fit between an elastomeric plunger and the syringe barrel. Studies evaluating the inherent integrity of this fit provides insight into the quality of the seal that is likely to be present in final production units. Similarly, helium leak testing at the extreme ranges of the dimensional tolerance stack-up between the barrel inner diameter and plunger outer diameter can ensure integrity at the full range of possible dimensional combinations. This type of study can yield significant insight into seal robustness.

The opposing end of a PFS is unique in that it includes a staked needle or luer-type connection for a needle to attach. From a helium leak testing perspective, however, there is nothing unique about it. The product-holding volume of the syringe is filled with helium while the needle region of the PFS is exposed to vacuum. If a leak is present, helium will migrate through the leak path and result in an increase in helium leak rate measured by the system. Complete syringe units can even be tested by sealing the opposing end with a plunger and subjecting the entire package to vacuum in a chamber, though proper fixturing is required.

In addition to the unique configuration on a PFS, the staked needle or luer lock seal of a PFS also has another unique property. Since prefilled syringes are supplied as assembled units to drug manufacturers and CMOs, they are one seal not subject to optimization or validation during the manufacturing process. Whereas the plunger seal can be characterized by helium as a function of the compression fit between the two components, the dimensions of which can be monitored, the needle end of a PFS is subject to supplier practices. For this reason, some manufacturers also choose to implement helium leak detection of PFS units on an incoming lot inspection basis, as would be done for component dimensions. This provides some level of ongoing integrity assurance of these unique package systems in the production process. The SIMS 1284+ helium leak detector routinely and successfully supports these types of studies and ongoing analysis to fulfill modern CCI guidance and requirements.

helium leak testing, helium leak detection for prefilled syringes
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