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Pre-filled syringes (PFS) have become a cornerstone of modern drug delivery, offering convenience, accuracy, and safety for both healthcare providers and patients. Their growing adoption, especially in biologics and vaccines, brings an equally growing responsibility: ensuring that these drug delivery systems remain sterile and stable throughout their lifecycle. Even microscopic leaks in the container closure system can compromise product quality, patient safety, and regulatory compliance.

To address these risks, USP <382> provides a framework for evaluating the functional suitability of elastomeric components in parenteral packaging and delivery systems. Within this framework, helium leak detection has proven to be one of the most reliable and sensitive methods to safeguard pre-filled syringe integrity.

Understanding the Structure and Leak Risks of Pre-Filled Syringes

A pre-filled syringe is made up of multiple components: glass barrel, elastomeric plunger, needle shield, and closure systems that must work together to ensure complete sealing. Each of these interfaces can be a potential weak point. Even the smallest breach can allow microbial ingress or lead to chemical degradation of sensitive formulations, making robust container closure integrity (CCI) testing essential.

USP <382>: A Shift Toward Deterministic Leak Testing

Historically, probabilistic tests like dye ingress or bubble emission were used to assess packaging integrity. However, these methods rely heavily on operator interpretation and often lack the sensitivity to detect micro-defects.

USP <382> emphasizes the importance of functional suitability testing for elastomeric components and aligns closely with the deterministic principles outlined in USP <1207>. This shift underscores the industry’s move toward highly sensitive, quantitative methods that provide scientific, repeatable, and verifiable results.

Helium Leak Detection: Meeting and Exceeding USP <382> Regulation

Helium leak testing has become a benchmark method for CCI testing in pre-filled syringes because of its ability to detect extremely small leaks down to 10?¹° mbar·L/sec.

Key benefits include:

• Exceptional Sensitivity – Detects micro-channels that traditional tests miss.
• Quantitative Results – Provides measurable leak rates for precise analysis.
• Regulatory Alignment – Supports USP <382> compliance and satisfies global regulatory expectations.
• Wide Applicability – Effective for syringes, vials, cartridges, and other parenteral packaging systems.

For pre-filled syringes, helium testing is particularly valuable in verifying the integrity of elastomeric plungers and needle-shield assemblies components most vulnerable to leakage. By integrating helium leak detection in development, validation, and routine quality control, manufacturers can build confidence in packaging integrity and reduce the risk of compliance failures or recalls.

As injectable therapies continue to dominate the pharmaceutical landscape, ensuring the integrity of pre-filled syringes is critical for both patient safety and regulatory compliance. USP <382> sets clear expectations for functional suitability, pushing the industry toward deterministic and highly sensitive test methods. Helium leak detection not only meets these standards but exceeds them, providing unmatched sensitivity and quantitative assurance of container closure integrity.

By adopting helium leak testing, pharmaceutical companies can confidently safeguard product sterility, extend drug stability, and maintain compliance in an increasingly demanding regulatory environment.

In pharmaceutical manufacturing, ensuring the highest level of Container Closure Integrity (CCI) is essential. For sterile injectables, biologics, and advanced therapies, even the smallest leak can compromise sterility, introduce contaminants, or cause product degradation. Regulatory agencies and global standards have moved toward deterministic, quantitative methods to evaluate package integrity, pushing the industry to adopt more advanced leak detection solutions.

Among these, Helium Leak Detection stands out as one of the most precise methods, offering unmatched sensitivity to detect leaks at levels far beyond the capabilities of traditional approaches.

What is Sensitivity in Leak Detection?

Sensitivity in leak detection refers to the smallest defect or leak path that a testing method can reliably identify and measure. It is typically expressed as a leak rate, measured in mbar·L/sec. The lower the value detectable, the more sensitive the method. Traditional dye ingress testing might only detect leaks larger than 1×10–10, while advanced helium-based systems, like those from PTI, can detect leaks as small as 10?¹¹mbar·L/sec.

This difference highlights why sensitivity is such a defining factor in evaluating CCI. A method with low sensitivity may pass a container as “integral” even when microscopic leaks exist, whereas highly sensitive helium testing provides definitive, quantifiable data.

Why Sensitivity Matters in Pharmaceutical Packaging?

Pharmaceutical packaging is not uniform, it varies by container type, material, closure system, and storage environment. Each factor introduces unique risks for leakage. The sensitivity of the helium leak testing method must therefore be aligned with the product’s risk profile.

• For sterile injectables, a micro-leak too small to be seen can still allow microbial ingress, directly threatening patient safety.
• For moisture-sensitive biology, even trace amounts of water vapor entering through microscopic pathways can degrade active ingredients.
• For advanced therapies stored under ultra-low or cryogenic conditions, material contraction can generate stress points that lead to leaks.
• And for high-value, limited batch drugs, missing a small defect could result in significant financial loss and supply chain setbacks.

The more sensitive the leak detection method, the greater the assurance that packaging failures will be identified before products reach patients.

Helium as a Tracer Gas: A Sensitivity Advantage

Tracer gas leak testing is a highly effective method for detecting leaks with outstanding sensitivity, accuracy, and repeatability. Using helium as the tracer gas, it can identify micro-leaks as small as 1x10?4 to 10?? scc/s. The test is done either by injecting helium into sealed packages or filling the headspace after sealing, allowing precise detection of any leakage. The vacuum test method is the most widely used approach, placing seals under stress to capture helium transmission through both the material and closure system. This technique offers superior leak detection by monitoring helium gain in the external environment of the enclosed sample.

Ensuring seal integrity is critical to protecting pharmaceutical products, maintaining patient safety, and supporting evaluations of sustainable or cost-optimized packaging. To meet these needs, PTI’s Helium Leak Detection systems provide advanced, high-performance solutions designed to deliver unmatched sensitivity, accuracy, and reliability for pharmaceutical and biological applications. By setting and validating appropriate sensitivity thresholds, pharmaceutical manufacturers can achieve a higher standard of quality assurance, protecting both product and patient with confidence. Helium’s unique role as a tracer gas makes it not just a testing tool, but an enabler of safety, innovation, and trust in the pharmaceutical supply chain.

The stability of injectable and lyophilized drugs relies heavily on the integrity of their container-closure systems. Vials are designed to act as protective barriers, yet even tiny leaks can compromise product quality by allowing moisture, oxygen, or microbes to enter, or by causing the loss of volatile compounds. Such breaches not only reduce efficacy but also pose serious risks to patient safety and regulatory compliance.

To safeguard against these issues, pharmaceutical manufacturers turn to advanced testing methods that ensure reliable container closure integrity. Among the most effective is helium leak detection, a highly sensitive and quantitative technique that can identify microscopic leaks undetectable by conventional methods. By verifying that vials remain airtight throughout the product’s shelf life, this technology provides confidence in long-term drug stability while supporting global quality standards.

Importance of Container Closure Integrity for Drug Stability

The purpose of a container-closure system is to provide a protective barrier against external factors that can threaten product quality. Common risks include:

• Microbial contamination: Even the tiniest breach can allow bacteria or fungi to enter, compromising sterility.
• Moisture ingress: Sensitive formulations such as lyophilized (freeze-dried) drugs can rapidly degrade in the presence of water vapor.
• Oxygen exposure: Oxidation can alter the chemical structure of certain active pharmaceutical ingredients (APIs), reducing efficacy.
• Volatile loss: For drugs formulated with solvents or sensitive compounds, improper sealing can result in evaporation or potency loss.

How Helium Leak Detection Works in Vial Testing

Helium leak detection is considered to be one of the most precise methods for verifying vial integrity. In this technique, vials are exposed to a helium-rich environment, allowing the gas to penetrate any potential microchannels or defects in the container-closure system. The vials are then placed in a vacuum chamber connected to a mass spectrometer, which detects and quantifies the presence of helium that has escaped. This process is highly sensitive and can identify leaks that are too small to be detected by traditional methods.

Because helium is an inert and tiny molecule, it provides a reliable indication of whether a vial is truly airtight. As a result, manufacturers can confidently verify the robustness of their packaging systems and ensure that the drug remains stable throughout its intended shelf life. The method also delivers quantitative results, expressed as a measurable leak rate, which helps in setting clear acceptance criteria. Unlike qualitative tests, it allows for consistency and repeatability in quality control. Helium leak detection can be applied during R&D phase, production, and validation phases, making it versatile across the product lifecycle. Ultimately, it helps pharmaceutical companies meet stringent global regulatory requirements while minimizing the risk of product recalls.

In conclusion, ensuring the stability of drugs stored in vials is critical to patient safety, product effectiveness, and regulatory compliance. While formulation science plays a key role, the integrity of the container-closure system is equally important. Helium leak detection offers one of the most precise and reliable methods for assessing vial integrity, providing sensitive, quantitative data that ensures drugs remain stable throughout their intended shelf life. By integrating helium leak detection into their quality assurance programs, pharmaceutical manufacturers can not only meet regulatory expectations but also reinforce confidence in the reliability of their products. In the end, this technology safeguards what matters most: the health and safety of patients who depend on these life-saving products and therapies.

In pharmaceutical and medical device packaging, maintaining the integrity of sealed systems is not only a quality requirement but also a critical regulatory and patient safety obligation. As leak detection technologies evolve, helium has emerged as one of the most effective tracer gases for identifying even the smallest breaches in packaging systems. Its unique properties make it particularly well-suited for Container Closure Integrity (CCI) testing, where precision and reliability are essential.

Before helium leak testing became an industry standard, pharmaceutical manufacturers relied heavily on probabilistic methods such as bubble testing, dye ingress, and microbial ingress tests. While these methods could detect significant leaks, they lacked the sensitivity to identify microscopic pathways that could still compromise product sterility.

The introduction of helium as a tracer gas in the mid-20th century revolutionized leak testing. Its adoption in pharmaceuticals followed as industry demand for more deterministic, highly sensitive, and quantitative methods grew. Today, with guidance from USP <1207> and increased regulatory focus on deterministic CCI testing, helium leak detection has become a trusted method for safeguarding product quality and patient safety

Reasons for Using Helium in Pharmaceutical Leak Testing

1. Unique Physical Properties: Helium is an inert, monoatomic gas with the second smallest atomic radius, smaller than hydrogen, which allows it to pass through extremely small leak paths that other gases cannot. Its non-reactive nature ensures it does not interact with packaging materials.

2. Precise Detection Process: In a typical test, a sealed container is placed under vacuum and exposed to helium internally or externally. Any breach allows helium to pass through, where it is detected by a helium-specific mass spectrometer. This enables accurate identification of both the presence and location of leaks.

3. Performance Advantages: Helium’s low molecular weight allows it to diffuse rapidly for quick responses. It clears from the test environment swiftly, enabling faster test cycles and repeatable results, critical for high-volume production where speed, sensitivity, and consistency matter.

4. Critical Applications in Pharmaceuticals: In pharmaceutical manufacturing, particularly for parenteral products, leak testing using helium ensures container closure integrity to maintain sterility, stability, and patient safety. Its high sensitivity, capable of detecting leak rates as low as 10?¹° mbar·L/s, makes it suitable for detecting even microscopic defects that could lead to contamination. Its precise, quantitative results help in:

• Validating new packaging formats and materials
• Verifying the seal integrity of prefilled syringes, vials, ampoules, and blister packs
• Supporting stability studies by confirming packaging robustness over time
• Identifying packaging issues early in production before they escalate into larger quality concerns

In conclusion, helium's unique physical and chemical properties make it an ideal tracer gas for leak detection in pharmaceutical and medical device packaging. Its small atomic size, inertness, and rapid diffusion under vacuum conditions allow for highly sensitive and reliable testing. As regulatory standards continue to prioritize deterministic methods, helium leak detection stands out as a powerful and proven approach for ensuring container closure integrity. For manufacturers committed to product quality and patient safety, helium plays a central role in modern, science-based quality assurance practices.

Pre-filled syringes are increasingly used in modern pharmaceutical delivery due to their convenience, accuracy, and patient-friendly design. However, ensuring the integrity of these devices presents significant challenges. Even the smallest breach in container closure can compromise sterility, pose safety risks, and affect drug efficacy. As regulatory expectations become more stringent, pharmaceutical manufacturers are seeking advanced methods to ensure absolute integrity. One such method is Helium Leak Detection, which offers unmatched sensitivity and reliability in detecting micro-leaks in pre-filled syringes.

Why Traditional Methods Fall Short?

Conventional leak testing methods such as dye ingress have long been used to assess container closure integrity. While suitable for certain applications, these techniques often fall short when applied to complex systems like pre-filled syringes. Its limitations include:

• Low sensitivity: They may not detect sub-micron leaks that are clinically significant.
• Geometry limitations: Irregular surfaces and tight spaces, such as the needle hub or under the plunger, can limit test effectiveness.
• Environmental dependence: Temperature, pressure, and viscosity variations can influence test outcomes, making results less reliable for high-risk products.

Pre-filled syringes have several components: barrels, plungers, and needle shields that create multiple potential leak paths. Traditional methods may struggle to detect extremely small defects, especially those in critical areas such as the needle hub or plunger interface. Furthermore, variations in materials and geometries can impact test sensitivity and consistency. As a result, manufacturers may face limitations in confidently identifying integrity breaches before products reach the market.

Helium Leak Detection: A High-Sensitivity Solution

Helium Leak Detection offers a powerful alternative that addresses these limitations. Using helium a small, inert gas with excellent diffusion properties this method can detect leaks as small as 10?¹° mbar·L/s, far beyond the capabilities of most traditional approaches. During testing, the pre-filled syringe is exposed to helium under controlled conditions. Any escape of helium from the system is measured with precise instrumentation, indicating the presence and size of a leak. This approach provides a quantitative, repeatable measure of integrity, which is critical for high-risk pharmaceutical applications. Additionally, helium’s small atomic size enables it to detect leaks in areas that are otherwise difficult to assess using liquid- or pressure-based methods.

Enhancing Confidence in Product Integrity

Incorporating helium leak detection into the quality control process significantly enhances confidence in the integrity of pre-filled syringes. By reliably identifying microscopic leaks, manufacturers can ensure product sterility, protect patients, and meet evolving regulatory demands. Moreover, the data-driven nature of helium testing allows for better process control and continuous improvement. Manufacturers gain actionable insights into potential failure modes, helping them fine-tune packaging designs, materials, and sealing processes.

In summary, helium leak testing offers the sensitivity and reliability needed to meet the unique integrity challenges of pre-filled syringes. As traditional methods fall short, this advanced technique provides manufacturers with the assurance required to protect product quality, ensure patient safety, and maintain regulatory compliance reinforcing trust in every dose delivered. Its adoption reflects a forward-thinking approach to quality assurance in an increasingly demanding pharmaceutical landscape.

As pharmaceutical and biologic products such as mRNA vaccines, cell therapies, and other biologics become more temperature-sensitive, the need for ultra-cold storage conditions (as low as -80°C or below) is growing rapidly. These extreme environments place significant stress not only on packaging systems but also on the methods used to verify Container Closure Integrity (CCI).

Traditional leak testing methods often fall short under cryogenic conditions. Materials may contract, seals can become brittle, and closures once deemed secure may form micro-leaks that go undetected. This is where helium leak detection offers a unique and powerful advantage.

Key Considerations for Helium Leak Detection in Cryogenic Applications

• Helium's Behavior at Ultra-Low Temperatures

Cryogenic storage often leads to sub-micron leaks that are undetectable by traditional methods. Helium’s small atomic size and low viscosity allow it to penetrate even the tiniest flaws in packaging seals or material interfaces.

Helium leak detection systems can measure leak rates as low as 10?¹¹ to 10?¹² mbar·L/s, offering the deterministic and quantitative results needed for high-risk, sterile pharmaceutical products. This level of precision is essential in cold chain logistics, where even minor integrity breaches can lead to microbial ingress or product degradation.

• Compatibility with Cold-Stored Packaging Materials

Packaging materials behave differently at ultra-low temperatures they may shrink, fracture, or become brittle. Some leak detection methods can interact negatively with these materials, distorting results or causing damage. Helium, however, is an inert, non-reactive gas that does not alter the physical or chemical properties of the packaging during testing. Its non-invasive nature ensures accurate leak detection without compromising the integrity of the primary container even in the harshest cryogenic conditions.

• Fast Detection and Clean Testing Environment

Time and cleanliness are critical in pharmaceutical production. Helium’s rapid diffusion rate allows for fast test cycles, helping maintain productivity even when handling frozen or temperature-sensitive products. Additionally, because helium is non-toxic, odorless, and leaves no residue, it supports a clean testing environment, avoiding contamination risks especially important when dealing with sterile drug products or sensitive biologics.

• Ensuring CCI in Cryogenic Environments with Helium

Leak behavior changes significantly under cryogenic stress, where extreme cold can cause materials to contract, seals to become brittle, and closures that were previously secure to develop micro-gaps. These subtle shifts can compromise Container Closure Integrity (CCI) even in packaging that performs well at room temperature. These micro-leaks can compromise Container Closure Integrity (CCI), allowing moisture, oxygen, or microbes to enter the container, or enabling valuable vapor or active pharmaceutical ingredients to escape. Such breaches not only threaten product efficacy but also pose serious safety risks and potential regulatory non-compliance.

These capabilities make helium leak detection ideal for testing cold chain packaging components, including:

• Vials
• Cartridges
• Pre-filled syringes
• Cryogenic storage containers

With helium’s unmatched ability to detect the smallest breaches, manufacturers can be confident that CCI is maintained even under extreme cold chain conditions.

In conclusion, helium leak testing is the gold standard for ensuring container integrity in ultra-cold storage applications. Helium’s unique properties stability at low temperatures, microscopic detection capability, inertness, and clean test behavior make it the most effective and reliable tracer gas for cryogenic testing. By selecting a helium-based system designed for ultra-cold applications, manufacturers can confidently protect product quality, meet strict regulatory standards, and ensure patient safety across the supply chain.

In the pharmaceutical industry, packaging integrity is a fundamental aspect of ensuring drug safety, efficacy, and regulatory compliance. New packaging formats are constantly being developed to address challenges such as improving product stability, ease of use, and sustainability. However, any compromise in the packaging barrier, no matter how small, can lead to contamination, loss of sterility, or reduced shelf-life issues. These issues carry significant consequences for patient health, manufacturer liability, and brand reputation. Validating packaging integrity during product development is therefore critical.

Helium leak detection is among the most sensitive and accurate methods available to detect extremely small leaks in packaging systems. Its application early in the product lifecycle provides valuable insights that help pharmaceutical developers optimize packaging designs, ensuring robust container closure integrity (CCI) before the product is commercialized.

The Role of Helium Leak Detection in Early-Stage Testing

Packaging for sterile pharmaceuticals, such as parenteral drugs, biologics, and injectables, must maintain a perfect barrier against environmental contaminants throughout the product’s shelf life. Traditional leak detection methods often lack the sensitivity required to identify micro-leaks that can compromise this barrier.

Helium leak detection overcomes this limitation through its use of helium gas, which has unique physical properties: it is inert, non-toxic, and has the smallest atomic size among gases. This allows helium atoms to pass through microscopic openings that other gases cannot. During testing, the new packaging format is filled with helium gas or exposed to it externally and then placed into a vacuum chamber connected to a mass spectrometer.

The vacuum environment inside the chamber causes any helium escaping through leaks to be detected at exceptionally low concentrations. The mass spectrometer precisely measures the amount of helium that escapes, quantifying the leak rate in units as small as 10^-10 mbar·L/s. This quantitative data allows manufacturers to identify even the smallest defects in seals, closures, or materials that could pose a risk.

Testing can also be conducted under various simulated conditions such as temperature fluctuations, mechanical stress, or after transportation simulation to evaluate how the packaging will perform in real-world scenarios. This early detection of potential failure modes allows product developers to modify design parameters, materials, or manufacturing processes to enhance overall package integrity.

Ensuring Compliance Before Commercialization

Regulatory agencies worldwide, including the FDA, EMA, and ICH, have increasingly emphasized the importance of scientifically sound, quantitative testing methods for packaging integrity. Container Closure Integrity Testing (CCIT) guidelines like USP <1207> highlight leak testing as a critical requirement for sterile pharmaceutical products.

Helium leak detection is often considered the benchmark method due to its sensitivity and ability to provide clear, numerical leak rates that can be benchmarked against acceptance criteria. This helps manufacturers demonstrate to regulators that their new packaging formats consistently meet or exceed safety thresholds.

By incorporating helium leak testing into the product development and validation process, pharmaceutical companies can:

• Mitigate risk: Identify and correct packaging flaws before commercial production, reducing the chance of product recalls or contamination events.
• Strengthen regulatory submissions: Provide robust, quantitative data supporting packaging claims that align with evolving regulatory expectations.
• Enhance quality control: Develop acceptance criteria and quality checks that ensure ongoing packaging integrity throughout production and distribution.
• Optimize design: Use early-stage test results to refine materials, closure systems, and manufacturing parameters to improve performance.

Validating new pharmaceutical packaging formats using helium leak detection is a crucial step in ensuring product safety and regulatory compliance. Its exceptional sensitivity to microscopic leaks allows manufacturers to uncover and address potential packaging failures early in the product lifecycle. By integrating helium leak testing into development workflows, pharmaceutical companies can optimize packaging design, meet stringent regulatory requirements, and ultimately deliver safer, more reliable sterile products to market.

In the pharmaceutical industry, product recalls are more than just a financial burden; they carry serious consequences for patient safety, brand credibility, and regulatory standing. A large percentage of recalls can be traced back to packaging failures that compromise Container Closure Integrity (CCI). When the packaging of sterile drug products fails, even at a microscopic level, it can lead to contamination, loss of sterility, and reduced drug efficacy.

This risk is especially critical for parenteral drugs, biologics, and sterile injectables, where maintaining a sterile barrier is essential. To minimize such risks and meet evolving regulatory expectations, pharmaceutical manufacturers must adopt more precise and reliable quality assurance technologies. Among the most advanced and effective of these is PTI’s Helium Leak Testing equipment and services. Helium is a highly sensitive method for ensuring package integrity.

Why Traditional CCI Testing Methods Fall Short in Preventing Recalls

Traditional testing methods such as dye ingress, bubble tests, and microbial immersion have been widely used for CCI testing. However, their limitations leave gaps in detection that can allow compromised units to pass inspection.

• Low Sensitivity Leads to Missed Defects: Traditional methods often cannot detect leaks below 10–20 microns, small enough to allow microbial ingress but too small to be seen by dye tests.
• Inconsistent, Subjective Results Increase Risk: Manual methods depend on human judgment, leading to variability and missed leaks, especially in high-throughput environments.
• Lack of Quantitative Data Weakens Quality Assurance: Without measurable leak rates, it’s difficult to establish compliance or justify batch release decisions during audits.

Helium Leak Testing Enables Early Detection and Prevents Market Failures

PTI’s Helium Leak Detection systems offer unmatched precision by detecting submicron leaks that traditional methods miss. This is vital in sterile product manufacturing, where even the smallest breach can lead to a recall.

How the Technology Works:

• The container is filled with or exposed to helium gas.
• It is placed in a vacuum chamber.
• If there’s a leak, helium escapes and is measured by a mass spectrometer.
• The leak rate is calculated and compared to acceptance criteria.

Product recalls in the pharmaceutical industry are often the result of packaging failures that compromise container closure integrity. As regulatory expectations rise and drug products become more sensitive, the need for highly accurate, reliable, and reproducible testing methods becomes critical. Helium Leak Testing stands out as a proven, data-driven solution that enables manufacturers to detect microleaks early, ensure product sterility, and prevent defective units from reaching the market.

As the demand for biologic drugs continues to grow, so does the need for robust container closure integrity solutions. These high-value, sensitive products require the highest assurance of package integrity to ensure patient safety and therapeutic efficacy. Even microscopic leaks in a container closure system can compromise sterility, leading to product degradation or contamination.

PTI’s helium leak detection method offers a highly sensitive and reliable solution for detecting leaks in pharmaceutical packaging, especially for biologic drug products. This advanced approach plays a crucial role in enhancing pharmaceutical leak detection standards and ensuring that every dose delivered to the patient is safe and effective.

Limitations of Traditional Leak Testing Methods

Conventional leak testing technologies, such as dye ingress or visual inspection have long been used for integrity testing. While these methods are accessible and straightforward, they come with critical limitations, particularly when testing complex or high-risk drug products.

• Limited Sensitivity: Traditional methods often lack the sensitivity needed to detect tiny leaks that could still allow microbial ingress.
• Subjectivity: Visual-based tests, such as dye ingress, can lead to inconsistent results due to human interpretation.
• Incompatibility with Certain Formats: Some test methods may not be suitable for testing modern container systems such as pre-filled syringes or flexible packaging.
• Slower Throughput: Testing time and lack of repeatability can hinder efficiency, especially in high-volume manufacturing settings.

Helium Leak Detection for Biologic Drugs

PTI's helium leak testing technology addresses the shortcomings of traditional methods by offering a more precise and science-driven approach to pharmaceutical leak detection.

Helium, an inert gas with extremely small molecules, is used as a tracer to detect the smallest of leaks with unmatched accuracy. In PTI’s systems, the test sample is filled with helium and placed in a vacuum chamber. Any helium escaping through leaks is quantitatively measured using a mass spectrometer.

Key Benefits of PTI’s Helium Leak Testing Approach:

• High Sensitivity: Capable of detecting leak rates as low as 1 x 10?¹° mbar·L/s, far exceeding the detection limits of traditional methods.
• Quantitative Results: Provides measurable and reproducible data rather than subjective pass/fail outcomes.
• Versatility: Suitable for a wide range of container types, including vials, syringes, and flexible formats used for biologic products.
• Regulatory Alignment: Aligns with current FDA and USP expectations for deterministic leak testing approaches.

The rise of biologic drugs demands a new standard in container closure integrity testing. Relying on traditional leak detection methods may no longer be sufficient to ensure product safety and regulatory compliance. PTI’s helium leak testing offers a highly sensitive and accurate solution tailored to the unique requirements of biologics, reinforcing confidence in product quality and patient safety.

With a proven track record in pharmaceutical leak detection, PTI continues to lead the way in container integrity assurance, bringing science, precision, and reliability to the forefront of pharmaceutical manufacturing.

Foil pouches packaging solution for various industries, including pharmaceuticals and medical devices. Ensuring the integrity of these pouches is crucial to maintain product quality and safety. Helium leak detection systems such as SIMS 1915+ helium-based technology play a vital role in this process. By identifying potential leaks early on these systems help prevent product contamination, extend shelf life, and safeguard customer health.

Foil pouches offer a straightforward and effective solution for sterile barrier packaging, particularly well-suited for medical equipment and pharmaceuticals. Ensuring the integrity of these pouches is crucial to maintain product quality and safety. SIMS 1915+ helps in safeguarding product integrity. The integrity of foil pouches is crucial to maintain product quality and safety. Pouch defects can compromise product quality and introduce contamination risks, potentially leading to product degradation and health hazards for patients. Consequently, rigorous testing of foil pouches is essential to ensure package quality and reliability.

Why are foil pouches used in pharmaceutical industry

Foil pouches are lightweight, flexible, and cost-effective, making them easy to store and transport. Foil pouches can be resealed, extending product shelf life and preventing contamination. Package property of foil pouches help protect sensitive medications from moisture, oxygen, and light, ensuring product integrity. Foil pouches are also compatible with various sterilization methods, making them suitable for sterile product. It can be customized to accommodate different product sizes and shapes, offering versatility in packaging design. By using leak detection systems like SIMS 1915+, manufacturers can further enhance the quality and safety of foil pouch packaging, ensuring medications reach consumers in pristine condition.

Foil pouches package integrity testing using SIMS 1915+

The SIMS 1915+ is a helium leak detection system specifically designed for the pharmaceutical and medical device industries. It utilizes helium as a tracer gas to accurately detect leaks in a variety of packaging formats, including foil pouches, bottles, vials, blister cards, syringes, and cartridges. Unlike traditional methods like vacuum bubble and dye penetration tests, SIMS 1915+ provides quantitative measurements, ensuring a higher level of precision. This advanced system offers numerous applications, including package design validation, tooling certification, manufacturing line setup, and ongoing quality control. Its oil-free pump, detector, and integrated power system are tailored to the specific needs of the industry, enabling the detection of leaks as small as 1 x 10-10 mbar L/s at room temperature. Each SIMS 1915+ device can be customized to meet the unique requirements of individual clients, providing a flexible and reliable solution for maintaining product integrity.

Applications of SIMS 1915+ include:

• Pre-filled syringes
• Bottles
• Blister packs
• Foil pouches
• Vials
• Combination products (cartridges)

Benefits of SIMS 1915+ in foil pouches

• Detects microscopic defects invisible to the eye, ensuring product integrity.
• Provides precise leak rate measurements for rigorous quality control.
• Offers rapid testing cycles for efficient production.
• Adapts to diverse foil pouch configurations.
• Ensures adherence to regulatory standards and industry best practices.

The pharmaceutical industry needs deep cold storage for complex drug and biologic formulations. Traditional packaging may not withstand these extreme temperatures, leading to potential leaks and product degradation. The PTI LT add-on units for SIMS helium leak detectors offer advanced solutions that evaluates package integrity at temps ranging from 0°C to -160°C, helping manufacturers identify defects and optimize their packaging for deep cold storage.

Low Temperature Packaging - Overview and Applications

The pharmaceutical industry's increasing focus on complex drug and biologic formulations necessitates stringent temperature control to maintain product quality and efficacy. These sensitive products, often requiring storage at ultra-low temperatures, present unique challenges for packaging integrity.

Low-temperature packaging is critical for a diverse range of products, including:

• Vials
• Biologics and Gene Therapies: These complex biological products often require ultra-low temperature storage to maintain their potency and efficacy.
• Vaccines: Many vaccines, especially those derived from live viruses or fragile proteins, necessitate storage at low temperatures to prevent degradation.
• Pharmaceutical Ingredients: Certain pharmaceutical ingredients, particularly those derived from natural sources or with complex molecular structures, may require low-temperature storage to prevent degradation.

The Challenge of Low-Temperature Package

• Material Issues: Elastomers and plastics can become brittle, affecting seals and container integrity.
• Leakage Risks: Primary and secondary seals may fail at low temperatures.
• Testing Limitations: Traditional leak testing methods may be ineffective.
• Regulatory Compliance: Adherence to USP 1207 and international standards is crucial.
• Logistics and Transportation: Maintaining temperature control and ensuring package durability are essential.

Low Temperature Package Leak Detection using Helium Leak Testing

SIMS Low Temp Add-On units include models LT 80, LT 85 and LT 150, are designed to address the critical challenge of ensuring package integrity at extremely low temperatures. By combining a chiller with a helium leak detector, the LT80, for example, allows for accurate testing of packages down to -80°C. This enables manufacturers to identify potential leaks in packaging materials, such as elastomeric closures, that may occur at these low temperatures. By understanding the performance of packaging systems under extreme conditions, manufacturers can improve product quality, reduce waste, and comply with stringent regulatory standards.

The LT systems offer several key advantages for the pharmaceutical industry:

• Accurate Low-Temperature Leak Detection: Precisely identifies leaks in packaging materials at ultra-low temperatures
• Enhanced Product Quality: Ensures the integrity of sensitive products, preventing degradation and maintaining potency.
• Reduced Product Loss: Minimizes waste due to leakage and spoilage, optimizing inventory and reducing costs.
• Regulatory Compliance: Adheres to strict regulatory standards like USP 1207, ensuring product safety and quality.

The pharmaceutical industry's growing reliance on deep cold storage for sensitive products demand robust and reliable packaging solutions. Helium leak detection provides a powerful tool for assessing container closure integrity, ensuring that packages can withstand the rigors of ultra-low temperature environments. By proactively identifying and addressing potential leaks, manufacturers can safeguard product quality, reduce waste, and ultimately improve patient outcomes.

Pharmaceutical bottle integrity testing is an important step in assuring that the product is safe and unadulterated. It analyzes the strength and integrity of the closure mechanism as well as its capacity to maintain a sterile barrier. Container closure integrity testing analyzes the materials and chemicals for the possibility of migration or leaching into the drug product, resulting in contamination. Microorganisms, gases, and other chemicals are examples of contaminants. Container system integrity testing involves evaluating primary packaging, or everything that comes into direct touch with the product, as well as secondary packaging components required for package assembly. Helium leak detection, airborne ultrasound, vacuum decay, and high voltage leak detection are all methods for verifying the safety of container closures.

Helium Leak Detection to Ensure the Integrity of Bottles

Helium leak detection is referred to as a method of finding leaks in a sealed or enclosed system using the helium tracer gas method. The amount of helium that leaks through a breach is measured and is stated as a leak rate. It is an effective container closure integrity test technique for determining the integrity of pharmaceutical and parenteral products. Helium leak testing guarantees the sterility of drug substances and drug products packaged and, therefore, enhances patient safety.

In this method, the package is filled with helium and subjected to vacuum. The quantity of helium that exits the package is measured using a helium leak detector. The result is expressed as the leak rate. Helium leak testing, in addition to being a highly sensitive container closure integrity test technique, is also useful in product design, product quality analyses, failure analysis, and validation.

What are the Applications of Helium Leak Testing?

Some of the most important applications of helium leak testing include:

• Ensuring container closure integrity.
• Selecting closure formulation and configuration.
• Seal integrity monitoring during stability studies.
• Verification and prediction of shelf-life seal integrity.
• Useful in the early stages of developing a pharmaceutical product packaging system.

Helium leak detection offered by LDA (a PTI company) is one of the commonly used leak testing methods that can be used for pharmaceutical package leak detection. Bottles can be tested very effectively using this method. The applications of helium leak detection are also found in vials, prefilled syringes, foil pouches, and cold form blister cards. LDA has long-time expertise in designing leak testing equipment for pharmaceuticals and medical devices.

Food and Drug Administration (FDA) requirements for drug testing of combination products are strict. Companies seeking FDA clearance for such products must fully understand the requirements for FDA approval in order to prevent costly and time-consuming errors. 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. A combination product can combine at least two of these product categories, and sometimes all three. Traditional drug-device combination products, such as a syringe pre-filled with a drug, auto-injectors containing a filled cartridge and needle, and co-packaged or kitted products, are some of the most common types of combination products.

The constantly increasing demand for combination pharmaceutical products continues to fuel innovation and creates numerous interesting opportunities that will provide the medical community with promising new alternatives for improving patient care and results. However, bringing bio/pharmaceuticals and medical devices together to form a combination product necessitates extensive testing of all product ingredients.

Why Use SIM 1915+ for Leak Testing Combination Products?

A Helium-based leak detection system-Seal Integrity Monitoring System (SIMS) 1915+ is an excellent solution for detecting leaks in combination products. Packages may be quantitatively evaluated using helium as the tracer gas, which assures better levels of accuracy when compared to traditional vacuum bubble and dye penetration test procedures. SIMS 1915+, which has been proven to be an effective leak detection approach, may also be utilized for package design, tooling certification, manufacturing line setup, and ongoing product quality monitoring. PTI custom builds each SIMS 1915+ Helium Leak Testing device to customer specifications. Cold form blister cards, foil pouches, parenteral vials, syringes, pre-filled syringes, and unique medical devices can also be tested using SIMS 1915+.

Technology Overview

SIMS Model 1915+ helium-based leak testing system offered by PTI is specifically designed for medical and pharmaceutical package leak detection. The SIMS 1915+ enables quantitative analysis of package systems at sensitivity levels as low as 1 x 10 -10 cc/s at room temperature. The Helium Leak Detector Module (HLDM), the most crucial component, is built within a Console Frame Assembly with a Stainless Steel working surface and an optional Dual Test Port Manifold. The consoles have a locking wheel and an articulating arm system for attaching the computer and peripherals, making the independent device simple to operate and maneuver.

The SIMS 1915+ Leak Detection System specs and add-on components are shown below.

• Helium Leak Detector Module (HLDM): Oil-Free, Production Version in Console Frame Assembly with Stainless Steel Working Surface and Dual Test Port Manifold.
• Vacuum Test Fixture Model (VTFM): a custom-made fixture for testing vial container samples.
• Head Space Analyzer Module (HSAM): Model VM-2 that includes three (3) Puncture Probes (two spares) for determining the concentration of helium in the headspace of vial containers.
• Integral Calibration Chamber (with Calibrant Gas Flow Meter/Controller) for HSAM Calibration and a Universal Holder for various vial diameters are offered.
• Helium Filling Device designed specifically for vial testing sample prep that allows vials to be filled with helium.
• Low Temperature (LT) Add-on devices created particularly for evaluating products in ultra-cold storage temperatures as low as –140 °C.

SIMS 1915+ Applications

Common applications of SIMS 1915+ include:

• Pre-filled syringes
• Vials
• Bottles
• Combination products
• Foil pouches
• Blister packs

Combination products provide a safe, effective, and convenient method of administering the drug or biologic therapies. The purpose of testing combination products is to obtain information to support the claim that all use-related hazards connected with the product have been reduced to the greatest extent possible. PTI is well-versed in the extensive testing requirements and regulatory criteria for bio/pharmaceutical products and medical devices, and provides complete testing services for these components, both individually and in combination.

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. PTI provides professional engineering solutions for the Active Pharmaceutical Ingredient (API) sterile container testing.