The USP <1207> Package Integrity Evaluation of Sterile Products provides an overview of relevant and acceptable test methods that may be employed in meeting you package system qualification requirements. Developing a basic understanding of these methods will enable you to make a more informed decision on the most effective test approach for your specific container and package system. In this educational document, we provide an overview of the High Voltage Leak Detection method.
High voltage leak detection is an approach for detecting the presence, and potentially the location, of a leak(s) in the wall of a nonporous, rigid or flexible package containing liquid or semi-liquid product. Numerous instrument parameters exist, which must be optimized. As with all CCI technologies, an HVLD method must be developed and validated for its intended use specific to the package and product it is intended to hold.
High voltage leak detection operates on the principle of electrical conductivity and resistance. A sample is rotated on a platform as voltage and detection probes located on opposing sides of the sample physically scan the geometry of the package during test. The voltage probe emits a current, and the detection probe measures voltage received as a function of travelling through the container. In a non-leaking package, the walls of the package on either side of the liquid cavity act as capacitors, insulating the liquid-filled cavity, the resistor, from the current. Thus, a relatively low voltage will be registered by the detection probe when testing an integral package. In a leaking package with a defect, such as a crack in a vial wall, capacitance on one side is eliminated, enabling flow of current to the high-conductivity liquid, and in turn yielding a higher voltage reading registered by the detection probe of the instrument.
Parameters such as voltage applied, detection board gain value (sensitivity), and probe movement speed and pattern must be tailored specifically to the product-package system in question. These parameters are optimized during method development to yield a measurable and repeatable difference between negative and positive controls. Method limit of detection is typically down to 2-3 microns in nominal defect size, however, specific product-package attributes impact this, and acceptance criteria should be justified with robust statistical analysis. Even in ideal circumstances, HVLD is unable to test to the maximum allowable leakage limit (MALL) of most products but remains the go-to analysis for liquid product-filled packaging, but as part of a broader CCI test and control strategy incorporating helium or headspace analysis in package development phases.
Because HVLD relies on “flow” of current rather than flow of gas or liquid to indicate leakage, there are fewer challenges with defect clogging when compared to other flow-based analyses such as vacuum decay. A defect that prohibits flow of gas or liquid may still conduct current. However, because defective samples behave similarly regardless of defect size, but dependent on physical location and distance to the probes, HVLD is quantitative and deterministic in that it is predictable and measurable, but results are typically interpreted qualitatively as Pass / Fail. Linearity of test results relative to defect size is not intended. HVLD is considered nondestructive in many cases, so long as exposure to high voltage does not have a negative effect on any product quality attributes, something that should be evaluated in each case.
When developing and validating High Voltage Leak Detection CCI methods, CS Analytical uses state-of-the-art Micro-Current HVLD Systems that represent the cutting edge of best practices. Micro-current systems show promising improvement with respect to their ability to remove noise from the measurement process, minimize impact to product quality, and maximize leak response even with very low-conductivity solutions.