Technology Introduction USP <1207> | Helium Leak Testing (Mass Spectrometry)

In a retrospective published in 1991, Albert Nerken traces the origins of helium leak detection to development of the Uranium 235 bomb via the Manhattan Project. The process and equipment designed to isolate this U (235) isotope required the absolute absence of ambient moisture, and thus, leak assurance 500 times lower than commercially available equipment at the time. To test the 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: speed, sensitivity, and selectivity.

Since its introduction and subsequent commercialization as a technology following WWII, 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. An ASTM standard for testing package systems is available for reference: ASTM F2391-05 (2011) – “Standard Test Method for Measuring Package and Seal Integrity Using Helium as the Tracer Gas”.

Principle of Operation USP <1207> | Helium Leak Testing (Mass Spectrometry)

Although 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.

Applications and Limitations USP <1207> | Helium Leak Testing (Mass Spectrometry)

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.

The team at CS Analytical consists of founding members of the world’s first cGMP, FDA-registered contract CCI laboratory housing all deterministic technologies as listed in USP <1207>. The resulting laboratory set standards and best practices for industry still used today, many of which are directly incorporated into USP <1207>. CS Analytical is the most trusted source for advisory services on CCI method selection, and creating and implementing methods using 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.