Helium Leak Detection

Helium leak testing is a highly sensitive container closure integrity testing method used to detect and quantify small leaks in pharmaceutical packaging and medical device components. By using helium as a tracer gas and a helium mass spectrometer as the detector, the method provides objective leak-rate data for package development, process validation, quality investigation and stability studies.

Zholion provides helium leak testing equipment, laboratory testing and method development support for different pharmaceutical packaging systems.

 

What Is Helium Leak Testing?

 

Helium leak testing, also called helium leak detection or helium tracer gas testing, measures the amount of helium passing through a package defect or closure interface.

Because helium is chemically inert, has a small atomic size and is present at a relatively low concentration in the surrounding atmosphere, it can be detected at very low levels. This makes the method suitable for evaluating microleaks that may not be reliably identified by traditional dye ingress or bubble testing.

Helium leak testing can be used to evaluate:

• Package and closure design
• Sealing and assembly parameters
• Container closure integrity
• Package performance after transportation
• Package integrity during stability studies
• Root causes of package leakage
• Changes in packaging materials or suppliers

 

Test Principle of Helium Leak Testing

 

The detection principle relies on helium mass spectrometry. The sealed container is either filled with helium (introduced into the headspace before sealing) or externally flooded with helium under controlled conditions. A helium mass spectrometer leak detector measures any escaping helium that passes through leak pathways.

If the measured helium leak rate exceeds a pre-established threshold, the container closure system is deemed non-integral. Conversely, a helium leak rate below the threshold indicates integrity. 

 

Why Is Helium Used as a Tracer Gas?

 

Helium offers several characteristics that make it suitable for high-sensitivity package leak testing:

• Small atomic size for detecting fine leak paths
• Chemically inert and non-reactive
• Non-toxic under normal testing conditions
• Low natural background concentration
• Fast response during mass spectrometer testing
• Suitable for quantitative leak-rate measurement
• Compatible with different package and closure designs

The actual test sensitivity depends on the equipment, package preparation, fixture design, helium concentration, pressure conditions and test procedure.

 

Test Equipments in Our Lab

 

PTI 1915+, Zholion MC-H52

 

 

Regulatory Requirements

USP<1207>

 

USP <1207> explicitly lists tracer gas leak detection with helium as a deterministic leak test method.

 

USP <1207> states that deterministic leak test methods using laser-based gas headspace analysis and helium leakage are those with the highest sensitivities.

Helium leak detection is classified as a deterministic technique, which USP <1207> strongly recommends over traditional probabilistic methods (dye ingress, microbial challenge) due to higher sensitivity, objectivity, and reproducibility.

USP <1207> references ASTM F2391 as the recognised consensus standard for helium tracer gas leak testing for package systems.

Method validation is required to demonstrate reliable detection of leaks at the product-specific Maximum Allowable Leakage Limit (MALL). Helium leak detection's high sensitivity allows testing to the MALL of most products.

 

USP 382

 

USP <382> points directly to USP <1207> for container closure integrity testing methodologies.

 

System-level integrity assessment using deterministic CCIT methods — including helium leak detection, high-voltage leak detection, vacuum decay, and laser headspace analysis — is required by 1 December 2025.

Deterministic methods are strongly recommended over traditional probabilistic methods.

 

EU GMP Annex 1

 

EU GMP Annex 1 contains container closure integrity requirements that are met using deterministic methods, including helium leak detection.

 

Deterministic CCI methods — including vacuum decay, HVLD, and helium leak detection — deliver results aligned with USP <1207> and global standards for Annex 1 compliance.

Helium leak detection is frequently and successfully used to explore, develop, and validate assembly parameters, and studies can be developed to evaluate the impact of distribution and storage on integrity as well.

Helium leak testing allows for a quality-by-design approach to package integrity, thus reducing the tendency to "test in" quality downstream.

Container closure integrity validation is mandatory for all sterile products. Deterministic methods are recognised as compliant with Annex 1 integrity requirements.

 

Sterile Pharmaceutical Packaging System Integrity Guideline Principles (2024, China)

 

In June 2024, the Chinese Pharmacopoeia Commission released the "9628 Sterile Pharmaceutical Packaging System Integrity Guideline Principle" (second draft) and "9650 Sterile Pharmaceutical Packaging System Integrity Guideline Principle" (first draft). These guidelines include deterministic CCIT methods and refer to approaches consistent with USP <1207>.

 

The 9650 guideline defines deterministic leak test methods as those "based on a series of predictable physical phenomena to detect or measure leakage — based on easily controllable and monitorable physical/chemical techniques, providing objective, quantitative data".

The guidance states: "Sealing test methods can be divided into two categories: deterministic methods and probabilistic methods".

While the 9628/9650 guidelines explicitly list vacuum decay, high-voltage leak detection (HVLD), and laser headspace analysis, helium leak detection — as a tracer gas method — is recognised as an advanced deterministic CCIT method under the framework of high-sensitivity integrity testing.

 

 

Packages Suitable for Helium Leak Testing

 

Helium leak testing can be developed for a variety of pharmaceutical packaging systems and sealed components, including:

• Pharmaceutical vials
• Ampoules
• Prefilled syringes
• Cartridges
• Injection pens
• Auto-injector components
• Stoppered glass containers
• Rigid and semi-rigid packages
• Medical device components
• Package seals and closure interfaces

Different container shapes and materials may require customized chambers, connectors or fixtures. Package samples and technical drawings should be evaluated before the test method is finalized.

 

Applications of Helium Leak Testing

Package Development

Helium leak testing can compare different container materials, stopper designs, closure systems and sealing configurations during package selection.

Sealing Process Optimization

The method can help evaluate capping force, stopper compression, sealing pressure, assembly position and other critical process parameters.

Method Development and Validation

Known-defect positive controls and intact negative controls can be used to establish detection capability, repeatability and an appropriate operating range.

Stability and Transportation Studies

Packages can be tested before and after storage, freeze-thaw exposure, temperature cycling, vibration or transportation simulation to determine whether integrity has changed.

Failure Investigation

Helium testing may help identify whether leakage originates from a package component, closure interface, seal channel, microcrack or assembly problem.

 

Advantages of Helium Leak Testing

• High sensitivity for detecting microleaks
• Quantitative leak-rate results
• Objective and repeatable measurement
• Suitable for package development and validation
• Can support leak-location investigations
• Applicable to different container and closure systems
• Useful for comparing sealing process parameters
• Suitable for laboratory and quality investigation applications

 

Frequently Asked Questions-Helium Leak Testing

 

Is helium leak testing destructive?

In many sealed pharmaceutical package applications, the package must be filled with helium, connected to a fixture or exposed to pressurized helium. Therefore, the tested sample is often considered unsuitable for normal product use afterward.

What does a helium leak test measure?

The method measures the rate at which helium passes through a package defect, seal or closure interface. The result is normally expressed as a helium leak rate rather than only a qualitative pass-or-fail result.

Can helium leak testing locate a leak?

A sniffer or spray method can help identify the approximate location of a leak. A vacuum chamber method mainly measures the overall leakage rate of the package.

How is the acceptance leak rate determined?

The acceptance criterion should be established based on package design, product sensitivity, microbial barrier requirements, gas or moisture protection requirements, stability data and the product-specific integrity control strategy.

Is helium leak testing suitable for vials and prefilled syringes?

Yes. Helium testing can be developed for vials, prefilled syringes, cartridges and other pharmaceutical packaging systems. Customized fixtures and helium preparation methods may be required.

What is the difference between helium leak testing and vacuum decay?

Helium leak testing uses helium as a tracer gas and offers very high sensitivity and quantitative leak-rate measurement. Vacuum decay detects changes in pressure inside a sealed test chamber and can provide non-destructive testing without introducing helium into the package.

Does helium leak testing require calibration?

The equipment and test method should be verified using suitable reference standards or known-defect samples. Calibration, background checks and system suitability testing help ensure reliable and repeatable results.

What information is needed before testing?

Customers should provide the package type, dimensions, materials, closure structure, product state, expected leak level, test objective, sample quantity and applicable regulatory requirements.

 

Request a Helium Leak Testing Solution

 

Not sure whether helium leak testing is suitable for your pharmaceutical package or medical device component?

Send Zholion your package samples, drawings and testing requirements. Our technical team can help evaluate the package, select an appropriate testing method and develop a reliable container closure integrity testing solution.