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 a history and overview of the use of helium as a leak testing method.

The use of helium as a leak testing method can be traced back to the Manhattan Project. To test the U (235) isotope isolation assembly, a mass- spectrometry-based helium leak detector was first conceived and chosen for development, its candidacy hinging on many of the same reasons it is still used today – it could provide the speed, sensitivity, and selectivity required for the mission. Since this first unique use, helium leak detection has been used across a range of industries including automotive, semiconductor, and, of particular interest to life sciences companies: pharmaceutical, biotech, and medical device products. Use of helium leak detection in the life sciences industry ranges from leak testing of process or production equipment, much in the way they were first used in the 1940s, to testing of sealed packages or hermetically sealed devices such as pacemakers. Guidance on its use as a test method can be found in an ASTM standard for testing package systems: ASTM F2391-05 (2011) – “Standard Test Method for Measuring Package and Seal Integrity Using Helium as the Tracer Gas”.

While the application of helium leak detection may vary with equipment, test article, study objective, and other variables, helium leak detection from an analytical measurement standpoint is fairly-consistent. Modern helium leak detectors operate using a series of pumps and internal valves referred to as a vacuum circuit, of which a mass spectrometer is part. Internal pumps draw vacuum on an orifice, which could be connected to a host of items such as sniffer probes, test chambers containing units to be tested, or test articles themselves. Escaping or travelling gas passes through an analyzer cell, which measures the helium leak rate. While the design of detectors and certainly application of helium leak detection may vary, generally, operation adheres to the principles described above. By manipulating test sample preparation, as well as what the vacuum circuit is connected to, methods to test using helium leak detection can be tailored. Different methods, alternately called techniques, approaches, or procedures, can expand the use of helium leak detection.

Understanding its use and limitations can be critical. Helium leak testing is typically destructive. Although advantages and limitations of helium may vary slightly according to the approach taken, helium leak detection as a test methodology shares some common elements. As helium is small, nonreactive, and atmospherically rare, helium leak testing is both selective and sensitive: only helium is being measured, down to very low leakage rates, without substantial interference from other atmospheric gases or moisture. Additionally, the vast array of potential connections, fixtures, chambers, and probes to a helium leak detector make its application extremely flexible within the bounds of its limitations, which include helium permeation through porous materials and the preference for samples to be run empty – an attempt to prevent leak path blockage and machine contamination. For these reasons, helium leak detection is not a one-size-fits all test but remains an invaluable tool in the package development arena, it is frequently incorporated into comprehensive container closure integrity and CCI control strategies. Its sensitivity allows for testing to the maximum allowable leakage limit (MALL) of most products, and its flexibility enables numerous study goals, including leak testing at cold temperatures down to -80°C or lower, such as liquid nitrogen deep storage and vapor phase, as well as plunger movement studies, and integration into capping studies.

When developing and validating helium based CCI methods, CS Analytical uses the state-of-the-art Leak Detection Associates SIMS 1915+ helium leak test systems and sample chillers that represent the cutting edge of best practices with respect to CCI testing.