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In the pharmaceutical, biotechnology, and medical device industries, the integrity of product packaging is critical to ensure product safety and efficacy. Container Closure Integrity (CCI) refers to the ability of a container closure system to maintain a sterile barrier against potential contaminants throughout the product's lifecycle. A failure in CCI can lead to product degradation, contamination, or sterility breaches, which can have serious health and economic consequences. To mitigate these risks, robust CCI testing methods are employed, with deterministic test methods emerging as the preferred approach due to their reliability and precision.

Container Closure Integrity is essential in preventing the ingress of microorganisms, moisture, or gases into sterile products, particularly in the pharmaceutical and medical sectors. As regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) emphasize the importance of CCI testing, manufacturers are increasingly adopting advanced methods to verify package integrity.

CCIT methods can be broadly classified into two categories: probabilistic and deterministic methods. Probabilistic methods, such as dye ingress and microbial ingress tests, are less reliable as they depend on operator technique and can be highly variable. Deterministic methods, on the other hand, are based on physics and provide more accurate, reproducible, and quantitative results.

Understanding Deterministic CCI Test Methods

Deterministic CCI test methods are designed to detect and quantify defects in packaging with a high degree of precision. These methods are non-destructive, highly sensitive, and capable of providing exact measurements for defects down to the sub-micron level. Unlike probabilistic methods, deterministic tests are not subject to operator variability and environmental conditions, making them ideal for ensuring reliable, repeatable results.

The following key principles differentiate deterministic test methods from probabilistic ones:

• Quantitative Data: Deterministic tests offer numerical data regarding the size and location of defects, which allows for better decision-making.
• Non-destructive Testing: Many deterministic methods allow testing without damaging the product or packaging.
• High Sensitivity: These methods can detect microleaks that may be missed by traditional probabilistic techniques.
• Repeatability: Consistency in results makes deterministic methods the preferred choice for regulatory compliance.

CCI Test Methods Offered by PTI

1. Vacuum Decay Technology

Vacuum decay testing is widely regarded as one of the most effective and precise vacuum-based methods for detecting leaks in packaging. This method offers quantitative measurements that are consistent, reliable, and accurate, along with clear pass/fail criteria.

PTI’s VeriPac series played a pivotal role in the development of the ASTM F2338 standard for vacuum decay leak testing. Recognized within the United States Pharmacopeia (USP) Chapter on Container Closure Integrity (CCI) and compliant with ISO 11607 guidelines, VeriPac technology utilizes absolute or differential pressure transducers to conduct non-destructive testing, enabling the identification of leaks and microscopic defects that might compromise package integrity.

2. MicroCurrent HVLD Technology

Deterministic CCI test methods, such as Vacuum Decay, Microcurrent HVLD, and Helium Leak Detection, represent the gold standard in package integrity testing. Their high sensitivity, repeatability, and quantitative nature make them indispensable tools for ensuring product safety and regulatory compliance. PTI offers a comprehensive suite of deterministic test methods, enabling manufacturers to confidently validate the integrity of their container closure systems across a wide range of applications.

As the regulatory landscape continues to evolve and product safety becomes an increasing priority, the role of deterministic methods in CCI testing will only grow in importance. By employing these advanced testing technologies, manufacturers can mitigate the risk of contamination, ensure product efficacy, and safeguard patient health.

3. Helium Leak Detection

Helium leak testing is a highly sensitive technique employed in container closure integrity testing (CCIT) to evaluate the seal integrity of closed systems by detecting micro-leaks. Leveraging helium’s small atomic radius and inert characteristics, this method uses helium as a tracer gas to identify extremely small breaches within the packaging

The testing process involves introducing helium into the container and subsequently applying a vacuum to generate a significant pressure differential. This pressure gradient causes helium, if there is any defect, to migrate from the container through potential leak paths. The escaping helium is then detected by a helium mass spectrometer, which measures the helium flow rate, commonly recorded as the leak rate, providing quantitative data on the package’s closure performance and integrity.

Deterministic CCI test methods, like Vacuum Decay and Helium Leak Detection, offer unmatched precision and reliability, ensuring product integrity and compliance. As regulatory standards rise, these advanced methods are crucial for safeguarding patient safety and product quality.

Ophthalmic products, which include eye drops, ointments, and solutions, and contact lenses are among the most sensitive pharmaceutical products in the market. Due to the critical nature of their application, any compromise in sterility can lead to serious infections or adverse reactions. Ophthalmic products are often packaged in containers such as multi-dose bottles, unit-dose ampoules, or tubes. These packaging systems are designed to prevent contamination while ensuring that the product is delivered in a sterile and precise manner. The most common materials used in ophthalmic packaging are plastics like Low-Density Polyethylene (LDPE) and High-Density Polyethylene (HDPE), which offer flexibility and durability.

However, the challenge lies in maintaining the integrity of these containers throughout their lifecycle—from manufacturing, transportation, and storage to consumer use. Even micro-sized defects in the packaging could allow the entry of contaminants, such as bacteria or fungi, compromising the sterility and effectiveness of the ophthalmic product.

Why Is It Important to Ensure the Integrity of Ophthalmic Product Packaging?

The sterility of ophthalmic products is directly tied to the packaging's ability to create a robust barrier against external contaminants. If the packaging is compromised, there can be serious health consequences for patients, including eye infections, irritation, or in extreme cases, vision loss.

Key reasons to ensure the integrity of ophthalmic product packaging include:

• Patient Safety: Preventing contamination is critical for avoiding infections, which could have irreversible consequences.
• Product Efficacy: Any breach in packaging can lead to contamination, potentially reducing the effectiveness of the product.
• Regulatory Compliance: Regulatory agencies such as the FDA and EMA have stringent requirements for sterility and packaging integrity. Non-compliance could lead to recalls or product bans.
• Brand Reputation: Packaging failures can result in damaged trust and brand reputation in a highly competitive market.

Helium Leak Detection for CCI Testing of Ophthalmic Products

Helium leak testing is a precise method for assessing container closure integrity testing (CCIT) by detecting leaks in sealed systems. Due to helium's small atomic size and inert properties, it serves as an ideal tracer gas for identifying even minute defects in packaging.

The testing process typically involves filling the container with helium and applying a vacuum, creating a pressure differential between the internal and external environment of the package. In the presence of leaks, helium will escape from the package and can be measured using a highly sensitive helium leak detector. The helium concentration is then quantified and reported as a leak rate, providing critical insights into the package's integrity and sealing performance.

Helium leak testing is widely utilized across industries, particularly in the pharmaceutical and parenteral product sectors, where maintaining sterile barriers is paramount to product safety and efficacy. It is also employed in design validation, quality control, failure analysis, and during the qualification of manufacturing processes.

By incorporating helium leak testing services into their quality control processes, manufacturers of ophthalmic products can significantly enhance the sterility and safety of their products, ultimately benefiting patients and healthcare providers.

Maintaining the sterility and efficacy of pharmaceutical products is paramount. Even the smallest breach in packaging can compromise a drug's integrity, leading to contamination or degradation. Helium leak testing offers a highly sensitive and reliable method for ensuring the integrity of pharmaceutical packaging.

Helium leak testing is a non-destructive Container Closure Integrity Test (CCIT) used to detect leaks in sealed systems. Helium, being the smallest and lightest gas molecule, readily permeates even minute leaks. The basic principle involves introducing helium into the package or placing it in a helium-rich environment. A highly sensitive detector then measures the helium escaping from any leaks present. Leak detection is achieved through mass spectrometry, where the detector isolates and measures the specific signal of helium ions.

Why is Helium Leak Testing Important for Pharmaceutical Packaging?

Pharmaceutical packaging plays a vital role in protecting the sterility and efficacy of drugs. Even microscopic leaks can allow for the ingress of contaminants like moisture, oxygen, or microorganisms. This can lead to:

• Product degradation: Exposure to air or moisture can alter the chemical composition of a drug, rendering it ineffective or even harmful.
• Microbial growth: Leaks can allow for the introduction of bacteria, fungi, or other microorganisms, posing a serious health risk.
• Reduced shelf life: Compromised packaging can shorten the shelf life of a drug, leading to product waste.

Helium leak testing offers several advantages over other leak detection methods:

• High sensitivity: Helium leak testing can detect leaks significantly smaller than those identified by other methods.
• Non-destructive: This technique does not damage the packaging, allowing for post-testing evaluation and analysis.
• Broad applicability: Helium leak testing is suitable for a wide range of pharmaceutical packaging materials and formats.

Helium Leak Services: Benefits of Partnering with PTI

PTI offers a comprehensive suite of helium leak testing services specifically tailored to the pharmaceutical industry. Our benefits include:

• Advanced instrumentation: We utilize state-of-the-art leak detectors with exceptional sensitivity and accuracy.
• Expert technicians: Our highly trained technicians possess in-depth knowledge of helium leak testing principles and pharmaceutical packaging applications.
• Customizable testing protocols: We work collaboratively with clients to develop testing protocols that meet their specific needs and product requirements.
• Rigorous quality control procedures: PTI adheres to the strictest quality control standards to ensure the reliability and consistency of our testing results.

By partnering with PTI for your helium leak testing needs, you gain access to a reliable and efficient solution that safeguards the integrity of your pharmaceutical products. This, in turn, protects patient safety, ensures product efficacy, and promotes brand reputation.

In the pharmaceutical industry, ensuring the safety and efficacy of medication is paramount. This responsibility extends beyond the drug itself and encompasses the entire delivery system, including the vial packaging. Vials act as critical barriers, protecting sensitive medications from contamination, degradation, and physical damage throughout their journey from manufacturing to administration. Maintaining the integrity of this packaging is essential to guarantee product quality and patient safety.

Applications of Vials in the Pharmaceutical Industry

In the pharmaceutical industry, vials are used for a wide range of products, including:

• Injectable medications (liquids, suspensions, powders)
• Lyophilized drugs (freeze-dried medications)
• Ophthalmic solutions (eye drops)
• Vaccines
• Clinical trial samples

The specific type of vial used will depend on the properties of the medication it contains. For instance, some vials may require light or moisture barrier properties, while others may need to withstand extreme temperatures during transport.

Why is Package Integrity Testing of Vials Important?

• Contamination: A compromised vial can allow contaminants like bacteria or moisture to enter, rendering the medication unsafe for use.
• Product Degradation: Exposure to air, light, or moisture can trigger chemical reactions that degrade the medication, reducing its potency or even creating harmful byproducts.
• Loss of Sterility: In the case of sterile medications, a compromised vial can introduce microorganisms, jeopardizing the product's sterility and potentially causing infections.
• Leakage: Leaking vials can lead to product loss, impacting both financial and safety aspects.

Furthermore, compromised vial integrity can damage a pharmaceutical company's reputation and lead to product recalls. Regular and rigorous package integrity testing is crucial to prevent these issues and ensure patients receive safe and effective medications.

Methods to Inspect Vial Packaging

1. Helium leak testing

Helium leak testing, utilizing helium gas as a tracer, is a method employed to detect and quantify leaks within sealed systems. It serves various purposes such as ensuring Container Closure Integrity, aiding in package design, monitoring product quality, conducting failure analysis, and validating line setups. A Mass Spectrometer Leak Detector (MSLD), commonly known as a helium leak detector, is utilized in this process to identify leaks and determine their size. The test involves connecting the test part to the leak detector and introducing helium gas. If a leak is present, helium escapes from the test part, and the partial pressure is measured and displayed on the meter. This method, recognized by the FDA and referenced in the US Pharmacopeia Chapter <1207>, is a consensus standard for package integrity evaluation.

2. Microcurrent HVLD Technology

PTI's MicroCurrent HVLD technology is a non-destructive, non-invasive method for container closure integrity testing. It's highly effective across various applications, including pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. This technique precisely detects leaks in liquid-filled products, including those with extremely low conductivity like sterile water for injection (WFI) and proteinaceous suspensions. By scanning sealed containers with electrode probes, it identifies leaks by analyzing changes in current flow, pinpointing defects and their approximate locations. Compared to conventional HVLD solutions, MicroCurrent HVLD technology uses approximately 50% less voltage and exposes the product and environment to less than 5% of the voltage, making it one of the most effective container closure integrity technologies for parenteral and biologic products.

3. Vacuum Decay Technology

Vacuum Decay serves as a non-destructive method for Container Closure Integrity Testing CCIT adept at detecting leaks in both rigid and flexible packages with nonporous materials. This straightforward approach relies on fundamental physical principles to assess container integrity. Essentially, the process involves subjecting the package to a vacuum within a test chamber and then monitoring any decline in vacuum levels, indicative of a leak. The standard vacuum decay leak test method (ASTM F2338), developed with PTI's VeriPac instruments, holds FDA recognition as a consensus standard for CCI testing. This method is incorporated into ISO 11607 and cited in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207).

In the high-stakes world of pharmaceuticals and medical devices, ensuring the integrity of packages isn't a mere formality; it's a fundamental pillar of safety and efficacy. For decades, meticulous package integrity testing methods have served as the gatekeepers, diligently sniffing out potential breaches that could compromise lives and livelihoods. Yet, traditional approaches often fell short – lacking the sensitivity to detect microscopic flaws, the versatility to handle diverse package formats, and the quantitative data to provide actionable insights. In order to overcome the shortcomings of traditional methods, manufacturers now rely on non-destructive, deterministic package testing alternatives.

Helium Leak Detection - An Overview

Helium leak testing refers to the process of finding leaks in some type of enclosed or sealed system using helium as a “tracer” gas and measuring its concentration as it escapes due to leakage. It is an effective container closure integrity test method, aimed at evaluating the integrity of pharmaceutical and parenteral products. The process involves filling the package with helium and subjecting it to vacuum. A helium leak detector is then utilized to quantitatively measure the amount of helium escaping from the package, which is expressed as a leak rate. Beyond evaluating container closure integrity, helium leak testing finds applications in product design, quality analysis, failure analysis, and validation. It offers flexibility as it can be conducted with or without a test chamber, enabling testing for "in-leakage" or "out-leakage," as well as locating leaks.

Helium is considered an ideal choice of tracer gas because of multiple reasons. Helium is non-toxic, non-flammable, non-condensable and its presence in the atmosphere is not more than 5ppm. The small atomic size of helium makes it easier to pass through leaks. Since helium does not react with other materials, it is relatively safe to use. Additionally, compared to other tracer gases helium is less expensive and is available in multiple cylinder sizes.

Helium Leak Testing Using SIMS 1915

The Seal Integrity Monitoring System (SIMS) 1915+ stands out as the ideal solution for helium-based leak detection across a range of pharmaceutical and medical device packaging systems, including vials, syringes, cartridges, and blister cards. It's particularly effective for parenteral products, such as ensuring the integrity of rubber stoppers on vials or plungers on syringe assemblies.

Utilizing helium as the tracer gas, this system allows for quantitative testing that surpasses traditional methods like vacuum bubble and dye penetration tests by a significant margin. This quantitative approach facilitates direct comparisons among different packaging materials, formats, production line settings, and storage conditions, supporting the entire product lifecycle. The SIMS 1915+ offers the capability for quantitative analysis with a sensitivity level as low as 1 x 10-10 mbar/L/sec. It provides comprehensive data sets instead of simplistic pass/fail criteria and can conduct testing at room temperature.

Each SIMS 1915+ Helium Leak Testing instrument is meticulously crafted to meet client-specific standards and package configurations. We specialize in engineering custom test fixtures tailored to the components being tested, ensuring precision and accuracy to fulfill your study objectives, accommodate various package configurations, and meet quality monitoring requirements.

SIMS 1915+ Options:

• LT 80 and LT 150 Cryo-Chiller Low Temperature Add-on Modules for ultra-cold Container Closure Integrity testing using helium leak methodology.
• Various sizes of Vacuum Test Fixtures to accommodate all package types and sizes
• Custom Test Fixtures to allow Helium leak testing for non-vacuum chamber applications.
• Additional External Helium Leak standards in various leak rate ranges.
• Helium Sniffer probe – for site specific determination of leak sites.

Biologics, a class of pharmaceutical products derived from living organisms, have revolutionized the field of medicine by offering targeted and highly effective treatments for various diseases. Biologics, including vaccines, monoclonal antibodies, and gene therapies, being highly sensitive and complex products, require meticulous handling and storage.

As the demand for these innovative therapies continues to rise, the importance of robust biologics packaging becomes paramount. In this blog post, we will delve into the significance of biologics packaging inspection, specifically container closure integrity, and explore how helium leak detection plays a crucial role in ensuring the quality and safety of these life-changing medications.

Biologics are inherently vulnerable. Their intricate structures and potent nature necessitate a delicate balance between protection and functionality. Packaging plays a pivotal role in this, acting as a shield against environmental threats like moisture, oxygen, and microbial contamination.

Failing to meet stringent packaging requirements can have dire consequences. Leaky packages could lead to microbial contamination, compromising patient safety. Uncontrolled temperature exposure can render the drug ineffective. Even minor packaging flaws can impact dosage accuracy, potentially jeopardizing treatment efficacy. Therefore, thorough and reliable packaging inspection is not just a quality control measure; it's a critical safeguard for patient well-being. This is where helium leak detection emerges as a powerful tool.

Helium leak detection (HLD) is a precise and reliable technique designed to identify even the smallest leaks in sealed systems. This method utilizes helium as a tracer gas, leveraging its inert, non-condensable, non-flammable, and safe properties. The small atomic size of helium allows it to easily penetrate leaks, facilitating the detection of minute imperfections. The variation in helium concentration is measured and expressed as a leakage rate.

The benefits of using helium include its lower weight compared to other inert gases like neon, its cost-effectiveness, and its availability in various cylinder sizes and pure forms. Unlike hydrogen, which is smaller than helium but not inert, helium provides a dependable and efficient solution for leak detection in diverse applications.

The functionality of a helium leak detector is based on the principles of a field mass spectrometer. An electric beam emitted from the filament ionizes the leaked helium gas, and the resulting ions are accelerated by increased voltage. These ions escape through a split and enter the magnetic field of the analyzer. Due to the mass-dependent circular paths of the ions, only helium ions reach the collector. A specialized detector converts the ion current into an electrical current, which is then amplified by leak detection devices and displayed on a screen. The measured current corresponds to the helium concentration, indicating the presence and magnitude of a leak.

Compared to conventional vacuum bubble and dye penetration test methods, packages can be quantitatively tested using helium as the tracer gas that ensures higher levels of accuracy. Such an approach allows a comparison between multiple packaging materials and forms production line settings and stability storage conditions, supporting the entire lifecycle.

• Helium is a highly sensitive leak test technology, equipped with the detection of extremely small leaks which is not possible with other leak testing methods.
• Using a high vacuum technique, the leak test thresholds to be set down as low as 1×10-12l.sec-1, a sensitivity level allowing unique comparisons between package components, for example.

Combination products are made up of two or more regulated components, such as pharmaceuticals, devices, or biologicals, that have been physically, chemically, or otherwise combined and formed as a single entity to achieve a therapeutic effect.

Combination products can be divided into three main categories:

• Drug-device combination products: These products combine one or more drugs with a medical device. Examples include prefilled syringes, inhalers, and insulin pumps.
• Deterministic, quantitative test method.
• Biological-device combination products: These products combine one or more biological products with a medical device. Examples include drug-eluting stents and tissue-engineered products.
• Drug-biological-device combination products: These products combine one or more drugs, biological products, and medical devices. Examples include gene therapy products and combination vaccines.

Combination products can be complex and challenging to test, as they require expertise in both the pharmaceutical and medical device industries. One of the most important tests for combination products is container closure integrity testing. CCIT ensures that the product container and closure system are properly sealed and will not leak during transport, storage, and use. Leaks can lead to product contamination, degradation, and even patient harm.

CCIT is important for all combination products, but it is especially important for products that contain sterile or sensitive ingredients. Leaks can allow bacteria and other contaminants to enter the product, which can lead to serious health problems for patients. Container closure integrity testing is also important for products that are used to deliver drugs or biological products directly to the bloodstream or other sensitive tissues. Leaks can cause the product to lose its potency or efficacy, or it can even cause an overdose.

SIMS 1915+ for Leak Testing Combination Products

SIMS 1915+ is a helium-based leak detection system that is well-suited for testing combination products. It is a highly sensitive and accurate system that can detect leaks as small as 1 x 10-10 mbar L/sec. SIMS 1915+ is also very versatile and can be used to test a wide variety of combination product packages, including vials, syringes, cartridges, and blister cards.

SIMS 1915+ works by filling the test chamber with helium gas and then measuring the amount of helium that leaks out of the product package. If there is a leak, the helium leak detector will generate a signal. The size of the signal is proportional to the size of the leak.

SIMS 1915+ can be used to test combination products in both vacuum and sniffer modes. In vacuum mode, the test chamber is evacuated and then filled with helium. The helium leak detector is then used to measure the amount of helium that leaks out of the product package. In sniffer mode, the helium leak detector is used to scan the outside of the product package for helium leaks. This mode is useful for testing products that are difficult to place in a vacuum chamber, such as prefilled syringes and inhalers.

SIMS 1915+ Options

SIMS 1915+ is a modular system that can be customized to meet the specific needs of each customer. Some of the available options include:

• Dual test port manifold: Allows two product packages to be tested simultaneously
• Low temperature testing: Allows product packages to be tested at temperatures as low as -80°C.
• CFR 21 Part 11 compliance: Ensures that the system meets the data integrity requirements of the FDA's 21 CFR Part 11 regulations

SIMS 1915+ is a powerful and versatile helium leak detection system that is well-suited for testing combination products. It is a highly sensitive and accurate system that can detect leaks as small as 1 x 10-10 mbar L/sec. SIMS 1915+ is also very versatile and can be used to test a wide variety of combination product packages, including vials, syringes, cartridges, and blister cards.

In the pharmaceutical industry, ensuring the safety and integrity of drug products is of paramount importance. Contamination or compromise in the packaging of vials can lead to significant risks for both patients and manufacturers. Hence, meticulous quality assurance measures are implemented to guarantee that every vial meets the highest standards of quality.

One crucial aspect of quality control in vial production is Container Closure Integrity testing (CCIT). CCI inspection is a vital step to verify the hermetic sealing of vials, ensuring that no leaks or defects compromise the product's sterility or stability. Over the years, various technologies have emerged to improve CCI inspection processes, and one of the most advanced and sensitive methods available today is helium leak detection.

Testing Integrity of Vials using Helium Leak Detection Technology

Helium leak detection technology has revolutionized container closure integrity testing by providing highly sensitive and precise detection of leaks in vials. Helium leak detection can be understood as the process of identifying leaks in any closed or sealed system with the help of helium gas and measuring its concentration as it escapes due to leakage. Common applications of helium leak testing include pre-filled syringes, cold form blister packs, foil pouches and many other package formats. This technology can precisely determine integrity between specific primary container closure system components, making it an ideal choice for testing the integrity of pharmaceutical products.

This method utilizes helium gas, which has exceptional properties that make it an ideal tracer for leak detection purposes. By harnessing the unique characteristics of helium, manufacturers can perform comprehensive testing to identify even the smallest leaks, enhancing the overall integrity of vial packaging.

Why is Helium used as a Tracer Gas?

• Helium is used as a tracer gas because of certain unique qualities that make it ideal for leak testing.
• Non-toxic, non-condensable, non-flammable.
• Helium gas is inert, which means it does not interact with the components being tested.
• Since the atomic size of helium is very small, it can easily breach through pathways reliably and easily.
• Compared to other tracer gases, helium is less expensive and readily available.
• Its presence in the atmosphere is not more than ppm.

Technology Overview

The test process starts by introducing helium into the package, which is then subjected to a vacuum. The quantity of helium that escapes from the package is then measured using a helium leak detector, providing a quantitative measure known as the leak rate. In addition to leak testing, helium leak detection technology has proven to be effective for tasks such as package design, failure analysis, tooling qualification, packaging line setup and validation, and monitoring product quality. The use of helium leak detection in accordance with ASTM F2391 is a widely accepted and extensively utilized method in the pharmaceutical industry.

Overall, the adoption of helium leak detection revolutionizes CCI quality assurance, upholding high standards, and supports production quality monitoring at a higher more reliable level.

Testing the integrity of blister packages is essential to guarantee that the packaging safeguards the contents from oxygen, moisture or contaminants. Packaging keeps the product safe and functional by preventing air ingress.

Probabilistic test methodologies have been widely used to conduct blister package integrity tests, such as the blue dye test method. These tests rely on a range of sequential or simultaneous events, each with random results that are characterized by probability distributions. In order to acquire relevant results, it is necessary to use large sample sizes and strict test condition controls because the findings are related to uncertainty. Studies have also revealed the unreliability of such testing, which frequently fails to detect leaks that could endanger the quality of a product.

As a result, it is preferable that the integrity test method be deterministic. The leakage event being detected or measured in this type of test method is based on phenomena that follow a predictable chain of events. Helium leak detection is an example of a deterministic, highly sensitive method.

What is Helium Leak Detection Technology?

Helium Leak Detection Technology is a Container Closure Integrity test (CCIT) method found to be highly effective in evaluating the integrity of a wide range of complex pharmaceutical and parenteral products. Helium leak detection can be understood as the process of identifying leaks in any closed or sealed system with the help of helium gas and measuring its concentration as it escapes due to leakage. Common applications of helium leak testing include pre-filled syringes, cold form blister packs, foil pouches and many other package formats. The technique uses helium as a tracer gas and its concentration is measured as it escapes through the leaks. Under this method, the package is helium filled and subjected to vacuum. The amount of helium escaping the package is quantitatively measured and stated as a leak rate.

Why is Helium used as a Tracer Gas?

Helium is used as a tracer gas because of certain unique qualities that make it ideal for leak testing.

• Non-toxic, non-condensable, non-flammable.
• Helium gas is inert, which means it does not interact with the components being tested.
• Since the atomic size of helium is small, it can easily breach through pathways reliably and easily.
• Compared to other tracer gases, helium is less expensive and readily available.
• Its presence in the atmosphere is not more than 5ppm.

Technology Overview

The procedure begins with filling the package with helium, after which vacuum is applied within a chamber. The amount of helium escaping from the package is then quantified using a helium leak detector. This is then referred to as the leak rate. Helium leak detection technology is also suitable for package design, failure analysis, tooling qualification, packaging line setup and validation, and product quality monitoring, in addition to leak testing. ASTM F2391 helium leak detection is a well-established method recognized and widely used in the pharmaceutical industry.

Applications of Helium Leak Testing

• Ensuring Container Closure Integrity.
• Selecting closure formulation and configuration.
• Seal integrity monitoring during stability studies.
• Extremely valuable in early-stage pharmaceutical product package system development.

Over the last two decades, pharmaceutical industry has seen tremendous growth in the form of technological advancements and drug delivery system innovations. However, such innovations have increased quality assurance challenges for drug manufacturers. For this reason, drug product manufacturers give at most importance to their quality control procedure as well as package integrity tests.

Packaging plays a vital role in preserving product quality and maintaining a sterile barrier against external damaging force. Even a minute breach in the package can cause moisture, reactive gases, or other harmful substances to enter the product- thus compromising its healing properties. Moreover, a contaminated drug product can cause serious health issues to the user, making it more of a threat than treatment. Given the sensitive nature of pharmaceutical products, ensuring Container Closure Integrity holds high relevance.

Container Closure Integrity testing (CCIT) is a leak detection technique for evaluating the ability of container closure systems in maintaining sterile barrier against external contaminations. Such tests can be broadly classified into Probabilistic and Deterministic test methods. Although Probabilistic test methods like Bubble Tests and Dye Ingress were initially popular, with more technical advances, better, non-destructive methods are now the go-to solutions to insure container integrity. Manufacturers are encouraged to switch to more reliable Deterministic test methods that provide guaranteed quantitative results with precision. In this blog we will be discussing in detail Helium Leak Detection Technology.

What is Helium Leak Detection Technology?

Helium Leak Detection Technology is a Container Closure Integrity test method that is used to find leaks in different types of enclosed or sealed systems. The technique uses helium as a tracer gas and its concentration is measured as it escapes through the leaks. Under this method, the package is helium filled and subjected to vacuum. The amount of helium escaping the package is quantitatively measured and stated as a leak rate. Helium is an ideal choice for package leak testing and container closure integrity testing in particular during container closure development for pharmaceutical products, due its key qualities:

• It is inert, non-toxic, non-condensable and non-flammable.
• Being inert, it is safe to use as it will not react with other materials being tested.
• The atom size of helium is really small therefore it can easily pass through leaks.
• The instrument noise due to environmental helium is inherently low because of its limited presence in the atmosphere at less than 5ppm and thus gives incredibly accurate reports.
• Helium is relatively inexpensive and is available in multiple cylinder sizes.

Seal Integrity Monitoring System

The Seal Integrity Monitoring System (SIMS) 1915+, is the ideal choice for your helium-based leak detection system for testing rigid containers including vials, syringes, and cartridges and blister cards. Using helium as the tracer gas, packages can be quantitatively tested to levels far exceeding the vacuum bubble and dye penetration test methods. This quantitative approach allows direct comparison across various packaging materials and forms, production line settings and stability storage conditions, supporting the entire lifecycle.

THE SIMS 1915+. features an oil-free detector and power system that is designed for the needs of the pharmaceutical and medical device industries. In addition, this system will enable you to quantitatively analyze package system at a sensitivity level as low as 1 x 10 -11 mbar-L/s and provides relevant data sets in place of a simple pass/fail criteria while enabling testing to be performed at room temperature.

Each SIMS 1915+ Helium Leak Testing instrument manufactured by Leak Detection Associates is custom built to client specific standards and package configurations.

Custom Built to Client Specification SIMS 1915+ Leak Detection System with Add -On Components

• Helium Leak Detector Module (HLDM): Oil Free, Production version in Console Frame Assembly, with Stainless Steel working surface and Dual Test Port Manifold (allows concurrent use of VTFM & HSAM on HLDM unit).
• Vacuum Test Fixture Model (VTFM) – custom designed for use in testing of vial container samples
• Head Space Analyzer Module (HSAM) – Model VM-2 that includes three (3) Puncture Probes (two spares) for determination of Helium Concentration in the headspace of vial containers.
• Integral Calibration Chamber (w/ Calibrant Gas Flow Meter/Controller) provided for HSAM Calibration and a Universal Holder to be used for various vial diameters.
• Helium Filling Device specific for vial testing sample prep to enable vials to be filled with helium