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Maintaining the integrity of products from the time it is manufactured to the time it is distributed to the patient is a great challenge. Liquid pharmaceuticals, capsules, and formed tablets are typically packaged in bottles. To assure the quality of these items, leak testing is carried out on each bottle to ensure that it does not leak. Testing pharmaceutical bottles or pharmaceutical package leak detection before filling is a critical step in ensuring the integrity of the container.

Helium leak testing is one of the most sensitive Container Closure Integrity (CCI) testing techniques that can be applied to pharmaceutical bottles for testing quality. Helium is used as a tracer gas, and the quantity of helium leaving through the package is measured and stated as leak rate. Since it is non-toxic, non-flammable, and non-condensable, helium is an ideal tracer gas for finding leaks. Its atmospheric presence is restricted to 5ppm. Due to its tiny atomic size, helium can easily pass-through leaks. Helium is also safe to use since it does not react with the materials of the components under test.

Significance of Helium Mass Spectrometry in Leak Testing Pharmaceutical Bottles

Helium mass spectrometry is a leak detection standard for pharmaceutical containers including bottles. Helium mass spectrometer, a commonly used instrument detects and locates tiny leaks. It usually works with a vacuum chamber and a sealed container filled with helium. A mass spectrometer detects the rate at which helium is leaking out of the container. This method uses tracer gas - helium to fill the product attached to the detector. The tested product leaks helium into the detector, where its partial pressure is measured and displayed.

The leak detector's principle is based on a sector field mass spectrometer. In vacuum, entering helium gases are ionized. The helium ions are then accelerated by adding voltage and then separated in a magnetic field. The ion current is converted to an electric current by using a particular detector. This current is accelerated using leak detection units and displayed on the screen. The current measured will be directly proportional to the concentration of helium and therefore equal to the leak measured.

Applications of Helium Leak Detection

• Ensure container closure integrity.
• Seal integrity monitoring during stability studies.
• Verify and predict shelf-life seal integrity.
• Useful in the early stages of the development of a pharmaceutical product packaging system.
• Closure formulation and configuration selection.

Bottles are useful in the healthcare industry, hence evaluating them is a challenging task nowadays. These containers are extremely difficult to test, however, helium leak detection can be used to qualify them prior to use or as a proof of concept. LDA provides professional engineering solutions for the Active Pharmaceutical Ingredient (API) sterile container testing.

Blister packaging is a type of pre-formed plastic packaging that includes a base card with artwork and a clear plastic pocket called the blister. The cavity, which is composed of either plastic or aluminum foil, and the lid, which is made of paperboard, paper, plastic, or aluminum, are the two main components of blister packaging. The product is enclosed in the cavity, and the lid seals the package. Blister packing is used in the pharmaceutical industry to pack tablets, pills, capsules, granules, and lozenges. Blister packaging gets its name from the fact that each item is kept within its own small plastic bubble or blister. Blister packs can provide tamper resistance as well as barrier protection for shelf-life requirements.

Due to its extreme sensitivity, a helium-based test method is used for verifying the integrity of the blister pack. The test method operates by detecting helium that has been enclosed in the package system and is escaping through micro-channels in the package. This test sequence begins with the package being placed in the test fixture and immediately drawing a vacuum. The helium thus escapes through potential holes or cracks in the packaging as a result of the pressure differential.

Blister Pack Leak Testing Using Helium Mass Spectrometry

The Mass Spectrometer Leak Detector is a comprehensive system for locating and detecting leaks within or outside of product. This approach employs the use of helium as a tracer gas, which is utilized to fill the product attached to the detector. Helium leaks into and out of the tested product, causing its partial pressure to be measured and shown on a screen.

The leak detector works on the principle of a sector field mass spectrometer. Helium gas is ionized in a vacuum. Helium ions are accelerated and separated in a magnetic field using additional voltage. The ion current is converted to an electric current using a specific detector. The current is accelerated by leak detection units and displayed on the screen. The measured current is proportional to the helium concentration and equal to the observed leak. Helium leak detection using helium mass spectrometry is widely known for its suitability for packaging such as blister packs.

Helium Leak Detection Benefits

• With a high degree of sensitivity, leaks can be identified and measured
• No effect on the materials under test, due to the inert properties of the helium
• The testing procedure is mostly dry and temperature-independent
• Helium leak testing has a faster cycle time, which reduces the cost and overall processing time

Helium leak detection offered by Leak Detection Associates (LDA) can greatly improve the safety and health of blister package users. Blister packaging ensures that tablets and capsules are properly sealed. It is simple to do a leak test after packaging. Blister packaging is popular because of its convenience of packing, easy dosing for the patient, with its popularity increasing for many new drug solid dose/oral dose products.

Using helium as a tracer gas is the most sensitive and commonly used tracer gas leak detection technique for CCI. When moisture-sensitive pharmaceutical products are lyophilized, their shelf life is extended, and they are better prepared for storage and transportation. A lyophilized medicinal product's quality is ensured by maintaining consistent moisture content. Proper container closure system (vial, stopper, seal) selection and sealing conditions are equally important factors. Demonstrating Container Closure Integrity (CCI) is one way of achieving this goal.

Why use helium?

Helium gas is one of the smallest molecules. In addition to being non-flammable, non-destructive, non-toxic, and inert, helium only has a trace presence in the atmosphere. Helium is generally safe to employ (compared to hydrogen) since it will not react with any of the components in the test part. Mass spectrometers detect helium in the vast majority of leak testing applications. A residual gas analyzer, on the other hand, is also an option. In general, helium leak testing ensures higher levels of sensitivity than conventional pressure decay methods.

Tracer gas method to test seal integrity

Tracer gas leak testing is a simple and very effective way of detecting leaks that offer great sensitivity, accuracy, and repeatable results. Being one of the most effective method of leak detection, tracer gas leak testing offers great sensitivity and accuracy. Micro-leaks between 1x10-4 to 10-9 scc/s can be detected using the tracer gas leak test, which utilizes the tracer gas - helium. Tracer gas leak testing can be done with either pure helium or by mixing it with another gas such as nitrogen or dry air to reduce the overall cost. A mass spectrometer is used in the standard test method for measuring package and seal integrity. Due to its low concentration in the atmosphere, and its detection using a mass spectrometer, helium is employed. It is done by injecting helium into sealed packages or adding it to sealed package’s headspace after sealing. In the following step, a mass spectrometer is used to identify and measure the presence of helium in the surrounding enclosed space.

Vacuum test method is the commonly employed tracer gas method for testing the seal integrity of pharmaceuticals products. In this method, seals are put under stress by a vacuum, which measures tiny leaks. Helium transfer rate captures the real transmission rate through the material as well as via the seals. Transmission of helium through the material as well as seals is captured by helium transmission rate. As a result, the vacuum technique is more effective in detecting leaks since it monitors helium gain in the external environment within the enclosed sample.

When packaging seals are tested for integrity, it helps guarantee that the packaging offers necessary product protection for patient safety. To ensure product quality, package seals must be reliable. Seal integrity tests are commonly used to evaluate sustainable packaging options, lower-cost packaging, and changes in manufacturing line sealing parameters, among others. Evaluating the seal strength of packing materials with reduced costs and alternative sealing procedures confirms that the seals do not leak over time.

Leak Detection Associates (LDA) designs and manufactures high-performance tracer gas (helium) leak detection systems to ensure the integrity of seals for the pharmaceutical and biological industries. Helium leak detection is the one of the most effective leak detection method to identify and locate leaks in a closed system.

In World War II, helium mass spectrometry was used in Uranium enrichment plants for leak detection. This approach is still in use today, with some adjustments, as it is regarded to be one of the most accurate ways for locating leaks. Helium gas is utilized in this approach as a tracer gas. This occurs when helium leaks in/out of the tested product and enters the detector, where its partial pressure is recorded and shown on a screen. Leakage is detected using an instrument called a Helium Mass Spectrometer, which also measures the rate of leakage.

Principle of helium leak detector

Leak Detector works on the concept of a sector field mass spectrometer. Containers that need to be tested for leakage are usually filled with Helium and put in a vacuum chamber. The tracer gas helium is ionized in a vacuum after analysis. With the addition of voltage, helium ions are accelerated and then separated in a magnetic field. Using a particular detector, the ion current is converted to an electric current. Leak detecting units accelerate the current and display it on the screen. Helium concentration determines the measured current, which is equivalent to the measured leak.

What makes helium suitable for leak detection?

Due to its numerous advantages, helium is the ideal choice for leak detection purposes.

• Non-toxic and non-flammable
• Inert and non-condensed
• Low cost
• Due to its low atomic mass, it can easily pass through even very small leaks
• Present in the atmosphere, only in trace amount

Leak detection methods using helium mass spectrometer

There are two primary methods of testing: vacuum testing and pressure testing. The goal is to find the leak and determine how much or how fast it is leaking. When using either technique, it's vital to maintain circumstances that are comparable to what the system would encounter in real life.

As part of the vacuum testing, the leak detector is inserted into the system or product that has to be tested for leaks. In order to remove air from a system and create a vacuum, a pump is utilized. Helium is then sprayed on locations where the leakage is likely to occur. Spraying should be done with proper care to ensure that no portion of the body is skipped. As soon as the detector detects a leak of Helium, it alerts the user. This approach is also known as the spray probe method, or the spray probe technique.

Under pressure testing, the product must be placed within a vacuum chamber that has been properly constructed. Helium is pumped into the chamber, and the detector is used to check for leaks. This method is also known as the sniffer probe method. Helium filled system put in a chamber with a detector attached to a vacuum pump is another mode of this approach for determining leakage rate. If there is a leak, Helium will leak out of the pump and the detector will calculate the rate of leaking once the pump is running.

Helium mass spectrometry can be used in a variety of ways to discover extremely small leaks.