Applications of HeLD to Cartridge Package Development and Validation

In a recent blog, we discussed the application of helium leak detection (HeLD) as part of a capping optimization study or assembly validation for glass and plastic vials. A defining characteristic of helium leak detection, instruments such as the SIMS 1284+ have sensitivity capable of measurement below the maximum allowable leakage limit (MALL) of many pharmaceutical and medical device products. This allows for study-based comparisons and data-informed decision making at a very fine scale. More importantly, these types of studies can be used to support regulatory documentation and in fulfillment of guidance such as USP <1207>.

While applications of this approach to vials are well established, if increasingly popular, very similar approaches can be taken for other common package systems used in the industry. Cartridges, which are frequently used as part of a device delivery system, are one such format. Similar to a traditional vial, one end of a cartridge is typically sealed with an elastomer-lined crimp. Compared to that of a 20mm or 13mm vial, cartridge crimp seals are relatively small and intricate. On the other end, a cartridge is typically sealed by an elastomeric plunger, similar to that which may be found on a syringe. Each of these unique sealing interfaces present specific challenges from a CCI perspective.

Considering the crimp interface of the cartridge, similar studies as for a vial can be performed to optimize and validate component choice as well as assembly parameters and processes. Comparative studies can be performed to choose the most robust cartridge-seal combination given machinability limits. Studies involving multiple crimp configurations, in conjunction with HeLD and RSF, can help elucidate a set of capping parameters that consistently yields an integral seal with low leakage. As with vials, it is possible that dimensional stack-ups, in conjunction with limitations in machinability, yield defects such as loose crimps, misaligned seals, stress cracking from high crimp force, etc. Characterizing these risks through quantitative, deterministic analyses can inform mitigation strategies and quality decision making about the assembly process. With final components and assembly parameters chosen, assembly validation using cartridges capped real-time can be performed, fulfilling best practices outlined through industry standard guidance such as USP <1207>.

Unlike the crimp-sealed end, the barrel end of a cartridge is less a function of an applied force. However, similar optimization and assembly validation practices apply. As with any package system requiring a high degree of leak protection, early on in the development process, the inherent integrity of the chosen product-package system should be evaluated, essentially answering the question: “Are these components, when mated optimally, capable of creating an integral seal?”. This extends to the choice of suitable barrel-plunger interfaces as well. Arguably, since the barrel-plunger interface is not a function of a controllable process such as crimping, inherent integrity evaluations become even more critical. The achieved seal will be primarily a function of the dimensional overlap between the cartridge inner diameter and the plunger outer diameter.

In a laboratory setting, consider a study designed to evaluate barrel-plunger samples paired at dimensional extremes. Within their respective dimensional tolerances, the widest barrel inner diameter paired with the smallest plunger presents the highest risk for leakage, as there may be insufficient or inconsistent compression of the plunger against the cartridge wall. On the other hand, consider the smallest barrel inner diameter paired with the widest plunger. In this case, it is critical to ensure proper function, lack of stress-related defects such as cracking or fitment-related issues risking leakage, such as mis-aligned plungers. A study exploring these dimensional extremes provides confidence that components, within their dimensional stack-up ranges, will provide integral seals. This can be further confirmed by assessing real-world cartridges assembled on the line.

This type of work can be performed at a production facility, using client-owned instrumentation or in-house contract services. Additionally, LDA’s sample filler allows for sample preparation at time of test, enabling analysis of samples previously produced and sealed, or transfer of samples between manufacturing and testing sites. With increasing regulatory scrutiny as well as risk in poor package development and validation practices, helium leak detection, as enabled by the LDA SIMS 1284+ system, is a versatile tool in generating a robust foundation of CCI data for modern package systems

2019-06-26T21:45:55+00:00