The USP <1207.2> Package Integrity Leak Test Technologies provides an overview of relevant and acceptable test methods that may be employed in meeting your package system container closure integrity testing (CCIT) requirements. Developing a basic understanding of these methods will enable you to make a more informed decision on the most effective test technology for your specific product, package system, and study goals. In this educational document, we provide an overview of the applications of a USP <1207> High Voltage Leak Detection method and current challenges they may present.

A High Voltage Leak Detection (HVLD) test method can be a powerful tool for evaluating the container closure integrity (CCI) of your product-package system when the right conditions are met. Product-Package requirements are defined as being “Rigid or flexible packages of nonporous components containing liquid or semi-liquid product”. However, USP <1207> lists several additional requirements, some of which present challenges that are unique to High Voltage Leak Detection. Such examples of the application of HVLD, as described in USP<1207.2> and common examples of challenges include:

“Package components must be relatively electrically nonconductive.  Product must be electrically conductive, relative to the package”

Recent improvements to HVLD systems include the ability to test samples with low conductivity, including sterile water for injection (WFI).  However, careful consideration should be given to packages containing products with extremely high conductivity, as this may potentially affect the variability (noise) of the signal, requiring thorough optimization of all test parameters to properly differentiate between negative and positive controls, which may decrease the sensitivity (limit of detection) of the test method.

“Product must not be flammable, or at risk of combustion”

Certain products that contain any concentration of alcohols may need to be evaluated by the OEM for compatibility, however, small amounts do not immediately disqualify the product from evaluation by an HVLD test method.

“Product must be near or at the leak inspection location at the time of the leak test.”

A liquid-filled vial product package system would likely contain some amount of headspace, whether that headspace is ambient air or a back-fill of inert gas.  It is also common for a pre-filled syringe to contain some amount of headspace as well – even if only a small bubble. Rotation of the sample during testing serves to keep internal surfaces wet. However, depending on several factors, challenges may exist with even the most standard product-package systems.

For example, a 1mL glass syringe with .5mL of a viscous liquid and 3mm of headspace near the plunger would significantly decrease the likelihood of detecting defects near the plunger.  Additionally, if a vial turned on its side (the orientation required for HVLD testing) is observed to have a liquid level that does not reach the neck of the package, the reliability of detecting defects in the neck of the vial would be reduced.

These two examples would not immediately disqualify the package from evaluation by an HVLD method- depending on the unique combination of package dimensions, headspace, and fill level, a proceduralized sample preparation of the test units may be necessary to ensure that liquid is present at all regions of the package to maximize reliability and sensitivity of the High Voltage test method.

“Solidified, electrically conductive product that blocks leak paths may be detected.”

As the properties of HVLD require a “flow” of current, rather than a flow of gas or liquid, clogged defects are not an inevitable setback for successfully developing and validating an HVLD test method as they may be for pressure-based analyses such as vacuum decay. However, careful consideration should be given during the development phase regarding the potential for dried product to limit the flow of current to maximize chances of successful and reliable validation of the test method.

“Metal caps used to seal stoppered vial or cartridge packages conduct current, improving the likelihood of finding leaks under a cap”

Package systems with different materials, such as glass vials stoppered with a metal crimp cap, present a challenge when developing and validating a high voltage test method. As the inspection probe scans the entirety of the package at a steady voltage, the varying resistivity of the materials may result in loss of sensitivity and reliability of a test method. As a recent improvement to PTI’s E-Scan 655 has the ability to subject different parts of the package to different amounts of voltage which increases both sensitivity and reliability of the test method.

Despite these challenges, HVLD remains a top choice for the evaluation of container closure integrity of the right product-package system. When developing and validating High Voltage Leak Detection test methods, CS Analytical uses state-of-the-art Micro-Current HVLD Systems that represent the cutting edge of best practices to maximize the sensitivity and reliability of your test method.