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Maintaining container closure integrity (CCI) in radioactive pharmaceuticals safeguards safety and regulatory compliance. Even small leaks can result in contamination, radiation exposure, and decreased drug effectiveness. For these sensitive products, advanced CCI testing accurately detects any breaches that could compromise packaging integrity. The complexities of handling radioactive materials demand specialized approaches to ensure reliable assessments without affecting product quality. By applying precise and consistent testing methods, manufacturers protect the integrity of radioactive pharmaceuticals throughout their shelf life, supporting both patient safety and healthcare standards.

What are Radioactive Pharmaceuticals?

Radioactive pharmaceuticals, or radiopharmaceuticals, are specialized medications containing radioactive isotopes, used primarily in diagnostic imaging and targeted therapy. These compounds emit controlled radiation, enabling healthcare professionals to visualize internal organs, assess tissue function, and treat diseases like cancer with precision. In diagnostics, they emit radiation that is detected by imaging devices, offering detailed insights into organ function and disease. In treatment, radiopharmaceuticals deliver targeted radiation to diseased cells, particularly in cancer therapy, thereby reducing damage to surrounding healthy tissues. Their unique ability to target specific areas makes radiopharmaceuticals indispensable in modern medicine, providing accurate diagnoses and effective treatments while minimizing systemic side effects.

Challenges of CCI in Radioactive Pharmaceuticals

Container Closure Integrity (CCI) testing for radioactive pharmaceuticals presents unique challenges due to the specialized nature of these products. Here are some key challenges:

• Cost-Efficiency: Unlike more complex testing methods, this approach allows for immediate testing and precise data collection, reducing the time spent on preparation and analysis. This results in faster decision-making, quicker time-to-market, and lower overall costs, all while maintaining high levels of accuracy and reliability in detecting leaks.
• Radiation Safety: Handling radioactive materials requires strict safety protocols, complicating testing environments. Specialized containment may be necessary to reduce radiation exposure risks.
• Material Compatibility: Packaging must resist radiation-induced degradation over time. Selecting materials that maintain integrity despite exposure is crucial.
• Test Method Selection: Traditional CCI methods may not be suitable for radioactive products. Non-destructive techniques, such as vacuum decay or helium leak testing, are often preferred.
• Regulatory Compliance: Radiopharmaceuticals face stringent pharmaceutical and radiation safety standards. Meeting dual regulatory requirements can complicate CCI validation.
• Sterility Assurance: Maintaining sterility without compromising the product is essential. Traditional sterilization methods may not be suitable for radioactive pharmaceuticals.

Testing Integrity in Radioactive Pharmaceuticals Using Vacuum Decay Technology

Vacuum Decay leak testing is a non-destructive Container Closure Integrity Test (CCIT) method commonly used to detect leaks in sealed packaging. Known for its sensitivity and practicality, it can identify leaks in rigid, semi-rigid, or flexible packages, whether made from porous or non-porous materials. This method offers reliable, accurate, and consistent results, ensuring precise package integrity testing. As a non-destructive alternative to traditional water bath and dye ingress tests, vacuum decay provides an effective solution for leak detection in the pharmaceutical and medical device sectors.

Vacuum Decay operates on fundamental physical principles of container integrity. The package is placed inside a sealed vacuum chamber connected to an external vacuum source. A specific vacuum level is applied based on the packaging type and required sensitivity. The system then monitors the chamber and any dead space for a set duration. Sensitive differential pressure transducers track changes in vacuum levels over time. A pressure increase beyond the pre-defined pass/fail limit signals a leak in the container.

As the pharmaceutical industry continues to evolve, adopting specialized CCI testing enhances product quality and builds trust in the supply chain. Prioritizing precise and thorough CCI evaluations contributes to safer and more reliable radioactive pharmaceuticals in the market.

Container Closure Integrity Testing (CCIT) is an essential process in the pharmaceutical and medical device industries, ensuring that products remain safe and effective throughout their shelf life. Among the various methods available, helium leak testing stands out for its precision and reliability. PTI specializes in offering expert Helium Leak Testing services tailored specifically for pharmaceutical packaging, a critical component in ensuring product safety and efficacy. Our helium leak testing combines advanced technology with industry expertise to provide cost-efficient solutions without compromising on quality. This method not only delivers reliable data but also allows for significant flexibility in testing parameters, accommodating the unique needs of each client. With a focus on speed, our services ensure rapid turnaround times, enabling manufacturers to make timely decisions and maintain production schedules.

Helium Leak Testing for Pharmaceutical Packaging

Helium leak testing is a highly effective and precise method used in the pharmaceutical industry to ensure the integrity of packaging. This method leverages helium’s small atomic size and inert properties, making it ideal for detecting even the smallest breaches in packaging that could compromise product safety. In this process, helium is introduced into or around the pharmaceutical package—such as vials, ampoules, or blister packs. If there is any leakage, highly sensitive detection instruments can identify and trace the helium escaping from the tiniest of openings. This method offers a high level of precision, capable of detecting leaks as small as 10^-10 mbar L/s, which ensures the highest level of packaging integrity.

Unlike other leak detection methods, helium testing is both highly sensitive and safe, as helium does not react with the product or packaging materials. It ensures compliance with stringent regulatory requirements, like USP <1207>, which focus on container closure integrity. The ability to accurately detect micro-leaks helps prevent contamination, ensuring that pharmaceutical products remain sterile and effective throughout their shelf life. By employing helium leak testing, pharmaceutical companies can not only maintain product quality and safety but also optimize their quality assurance processes, reducing waste and avoiding costly recalls, all while delivering confidence to regulators and patients alike.

CCIT Helium Leak Testing Services

• Cost-Efficiency: Unlike more complex testing methods, this approach allows for immediate testing and precise data collection, reducing the time spent on preparation and analysis. This results in faster decision-making, quicker time-to-market, and lower overall costs, all while maintaining high levels of accuracy and reliability in detecting leaks.
• Reliable Data: Unlike probabilistic methods, where outcomes can vary and are influenced by factors like chance or operator judgment, helium leak testing delivers precise, objective results. Since it relies on measurable physical principles, the data is free from operator subjectivity, ensuring accuracy and repeatability. This makes helium leak testing a trusted solution for industries that require stringent quality control, as it guarantees dependable leak detection every time.
• Time Savings: Reduces the time required for leak detection compared to headspace analysis, often completing the process in less than a day. While headspace analysis can take several days due to its complex sample preparation and analysis procedures, helium leak testing streamlines the testing process with its straightforward methodology. This rapid turnaround enables companies to quickly assess the integrity of their products, leading to faster decision-making and minimizing delays in production.
• Flexibility: Our testing services provide exceptional flexibility, allowing us to customize our approach to meet your specific requirements without the additional costs associated with adhering to stringent Good Manufacturing Practice (GMP) guidelines. This adaptability means we can adjust testing parameters, methodologies, and timelines based on your requirements, ensuring that you receive the most relevant and effective solutions.

Helium leak testing services offer vital benefits for the pharmaceutical industry. They enable immediate, precise data collection, enhancing cost efficiency while ensuring product integrity and safety. The objective results from this deterministic method eliminate uncertainties, boosting confidence in quality control. Rapid testing further streamlines operations and enables quick responses to market demands. With the flexibility to tailor methodologies to specific client needs, helium leak testing services are essential for maintaining high standards and ensuring the reliability of pharmaceutical packaging throughout its shelf life

Packaging integrity is a critical factor for collagen-based products, particularly due to their sensitive nature and diverse applications in medical, cosmetic, and pharmaceutical fields. These products, whether used in wound healing, reconstructive surgery, or skincare, require stringent packaging standards to maintain sterility and efficacy throughout their lifecycle. Even the smallest compromise in packaging can lead to contamination, which poses serious risks to patient safety and product effectiveness.

Ensuring the integrity of packaging for collagen-based products is not only essential for preserving their quality but also for meeting strict regulatory requirements. As a result, advanced testing methods like Vacuum Decay have become crucial tools for verifying that the packaging is secure and free of leaks, ensuring the product remains uncontaminated from production to end-use.

Why Sterility is Critical in Collagen-Based Products?

Sterility is of utmost importance in collagen-based products, especially those intended for medical use, such as wound healing, tissue engineering, or reconstructive surgery. These products often interact directly with the human body, meaning that any contamination can lead to serious health risks such as infections or adverse reactions. For cosmetic applications like dermal fillers, contamination can affect the product’s performance and cause harm to the skin, resulting in potentially severe complications.

Due to their biological nature, collagen-based products are particularly susceptible to microbial contamination, which can degrade the product’s quality and reduce its effectiveness. Maintaining sterility ensures that the product remains safe for use throughout its shelf life. It also upholds the therapeutic and aesthetic benefits of collagen-based products. For manufacturers, ensuring sterility is not only a matter of product quality but also a key factor in meeting regulatory requirements for safety and efficacy.

Role of Vacuum Decay in Sterility Testing for Collagen Products

Collagen products, often used in medical applications such as wound healing and tissue regeneration, must maintain a sterile environment to preserve their safety and efficacy. Vacuum Decay plays a critical role in sterility testing for collagen-based products, ensuring that their packaging remains airtight and free from contamination. The Vacuum Decay leak testing works by detecting microleaks in sealed packaging. By applying a vacuum to the package and measuring any changes in pressure, it identifies breaches that could allow bacteria or contaminants to enter. This method is highly sensitive, capable of detecting even the smallest leaks, which is crucial for ensuring the sterility of collagen-based products. One of the key benefits of Vacuum Decay is its cost-effectiveness. As the leak test does not waste any product, it results in considerable savings.

By preventing compromised packaging, the Vacuum Decay helps manufacturers meet stringent regulatory standards while maintaining the quality of the product throughout its shelf life. This ensures that collagen products remain safe for use, protecting both patient health and the product’s effectiveness.

Benefits of Vacuum Decay Technology

• Non-destructive, non-subjective, no sample preparation.
• Capable of detecting defects down to 0.05 ccm.
• Accurate, reliable, repeatable results.
• Supports sustainable packaging and zero waste initiatives.
• FDA recognized standard for package integrity testing.

Vacuum Decay technology brings a new level of precision and reliability to packaging integrity testing for collagen-based products. Its non-invasive nature and exceptional leak detection capabilities help manufacturers safeguard the sterility and quality of these sensitive products. By reducing the risk of contamination and ensuring regulatory compliance, this technology not only enhances product safety but also strengthens consumer trust in collagen-based medical and cosmetic solutions. In an industry where quality is paramount, the Vacuum Decay is transforming how packaging integrity is maintained, ultimately benefiting both manufacturers and patients.

In the dynamic and highly regulated world of pharmaceuticals, biotechnology, and medical devices, ensuring the integrity of product packaging is vital for maintaining safety and compliance. Container Closure Integrity Testing (CCIT) play a crucial role in verifying that packaging systems effectively safeguard products from contamination, leakage, and environmental factors. From initial feasibility studies to the development of precise test methods, and from stability testing to specialized helium leak detection, these services provide essential insights into the effectiveness of packaging solutions. By leveraging advanced technologies and methodologies, CCIT ensure products remain protected and meet stringent regulatory standards throughout their lifecycle.

Advanced Laboratory Testing Services

CCI testing services provide a comprehensive suite of solutions designed to assess and verify the integrity of packaging systems. Our CCI testing services encompass a range of specialized offerings, including:

Feasibility Studies: These experimental studies are the first step in determining the most suitable inspection technology and test method for a specific application. Our feasibility studies are backed by detailed reporting and comprehensive test result data, providing a solid foundation for subsequent testing and validation.

Test Method Development Support: Our services include the development and documentation of test methods, including advanced initial recipe creation, container qualification, and system suitability testing. We provide thorough testing and documentation to ensure the accuracy and reliability of test methods.

Stability Testing: This service ensures that products maintain container closure integrity throughout their stability period. Stability testing is crucial for verifying that packaging continues to protect the product over time, under various storage conditions.

Recall & Batch Release Testing: Designed for recalled products, products on hold, and batch release, this service provides critical testing to ensure product integrity and compliance before market release.

Helium Testing Services: Helium testing is used for a variety of purposes, including R&D work, component/material selection, packaging equipment qualification, and ongoing quality monitoring. Our helium testing services cover:

• Cold storage testing at temperatures ranging from -0°C to -160°C.
• Helium pre-filled and 100% Helium Flow Method testing.
• Compliance with USP 1207 standards.
• Testing for parenteral formats, blister cards, pouches/sachets, and various industrial applications.
• Package validation, component selection, stability sample testing, and R&D studies.

All leak testing is conducted in a non-GMP environment, ensuring flexibility and efficiency in testing procedures. Our CCI testing services are designed to meet the unique needs of each client, providing reliable and accurate results that support product quality and safety. These services are not just a regulatory requirement but a fundamental component of a commitment to quality and safety in product development and manufacturing.

Ensuring the integrity of container closures is a critical aspect of pharmaceutical and medical product safety. Container Closure Integrity Testing (CCIT) is essential to confirm that containers such as vials, syringes, and ampoules maintain their seal and protect the contents from contamination throughout their shelf life.

E-Scan MicroCurrent High Voltage Leak Detection (HVLD) technology has emerged as the optimal solution in advancing CCIT methodologies. E-Scan MicroCurrent HVLD technology significantly enhances container closure integrity testing by providing accurate, non-destructive, and efficient solutions. Its integration into CCIT processes helps ensure that pharmaceutical and medical products are safe, reliable, and of the highest quality.

MicroCurrent HVLD for Pharmaceutical Package Testing

MicroCurrent HVLD is a non-destructive method for evaluating the integrity of container closures in non-porous pharmaceutical and parenteral products. This technique utilizes low electrical current to detect leaks in various liquid-filled products, including those with extremely low conductivity such as sterile water for injection (WFI) and products containing proteins or suspensions. Unlike conventional HVLD technology, MicroCurrent HVLD reduces product voltage exposure to less than 5%, eliminating any potential risk to the product and reducing ozone formation during testing.

In this method, high voltage probes scan the container. One side is subjected to high voltage, while a ground probe is attached to the other side. If the container is intact, both sides offer complete electrical resistance, and no significant current passes through. However, if a micro-leak or fracture is present, resistance breaks down, allowing current to flow through the defect. HVLD is unique among leak detection methods as it does not require mass to pass through the defect site; instead, it transmits electricity through the crack.

E-Scan Technologies: E-Scan 605, E-Scan 615, E-Scan 655, E-Scan RTX

E-Scan 605: E-Scan 605 is designed for non-destructive evaluation of container closure integrity in pharmaceutical and parenteral products. Its rapid testing capabilities make it a cost-effective and efficient solution for ensuring the integrity of parenterals.

E-Scan 615: E-Scan 615 is designed to handle a wider range of product types and configurations, making it suitable for more complex testing scenarios. It ensures accurate detection of leaks, providing high levels of safety and quality assurance for pharmaceutical packaging. With its easy operator HMI screen, the E-Scan 615 enhances workflow efficiency.

E-Scan 655: E-Scan 655 is the advanced analytical version in the E-Scan series, offering enhanced capabilities for container closure integrity testing. It uses state-of-the-art MicroCurrent HVLD technology to provide highly accurate leak detection across a broad spectrum of pharmaceutical and parenteral products. The E-Scan 655 is equipped with advanced features for handling diverse product sizes and shapes, ensuring comprehensive testing coverage.

E-Scan RTX: E-Scan RTX represents the latest innovation in the E-Scan product line, offering a comprehensive technology for automated container closure integrity testing. It incorporates advanced MicroCurrent HVLD techniques with automated pick & place of pre-filled syringes. Its intuitive interface and automated testing capabilities make it a powerful tool for ensuring the highest standards of product integrity and safety of pre-filled syringes.

E-Scan MicroCurrent HVLD Series offers a powerful solution for parenteral container closure integrity testing. Its advanced technology, combined with its non-destructive nature, reduced voltage exposure, and automation features, ensures high-quality, reliable testing results. By integrating these systems into CCIT processes, pharmaceutical and medical industries can uphold the highest standards of product safety and efficacy.

In the rapidly evolving field of biologics, maintaining container closure integrity is essential for product safety, regulatory compliance, and overall efficacy. By employing advanced CCI testing methods, manufacturers can ensure their packaging systems provide robust protection for sensitive biologic products, ultimately contributing to better patient outcomes and advancing the field of pharmaceutical science. As the demand for biologics continue to grow, the importance of rigorous CCI testing will only become more pronounced, underscoring the need for continued innovation and adherence to best practices in packaging integrity.

Importance of Maintaining Sterility and Efficacy in Biologic Products

Biologic products, which include vaccines, monoclonal antibodies, and therapeutic proteins, are essential in treating a wide range of diseases. Ensuring their sterility and efficacy is vital for several reasons:

• Patient Safety: Sterility is critical to prevent contamination by harmful microorganisms, which can lead to severe infections or adverse reactions. A lapse in sterility can compromise patient safety, potentially causing serious health issues.
• Product Integrity: Maintaining both sterility and efficacy is essential for the product’s overall quality and reliability. Consistent quality reassures healthcare providers and patients, reinforcing trust in the therapy and supporting its widespread adoption.
• Minimizing Risks: Ensuring that biologic products are sterile and effective minimizes the risk of treatment failures and associated complications. This contributes to better patient outcomes and enhances the overall success of therapeutic interventions.

Prioritizing these factors supports the successful application of biologic therapies and upholds the high standards required in the biotechnology industry.

Package Integrity Solutions for Biologics Packaging

Helium Leak Detection Technology

Helium leak testing detects leaks in sealed systems by using helium as a tracer gas and measuring its escape. This method provides highly accurate leak rate data, surpassing other techniques. It is particularly effective for evaluating the integrity of pharmaceutical and parenteral packaging. The process involves filling the package with helium, applying a vacuum, and using a detector to measure the escaping helium, determining the leak rate. This technology is crucial for package design, failure analysis, tooling qualification, packaging line validation, and quality monitoring.

For cold storage CCI applications, helium is a highly sensitive and reliable technology for assessing the performance of vials, syringes, and cartridges at cryogenic temperatures.

MicroCurrent HVLD Technology

MicroCurrent HVLD technology is an innovative High Voltage Leak Detection method for container closure integrity testing (CCIT), proving highly effective for a wide range of applications including pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. This non-destructive, non-invasive technology uses approximately 50% less voltage, exposing the product and environment to less than 5% of the voltage compared to conventional HVLD solutions. It stands as one of the most effective CCI technologies for all parenteral and biological products.

To ensure Container Closure Integrity, the method uses electrode probes to scan a non-conductive sealed container. Defects in the package cause a resistance differential, altering the current flow within the container. The MicroCurrent HVLD test method can accurately detect and locate defects such as pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping, and more.

Advanced CCI testing methods, including Vacuum Decay and MicroCurrent HVLD, offer diverse and highly accurate solutions for detecting potential leaks and defects. By employing these techniques and adhering to best practices, manufacturers can ensure that their packaging systems effectively preserve the quality and safety of biologic products, ultimately enhancing patient outcomes and advancing the pharmaceutical industry.

In the field of pharmaceutical packaging, the quest for robust Container Closure Integrity (CCI) testing methods has evolved significantly beyond traditional approaches such as blue dye testing. As the industry continues to prioritize safety, efficacy, and regulatory compliance, innovations in CCI testing are poised to redefine standards and practices.

Recent advancements in CCI testing methods are driving a transformative shift towards more sensitive, reliable, and versatile techniques. These innovations are not only enhancing detection capabilities but also addressing the limitations that have historically challenged conventional methods like blue dye testing.

Limitations of Blue Dye Testing

Blue dye testing, a traditional method for leak detection in packaging, has several limitations that make it less favourable compared to more modern techniques. Here are some of the key drawbacks:

• Destructive testing: The biggest disadvantage is that the test destroys the packaging being tested.
• Subjectivity: Relying on visual inspection of the packaging for dye presence can be subjective.
• Limited leak detection: Blue dye tests are not very sensitive and may miss certain types of leaks, particularly those with low permeability or microscopic tears.
• Environmental concerns: The disposal of the dye solution used in the testing process can raise environmental concerns.

How Modern CCI Testing Methods Detect Issues that Blue Dye Might Miss?

Modern CCI testing methods offer significant advantages over traditional techniques like blue dye testing by providing sensitive, quantitative, non-destructive, and versatile approaches to assessing container closure integrity. These advancements enhance the reliability and effectiveness by ensuring product quality and patient safety.

MicroCurrent HVLD Technology

MicroCurrent HVLD is a non-destructive technology for Container Closure Integrity Testing (CCIT) used to assess the integrity of parenteral product packaging. This approach employs quantitative electrical conductivity measurements inherent to HVLD technology, which relies on the fundamental principle of electrical current. During testing, the container is positioned horizontally on a rotating stage. As the container rotates, one side receives a high voltage, while a ground probe is connected to the opposite side. If the package remains intact without leaks, the two container surfaces (high voltage and ground) exhibit complete electrical resistance, resulting in minimal current flow through the vial. However, if there is a micro-leak or crack in the container walls, the electrical resistance is compromised, allowing current to pass through. MicroCurrent HVLD finds application in testing various types of pharmaceutical packaging, including pre-filled syringes, ampoules, drug product cartridges, liquid-filled vials, and Blow-Fill-Seal (BFS) containers.

Vacuum Decay Technology

Vacuum Decay is a non-destructive approach to assessing container closure integrity, focusing the detection of package integrity and leak paths. The test procedure is simple, evaluating container integrity based on critical physical attributes. This technique has proven to be a non-destructive alternative to traditional water bath leak testing. In this method, packages are placed within an evacuation test chamber that utilizes an external vacuum source. The test continuously monitors vacuum levels to identify any deviations from a predefined target vacuum level. If a package is defective, it allows air to escape into the test chamber. Conversely, intact packages maintain a stable vacuum level within the chamber. Over time, Vacuum Decay technology has established itself as one of the most effective and sensitive solutions for vacuum-based leak detection.

Helium Leak Detection Technology

Helium leak detection technology has revolutionized Container Closure Integrity Testing (CCIT) by offering extremely sensitive and accurate detection of leaks. This method involves using helium gas to identify leaks in sealed or closed systems, measuring its concentration as it escapes through any leaks present. Helium leak testing finds diverse applications across various packaging formats, such as pre-filled syringes, vials, cold form blister packs, foil pouches, and others. This technology excels at precisely evaluating the integrity of specific components within primary container closure systems, making it highly suitable for ensuring the integrity of pharmaceutical products. Helium gas is uniquely suited as a tracer for leak detection due to its exceptional properties. Manufacturers leverage these properties to conduct thorough testing that can pinpoint even minute leaks, thereby enhancing quality control and product safety.

Innovations in Container Closure Integrity (CCI) testing have propelled the field beyond traditional methods like blue dye testing, ushering in a new era of enhanced precision and reliability. Technologies such as MicroCurrent HVLD, Vacuum Decay, and Helium leak detection have revolutionized how pharmaceutical packaging integrity is assessed, offering sensitive, non-destructive, and comprehensive approaches.

With ongoing developments in analytical capabilities and testing methodologies, the landscape of CCI testing is poised for further advancements, driving towards greater efficiency, accuracy, and compliance. By embracing these innovations, pharmaceutical manufacturers can confidently navigate the complexities of packaging integrity, setting new benchmarks for quality assurance in the healthcare sector.

Container Closure Integrity Testing is a leak detection test conducted using non-destructive package inspection systems, to evaluate whether container closure systems can maintain sterile barriers against potential damages. CCIT plays a vital role in ensuring that the products are free from any possible contamination. Container closure systems are made up of primary packaging components and secondary packaging components. Components like glass, vials or syringes that are in direct contact with the product are called primary packaging components. Secondary packaging components include aluminum caps, cardboard boxes etc. that are not in direct contact with the product.

While there are multiple ways to conduct a Container Closure Integrity test, these methods can be broadly classified into probabilistic and deterministic test methods. Traditional methods like bubble tests, dye ingress and microbial challenge by immersion come under probabilistic test methods. Since it was found that such test results lacked accuracy and reliability, the United States pharmacopeia released guidance in 2016 stating that deterministic methods are preferred over probabilistic test methods. Let us now understand how Microcurrent HVLD technology ensures sensitive CCI testing across different industries and applications.

MicroCurent HVLD technology is a non-destructive test method capable of achieving high levels of CCI assurance across the entire range of parenteral products. It is an FDA recognized ASTM test method capable of detecting the presence and location of pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping and many other defects. Additionally, MicroCurent HVLD technology is found to be effective in detecting leaks in a wide range of liquid- filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. A unique feature of Microcurrent HVLD technology is that it does not require mass to pass through a defect site, requiring only the passage of electricity through a crack.

How does MicroCurrent HVLD technology work?

MicroCurrent HVLD technology functions on the simple property of electrical current. The first step is to place container horizontally on the rotating stage. While rotating the container, high voltage is applied on one side of the container and a ground probe on the opposing side. In the presence of a micro-leak or crack in one of the container walls, break-down resistance is reached and the current passes through. On the other hand, if there is no leak, the two container walls (high voltage side and ground side) provide full electrical resistance and no significant current is measured passing through the package.

MicroCurrent HVLD reduces voltage exposure to the product to less than 5% of the voltage exposure experienced when testing with other HVLD solutions. Reduced voltage exposure has twin benefits- limits any risk that the voltage may cause to the product, and greatly reduces production of ozone during operation. In fact, experiments have shown that MicroCurrent HVLD produces essentially no Ozone

Benefits MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation.
• High level of repeatability and accuracy.
• Effective across all parenteral products, including extremely low conductivity liquids (WFI).
• Lower voltage exposure produces no ozone, eliminating risk to the product and environment.
• Listed in USP Chapter as recommended method for parenteral liquid package inspection.
• Robust method and approximate 3x Signal-Noise-Ratio for a wide range of product classes and package formats.
• Simplifies the inspection and validation process.

Non-destructive testing (NDT) plays a pivotal role in ensuring the quality and reliability of various products across industries. In the realm of contact lens manufacturing, where precision and safety are paramount, the VeriPac system stands out as a game-changer. This innovative technology revolutionizes the quality control process by offering a non-invasive means to inspect and validate contact lenses without compromising their integrity.

The VeriPac system employs advanced inspection techniques that eliminate the need for destructive testing methods, preserving the integrity of each lens while providing comprehensive analysis. By utilizing non-destructive methods such as Vacuum Decay technology, the VeriPac system can detect even the slightest defects or irregularities in contact lenses, ensuring that only products meeting the highest standards are delivered to consumers.

Challenges in Contact Lens Manufacturing

Contact lens manufacturing involves intricate processes to ensure the production of high-quality lenses that are safe and comfortable for wearers. Here are some of the challenges faced in contact lens manufacturing:

• Material Selection: Choosing the right material is crucial. It needs to be biocompatible, allowing oxygen transmission to the cornea, and have appropriate mechanical properties to ensure comfort and durability.
• Sterilization: Ensuring lenses are free from contaminants and microorganisms is essential to prevent eye infections. Sterilization methods must be effective without altering the properties of the lens material.
• Quality Control: Maintaining consistent quality across batches is challenging. Quality control measures are necessary at every stage of production to identify and rectify any defects.
• Regulatory Compliance: Contact lenses are medical devices, so manufacturers must comply with strict regulatory standards set by organizations such as the FDA in the US and the CE in Europe.
• Cost-Efficiency: Balancing quality and cost is a constant challenge. Manufacturers need to invest in advanced technologies while keeping the production cost-effective to remain competitive.
• Environmental Impact: With increased awareness of sustainability, manufacturers face pressure to develop eco-friendly materials and reduce waste generated during production.

Role of VeriPac System in Enhancing Contact Lens Manufacturing

VeriPac 410 is an innovative Container Closure Integrity Testing (CCIT) method, that uses force decay technology for non-destructive seal and leak detection for contact lenses. VeriPac 410 inspection technology platform integrates Vacuum Decay technology with a new force-based measurement system for enhanced performance. This advanced force decay technology can measure force by detecting the surface deflection of a package during a standard vacuum test cycle. By measuring the surface force of the package, the VeriPac 410 can not only identify defective packages but also perform leak tests on packages with minimal headspace.

The ability to inspect multiple packages in a single test cycle is one of the key features of VeriPac 410 technology. This capability streamlines evaluations, facilitating a faster processing rate for products. Furthermore, the system is engineered to identify the exact defective package or blister cavity, offering precise data to operators and quality control teams. The test results are quantitative, delivering a definitive PASS/FAIL determination. This eliminates any subjective interpretation from the evaluation process, thereby improving the dependability and precision of quality control measures.

Benefits of VeriPac 410 Technology

• Non-destructive, non-invasive, no sample preparation
• Non-subjective, accurate, and repeatable results
• Capability to test multiple packages in a single test cycle
• Identifies which package is defective
• Simplifies the inspection and validation process
• ASTM test method and FDA standard
• Cost-effective with rapid return on investment

As contact lens manufacturing continues to evolve, the VeriPac system stands as a testament to the power of technology in driving progress and innovation. Its impact extends beyond the manufacturing floor, influencing the standards of quality assurance and setting new benchmarks for excellence in product inspection. With its proven track record of reliability and precision, the VeriPac system remains an indispensable tool for ensuring the quality and safety of contact lenses, ultimately enhancing the overall experience for consumers worldwide.

The rise of flexible packaging has revolutionized various industries, offering lightweight, efficient, and versatile solutions. The global demand for flexible packaging is projected to continue its upward trajectory, driven by several factors. These include cost-effectiveness, sustainability, and versatility. Compared to rigid alternatives, flexible packaging offers significant cost advantages in terms of materials, transportation, and storage. Advancements in material science are leading to the development of eco-friendly flexible packaging solutions, catering to the growing demand for sustainable practices. Additionally, flexible packaging offers exceptional design flexibility, allowing for unique shapes, sizes, and printing options to enhance product branding and consumer appeal.

Despite these advantages, ensuring the integrity of these non-rigid packages presents certain challenges. The materials used in flexible packaging can be susceptible to puncture and tear, permeability, and microbial growth. Puncture and tear can occur during transportation, handling, or external pressure. Imperfections in seals or the material itself can allow the ingress of gases, moisture, and other contaminants, potentially impacting product quality and safety. If not properly protected, flexible packaging can create micro-environments conducive to microbial growth, posing a risk to perishable goods.

The pharmaceutical industry has increasingly embraced flexible packaging for various applications, including blister packs, pouches, and sachets. However, due to the critical nature of pharmaceutical products, ensuring package integrity is paramount to maintain sterility, efficacy, and safety.

To address the challenges and ensure the integrity of flexible packaging, various container closure integrity testing techniques are employed. These tests evaluate different aspects of the package, including seal strength, puncture resistance, permeability, and microbial barrier properties. Seal strength measures the ability of the seals to withstand pressure and prevent leaks. Puncture resistance assesses the package's ability to resist punctures from sharp objects. Permeability evaluates the rate at which gases, moisture, and other elements can permeate the packaging material. Microbial barrier properties test the package's resistance to microbial ingress.

VeriPac Flex Series for Flexible Package Integrity Testing

VeriPac Flex Systems offer flexible package testing using non-destructive methods based on ASTM standards. These systems, recognized by the FDA, are designed specifically for dry filled pouches and other flexible packaging. They provide high sensitivity and reliability without the need for settings or tooling changes, accommodating various package sizes and formats. Unlike methods like Water Bath and Dye Ingress, VeriPac systems offer objective results, reducing waste and providing quantitative data for leak detection. They give a clear PASS or FAIL result along with leak rate information, helping improve packaging processes.

Technology Overview

The VeriPac tester is connected to a FLEX chamber suitable for package size. Options like the integrated flexible test chamber (IFC) or drawer Style test chamber (D-Series) offer varied leak detection capabilities. The IFC suits sachets or stick packs with low headspace, while the D-Series is for large packages and bulk products. The VeriPac FLEX system uses a flexible membrane to test packages, preventing damage to the film. It's user-friendly, allowing multiple packages to be tested in one cycle.

Benefits of VeriPac Flex System

• Deterministic, non-destructive, non-invasive, non-subjective
• Vacuum Decay PERMA-Vac Technology
• ASTM Test Method F2338 and FDA Consensus Standard
• Non-destructive alternative to water bath leak test and other destructive test methods
• Testing is non-destructive allowing for increased sampling and testing frequency
• Capability to test different size pouches, stick packs or sachets without any changeover in parts or system settings.
• Deterministic, quantitative test method
• Non-destructive, non-subjective, no sample preparation
• Test multiple packages in a single test cycle
• Supports sustainable packaging and zero waste initiatives
• Simplifies the inspection and validation process
• Accurate and repeatable results

Package integrity testing plays a crucial role in ensuring that products are delivered to consumers in optimal condition. A package is not merely a container; it serves as a protective barrier against various external factors that could compromise the product's quality and safety.

Package integrity testing involves assessing the ability of packaging materials to maintain product quality and safety throughout the distribution chain. It encompasses various techniques and methods aimed at detecting any defects or vulnerabilities in packaging that could lead to product contamination, spoilage, or damage. It typically includes evaluating factors such as seal strength, leak detection, burst strength, and microbial barrier properties. These tests are essential for ensuring compliance with regulatory standards, meeting consumer expectations, and safeguarding brand reputation.

Why Consider Feasibility Studies for Package Quality Testing?

CCIT offers specialized expertise in the application of deterministic inspection technologies and test methods to assess the integrity of various packaging formats. An initial step in this process involves conducting either an experimental or a more comprehensive feasibility study to evaluate and determine the most suitable Container Closure Integrity (CCI) technology and test method for a specific application. The primary objective of such feasibility studies is to assess the efficacy of a recommended CCI solution and establish optimal test parameters, including the Limit of Detection (LoD). These studies are conducted in accordance with established standards such as USP 1207, ASTM, and ISO to ensure compliance with regulatory requirements, notably those set forth by agencies like the FDA.

The results obtained from these studies can be seamlessly integrated into production environments for rapid validation and deployment. Various test methods are available to assess and ensure package quality and performance, with the primary goal of identifying the most optimal inspection technology that yields accurate, sensitive, and reliable data for comprehensive package integrity verification.

Upon completion of a feasibility study, clients receive a detailed report outlining a quantitative test method tailored to their specific package format. This report encompasses the validation of the recommended approach, leveraging known good test samples and positive controls with predefined defects to establish the test method and confirm the Limit of Detection.

PTI is committed to delivering deterministic package integrity testing solutions to its customers, guiding them through the implementation of comprehensive CCI systems, and providing ongoing after-sales support and periodic certification mandated by regulatory bodies.

In conclusion, feasibility studies by PTI-CCIT are crucial for determining the most effective container closure integrity (CCI) solutions. Through meticulous assessment of inspection technologies and adherence to standards like USP 1207 and ASTM, PTI ensures clients receive compliant and tailored package integrity testing solutions. The detailed reports empower informed decision-making, enhancing product quality and regulatory compliance.

Class III medical devices in the United States are subject to stringent regulation by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act. These devices, characterized by their high-risk nature, include those vital to sustaining human life or preventing health impairment, as well as those posing potential, unreasonable risks of illness or injury.

Examples of Class III devices encompass implantable pacemakers, specific prosthetic devices, and innovative technologies such as certain in vitro diagnostic devices. Classification is determined by factors like intended use, indications, and associated risks. Due to their complexity and critical roles in medical procedures, Class III devices undergo a rigorous pre-market approval (PMA) process.

Manufacturers must furnish extensive scientific and clinical evidence to demonstrate a device's safety and efficacy before it can be marketed. This robust regulatory framework ensures that Class III medical devices meet the highest standards for safety and performance, safeguarding patient health.

Packaging for these devices plays a critical role in maintaining the integrity of the product, ensuring it reaches the end user in a safe and effective condition. The packaging of Class III medical devices faces unique challenges due to the stringent regulatory requirements and the critical nature of the enclosed products. Ensuring the integrity of the packaging is essential to prevent contamination, maintain sterility, and safeguard the efficacy of the medical devices.

How to Ensure Container Closure Integrity of Class III Medical Device Packaging

Container Closure Integrity (CCI) is a vital aspect of ensuring the reliability of Class III medical device packaging . CCI testing involves assessing the seals and closures to confirm they effectively prevent the ingress of contaminants and maintain the sterility of the device. This testing is crucial to meeting regulatory standards and ensuring patient safety.

PTI’s VeriPac series are non-destructive, non-invasive inspection systems for leak detection and package integrity testing. These systems reduce waste and provide operators with a clear understanding of package quality. The VeriPac test system produces real time results from precise quantitative measurements that identify packaging defects before critical process issues get out of control. Tests can be performed in any sequence and even repeatedly on a single sample. Good packages can be returned undamaged to the packaging line. Testing is more reliable, sensitive and efficient than destructive methods. VeriPac series utilizes the ASTM approved patented Vacuum Decay leak test method F2338, recognized by the FDA as a consensus standard for package integrity testing.

Technology Overview

PTI’s VeriPac leak testers connect to a test chamber that is specially designed to contain the package to be tested. The package is placed inside the test chamber to which vacuum is applied. The absolute transducer technology is used to monitor the test chamber for both, the level of vacuum as well as the change in vacuum over a predetermined test time. The changes in absolute and differential vacuum indicate the presence of leaks and defects within the package. The test cycle takes only a few seconds, results are non-subjective, and testing is non-destructive to both product and package. The sensitivity of a test is a function of the sensitivity of the transducer, the package design, the package test fixture and critical test parameters of time and pressure. Test systems can be designed for manual or fully automated operation. This inspection method is suitable for laboratory offline testing, QA/QC statistical process control, automated batch or 100% inline testing.

Benefits of VeriPac series

• Non-destructive, non-subjective, no sample preparation
• Deterministic, quantitative test method
• Defect detection down to single digit microns.
• High level of sensitivity, repeatability and accuracy
• Short cycle time provides operator with PASS/FAIL result
• Small footprint and modular portable design
• ASTM test method and FDA standard
• Referenced in USP 1207 guidance

In the pharmaceutical industry, the integrity of packaging plays a pivotal role in ensuring the safety, efficacy, and quality of medications. Packaging serves as a barrier that protects pharmaceutical products from external factors, such as moisture, air, light, and contaminants, which could compromise their stability and effectiveness. Ensuring the integrity of pharmaceutical packaging is not only crucial for regulatory compliance but also for maintaining patient safety and confidence in the products.

Traditional methods of package testing often involve destructive techniques, where samples are opened, punctured, or otherwise altered for assessment. However, these methods come with inherent drawbacks, including product wastage, the need for additional samples, and prolonged testing times. To address these challenges, the pharmaceutical industry has increasingly turned to non-destructive methods for package integrity testing.

What are the Non-destructive Methods Used for Pharmaceutical Package Testing?

Vacuum Decay Technology

Vacuum decay is a non-destructive Container Closure Integrity Test (CCIT) that provides reliable, repeatable, reproducible, and accurate results along with clear pass/fail quantitative data. The basic idea of Vacuum decay technology is to question the integrity of containers based on their fundamental physical properties. Sample packages are initially placed within a tightly sealed evacuation test room with an external vacuum source. Based on the test sample and the needed level of sensitivity, a predetermined vacuum level is selected. The test chamber and test system dead space must be evacuated after that for a certain period of time. To monitor variations in vacuum level over time, differential pressure transducers are utilized. The container is leaking if the pressure rises over the designated pass/fail limit.

Volumetric Imaging Technology

Non-destructive leak detection of blister packages is done using OptiPac One-Touch Tool-less technology. The OptiPac uses volumetric imaging technology to monitor the movements of a blister package while it is under vacuum in order to identify leaks. The interface is practical and simple to set up with new blister package forms, necessitating no tooling changeover or significant parameter revisions as with previous non-destructive blister package inspection systems. In response to different cavity shapes, sizes, and combinations of various blister pack types, the system gathers volumetric data from each cavity.

Airborne Ultrasound Technology

Airborne ultrasound is a deterministic test technique for seal quality inspection in materials including aluminum, foil, paper, plastic, poly, film, and Tyvek. It has been proven to be one of the most effective non-destructive testing techniques for flexible package seals. According to studies, conventional seal inspection methods are ineffective because they miss undetectable defects and incorrectly reject pouches that are tightly sealed. On the other hand, Airborne ultrasound technology has been successful in both online and offline solution options. Airborne ultrasound is a typical test method for evaluating seal quality and integrity in accordance with ASTM F3004-13.

Microcurrent HVLD technology

High Voltage Leak Detection, often known as HVLD, is a deterministic, non-destructive leak detection technique used to evaluate the Container Closure Integrity of vials, cartridges, and other liquid-filled parenteral products. It is one of the most efficient approaches for online container closure testing. MicroCurrent HVLD uses around 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to standard HVLD systems. This technique doesn't require sample preparation and is non-invasive. Pre-filled syringe testing is one of the main uses of MicroCurrent HVLD, along with vial leak testing.

Non-destructive Package Integrity Testing Method Benefits

Non-destructive package integrity testing holds significant importance in the pharmaceutical industry due to the critical nature of pharmaceutical products and the strict regulatory requirements in place. Here are some key benefits of using non-destructive package integrity testing in the pharmaceutical industry:

• Product Safety: Ensuring the integrity of pharmaceutical packaging is paramount for product safety. Non-destructive testing methods can identify leaks, defects, or breaches in packaging that could lead to contamination, spoilage, or compromised efficacy of the medication.
• Regulatory Compliance: The pharmaceutical industry is heavily regulated to ensure patient safety and product quality. Non-destructive package integrity testing helps companies meet regulatory requirements outlined by agencies such as the FDA (U.S. Food and Drug Administration) and other international regulatory bodies.
• Reduced Risk of Contamination: Non-destructive testing methods can detect micro-leaks or breaches in packaging that may not be immediately visible to the naked eye. This reduces the risk of contamination from external factors like air, moisture, or pathogens.
• Preservation of Sterility: Many pharmaceutical products require a sterile environment to maintain their efficacy and safety. Non-destructive testing ensures that the packaging's sterile barrier is intact, preventing any potential breach of sterility.
• Enhanced Product Quality: Maintaining package integrity helps prevent degradation of pharmaceutical products caused by exposure to light, moisture, or air. This ensures that medications maintain their intended potency and effectiveness.
• Cost Efficiency: Non-destructive testing methods save costs by preventing the need for destructive testing, which would require additional samples for analysis. This also reduces the need for retesting, minimizing waste and resource consumption.

As the demand for stringent quality control and regulatory adherence in the pharmaceutical sector continues to grow, understanding the nuances of non-destructive package testing methods becomes essential. By adopting these innovative techniques, pharmaceutical manufacturers can uphold their commitment to patient safety, product efficacy, and overall excellence in the field.

Leak testing is an essential process in the pharmaceutical industry to ensure the safety and quality of the products. The purpose of leak testing is to detect any leaks or defects in the packaging, that could compromise the integrity of the product.

There are different methods of leak testing available, and the choice of method depends on various factors, including the type of packaging, the product being packaged, and the desired sensitivity of the test. Some of the commonly used methods for leak testing in the pharmaceutical industry are:

Vacuum Decay Technology

Vacuum Decay is a non-destructive container closure integrity test (CCIT) method that focuses on package integrity and detecting leak paths. Compared to manual inspection and other non-deterministic test methods, Vacuum Decay measurements offer deterministic and reliable test results to ensure package integrity. Vacuum Decay technology can accommodate a wide variety of packaging formats, including filled and sealed rigid, semi-rigid, flexible, non-porous or non-porous materials. This test works by placing packages in a well-equipped evacuation test chamber with an external vacuum source. Vacuum levels are continuously monitored to detect any deviations from predetermined targeted vacuum levels. A defect in the package can cause air to escape from the package into the test chamber. On the other hand, defect-free packages hold in air by maintaining a constant chamber vacuum level. Vacuum Decay technology has proven over the years to be one of the most practical and sensitive vacuum-based leak detection solutions.

MicroCurrent HVLD Technology

High Voltage Leak Detection (HVLD) is a non-destructive container closure integrity test (CCIT) for evaluating parenteral product packaging integrity. The concepts of quantitative electrical conductivity measurement are used in HVLD technology. HVLD is based on the fundamental nature of electric current. The package barrier must be non-conductive and prevent the flow of electricity, while the package contents must generally be able to carry voltage. The container is placed horizontally on the rotating stage. As the container rotates, a high voltage is applied to one side, and a ground probe is attached to the opposite side. If the package does not leak, the two container walls (high voltage and ground) offer complete electrical resistance and will not record significant current as it travels through the bottle. Breakdown resistance is encountered if there is a micro-leak or crack in one of the container walls and the current passes through. Examples of high-voltage leak detection technology applications include pre-filled syringes, ampoules, drug product cartridges, liquid-filled vials, and blow-fill-seal (BFS) containers.

Force Decay Technology

Force Decay is a quantitative leak detection method that works particularly well with low-headspace packaging. Non-porous materials such as foils, laminates, and films can be used for packaging types. Since it is a non-destructive test procedure, the sample packets are not harmed or changed. Packages do not need to be discarded away when the test is over; they can be added back to the batch. The test system use nested tooling to place the package in the same place and to prevent unmeasured extension of the package under test. Once the test is started, a vacuum is drawn onto the test chamber, which causes the package to expand inside the chamber. The ASTM F2338 vacuum decay leak test technique monitors vacuum levels during the test cycle to evaluate the package. The expansion of the package being tested applies force to the VeriPac force measurement system.

Volumetric Imaging Technology

OptiPac Leak Detection System is one of the deterministic non-destructive package integrity test solutions made especially for blister packs. The One-Touch Technology used in the design and engineering of OptiPac allows for a quick test cycle without the need for sample preparation or changeover. Depending on the size of the blister cavity, this unique technique can quickly identify defects less than 5 microns. Although the OptiPac system employs similar concepts to those used in a vacuum-based blue dye test, it uses controlled inputs and monitored outputs without the hassle and reliability issues of the dye ingress technique. To identify leaks, OptiPac use volumetric imaging technology to measure the motion of a blister package while it being vacuumed.

It is important to note that leak testing should be done at various stages of the packaging process, including before and after filling, and during storage and transport. Proper leak testing can help ensure that the pharmaceutical product is safe and of high quality, which is crucial for patient safety.

Automated pouch seal inspection is a technology-driven quality control process used to evaluate the integrity of seals on pouch packaging. It employs advanced machinery, sensors, and algorithms to detect and analyze seal defects, ensuring the quality, safety, and reliability of packaged products.

The purpose of automated pouch seal inspection is to identify and address any issues that may compromise the integrity of the seals. By automating the inspection process, manufacturers can achieve higher inspection speeds, greater accuracy, and improved overall efficiency compared to manual inspection methods. By implementing automated pouch seal inspection, manufacturers can improve their quality control processes, minimize the risk of product defects, and enhance customer satisfaction. The technology allows for increased inspection throughput, reduced labor costs, and the ability to detect even subtle seal defects that may be missed by manual inspection methods. Read on to learn more about the automated pouch seal inspection techniques offered by PTI.

Seal-Sensor Technology

Seal-Sensor™ is an airborne ultrasonic technique that inspects the final pouch seal 100% online non-destructively. The Seal-Sensor is an accurate, quantitative, fast and reliable method of testing pouch seals for defects. The Seal-Sensor detects incomplete seals, partial or weak areas of seals, and many other common defects in seals that appear visually acceptable but affect product quality, value and shelf life. In less than a second, a single linear scan (L-scan) of the pouch seal provides a pass/fail result and quantitative, traceable data.

Benefits of Seal-Sensor Technology

• Deterministic inspection method producing quantitative results.
• Non-destructive, non-invasive, no sample preparation.
• Works for any material and combinations, regardless of color, transparency, print, surface finish and porosity.
• Can be integrated for 100% online defect detection of the final pouch seal.
• Repeatable and reliable results.
• Eliminates subjective, manual vision inspection methods.
• Economical, cost-effective solution for seal integrity testing of the final pouch seal.

VeriPac LPX Technology

Based on decades of consistent performance in the pharmaceutical, biologics, and medical device sectors, VeriPac vacuum decay technology has been proven to be the most sensitive and reliable vacuum-based leak testing method available. It is a fully automated package quality inspection system for 100% inline testing. The LPX enables enhanced automated testing that offers a high degree of confidence in the efficiency of the packaging procedure. The LPX is an effective and reliable solution that enables process-related quality issues to be identified and resolved as soon as possible.

The VeriPac LPX has a dynamic robotic design that is adjusted to your production needs. To fulfill the demands of a manufacturing line, the LPX Series offers modular, scalable solutions. With the help of this flexible platform, a range of package forms may be reliably tested. Flexible packaging, rigid containers, and parenteral pharmaceuticals are some of the applications of LPX automation.

Benefits of VeriPac LPX Technology

• Automated testing enables the highest level of container quality assurance.
• Deterministic, quantitative test method.
• ASTM Test Method F2338 and FDA standard, ISO 11607.
• Highly accurate test results - low false positives and false negatives.
• Non-destructive, non-subjective, no sample preparation.
• Pick-and-Place option back into the production line.
• Auto reject option of defects removed from the production line.
• USP <1207> compliant.

Automated pouch seal inspection relies on various technologies to ensure the quality and integrity of pouch seals. Manufacturers can achieve comprehensive and reliable pouch seal inspection, ensuring product quality and customer safety. The specific technologies employed may vary depending on the industry, application, and quality standards. Automated pouch seal inspection plays a crucial role in maintaining the integrity of packaged products and preventing issues such as leaks, contamination, or compromised freshness.

Since many years ago, manufacturers have tested the quality of container closures, and their perceived value has constantly grown. Companies that once relied on probabilistic techniques like the blue dye test are now aiming to use a more reliable and predictable procedure for integrity testing of various package formats. The pharmaceutical industry is getting ready to adapt to the deterministic testing world in order to enhance quality, increase efficiency, and comply with changing regulatory standards.

Overview of Airborne Ultrasound Technology

Airborne ultrasound technology is a seal quality inspection technique. It is an ASTM test method F3004, the FDA approved standard for seal quality testing. Such tests are mainly performed to provide enhanced seal quality testing of pouches, flexible packages and tray seals. Airborne ultrasound technology ensures in-depth seal quality analysis and applies to multiple packaging materials including Tyvek, paper, foil, film, aluminum, plastic and poly.

In this technique, sound waves are reflected when ultrasound waves pass through the package seal. Signal strength is reduced or eliminated in the presence of leakage / fault. Such deviations are closely monitored to detect leakage. The inability to detect non-leak defects is a common challenge faced by most leak test methods. However, with Airborne ultrasound technology, users can identify various types of seal defects; visible and invisible, leaky and non-leaky, process-related and random.

Seal-Scan and Seal-Sensor Technology

Seal-Scan and Seal-Sensor are the two variants of Airborne ultrasound technology that utilizes non-contact airborne ultrasonic testing technology. With advancements in the form of seal-scans and seal-sensors, Airborne ultrasound technology has proven to be the most effective method for non-destructive seal integrity testing in both offline laboratory testing for seal quality analysis and 100% inline testing on the production line.

Seal-Scan® is a non-destructive offline technology that is highly effective in inspecting and analyzing pouch seal defects. It is a deterministic, quantitative, high-resolution package integrity testing method for identifying defects and sealing integrity for consistency. What makes this technique unique is that it is a non-invasive technique and requires no sample preparation. Seal-Scan® provides advanced digital imaging software tools for process control, offering in-depth seal quality analysis. This technology is capable of producing opto-acoustic images and detailed statistical analysis using L-scan and C-scan modes. An L-scan is a single linear scan along the x-axis of the seal that provides a line graph of seal integrity and simulates an online inspection. A C-scan produces multiple scans (in the X and Y-axis of the seal area) that provide a high-resolution ultrasonic image of the seal structure.

Seal-Sensor™ is an Airborne ultrasonic technology (ABUS) that non-destructively inspects the final pouch seal 100% online. The seal sensor detects incomplete seals, partial or weak areas of the seal, and many other common defects in a seal that are visually acceptable, but have that affect product quality, value, and shelf life. A pass/fail result and quantitative, traceable data are produced in less than a second by a single linear scan (L-scan) of the pouch seal. The Seal-Sensor is a definitive, quantitative, rapid and reliable approach to inspecting pouch seals for defects.

Benefits of Airborne Ultrasound Technology

• Non-destructive, non-subjective, no sample preparation.
• Accurate and reliable results.
• Can accommodate a number of packaging formats and materials.
• Eliminates subjective manual inspection methods.
• Deterministic inspection method producing quantitative results.
• ASTM Test Method F3004 and FDA Standard for seal quality inspection.

Today, package integrity test solutions continue to evolve, driven by industry demands, regulatory requirements, and advancements in technology. The focus remains on improving sensitivity, accuracy, and efficiency to ensure the integrity and safety of packaged products.

Container closure integrity (CCI) testing of intravenous (IV) bags is an important quality control measure to ensure the safety and efficacy of the products. CCI testing helps verify that the container closure system, including the bag and its closure, maintains its integrity throughout the product's shelf life and prevents any leakage or contamination.

Various methods, including visual inspection, dye immersion testing, bubble emission testing, headspace gas analysis, and Vacuum decay testing can be employed to assess the integrity of the container closure system. These methods help to identify any defects or breaches that may compromise the sterility and stability of the IV bags. Manufacturers should select an appropriate method based on their specific requirements and regulatory guidelines to ensure the quality and safety of the IV bags.

Vacuum Decay Technology for CCI Testing of Intravenous Bags

Vacuum decay technology is an FDA-approved leak detection technique that can be used for CCI testing of high-risk package applications. The non-destructive nature of the process allows for greater understanding of packages, testing at a greater frequency with more accuracy and with less waste. Vacuum decay technology is capable of detecting leaks in sealed rigid, semi-rigid and flexible packaging made of non-porous or porous materials and has been proven to provide repeatable, reliable and quantitative test results.

VeriPac testing systems using Vacuum decay leak testing are highly effective for leak testing of IV bags. Using a differential pressure transducer leak test system, the test method is capable of detecting package leaks and invisible defects in the IV bag body and also in seams, welds and port areas. This method is non-invasive, non-subjective and does not require sample preparation.

The test method works by connecting the VeriPac test systems to a manually operated test chamber containing an IV bag. The next step is to draw a vacuum on the IV bag in the test chamber and observe any changes in the vacuum level. If there is any damage to the package, air or liquid will flow from the package into the chamber, causing pressure fluctuations. On the other hand, defect-free packages do not leak any pressure into the chamber, keeping the chamber vacuum level constant. Regardless of the location of the defect, the vacuum decay system can pick up both large and small defects. It takes about 30 seconds for testing IV bags, repeatable and sensitive to 15 microns for liquid and gas leaks.

Benefits of Vacuum Decay Technology

• Eliminates destructive, subjective testing methods.
• Non-destructive technology.
• Accurate, repeatable results.
• Pass/fail results backed by quantitative test data.
• Eliminates destructive, subjective testing methods.
• ASTM Test Method F2338, FDA Consensus Standard and referenced in USP 1207 Guidelines.
• Meets Annex 1 regulatory guidelines.

Recent regulatory changes have shifted requirements and strategies for container closure integrity. IV bags and flexible parenteral presentations have experienced the greatest impact from these new perspectives on quality. IV bags have always presented a significant risk. New provisions to Annex 1 have made the requirements for quality risk management (QRM) clear, and USP guidance documents outline the need for greater control. Based on the regulatory requirements and guidance, practical solutions for IV bag container closure integrity should offer non-destructive, practical and deterministic approaches to assure integrity. There are critical considerations for IV bag QRM, and strategic approaches to assuring integrity of IV bags and flexible parenteral presentations to satisfy the shifting regulatory environment.

Parenteral preparations are sterile medicinal products that are administered by injection, infusion or implantation into the body. They are used to deliver medications directly into the bloodstream, bypassing the digestive system and providing a rapid onset of action. There are different types of parenteral preparations, including intravenous (IV) injections, intramuscular (IM) injections, subcutaneous (SC) injections, and intradermal (ID) injections. Each type of administration is chosen based on the specific medication being delivered and the patient's condition.

Parenteral preparations can be single-dose or multi-dose and are usually packaged in vials, ampoules, or pre-filled syringes. These products must be sterile, pyrogen-free, and free from any particulate matter to prevent infections and other adverse reactions in patients. Parenteral preparations can include a wide range of medications, including antibiotics, anticoagulants, vaccines, chemotherapy drugs, and many others. They are typically prepared in a controlled environment, such as a hospital or pharmacy, and are subject to strict quality control measures to ensure their safety and efficacy.

Overall, parenteral preparations play a critical role in modern medicine, allowing for the delivery of life-saving medications directly into the bloodstream.

Overview of Automated Parenteral CCI Solutions

1. E-Scan MicroCurrent RTX

E-Scan RTX is a practical, reliable and entirely automated container closure integrity test (CCIT) approach for pre-filled syringes. The dynamic robotic design of the RTX platform can be customized to meet your manufacturing requirements. The E-Scan RTX uses MicroCurrent HVLD technology, a ground-breaking variation of HVLD, the optimal CCI solution for high-risk biological fluids. It can be used for batch release testing in the lab, on the production line, or in both environments. The test cycle only lasts for a short period of time. The HVLDmc test method checks the entire package for small pinholes, microcracks and defects in the closing seal. This ensures the integrity of the product seal. The HVLDmc has proven to be a highly sensitive leak test method for a variety of liquid-filled pharmaceutical packaging types, including pre-filled syringes, vials, blow-fill-seal containers, and other liquid-filled packages.

Benefits of E-Scan MicroCurrent RTX

• MicroCurrent HVLD technology is effective across all parenteral products, including biologics and extremely low conductivity liquids including sterile water (WFI).
• Listed in USP Chapter 1207 as recommended method for parenteral liquid package inspection.
• Robust method and good Signal-Noise-Ratio between good and defective products.
• Low voltage exposure reduces production of ozone.

2. VeriPac LPX Technology

VeriPac LPX is an automated inspection solution for CCI testing of parenteral products. The VeriPac LPX series is a line of fully automated instruments for 100% inline testing of package quality inspection. The performance of the packing line may be highly assured due to the enhanced automated testing accessible by LPX. The dynamic robotic design of the VeriPac LPX can be customized according to manufacturing needs. The LPX series offers flexible and scalable solutions to satisfy manufacturing line needs. Rigid containers, parenteral products, and flexible packaging are some applications of LPX technology. Systems using VeriPac LPX use Vacuum Decay technology and ASTM Test Method F2338. The FDA recognizes the test technique as a consensus standard for pharmaceutical package testing and is listed in ISO 11607 and USP Chapter 1207 guidelines.

Benefits of VeriPac LPX Technology

• Automated testing enables the highest level of container quality assurance.
• Deterministic, quantitative test method.
• ASTM Test Method F2338 and FDA standard, ISO 11607.
• Non-destructive, non-subjective, no sample preparation.
• Pick-and-Place option back into the production line.
• Auto reject option of defects removed from the production line.
• USP <1207> compliant.

Parenteral products are typically tested for their container closure integrity (CCI) to ensure that the product remains sterile and safe for use. Automated CCI solutions can provide a fast and reliable method for testing CCI in parenteral products. These solutions offer several benefits over traditional manual testing methods, including increased efficiency, consistency, and accuracy. Automated CCI solutions typically use non-destructive testing methods, such as vacuum decay or high voltage leak detection, to identify any leaks or defects in the container closure system. These methods are highly sensitive and can detect even the smallest leaks that may compromise the sterility of the product.

Automated Container Closure Integrity Testing (CCIT) is a specialized form of testing that focuses on verifying the integrity of the container closure systems of several types of containers used to store and transport products. This can include vials, pre-filled syringes, bottles, pouches, and other types of containers. The container closure system includes the closure device (such as a stopper or cap) and the container or package itself (such as a glass or plastic vial or bottle), and it is essential to ensure that it is properly sealed so that it does not allow any leaks or contaminants to enter the container.

Automated CCI testing of pre-filled syringes involve using specialized testing equipment and techniques to simulate real-world conditions and test the container closure system's integrity. This testing process can be done in the laboratory by an operator or fully automated to increase efficiency and accuracy.

Testing Pre-filled Syringes Using E-Scan RTX

The E-Scan RTX platform is a modular, fully automated container closure integrity solution for pre-filled syringes. The RTX is a practical and dependable CCI solution with a dynamic robotic design that is adjusted to meet your production needs. This robust, flexible platform uses MicroCurrent HVLD technology, a revolutionary form of HVLD that is the optimal CCI solution for fragile, high-risk biologic liquids. It is appropriate for batch release testing at the production line, in the lab, and provides a quick PASS/FAIL result with a test cycle of only seconds.

A robotic arm will track and pick up nested syringe trays from a standard single lane conveyor. The robot removes the syringes from the nested tray and rotates the syringes through two test stations, one to detect needle shield defects and the other to inspect the rest of the syringe body. The test starts automatically and gives a fixed PASS/FAIL signal on completion of the test. An adjustable failure reference can be set to allow PASS/FAIL based on a predetermined LOD (limit of detection) setting in the initial recipe. After testing, syringes are automatically loaded back into the syringe tray, defective syringes are collected in the reject tray.

Benefits of E-Scan RTX

• MicroCurrent HVLD technology is effective across all parenteral products, including biologics and extremely low conductivity liquids including sterile water (WFI).
• Listed in USP Chapter 1207 as a recommended method for parenteral liquid package inspection.
• Robust method and good Signal-Noise-Ratio between good and defective products.
• Low voltage exposure reduces the production of ozone.

Automated pre-filled syringe testing is critical to ensuring the safety and efficacy of pre-filled syringes used in the pharmaceutical industry. By using automated testing techniques, manufacturers can ensure that the container closure system is reliable and free from defects, reducing the risk of contamination or other safety concerns.

Tyvek is a highly durable and lightweight material that is commonly used in the medical industry for the packaging and sterilization of medical devices and equipment. It is a non-woven material made from high-density polyethylene fibers that are bonded together using heat and pressure. Medical device manufacturers and packaging professionals prefer Tyvek packaging because it is a sterile barrier that protects against bacteria and other contaminants. Tyvek is also breathable, allowing for sterilization methods such as ethylene oxide and gamma irradiation to be used effectively.

Tyvek packaging is used in a variety of medical applications, including surgical gowns, drapes, and covers, as well as in medical device packaging such as catheters, implants, and instruments. Its use in the medical industry is regulated by government agencies such as the FDA to ensure that it meets the necessary standards for safety, sterility and efficacy.

What are the Challenges Associated with Tyvek Package Testing?

Leak testing of Tyvek packages is a critical step in ensuring the integrity of the package and the safety of its contents. However, there are several challenges associated with leak testing Tyvek packages, including:

• Sensitivity of the test method: The sensitivity of the leak testing method can impact the ability to detect leaks in Tyvek packages. For example, some testing methods may not be able to detect very small leaks or may be impacted by the size or shape of the package.
• Environmental conditions: Environmental factors, such as temperature, humidity, and pressure, can impact the results of the leak test. For example, changes in temperature can cause the package to expand or contract, which can impact the tightness of the seal and the results of the test.
• Interference with product properties: Some leak testing methods may use test gases or liquids that can interact with the product inside the package. For example, the test gas may cause the product to degrade or impact its efficacy, which can affect the overall performance of the package.

In summary, leak testing of Tyvek packages requires careful consideration of the test method, the packaging process, and the environmental conditions to ensure accurate and reliable results.

Testing Tyvek Packages Using Airborne Ultrasound Technology

With today’s sensory technology advancements, Tyvek packages can be tested using Airborne Ultrasound technology. Airborne Ultrasound technology is a seal quality testing method that uses airborne ultrasound to evaluate seals for flaws and defects non-destructively. It is an ASTM Test Method F3004 for testing the seal quality and a recognized FDA standard for seal quality inspection. These tests are mostly carried out to improve seal quality inspection of pouches, flexible packaging, and tray seals. Tyvek, paper, foil, film, aluminum, plastic, and poly are just a few of the packaging materials that may be used with Airborne Ultrasound technology to enable thorough seal quality evaluations.

In this method, sound waves are reflected as ultrasonic waves are transmitted through the packaging seal. If there is a leak or flaw, the signal intensity is decreased or lost. To find the leak, these differences are closely monitored. Most leak test techniques encounter the problem of being unable to identify non-leaking defects. By using Airborne Ultrasound technology, users may recognize a variety of seal faults, including visible and invisible, leaking and non-leaking, process-related and random. Airborne ultrasound can be applied in the laboratory for offline in-depth seal quality analysis as well as for 100% online seal quality inspection on the production line.

Benefits of Airborne Ultrasound Technology

• Non-destructive, non-subjective, no sample preparation.
• Deterministic inspection method producing quantitative results.
• Can be integrated for 100% online defect detection of the final pouch seal.
• Repeatable and reliable results.
• Eliminates subjective manual vision inspection methods.
• Characterizes overall quality and uniformity of the seal.
• Economical cost-effective solution for seal integrity testing the final pouch seal.

The method used for leak testing Tyvek packages will depend on the specific requirements of the medical device or equipment being packaged and the regulations set forth by regulatory agencies such as the FDA. It is important to use a validated and appropriate method for leak testing to ensure the safety and effectiveness of the packaged medical devices or equipment. Airborne Ultrasound is one such technique.

Container Closure Integrity (CCI) refers to whether a container keeps the sterile barrier intact. Environmental pollutants can quickly turn a life-saving therapy into a microbial soup if there is a leak or breach of the sterile barrier. The CCIT of blister packages is a critical process in ensuring the quality and safety of pharmaceutical products. Blister packages are commonly used to package solid-dose medications such as tablet and capsules.

The CCI testing of blister packages is performed to ensure that the package is properly sealed and that there are no leaks or defects that could compromise the quality of the medication inside. This testing is important because if the package is not properly sealed, moisture and oxygen can enter, potentially degrading the medication and reducing its effectiveness.

Overview of OptiPac Technology

OptiPac One-Touch Tool-less Leak Detection Technology is a non-destructive method for testing the integrity of blister packaging that is designed to detect any leaks or defects in the package's seal. OptiPac uses volumetric imaging technology to measure the blister cavities under vacuum and identify leaks. The OptiPac applies controlled inputs and measurable outputs without the inconvenience and reliability concerns of the dye ingress approach. It is designed with One-Touch Technology to accomplish a quick test cycle needing no changeover or tools for various blister formats. Unlike other non-destructive blister package inspection systems that demand complicated parameter modifications, OptiPac requires no tooling replacement with new blister package forms.

The test begins by placing the sample on the testing area for vacuum-based measurement. Vacuum is pulled to a definite vacuum after pushing the start button. Under vacuum, blisters expand and push air out of the blister through any leaks that may be present. If there is a leak in the blister, air leaks into the chamber and collapses the blister package. The defective blister cavities are identified using a volumetric measurement reading during the dynamic vacuum test cycle. Along with the quantitative measurement related to each package test, a clear pass/fail result is displayed.

Functions Offered by OptiPac's Insightful Technology

• Auto configuration for easy recipe setup and validation of new blister formats.
• Auto orientation of blister packs (test blister packs in any position –no specific orientation).
• Auto calibration is an integrated one-touch function.
• Advanced batch reporting with audit trail including image of blister pack and defect results.

OptiPac Benefits

• Non-destructive technology - Pass/Fail results backed by quantitative test data.
• Completely tool-less.
• No changeover to test different blister formats.
• Identifies defective cavity.
• Pre-loaded recipe library with easy recipe setup and validation of new blister formats.

In addition to selecting the appropriate method for leak testing, other factors to consider when performing blister package leak testing include the type of material used for the package, the seal strength of the package, the packaging process, and the potential for environmental factors to affect the package's integrity. By carefully considering these factors and implementing an effective leak testing (pharmaceutical package testing) process, pharmaceutical companies can ensure that their products are of the highest quality and meet regulatory requirements.

Meat processors are relying on technologies to extend product shelf life more than ever before, which puts concerns like shelf-life stability and packaging quality to the forefront of challenges. Although meat-based snack products and pet products come in a variety of packaging formats, they all require package integrity assurance/container closure integrity testing for extended shelf life.

Flexible packaging, particularly pre-made pouches and form-fill-seal pouches and bags, is the most preferred format for meat-based snack foods and pet food products. With its capacity to provide shelf stability and ease of opening, flexible packaging makes for the best package appearance. The market for meat products for animals has grown rapidly, as consumers are willing to spend more and demand higher-quality products. Meat snacks intended for animal consumption as well as human use must be free of mold or product deterioration.

Modified Atmosphere Packaging (MAP) tray packs are a common packaging option for fresh beef, hog, and poultry products as well as many other processed meats. By significantly reducing spoilage and extending shelf life, the MAP method provides consumers with fresh items that look good. Once an MAP package is sealed, it is essential to maintain the seal integrity to avoid leaks that can let O2 or other environmental pollutants enter the package.

Explain MAP

Modified Atmosphere Packaging (MAP), which can detect leaks as small as 10 microns, is widely used for perishable products. Package integrity can be tested by monitoring the amount of residual oxygen in the headspace of the package. According to the method, the product must be set up for stability and the headspace must be measured at various time intervals. The six-day test, which frequently measures O2 levels over the maximum threshold (about 3%), is used for production purposes. A 50-micron defect significantly reduces a product's shelf life, but it typically passes a six-day O2 test with flying colors. Six days of output are already palletized and stored in case the O2 test identifies a quality issue. Vacuum Decay can find breaches as small as 10 microns, detect oxygen-critical defects in real time at the source, and prevent extensive quality issues.

VeriPac Series for Testing MAP Meat Packages

The VeriPac Vacuum Decay Series of inspection systems have a proven capacity to non-destructively test packaging down to O2 sensitive leak sizes, which reduces waste and enhances testing capabilities. By consistently detecting leakage as tiny as 10 microns, the technology may identify process issues before they become critical. VeriPac offers quantitative data that is correlated to leak rate and leak size in addition to a clear attribute result (PASS or FAIL).

The VeriPac D-Series uses a revolutionary FLEX-Chamber to test flexible packaging formats since it is resistant to package changes and removes the requirement for changeover when testing different size pouches. Additionally, more than one package may be tested during a single test cycle. The VeriPac Series utilizes a rigid packaging test chamber for MAP Meat Tray Package testing. Depending on the needs of the production, the test system operation can be set up for either semi-automatic or manual operation.

Advantages of VeriPac Series

• Non-destructive, no sample preparation.
• Deterministic, quantitative test method.
• Defect detection down to 0.2 ccm.
• High level of sensitivity, repeatability and accuracy.
• Short cycle time provides operators with PASS/FAIL results.
• Small footprint and modular portable design.
• ASTM test method and FDA standard.
• Referenced in USP 1207 guidance.

Since it eliminates subjective results, the VeriPac series is a practical alternative to destructive testing. Case studies have proven that Vacuum decay leak testing technology offers a rapid return on investment when evaluating the dramatic decrease in waste created by destructive test techniques.

The sensitivity of a test method is necessary for several reasons, but it is most crucial in ensuring the final product is of high quality. Powdered dairy products (milk powders, infant formula, protein-based powders) are kept in a modified environment to avoid spoilage and maintain the nutritional value of the product throughout its shelf life. Before usage, the product will quickly deteriorate due to oxygen and moisture intrusion, affecting the flavor and texture and finally converting any desirable commodity into a liability. The quantity and impact of oxygen ingress depend on a number of variables, and it will occur in the presence of tiny leaks. Leaks as small as 10 microns will have an immediate impact on the product for smaller packaging types. Current conventional test techniques are completely insufficient for identifying such defects, leaving manufacturing operations exposed to severe quality variations. Applying techniques with greater sensitivity provides the highest level of quality assurance, rather than just locating minor leakage.

Ensuring Dairy Products Package Integrity with VeriPac FLEX Series

For pouches and other flexible packaging, VeriPac FLEX systems are versatile non-destructive package inspection systems. These are available in a variety of configurations for the leak test instrument and the test chamber capacity, with solutions to accommodate small format sachets and stick packs up to bulk size pouches and bags. This is done to accommodate different package specifications and test sensitivity requirements. The Food and Drug Administration (FDA) has recognized the ASTM technique for Vacuum Decay leak testing (F2338) defined in ISO 11607 as a consensus standard for pharmaceutical package testing. This approach is used by VeriPac FLEX Systems.

VeriPac inspection systems are the best alternative for destructive testing since they eliminate the subjectivity of test results and reduce the waste and costs associated with these techniques. Comparing Vacuum Decay leak testing technology to destructive techniques like the water bath or blue dye leak test, it has been found to offer a quick return on investment. The VeriPac test provides reliable critical packaging failure detection and useful packaging process insight.

Technology Overview

The VeriPac test instrument is attached to the appropriate FLEX chamber based on the size range of the packages. Depending on the application, two VeriPac systems combined with the FLEX chamber offer varying levels of leak detection capabilities. The Integrated Flexible test chamber (IFC) is designed for low-headspace sachets or stick packs. Depending on the package size and requirements, the Drawer Style test chamber (D-Series) comes in two common sizes, the Small (D) or Large (DXL). Custom designs are capable of being produced for huge package forms and bulk products. The manner in which the package is tested is the unique difference with VeriPac FLEX systems. Multiple packages can also be tested in a single test cycle.

VeriPac FLEX Series Benefits

• Non-destructive, deterministic and quantitative test method.
• Does not require any sample preparation.
• Perform a single test cycle for several packages.
• USP < 1207> compliant.
• Promote zero-waste initiatives and sustainable packaging.
• Makes the inspection and validation procedure easier.
• Reliable and repeatable outcomes.
• FDA standard and ASTM test methods.
• Inexpensive with a quick return on investment.

Flexible packaging is highly susceptible to routine microleaks that reduce shelf life and contaminate dairy proteins, considered a very high-risk product. VeriPac FLEX is an optimal solution for powdered dairy products package integrity testing. They offer a definite PASS or FAIL in addition to quantitative data corresponding to a leak rate.

The quality of the product and the maintenance of the sterile barrier against outside forces are both critically dependent on the packaging. Even a tiny hole in the packaging might allow moisture, reactive gases, or other dangerous elements to enter the product, limiting its ability to heal. Additionally, a contaminated pharmaceutical product can cause serious health issues to the user, making it more of a threat than a treatment. Maintaining Container Closure Integrity is extremely important due to the sensitive nature of pharmaceutical products.

Container Closure Integrity testing is a leak detection technique for determining how well sterile barriers are maintained against external contamination. These tests may be roughly divided into probabilistic and deterministic test methods. Manufacturers choose deterministic test procedures since they provide precise, guaranteed quantitative results. One such test method is helium leak detection technology.

Helium Leak Detection Technology Overview

Helium leak testing is the method of identifying leaks in various enclosed or sealed systems by utilizing helium as a "tracer" gas and measuring the concentration of the gas as it leaves due result of a leak. A vial is a good example of package system. A pre-filled syringe, a foil pouch, and a cold form blister card are some other examples. Each of these package types is intended to keep the pharmaceutical product contained while preventing the entry of potentially dangerous environmental contaminants like dust, bacteria, or even gases. Helium leak testing method can evaluate these package types. It is a highly efficient approach for finding leaks that provide quantitative leak rate data considerably beyond the capabilities of existing leak testing techniques.

The following describes how helium leak detection works: The package is initially vacuumed and helium-filled. The amount of helium escaping the package is then measured quantitatively and expressed as a leak rate using a helium leak detector. The technique is also ideally suited for packaging line setup and validation, failure analysis, tool qualification, monitoring product quality, and package design.

Why Use Helium as a Tracer Gas?

• Deterministic seal quality inspection method that produces quantitative outcomes.
• Regardless of color, transparency, print, surface polish, or porosity, this method works for all material types and combinations.
• Non-destructive and non-subjective test technique that does not require any sample preparation.
• Technology may be used for 100% online final pouch seal defect detection.
• Seal quality inspection results are repeatable, reproducible and reliable.
• Cost-effective solution for testing seal integrity and seal analysis that characterizes the overall quality and uniformity of the seal.

Helium Leak Detection Merits

• Practical and sensitive flow-based leak test method.
• Enables the discovery of extremely small microleaks.
• Detects leaks with sensitivity levels as low as 1x10-10 mbar L/sec.
• Helium is a non-explosive, non-toxic and non-destructive tracer gas.
• Applicable across package design, failure analysis, packaging line setup and validation.
• Faster test cycle reduces cost and total processing time.

Applications of Helium Leak Detection

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

Helium leak detection is the best option for evaluating the inherent integrity of specific primary container closure systems of pharmaceutical and parenteral products. It is a commonly used technology in early stage pharmaceutical package development and component compatibility evaluation. In comparison to other leak test techniques, helium leak testing has the highest level of sensitivity, making it the most used CCI test method. In accordance with ASTM F2391, helium leak detection is a widely used method in the pharmaceutical industry.

Vacuum Decay is a non-destructive method for testing the integrity of container closures for package integrity and leak path detection. The technology provides quantitative, deterministic, and reliable test results to assure package integrity in comparison to manual inspection and other non-deterministic test techniques. The vast range of package types that may be accommodated by Vacuum Decay technology includes filled and sealed rigid, semi-rigid, and flexible packaging consisting of non-porous or porous materials.

Vacuum Decay Technology

Vacuum Decay is one of the most efficient and accurate vacuum-based leak detection methods. The method operates by placing the package within a properly outfitted evacuation test chamber that contains an external vacuum source. To detect any deviations from a predetermined targeted vacuum level, the vacuum levels are continually monitored. If there is a defect in the packaging, air or liquid will leak into the chamber from the package and cause a change in pressure. On the other hand, non-defective packages do not leak any pressure into the chamber, maintaining the chamber vacuum level constant. The test cycle is quick, non-invasive, and non-destructive to both the product and the container. The Vacuum decay system can detect both major and minor defects, regardless of where they are located. The system has various applications in the field of pharmaceuticals and medical devices.

Applications of Vacuum Decay Technology in Various Industries

• Pharmaceutical

Pharmaceutical products are a range of substances used for treating, diagnosing, or changing organic processes to help the management of public health. Pharmaceutical products are tested to make sure they adhere to strict safety and quality requirements. Previously, pharmaceutical packaging was only subjected to sterility testing. However, the United States has recognized that sterility testing alone is not sufficient to maintain the integrity of pharma products. FDA (Food and Drug Administration) has published guidance related to pharma industry on submission of documentation for sterilization process evaluation in human and veterinary drug products.

Container closure integrity (CCI) testing is a non-destructive package inspection technology for finding leaks and avoiding potential contamination. A test like this is necessary since any defect in the container might allow foreign particles to enter the product and thereby reduce its shelf life. Since it impacts both the product and the patient, a manufacturer places high priority on implementing the proper container closure system. Thus, the relevance of container closure integrity testing in the pharmaceutical industry has increased substantially over time. Vacuum Decay and MicroCurrent HVLD are the most chosen technologies for testing pharmaceuticals.

• Medical Device

Maintaining medical device package integrity is essential to make sure the product is delivered to the end user unharmed. Medical device packaging and delivery options range from rigid non-porous containers to flexible porous packaging. Every packaging format has a different set of characteristics and requirements, so choosing the right inspection technique requires a thorough approach. Package challenges have risen along with packaging format and material innovations. Among all medical equipment, Class III devices produce the greatest risk to maintaining package integrity. These implanted devices preserve or maintain life. Pacemakers, cardiovascular stents, respiratory ventilators, and breast implants are a few examples of Class III medical devices. Since these devices are inserted into human bodies directly, even a small packaging defect puts patient’s safety at risk. Therefore, it is essential to evaluate the container closure integrity of medical devices.

Vacuum Decay Technology Benefits

• Non-destructive, non-subjective and does not require sample preparation.
• Detection of defects down to 0.01 cc/min.
• Results show that they are more accurate than dye ingress.
• Quantitative, deterministic testing technique.
• Supports initiatives for waste reduction and sustainable packaging.
• ASTM test method and FDA recognized standard.

When determining the integrity of pharmaceutical and medical devices, Vacuum decay leak testing is the best non-destructive option. The test measurement generates a reliable and accurate quantitative result, as well as a pass or fail decision. The FDA recognizes the standard Vacuum Decay leak test technique (ASTM F2338) as a consensus standard for evaluating container closure integrity (CCI). The test technique is referenced in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207) and listed in ISO 11607.

For packaging sterile devices in the medical industry, porous packaging materials are widely used. The sterile products are frequently packaged, shipped, and distributed to multiple places, where they may be exposed to a range of humidity conditions during the course of the distribution cycle. The leaks in the porous packaging materials can contaminate medical devices as well as products. These leaks are frequently observed at tiny pinholes or breaches in the seals between packing components. Hence, maintaining the microbial barrier of sterile medical devices is of grave importance. In order to maintain the sterility and microbial barrier, various package integrity test solutions can be used. Airborne Ultrasound technology is one such method.

Airborne Ultrasound Technology Overview

Airborne ultrasound is an inspection method for testing seal quality that is able to evaluate seals for defects without causing any damage. It is an FDA recognized standard and ASTM Test Method F3004 for testing seal quality. Such tests are mostly carried out to provide enhanced tray seals, flexible packages, and pouch seal quality inspection. Tyvek®, paper, foil, film, aluminum, plastic, and poly are just a few of the packaging materials that may be used with Airborne Ultrasound technology to ensure in-depth seal quality analyses.

Integrity Testing of Porous Packages using Airborne Ultrasound Technology

Airborne Ultrasound technology is one of the commonly used methods for testing the seal quality of porous packages. In this technique, sound waves are reflected when ultrasound waves pass through the packaging seal. The signal intensity is reduced or destroyed when there is a leak or defect. These variations are meticulously monitored to identify defects. With airborne ultrasound technology, it’s now possible to identify a variety of seal defects, including visible and invisible, leaking and non-leaking, process-related and random both offline in the lab and in automated production environment.

Airborne Ultrasound technology has been proven in the field with both online (Seal-Sensor) and offline (Seal-Scan) solution options. Both of these technologies make use of non-contact airborne ultrasonic testing. It is known to be among the best techniques for non-destructive testing of flexible packaging seals in both offline laboratory testing for seal quality analysis and 100% inline testing on the production line. According to ASTM F3004-13, this is the standard test procedure for the airborne ultrasound evaluation of seal quality and integrity.

Benefits of Seal-Scan and Seal-Sensor Methods

• Deterministic seal quality inspection method that produces quantitative outcomes.
• Regardless of color, transparency, print, surface polish, or porosity, this method works for all material types and combinations.
• Non-destructive and non-subjective test technique that does not require any sample preparation.
• Technology may be used for 100% online final pouch seal defect detection.
• Seal quality inspection results are repeatable, reproducible and reliable.
• Cost-effective solution for testing seal integrity and seal analysis that characterizes the overall quality and uniformity of the seal.

According to studies, the conventional seal inspection techniques are ineffective because they miss undetectable flaws and wrongly reject pouches that are tightly sealed. Airborne Ultrasound is a deterministic seal quality testing method. The technology has established itself as a highly practical solution for non-destructive testing of porous packages. The integrity of porous packages can be tested efficiently using Airborne Ultrasound technology.

The integrity of container closure systems can be interpreted as their capacity to maintain a sterile barrier against potential contaminants that could compromise the quality of the end product. The sterile barrier can be damaged by even the smallest leak, which might affect the product's healing properties. Over the years, dye ingress and microbial ingress are common leak testing methods. It has been proven that they provide inaccurate and subjective results. As a result, regulatory organizations have mandated a shift towards more deterministic test procedures that can be controlled, calibrated, and provide a definite determination of CCI. Airborne Ultrasound technology is a deterministic test method mentioned in the revised USP< 1207> Chapter Guidance for seal quality testing.

Explain Airborne Ultrasound Technology

Airborne Ultrasound Technology is a technique for testing the seal quality. It is an ASTM test method F3004 and the Food and Drug Administration (FDA) approved standard for seal quality testing. Such inspections are mainly done to provide improved seal quality inspection of pouches, flexible packages and tray seals. Airborne Ultrasound technology ensures in-depth seal quality analysis and is applicable to multiple packaging materials such as Tyvek, paper, foil, film, aluminum, plastic and poly.

In this technique, sound waves are reflected when ultrasound waves travel through the packaging seal. In the presence of a leak or fault, the signal intensity is diminished or removed. To find the leak, these fluctuations are carefully monitored. More sound is reflected, and less sound is transferred through the seal as the acoustic difference between the medium increases (most evident at the transition from a gas to solid state). The inability to detect non-leak defects is a common challenge faced by most leak test methods. However, users may recognize a variety of seal defects, including visible and invisible, leaky and non-leaking, process-related and random, using airborne ultrasound technology.

Seal-Scan and Seal-Sensor

Under this technique, VeriPac leak testers are connected to a test chamber specially designed to hold the sample package. The package that has been put inside the test chamber is subjected to vacuum. A single or dual vacuum transducer technology is used to monitor the vacuum level as well as how the vacuum changes during a predefined test period. The existence of leaks and other defects within the package is determined by monitoring variations in an absolute and differential Seal-Scan® and Seal-Sensor™ are the two configurations of Airborne Ultrasound technology. Seal-Scan® technology inspects and analyzes pouch seals non-destructively offline. This deterministic, quantitative, high resolution method inspects pouch seals for defects and seal integrity for consistency. Testing does not involve sample preparation, and is non-invasive as well. The technique includes advanced digital imaging software tools for process control that allow in-depth seal quality analysis. Utilizing Airborne Ultrasound technology, Seal-Scan® systems evaluate seal quality and integrity in accordance with ASTM Test Method F3004-13. Seal-Scan® is a semi-automatic inspection system with an x-y drive for the detection of seal defects, seal characterization, and material analysis.

Seal-Sensor™ is an Airborne Ultrasonic technology that inspects the final pouch seal 100% online in a non-destructive manner. Seal-Sensor™ is a deterministic, quantitative, fast, and reliable way to test for defects in pouch seals. The Seal-Sensor™ technology detects defective seals, seals with partial or weak areas, and several other typical seal defects that may not be physically visible but have an impact on the quality, and life span of the product. A pass/fail result and quantitative, traceable data are generated by a single linear scan (L-Scan) of the pouch seal in less than one second.

Why Use Airborne Ultrasound Technology?

• Deterministic inspection technique yielding quantifiable results.
• Non-destructive, non-subjective, and does not need sample preparation.
• Independent of color, transparency, print, surface polish, or porosity, it is applicable to all materials and combinations.
• Can be integrated completely online to identify defects in the final pouch seal.
• Consistent and dependable results.
• Referenced in USP Chapter 1207.Inexpensive method for evaluating the seal integrity of the final pouch seal.
• Describes the overall quality and uniformity of the seal.

Both Seal-Scan® and Seal-Sensor™ technologies utilize non-contact airborne ultrasonic testing technology. With the innovation of Seal Scan and Seal-Sensor, Airborne Ultrasound technology has emerged as the most reliable technique for non-destructive seal integrity testing, both in offline laboratory testing for seal quality analysis and 100% inline testing on the production line.

The difficulty of maintaining shelf life for packaged snack foods never end. The majority of snack foods are oxygen and moisture sensitive. Package integrity issues can lead to mold growth, oxidation, taste loss, and spoilage. Leaks smaller than 10 microns can contaminate a product with bacteria, and comparable leak sizes might allow moisture or oxygen in. Snack foods come in a wide range of packaging types, but they all require package integrity assurance for extended shelf life.

Even a tiny leak in the container might cause microbial contamination or oxygen penetration, and traditional test methods may not be able to find such leaks. The sensitivity of the testing method is crucial for preserving the quality of the product during its shelf life. In this blog, we will discuss how VeriPac Vacuum Decay technology can efficiently leak test snack food packages.

VeriPac Vacuum Decay Series for Snack Food Package Integrity Testing

VeriPac Vacuum Decay technology is an ASTM-approved, FDA-recognized test technique with the ability to deliver reliable, consistent, repeatable, and accurate quantitative data. It is a non-destructive container closure integrity testing method that can identify micro leaks while taking into consideration a variety of packaging types, including filled and sealed rigid, semi-rigid, and flexible packaging composed of non-porous or porous materials.

Vacuum Decay leak testing is recognized as an efficient alternative for destructive testing techniques like water bath or dye intrusion because it removes subjectivity and lowers waste and costs. It is proven to provide a short-term return on investment. Critical packaging defects are consistently found by the VeriPac test systems, which also provide useful packaging process insights. The VeriPac Series will evaluate a wide range of high-risk packaging applications and ensure that the final product satisfies consumer and regulatory requirements. The suitable VeriPac model is chosen, based on the intended package type and leak test sensitivity. Depending on the application, configurations can be optimized and customized.

Working Principle

Under this technique, VeriPac leak testers are connected to a test chamber specially designed to hold the sample package. The package that has been put inside the test chamber is subjected to vacuum. A single or dual vacuum transducer technology is used to monitor the vacuum level as well as how the vacuum changes during a predefined test period. The existence of leaks and other defects within the package is determined by monitoring variations in an absolute and differential vacuum.

VeriPac Inspection System Benefits

• FDA Consensus Standard and ASTM Test Method F2338.
• Cost-effective and quick return on investment.
• Simplifies the inspection and validation procedure.
• Non-destructive, non-subjective, no sample preparation.
• Supports sustainable packaging and zero waste initiatives.
• Referenced in USP Chapter 1207.

Flexible packaging such as sachets, stick packs, and pouches, composite cans, and modified atmosphere packaging (MAP) are common types for snack food packaging. For snacks like nuts, savory snacks, chips, crackers, cookies, beef jerky, nutrients, and granola bars, they provide the ideal packaging appearance. They offer shelf stability and simplicity of quick opening. While every packaging offers a different set of advantages and product appeal, every format also has a different set of difficulties for maintaining the integrity of the package and seal.

Pharmaceutical vials are small bottles or containers designed for parenteral administration (injection or infusion) in a single patient for a single case, procedure, or injection. They offer the highest Container Closure Integrity (CCI), which is a measure of how well a container protects the pharmaceutical ingredient against contamination by a variety of factors such as moisture, air, and chemicals.

In pharmaceutical manufacturing, the leak test is a critical parameter for vials. A visual inspection process may not detect defects that cause a sterile vial to leak. Thus, the pharma companies move toward CCI test methods. Many manufacturers are not sure how to conduct a container closure integrity test, but parenteral product leak testing is very important to assure that the product remains sterile in the packaging configuration throughout the duration of the product's shelf life.

What is CCIT?

Container Closure Integrity Testing (CCIT) is an important quality control technique for pharmaceuticals. It is an assay that evaluates the container closure and its capacity to keep possible contaminants out. Microorganisms, reactive gases, and other chemicals are examples of potential contaminants. This test is necessary for parenteral products since the seal quality is crucial to the drug product's sterility and quality throughout its shelf life. Inadequate sealing can accelerate the expiration of a drug product and cause significant risk to the patient's health if the product loses its sterility.

Previously, sterility testing was used to demonstrate container integrity. However, due to the insensitivity and other challenges associated with sterility tests, a variety of container closure integrity tests were developed. MicroCurrent HVLD, Vacuum Decay, and Helium Leak Detection are some of them. We give a brief overview of the above pharmaceutical package testing methods that can be used for testing pharmaceutical vials.

Leak Testing Vials Using Various CCI Techniques

• MicroCurrent HVLD Technology

High Voltage Leak Detection (HVLD) is a non-destructive Container Closure Integrity technology that is used to evaluate the closure integrity of parenteral product packaging. HVLD technology makes use of quantitative electrical conductivity and resistance principles. The technology works by transmitting high voltage microcurrent impulses through sample packages. The electrical resistance of the sample lowers in the presence of a leak, resulting in an increase in current. HVLD technology relies on the “flow” of current, while other leak detection methods rely on the flow of gas or liquid. The MicroCurrent HVLD lowers product voltage exposure to less than 5% of that experienced while testing with similar HVLD technologies. When compared to conventional HVLD systems, reducing exposure voltage not only eliminates any risk that the voltage provides to the product, but also significantly reduces Ozone formation during operation. MicroCurrent HVLD can be used to test for leaks in nonporous, rigid or flexible packages, as well as packages containing liquid or semi-liquid products.

• Helium Leak Testing

Helium leak testing is the method of locating leaks in enclosed or sealed systems by utilizing helium as a “tracer” gas and measuring the concentration as it exits owing to leakage. The package is filled with helium and vacuumed in this method. A helium leak detector is used to determine how much helium leaks from the container. The outcome is expressed as a leak rate. Helium leak testing is used in product design, product quality studies, failure analyses, and validation, in addition to being an effective container closure integrity test technique. Helium leak testing ensures high sensitivity leak detection, which is not achieved by many other leak test methods.

• Vacuum Decay Technology

Vacuum Decay is a deterministic Container Closure Integrity testing methodology that relies on package integrity and leak path detection. Unlike human inspection and other non-deterministic testing techniques, Vacuum Decay provides quantitative and reliable test results to assure package integrity. Vacuum Decay technique can handle a wide range of package types, including filled and sealed rigid, semi-rigid, and flexible packaging comprised of nonporous or porous materials. This test involves placing packages in an evacuation test chamber with an external vacuum source. Vacuum levels are regularly monitored to detect deviations from a predetermined intended vacuum level. A defect in the packaging will allow air to escape into the test chamber. Packages with no defects, on the other hand, maintain a steady chamber vacuum level. Over the years, Vacuum Decay technology has proven to be one of the most practical and sensitive vacuum-based leak detection technologies.

Historically, dye immersion and microbiological immersion were the two most popular methods for leak testing vials. Recently, the USP has issued guidelines requiring the use of deterministic methods in order to produce more consistent and predictable results. USP<1207> recommends that dye immersion tests are avoided and HVLD or Vacuum Decay tests are used instead.

Several leak detection methods, that are deterministic and non-destructive, are already available in the market. Pharmaceutical companies are urged to use technologies that significantly enhances quality assurance and leak detection rates. Appropriate leak detection technology is selected based on the specific characteristics of the product and container, such as conductivity, headspace parameters, contents, or API. Historically, dye immersion and microbial immersion have been the two main methods of vial integrity testing. Recently, the USP has issued guidelines that require critical methods to achieve more reproducible and predictable outcomes. USP <1207> encourages a move towards more deterministic methods, recommending the avoidance of dye immersion tests and the use of quantitative, non-destructive technologies instead.

Why High Voltage Leak Detection Method is Preferred for Testing Vials?

High Voltage Leak Detection or HVLD is a deterministic, non-destructive leak detection method to evaluate vials, cartridges, and other liquid-filled parenteral products for Container Closure Integrity. The current generation of PTI’s MicroCurrent HVLD may be utilized with a wide range of liquid-based products, from low conductivity sterile water for injection to highly proteinaceous drug preparations in suspensions. It is one of the most effective online container closure testing methods, requiring just minor infrastructure modifications. When compared to conventional HVLD solutions, MicroCurrent HVLD utilizes approximately 50% less voltage and exposes the product and environment to less than 5% of the voltage. This method is non-invasive and requires no sample preparation. Like vial leak testing, another major application of MicroCurrent HVLD is pre-filled syringe testing.

Working Principle of MicroCurrent HVLD Technology

In this method, the container is scanned using a set of high voltage electrode probes. A high voltage is applied to one side of the container, while a ground probe is attached to the other. If there is no leak in the package, the two container walls (high voltage side and ground side) offer complete electrical resistance, and no substantial current is measured flowing through the vial. If a micro-leak or fracture occurs in one of the container walls, the break-down resistance is achieved, and the current flows through. HVLD is the only leak detection method that does not require mass to travel through a defect location, instead of requiring just electricity to pass through a crack. Because of this feature, HVLD is sensitive to leaks that conventional leak detection technologies are unable to detect.

MicroCurrent HVLD Technology Advantages

• Deterministic and non-destructive test method.
• High level of repeatability and accuracy.
• Ensure more accuracy and dependability in results.
• At high production rates, both offline and 100% online inspections are performed.
• Simplifies the inspection and validation procedure.
• Highly effective in all parenteral preparations, even liquids with extremely low conductivity (WFI).
• Outlined in the USP 1207 Guideline.

Pharmaceutical containers like vials protect the product from contamination (sterile barrier) and prevent changes in product quality caused by external factors. In order to determine the functionality of such systems, container closure integrity testing is performed. CCIT provides sophisticated analytical methods for evaluating pharmaceutical containers.

Packaging has a significant impact on the quality of the products and influences customer purchase decisions. Both of these factors provide significant issues for product design, particularly in the case of food packaging. No other product incorporates as many innovative and improved packaging advancements as food. Due to the increased need for convenience, packaging should be easy to handle, easy to open, resealable, or must be able to be heated directly in a microwave. Furthermore, food packaging must be properly sealed to protect product quality and shelf life. Ensuring safe food packaging through testing and analysis is key to safeguarding human health and protecting the food product.

Food Package Integrity Testing Using VeriPac 310

The VeriPac 310 is a non-destructive, non-invasive leak detection and container closure integrity testing method for the food industry. VeriPac systems eliminate waste and provide operators with a comprehensive view of package quality. The VeriPac 310 test cycle generates real-time results from accurate quantitative measurements, identifying packaging defects before important process concerns develop. Tests can be run in any order and even on the same sample several times. Good packages can be returned to the packing line intact. Testing is more dependable, sensitive, and efficient than destructive procedures like the water bath or burst test. The ASTM-approved patented vacuum decay leak test technique F2338-09, acknowledged by the FDA as a consensus standard for package integrity testing, is used in the VeriPac 310.

Technology Overview

The test method begins by connecting the VeriPac leak testers to a test chamber that is specifically designed to accommodate the package to be evaluated. The package is placed into the vacuum-sealed test chamber. The absolute transducer technology is used to monitor the vacuum level as well as the change in vacuum throughout a predetermined test period in the test chamber. The presence of leaks within the package is indicated by the changes in an absolute and differential vacuum. Test systems can be configured to operate manually or automatically. This inspection method is appropriate for offline laboratory testing as well as production applications for QA/QC statistical process control. The test cycle is non-invasive and non-destructive to both the product and the package, taking only a few seconds.

VeriPac 310 Benefits

• Non-invasive inspection system for leak detection
• Deterministic, quantitative test method
• Non-destructive, non-subjective, no sample preparation
• ASTM test method and FDA recognized standard
• Cost-effective and economical
• Supports zero waste initiatives
• Measures integrity of the entire package

Every packaged food product has a seal that keeps the food item safe inside the packaging. Therefore, food package seal quality testing is performed to ensure that the food packaging used is safe for both customers and the environment. PTI offers a diverse range of testing methods that are applicable to food product packages.

For parenteral administration, compounded sterile preparations are often made from manufactured sterile materials. As a means of drug delivery, patients commonly require the administration of parenteral formulations. When compared to other methods of drug delivery, this method has both advantages and disadvantages. Nowadays, the ways of administration of new drugs are increasing all over the world. The range of possibilities for drug delivery containers must be reviewed on a regular basis, with the objective of improving compliance and delivery accuracy.

The packaging around a drug product is critical when establishing a new drug product or even re-facing an old one. There has also been an increase in the number of packaging formats for parenteral over the last ten years. Liquid-filled containers such as vials, ampoules, syringes, blow-fill seals, and auto-injectors, as well as containers filled with lyophilized products, are common parenteral packaging methods. Parenteral drugs are directly injected into the human body. Therefore, it is necessary to ensure the product quality of parenteral throughout its shelf life. Highly sensitive and reliable test methods are required. In this blog, we will discuss about parenteral product leak testing.

Why Use E-Scan HVLDmc for Testing Parenteral Products Packages?

E-Scan 655 is a revolutionary deterministic offline micro leak test equipment that inspects vials, syringes, and other liquid-filled parenteral products for container closure integrity using a new class of HVLD technology. The technique utilizes a non-contact, non-invasive test procedure that does not need sample preparation. E-Scan 655 is compatible with a variety of liquid-based products, including low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions, including vaccines. At high production rates, the offline E-Scan 655 approach may be converted from laboratory to 100 percent inline testing applications. The E-Scan 655 technology is a non-destructive MicroCurrent conductivity test technique for parenterals. This method exposes the packaging and product to a lower voltage than other conductivity-based solutions.

Using a series of electrode probes, the E-Scan tester scans a sealed non-conductive container. Glass, plastic, or poly laminate can be used to make the container. The liquid must be contained within the container or packet (minimum fill 30 percent). There is a resistance differential and a change in current flow if there is a pinhole, crack, or other flaw, indicating a container breach. The approximate position of the defect can be determined.

Benefits of E-Scan MicroCurrent technology

• Non-destructive, non-invasive, and no sample preparation is required.
• Greater accuracy and repeatability.
• Lower voltage exposure eliminates risk to the product and environment.
• Quick changeover and simple recipe set up to accommodate a wide range of products and applications.
• E-Scan MicroCurrent technology is effective across all parenteral products, including extremely low conductivity liquids (WFI).
• Listed in USP Chapter 1207> as a proposed methodology for parenteral liquid package inspection.
• The inspection and validation process is simplified.

E-Scan HVLDmc is one of the highly effective CCI technologies for parenteral. It is applicable to pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. The technology has a rapid test cycle and is easy to use. PTI’s E-Scan 655 is a patent-pending technology that uses a unique mode of MicroCurrent HVLD technique that requires less than half of the voltage required by existing high voltage technologies. MicroCurrent HVLD technology can be applied from the R&D laboratory to automated 100% inline CCI inspection.

The pharmaceutical packaging industry is constantly developing as pharmaceutical manufacturers require reliable and efficient packaging solutions that meet a variety of requirements. Packaging is essential for the safe storage and administration of pharmaceutical products. Packaging pharmaceuticals is important not only for storing and protecting products but is also helpful in identifying, marketing, and promoting different brands, and making pharmaceutical products easier to use. Vials, blister packs, bottles, syringes, ampoules, etc are the most common pharmaceutical packages. The packages must perform correctly to ensure that the drug product remains uncompromised throughout the distribution cycle and shelf life. These packages are later tested to guarantee their quality and integrity.

Testing Package Integrity Using VeriPac 355 Series

VeriPac 355 is a non-destructive micro leak detection device for testing container closure integrity and package integrity on a variety of products and packaging types. This system is specially designed to test containers for dry product gas leaks as well as liquid leaks. Since it is non-destructive and does not need sample preparation, the VeriPac 355 can be integrated into protocols at any step in the handling process. The VeriPac 355 is the ideal non-destructive quantitative test technique for various pharmaceutical and food applications, with the capacity to detect leak rates as low as 0.2 cc/min depending on package parameters. The VeriPac 355 core technology is based on the ASTM vacuum decay leak testing method (F2338-09), which is recognized by the FDA as a consensus standard for package integrity testing. VeriPac leak test instruments were used to develop this test method.

Technology Overview

The VeriPac 355 leak tester is connected to a test chamber intended to hold the package to be tested. The package is placed inside the vacuum-sealed test chamber. High-resolution absolute transducer technology is utilized to monitor the test chamber for, both the level of vacuum and the change in vacuum during a pre-defined test duration. This is capable of detecting both gross and micro leaks. The test cycle is only a few seconds long and the results are objective. The testing is non-destructive to both the product and the package.

The sensitivity of a test is determined by the sensitivity of the transducer, the package design, the package test fixture, and the crucial test parameters of time and pressure. Test systems can be configured to operate manually or semi-automatically. This method is suitable for offline laboratory testing and QA/QC statistical process control.

Advantages of VeriPac 355

• Non-destructive, non-subjective, and no sample preparation is required
• Deterministic, quantitative test method
• Detection of defects down to 0.2 ccm (5 microns)
• High sensitivity, repeatability, and accuracy
• Operator receives a PASS/FAIL result within a short cycle time
• Portable modular design with a small footprint
• FDA standard and ASTM F2338 test method

VeriPac technology is the optimal non-destructive solution for determining container closure integrity in a variety of package configurations. The strategy for choosing the right VeriPac model is based on the package type and the required leak test sensitivity. Configurations can be optimized and customized to the needs of each application. The VeriPac Series will analyze a wide range of high-risk package applications and ensure that the product fulfills regulatory standards and customer requirements for integrity.

Testing Container Closure Integrity (CCI) is crucial for ensuring the quality of Class III medical devices. Class III medical devices are sterile components that are designed to be inserted directly into the human body. These devices often sustain or support life, are implanted or pose an unreasonably high risk of disease or damage. A compromised package can serve as a vehicle for microbial transmission and compromised sterility, leaving patient safety at risk. When bacteria or other impurities enter the container, the device ceases to be a treatment and becomes a danger to the patient. Similarly, a breach of the seal affects the sterility of the device and may present a serious quality concern at a key point of usage.

Testing Challenges in the Medical Device Industry

There are three basic approaches to package integrity testing:

• 100% in-line testing: All products in a batch are tested on a high-speed production line at an acceptable level of CCI assurance.
• Small batch testing: Testing a statistically significant batch size for certain quality parameters and extrapolating to match the quality of the manufacturing lot.
• Testing Offline: Operators test packages individually or in smaller batches.

Dye penetration is a technique for identifying defects in package body and seals that has a variable detection capacity. When carried out correctly, the approach can identify pinholes and channel defects as small as 20 microns. This method is only used to validate the packaging process and offers minimal value to in-process quality monitoring. The method is time-consuming to implement and provides limited information in the effort to ensure the quality of high-risk applications.

For CCI testing, the majority of medical device manufacturers use a 100% in-line manual visual inspection technique. Manual visual inspection has been proved to be one of the least reliable techniques for ensuring quality. The failure of manual visual inspection is caused by a number of factors. According to ASTM test method F1886, a manual visual inspection may detect 75-micron channel defects in a transparent seal 60-100% of the time. Although manual visual inspection can be applied as a 100% test method, performance on the task decreases significantly over time. This method is not applicable if the package format is not transparent or semi-transparent.

How Vacuum Decay and Airborne Ultrasound Technologies are Automated?

Vacuum Decay is a deterministic method proven to offer predictable and reliable results for CCI testing of high-risk package applications. This is an ideal solution for non-porous medical device applications. When the major focus of the inspection is the final seal of a porous package, Airborne Ultrasound is exceptionally efficient and reliable at detecting seal defects that are invisible to the manual visual inspector. Both approaches have shown to be reliable non-destructive testing methodologies, and one or the other can be used for inspection based on the unique features of the product and container.

The automation of each technology looks a little different. Vacuum Decay enables approximately 25 to 50 samples per minute, with low throughput detecting single-digit micron leak sizes. Airborne Ultrasound is a rapid-fire sensor that transmits 1000 pulses per second of sound through the seal. The final seal of Tyvek® pouches and other flexible packaging systems may be scanned at a rate of 20 inches per second (~40 cm/sec), with the capacity to detect the most frequent seal faults and seal quality concerns. Both methods enable a production line to ensure quality while reducing production throughput.

The Airborne Ultrasound technology offered by PTI can be automated in many ways. Basically, the technology can measure the quality of a quantitative seal in any way that the pouch seal can pass through the ultrasound inspection head. Ultrasound can be applied to the production flow, which captures seal quality when exiting a band-sealer or transferring pouches through a production line. Robotic handling may also be used to do a full 360-degree seal inspection on all pouch seals. Airborne Ultrasound has the flexibility to be deployed in a variety of production lines and has high reliability in detecting critical defects.

Vacuum decay is often utilized for both Tyvek® trays and non-porous container types. While a vacuum takes longer to do a test (about 5 seconds on a Tyvek tray), the sensitivity and stability of this technology make it perfect for low output applications with high sensitivity requirements. Robotic handling solutions can serve many test stations at the same time, allowing for increased product throughput without losing sensitivity.

Medical devices are packaged and delivered in a variety of ways, ranging from porous flexible packaging to non-porous rigid containers. The range of product types and packaging options create unique inspection challenges that must be overcome in order to assure seal strength, sterility, and quality. Airborne Ultrasound and Vacuum Decay offer 100% testing capabilities as well as an accurate inspection that includes quantitative test results and a pass/fail result. These new automated technologies, with more sensitive leak detection capabilities, inspect containers at a higher rate.

Package integrity leak test methods offered by CCIT such as Seal-Scan utilize non-contact Airborne Ultrasonic technology for seal integrity testing and seal quality analysis of pouches and flexible packaging. The method is applicable to pharmaceutical as well as medical device packaging.

Seal Quality Testing and Seal Analysis using Seal-Scan Technology

Seal-Scan® is a non-destructive offline inspection and analysis technique for pouch seals using Airborne Ultrasonic technology (ABUS). Seal-Scan® offers advanced digital imaging software tools for process control, including in-depth seal quality inspection. Seal-Scan system uses the non-destructive ASTM Test Method F3004-13 for "Evaluation of Seal Quality and Integrity Using Airborne Ultrasound Technology." This test method was approved using PTI's ABUS technology. Seal-Scan® is a deterministic, quantitative, high-resolution technology for inspecting pouch seals for defects and ensuring seal integrity.

Seal-Scan has two scanning modes:

• Linear Scan (L-Scan) to simulate online defect identification (line graph)
• C-Scan for detailed seal analysis, resulting in pixel-by-pixel seal evaluation (Opto-Acoustic image)

Technology Overview

The pouch seal or packaging material is scanned between two focused ultrasonic sensors. Ultrasonic waves travel through single or several layers of bonded materials. The reflection of sound waves caused by ultrasonic transmission via different materials reduces/eliminates signal intensity. The signal level that passes through the seal is a function of the seal's quality. Defects of various forms, such as leaking and non-leaking, process-related and random, can be detected. Seal-Scan® can provide Opto-Acoustic images as well as thorough statistical analysis using one of two scan modes (L-Scan and C-Scan).

An L-Scan is a single linear scan along the seal's X-axis that generates a line graph of seal integrity and replicates real-time inspection. C-Scan generates a series of scans (along the X and Y-axis of the seal region), that offers a high-resolution ultrasonic image of the seal structure. This technology, via the Seal-Sensor, can be integrated into a pouch production process for 100% online seal defect detection.

Benefits of Seal-Scan Technology

• Deterministic inspection approach yielding quantitative results.
• Works with any material and combination, independent of color, transparency, print, surface polish, or porosity.
• Produces a high-resolution Opto-Acoustic seal image.
• Characterizes the overall quality and consistency of the seal.

Seal-Scan® is a semi-automatic inspection system with an x-y drive that is used to identify seal defects, characterize seals, and analyze materials. This approach is non-invasive, non-destructive, and does not need any sample preparation. The ability of PTI to adapt this technology to diverse production restrictions and conditions makes it an effective solution for flexible packaging systems.

The physical ability of a package to protect its contents with the necessary level of protection during a specific time is referred to as package integrity. Package integrity tests are performed to detect packaging issues that might affect the sterility of a medical device. Previously, microbial challenge or dye penetration testing was used to determine whether the product packaging has maintained its microbial barrier qualities. Due to technological advancements, VeriPac FLEX systems are currently being used for testing the package integrity of flexible packages.

VeriPac FLEX Systems to Ensure the Integrity of Flexible Packages

CCIT’s VeriPac FLEX systems are versatile non-destructive package inspection systems that are intended particularly for evaluating dry-filled pouches and flexible packaging. VeriPac FLEX systems are available in several configurations for both the leak test instrument and the test chamber capacity to accommodate various package specifications and test sensitivity requirements. VeriPac inspection systems provide a simple PASS or FAIL result, as well as quantitative test data. They offer unparalleled sensitivity, reliability, and practicality in testing a wide variety of flexible package formats and sizes, without changing settings or tools.

The ASTM technique for vacuum decay leak testing (F2338), which is specified in ISO 11607 and recognized by the FDA as a consensus standard for package integrity test solutions, is used by VeriPac FLEX Systems. As an alternative to destructive testing, they eliminate subjectivity while also reducing waste and cost. When compared to destructive techniques like water bath or blue dye leak test, vacuum decay leak testing technology has proven to provide a quick return on investment. The VeriPac test devices consistently detect significant packaging errors and provide useful packaging process information.

Technology Overview

On the basis of the package size, the VeriPac tester is initially attached to the appropriate FLEX chamber. The Integrated Flexible test Chamber (IFC) and Drawer Style test chamber (D-Series) are the two test chamber configurations available to connect with the VeriPac instrument depending on package specification and test sensitivity requirements. The Integrated Flexible test Chamber (IFC) is designed for low-headspace sachets or stick packs. Depending on the package size and requirements, the Drawer Style test chamber (D-Series) is available in 2 basic sizes: Small (D) and Large (DXL). Custom designs are possible for large packaging types and bulk products. The way the package is tested is what sets VeriPac FLEX systems apart. CCIT makes use of a flexible membrane that fits the shape and size of the package, preventing stress and damage to the film materials. In a single test cycle, several packages can be tested.

VeriPac FLEX System Advantages

• Non-destructive, non-subjective, no sample preparation
• Cost-effective with rapid return on investment
• Accurate and repeatable results
• USP< 1207> compliant
• Supports sustainable packaging and zero waste initiatives
• ASTM test method and FDA standard
• Deterministic, quantitative test method
• Simplifies the inspection and validation process

Manufacturers are still struggling with quality standards for flexible packaging. CCIT’s VeriPac FLEX has proven to minimize manufacturing waste and costs while boosting package quality assurance and brand value. It has high test sensitivity and is capable of identifying micro leaks down to the single digit micron range.

Pre-filled syringes are becoming more popular as a preferred container closure system for biologics. Pre-filled syringes must offer an inherent barrier that maintains drug product stability and sterility throughout its entire shelf life as a primary container closure system. The ability of the system to retain its microbial barrier integrity must be checked and demonstrated by the drug manufacturers. In 2008, the FDA endorsed CCI testing as part of the sterile product stability protocol.

The pharmaceutical industry has witnessed substantial technical developments in CCI testing in response to rising regulatory demands. MicroCurrent HVLD, Vacuum Decay Leak Testing and Helium Leak Detection are examples of new technologies that have proven enhanced detection capabilities above traditional Dye and Microbial Ingress approaches. Many of the technologies have been employed for CCI testing of drug product stability.

CCI Testing Strategy for Development

Many CCI failure modes can occur throughout the life cycle of a syringe, from component production to drug product filling and sealing, device assembly and packaging, and finally distribution and storage. It is critical to create a comprehensive plan for conducting CCI testing across the whole syringe life cycle.

The creation of the CCI testing technique begins with a detailed study of the construction, design, and manufacturing procedures used in syringes. The failure modes and impacts associated with each aspect of CCI were identified first. The next step was to evaluate whether CCI testing is required, as well as the intended uses and testing frequencies, using a risk-based approach. Knowing that the needle shield compartment seal integrity had been verified by the component supplier, apply a non-routine CCI test to validate its seal integrity during drug product loading and sealing, as well as during device assembly. To ensure CCI was achieved and successfully maintained, implement a complete set of CCI tests across the entire product development cycle for the product-containing syringe barrel compartment.

Method Development and Method Validation

Method development consists of optimizing testing parameters and determining the appropriate pass/fail threshold.

• Testing parameters optimization

Initially, several defect standards of known sizes were examined alongside undamaged samples using varied testing conditions. The relationships between key method parameters and instrument responses to intact and defect samples were comprehensively investigated, with the objective of determining a set of variables that give optimal separation between intact and defect samples. i.e. signal-to-noise ratio or SNR.

• Pass/fail threshold determination

The improved method was utilized to evaluate different lots of filled intact syringes representing relevant product variations, such as drug product batches, and packaging locations and lines, in order to define the preliminary pass/fail threshold. For intact samples, the results of the tests were statistically assessed to determine the instrument baseline and variation (σ). Typically, the pass/fail threshold should be 10 σ higher than baseline. The pass/fail threshold was then further refined and verified by testing defect standards of known sizes.

CCI testing techniques were validated for the pharmaceutical product package. Since the drug product formulation and package design may change during the early development stages, a step-by-step approach was adopted to validate the methods in line with the product development stages. Once product design and packaging design are complete, the methods are fully validated to support CCI testing for initial consistency and process evaluation. The power of the additional long-term method may be further validated before this method is implemented in QC laboratories for routine testing.

During package and pharmaceutical product development and manufacturing, properly selected and verified methodologies are critical for demonstrating container closure integrity. It should be noted that existing CCI testing methods do not provide an optimal solution for all pre-filled syringe CCI testing requirements. To maintain total container closure integrity, an integrated solution involving CCI testing as well as additional engineering and administrative controls is required.

Class III medical devices have a unique combination of criteria and package features that necessitate a comprehensive approach to determining the best inspection procedures. For medical package inspection, there are a variety of methods that require a thorough understanding to assure quality.

Manual visual inspection has been the most common form of inspection for medical device packaging. While an ASTM standard (ASTM F1886) covers this concept, it may not be applicable for all applications and has limitations. Even though a 75-micron channel defect can be detected by manual visual inspection, the ASTM method F1886 indicates that the chance of detection ranges from 60% to 100%. This vast range of uncertainty does not give the level of assurance required for the packaging of high-risk medical devices.

Although certain offline leak detection techniques can offer a quantitative evaluation of seal quality, they miss some of the most prevalent seal problems seen in Class III medical device packaging. Testing peel strength or utilizing other destructive methods will not reveal random seal problems. For class III medical devices, online non-destructive inspection procedures are excellent since they provide quality control with comprehensive manufacturing lot data.

All Class III medical devices must be sterile, however, container materials and design differ widely. A non-porous pouch or tray demands an entirely different technique than a porous pouch or tray. Tyvek® offers a sterile barrier, and the porosity of the material limits the leak test procedures that may be used on the package body. When it comes to porous packaging, the focus of online inspection moves away from leak detection and toward seal quality evaluation.

Technology Overview

Vacuum decay and Airborne ultrasound are the two main methods used by PTI/CCIT to inspect medical device packaging. Both methods are aimed at providing quantitative and deterministic test results in order to assess package quality. In terms of function and performance, the two technologies are entirely different. Package integrity and leak path detection are the main objectives of Vacuum decay. Meanwhile, Airborne ultrasound technology focuses on package seal inspection and seal quality. Both approaches aim to meet the basic requirements of being reliable and sensitive inspection procedures for Class III medical device applications.

Vacuum Decay (ASTM F2338)

Vacuum decay is the most practical and sensitive vacuum-based leak test method of CCI. When testing pouches, a versatile adjustable test chamber may be utilized to test pouches of various sizes. The package is then placed into the vacuum-sealed test chamber. The level of vacuum, as well as the change in vacuum during a pre-defined test duration, are both monitored during the short test cycle. The change in vacuum indicates the existence of leaks and defects within the package. Vacuum decay leak testing is a go-to standard for sterile products because of its sensitivity and dependability. The approach is ideal for laboratory offline testing and production applications for quality assurance process control, since test equipment may be developed for manual or automation operation.

The ASTM Vacuum decay leak test technique (F2338), which has been accepted by the FDA as a consensus standard for package integrity testing, was developed using PTI VeriPac technology. As a deterministic test technique for package integrity test solutions, Vacuum decay is mentioned in ISO 11607 and the new USP 1207 guideline document.

Airborne Ultrasound (ASTM F3004)

Airborne Ultrasound is an ASTM Test Method F3004-13 and is one of the most effective methods for non-destructive seal quality inspection of flexible packaging. It is mentioned in ISO 11607 and the new USP 1207 guidance document. Most inspection methods are challenged by the leaking nature of porous packaging, but Airborne ultrasound, with its non-destructive measure of seal quality, effectively overcomes those challenges.

The non-contact Airborne ultrasonic testing technique is used in both Seal-Scan (Offline) and Seal-Sensor (Online). Ultrasonic waves propagate through the material as a package seal passes through the sensor head, producing sound waves to be reflected. When defects are encountered, the signal intensity is reduced or eliminated. The larger the acoustic gap between mediums, the more sound is reflected and less sound is transferred through the seal.

The variety of package forms and materials makes inspecting the integrity of class III medical device packaging a challenge. CCIT's scientists and engineers have vast industry experience and can prove a complete solution, including test method development and equipment validation for Class III medical device packaging.

The integrity of the container closure system is crucial for ensuring that all portions of pharmaceutical products stay sterile during transportation, storage, and usage. Product contamination occurs as a result of leaking containers or closures. A non-destructive packaging inspection technology used to keep an aseptic barrier against possible contaminants is called Container Closure Integrity Testing (CCIT), commonly known as leak detection. The sterility and product quality of sterile final pharmaceutical and biological products should be maintained throughout their shelf life using container closure systems.

Various CCI Services

For testing the integrity of many package formats, CCIT offers expertise for the application of the best deterministic inspection technologies and test methodologies.

Feasibility Studies for Testing Package Quality

The first stage in evaluating and determining the optimal CCI technology and test technique for a certain application is to conduct an experimental or a more extensive feasibility study. To evaluate if a proposed CCI solution works and establish optimal test circumstances and Limit of Detection (LoD) is the goal of a feasibility study. CCIT’s aim is to provide clients with deterministic package integrity test solutions and help them in the installation of comprehensive CCI systems. This process starts with a client's problem description and ends with a clear approach to ensuring container closure integrity. Feasibility studies by CCIT for package quality testing provide customers with a complete report on the quantitative test technique.

Test Method Development for CCI Testing

CCIT conducts feasibility studies and develops test methods for package quality testing, recommending test methods based on the customer's needs for a given package or container. CCIT's Test Method Development focuses on the package/product characteristics and the extent to which the package attributes must be challenged to ensure closure integrity. The Test Method Development comprises adjusting test parameter settings for a given test method, such as vacuum or high voltage, test cycle periods, and pass/fail criteria. The comprehensive report will include precise test processes and criteria, as well as test findings and leak rates that the customer may expect, along with conclusions and recommendations. Before being included in the final report, all of the worked-out test methods go through validation checks to verify that they are reproducible, accurate, specific, exact, and acceptable for their intended application.

Equipment and Application Support

CCIT offers analytical leak detection services as well as package integrity testing equipment and applications knowledge. We also provide demonstrations on equipment and application services.

At CCIT's laboratory, we have the following technological platforms:

• VeriPac - Vacuum Decay applications
• E-Scan - MicroCurrent High Voltage Leak Detection( MicroCurrent HVLD)
• Seal-Scan®/Seal-Sensor - seal inspection through Airborne Ultrasound

CCIT also offers the following services:

• Installation, training, and validation services for CCI applications
• Calibration, technical assistance, and overall equipment maintenance
• Navigating USP 1207/ASTM/ISO standards - CCIT and regulatory consultancy services

CCIT.s.a is Europe’s leading package testing equipment provider for pharmaceutical, medical device, food, and nutrition companies. We have expertise in Test Method Development & Feasibility Studies. We focus on non-destructive technologies like Vacuum Decay, MicroCurrent HVLD, Airborne Ultrasound, and Helium Leak Detection for package quality testing.

Pharmaceutical package integrity testing has always been an important aspect of the quality control and manufacturing process. Container Closure Integrity is critical for protecting the product throughout its lifespan until it is delivered to the patient. CCIT uses non-destructive inspection technologies for ensuring container closure integrity of vials, ampoules, syringes, cartridges, and auto-injectors.

Ampoules must be properly sealed since any crack or defect might contaminate the sterile substance inside. Microbial contamination, exposure to gases, water vapor, and solvent loss can all cause product degradation if there is any breach in the package. Hence, container closure integrity is an essential stage in the lifecycle of a sterile pharmaceutical product. Patients may be at risk if the container closure integrity is compromised. Drugs that are meant to save lives might lose their effectiveness or cause fatal side effects. CCI defects can cause oxidation, which can reduce a drug's potency and shelf life.

Integrity Testing of Ampoules using MicroCurrent HVLD

MicroCurrent HVLD technology detects leaks in nonporous, rigid, or flexible packaging such as ampoules that contains liquid products. This is a non-destructive High Voltage Leak Detection Technology that is highly effective across all parenteral products (vials, syringes, ampoules and BFS). The test technique detects pinholes, microcracks, stopper/plunger leaks, non-visible leaks under crimping, and many other defects by scanning a non-conductive container sealed with electrode probes. Any crack or other defect in the container can cause a resistance difference and a change in the current flow, which would indicate a breach. It is also possible to determine the approximate position of the defect.

When compared to conventional HVLD technologies, MicroCurrent HVLD uses around 50% less voltage and exposes the product and environment to less than 5% of the voltage. At high production speeds, this HVLD method may be simply transitioned from offline to 100 percent inline testing applications. It is a cost-effective online container closure testing solution that requires only minor infrastructure changes. This method is non-invasive and does not need sample preparation. For all parenteral and biologic products, MicroCurrent HVLD is one of the most effective CCI methods.

MicroCurrent HVLD Benefits

• Effective in all parenteral preparations, even liquids with extremely low conductivity.
• At high production speeds, inspection can be done both offline and online.
• Non-destructive, non-invasive, and requires no sample preparation.
• High level of accuracy and repeatability.
• Deterministic method for parenteral liquid package inspection.
• A robust technique for a variety of product classes and packaging forms with an estimated 3x Signal-Noise-Ratio.

Ampoules are such little glass bottles containing a sterile pharmaceutical liquid for parenteral administration. Microbes or other harmful pollutants may enter the ampoules through capillary pores or microscopic breaks, or the contents may leak to the outside. This may result in contamination of the sterile contents as well as a deterioration of the appearance of the package. MicroCurrent HVLD technology offered by CCIT can be applied to a variety of pharmaceutical packing formats including ampoules for testing integrity.

Container closure integrity (CCI) testing requirements and regulatory guidelines have been rising steadily in the pharmaceutical industry in recent years. Parenteral products are often packaged in a variety of ways. The most common packaging formats are - vials, ampoules, syringes, BFS, and autoinjectors.

Microbial contamination, exposure to gases, water vapor, and solvent loss can all cause product degradation if the packaging is breached. As a result, container closure integrity is an important part of the sterile medicine product's lifespan. Patients may be at risk if the container closure integrity is compromised. Drugs that are meant to save lives might lose their effectiveness or cause catastrophic adverse effects. CCI defects might cause oxidation, hydrolysis, or a loss of vacuum, which would have a major influence on the drug's efficacy and shelf life.

MicroCurrent HVLD to assure CCI in parenteral products

The criteria and purpose of the test determine the optimal container closure integrity testing technique. The sensitivity and reliability of the test method, the material of the basic package, and the necessity for inline vs. offline testing are all considerations to consider when choosing the right CCI test method. CCI test procedures such as MicoCurrent HVLD can detect breaches before they become an issue with the product and ensure patient safety.

MicroCurrent HVLD is a non-destructive, highly sensitive technology for parenteral product leak testing. This test technique detects pinholes, microcracks, stopper/plunger leaks, non-visible leaks under crimping, and a variety of other defects by scanning a non-conductive container sealed with electrode probes. A change in current flow indicates the presence of a leak, along with the approximate location of the defect in the container. This is a patent-pending high voltage leak detection technique that has been found to be extremely effective in a variety of applications, including pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. Being one of the most effective online CCI testing methods, MicroCurrent HVLD requires very minor infrastructure modifications. This method is non-invasive and does not need sample preparation. It is one of the most effective CCI methods.

What sets MicroCurrent HVLD apart from traditional HVLD technology?

MicroCurrent HVLD, as referenced in USP 1207, is a unique High Voltage Leak Detection Technology for container closure integrity testing. When compared to traditional HVLD solutions, this method uses around 50% less voltage and exposes the product and environment to less than 5% of the voltage. MicroCurrent HVLD is a non-invasive CCI technique that does not require sample preparation, and has a high degree of reproducibility and accuracy throughout. This ground-breaking technique can be applied to a wide range of liquid-filled products including low conductivity sterile water for injection (WFI) and highly proteinaceous pharmaceutical products within suspensions.

Any breach in the sterile packaging systems can cause environmental pollutants to grow, turning a life-saving medicine into a potentially fatal microbial soup. This technology is highly effective across all parenteral and biologic products. At high production speeds, the MicroCurrent HVLD technique is scalable and can easily migrate from offline to 100% inline testing applications. It is a cost-effective online container closure testing solution.

The rapidly increasing preference towards parenteral products continues to fuel innovation, but it also faces distinct challenges in terms of implementing a container closure integrity testing strategy. Parenteral product packaging can be as complicated as the products themselves. To ensure package integrity, CCI testing in accordance with current USP 1207 guidance and regulation is required.

Sterile pharmaceutical products including vials are manufactured with extreme accuracy and zero tolerance for error. As a result, pharmaceutical manufacturers place a high value on their quality control procedures. This is to guarantee that the items meet the quality requirements for their intended application. Packaging is essential for maintaining product quality and providing protection from harmful external forces. Package integrity testing, in addition to selecting suitable packing material, is a crucial component in preserving product quality. It prevents external contamination that can have a negative influence on drug quality by ensuring that there are no leaks within the package.

An effective package integrity solution for vials will ensure:

• The vial is well-protected from external factors that might affect its quality, such as light, oxygen, moisture, and temperature
• It is safe from contamination

Various Container closure integrity testing (CCIT) technologies are available today. Helium leak detection is one of the leading methods used for testing the container closure integrity of vials.

Helium Leak Detection Technology for CCI testing of Vials

The process of detecting leaks in various enclosed or sealed systems by utilizing helium as a tracer gas and measuring its concentration as it leaves due to leakage is termed Helium leak testing. Simply say, a vial that consists of a container and an elastomeric closure is a good example for package system. The vial is filled with helium and evacuated. The quantity of helium that escapes from the package is quantified and expressed as a leak rate. A prefilled syringe, a foil pouch, or a cold form blister card are another example. Each of these package types is meant to keep the pharmaceutical product enclosed while keeping out potentially harmful environmental pollutants like germs, or even gases.

Helium gas has a number of qualities that make it the best choice for package leak testing

• As helium gas is one of the smallest molecules, it may reliably and rapidly breach pathways.
• It is an inert gas that won't react with the components being tested, therefore it's perfectly safe to use.
• Because of its limited presence in the atmosphere (less than 5ppm), instrument noise from atmospheric helium is intrinsically minimal, resulting in very precise findings.

Following are the advantages of using helium leak detection technology for CCI testing

• Highly sensitive leak test method for CCI
• Specially designed for detecting extremely small leaks that other leak test methods failed to detect.
• The leak test thresholds might be adjusted as low as 1 x 10 -10 cc/s using a high vacuum technique. This allows unique comparison amongst package components.

Sterility of vials is essential for reducing and preventing infection in patients when using the medicine. As a result, package integrity testing is essential for regulatory approval of sterile pharmaceutical products, and medical devices. When it comes to package integrity testing of vials, the terms packaging integrity and container-closure integrity are sometimes used interchangeably.

At CCIT, we provide a wide range of quality leak testing equipment for pharmaceuticals including vials. With our high-grade non-destructive testing equipment, you can ensure that your products meet stringent quality requirements.

Pre-filled syringes have a significant role in the injectable drugs market. Because of its convenience, efficiency, and patient safety, pre-filled syringes are now widely utilized in a variety of medical areas. Pre-filled syringes, which are rapidly replacing traditional syringes are frequently used to deliver vaccinations. Defects in pre-filled syringes are mostly determined by pharmaceutical product design and syringe process design. Patient-related concerns are also a regulatory concern. As a result, it is critical for manufacturers to have a thorough understanding of the various tests involved in order to assure patient safety.

Evaluating leak test using Vacuum Decay Vs MicroCurrent HVLD Test Methods

Manufacturers perform Container Closure Integrity testing to ensure that the product maintains sterility and microbiological quality until the point of use. Container closure integrity testing evaluates a container closure system's capacity to maintain a sterile barrier against contaminants that might affect the quality of the resulting pharmaceutical and biological products. Various test techniques may be used to challenge Container Closure Integrity (CCI), however, not all of them are equally capable of finding package leaks. Vacuum Decay and High Voltage Leak Detection (HVLD) are the two deterministic test techniques for CCI mentioned in USP 1207, that are frequently used for parenteral products.

Technologies Overview

Vacuum decay leak testing is a CCI test method that has been proven over decades and improved with new technology innovations. When compared to destructive testing techniques, non-destructive testing not only provides for a better knowledge of package quality but also minimizes waste. As a result of the waste reduction, the return on investment will be higher.

Vacuum Decay method operates by enclosing sample packages in a tight-fitting evacuation test chamber with an external vacuum source. The test chamber is monitored for both the level of vacuum and the change in vacuum during a set test duration using either single or dual vacuum transducer technology. The existence of leaks or flaws within the package is indicated by variations in an absolute and differential vacuum. The Vacuum Decay method for leak detection of pre-filled syringes have proven to be an effective method of testing.

Benefits of Vacuum Decay

• ASTM Test Method F2338 and referenced in USP 1207 Guidelines
• Deterministic, quantitative test method
• Repeatable, rapid, and reliable testing
• Non-destructive technology
• Completely tool-less with no changeover to test different packaging formats

High Voltage Leak Detection (HVLD) is a deterministic CCI test method for package inspection of non-porous pharmaceutical and parenteral goods. This technique is based on the fundamental characteristic of electricity. MicroCurrent HVLD technique, the latest evolution of HVLD developed by PTI, promises to provide a high degree of CCI assurance throughout the whole range of parenteral goods.

This method operates by scanning the container which can be done offline in the laboratory or online in an automated robotic platform. On one side of the container, a high voltage is supplied, while the other side has a ground probe. If there is no leak in the package, the two container walls (high voltage and ground) offer complete electrical resistance, and no substantial current is measured passing through the vial. The break-down resistance is achieved when there is a micro-leak or fracture in one of the container walls, and the current passes through. HVLD is the only leak detection technique that does not require mass to flow through a defect location, instead of relying on electricity to pass through a crack.

Benefits of MicroCurrent HVLD

• Non-destructive technology
• Non-invasive, no sample preparation
• High level of repeatability and accuracy
• Offline and 100% online inspection at high production speeds
• Low voltage exposure to product and environment

Pre-filled syringes have emerged as a practical and dependable source for unit dosage medication as the pharmaceutical industry continues to seek possibilities to create convenient drug delivery techniques. We, at CCIT put a lot of effort into developing customized handling solutions that guarantee that syringes are moved without touching their piston to minimize product loss.

Prior to commercialization, the development of new pharmaceuticals, particularly combination treatments, was a complicated process involving extensive research. When it comes to packing pharmaceuticals for patient use, several things must be considered to ensure that they satisfy the highest quality requirements and are safe to use.

Nowadays, the challenge of adopting traditional glass or specialized polymers as combination products has become common. Similarly, the demand for scientific evidence to support regulatory requirements for the pharmaceutical industry has also become more prevalent. For effective development and commercialization of a pharmaceutical product, it is important to understand the compatibility and performance of the primary packaging system with both, the pharmaceutical product and the delivery systems, regardless of the material.

Container Closure Integrity (CCI)

Container closure integrity (CCI) testing is important when ensuring the quality of all packaged products, especially when it comes to parenteral drugs. To evaluate the CCI of the packaging system, a pharmaceutical manufacturer must calculate the Maximum Allowable Leakage Limit (MALL) for the pharmaceutical product. MALL is defined by USP<1207> Package Integrity Evaluation – Sterile Products as the highest leak rate that may be tolerated for a specific packaging method while posing no harm to the safety and quality of the pharmaceutical product over its shelf life. In comparison to probabilistic approaches, USP <1207> provides guidelines on how to assess CCI, including deterministic methods, which are strongly encouraged. Helium leak detection, MicroCurrent HVLD, and Vacuum decay- are deterministic techniques. For the given system, these techniques must be created and validated.

Test methods

MicroCurrent HVLD

MicroCurrent HVLD is a non-destructive technique for determining the integrity of container closures for a variety of parenteral liquid products, including ultra-low conductivity sterile water for injection (WFI). A non-conductive container is examined for pinholes, micro-cracks, plunger leakage, and non-visible crimping leaks, among other things, using an electrode probe. Whenever a defect is identified, it causes a change in current flow and resistance differential, which indicates a breach in the container. The MicroCurrent HVLD is a High Voltage Leak Detection method effective across all parenteral products.

Helium Leak Detection

Helium leak detection is a deterministic method used to detect leaks in pressure vessels and other enclosed systems. In this technique, helium is used as a tracer gas. The change in helium concentration as it escapes through the container is monitored. For helium-based leak detection systems, the Seal Integrity Monitoring System (SIMS) 1915+ is a perfect choice. Helium as a tracer gas delivers excellent levels of quantitative accuracy when compared to traditional vacuum bubble and dye penetration test techniques. Helium is an optimal solution for product quality monitoring across the product lifecycle.

Vacuum Decay

A non-destructive CCI test method for evaluating medical device package integrity. Non-destructive testing improves package quality while decreasing waste when compared to destructive testing. This testing also saves time and money while ensuring product quality. This method operates by enclosing sample packages in a tight-fitting evacuation test chamber with an external vacuum source. A single or dual vacuum transducer is utilized in the test chamber to measure the level of vacuum as well as the change in vacuum over a pre-defined time period. The existence of leaks and defects is indicated by fluctuations in the package's absolute and differential vacuum.

Regardless of the pharmaceutical product, type of materials, devices used, developing a complete testing plan from initial compatibility to stability and release is critical. To assure the availability of scientific data that helps ensure optimal results for patients as well as rapid regulatory approval and delivery to the market, proper testing is required.

A significant challenge faced by the pharmaceutical industry is insuring the container closure integrity of parenteral products. Therefore, maintaining the quality of parenteral products is critical in order to make sure they are actually sterile and safe for delivery to patients. Parenteral products are often packaged in a variety of formats. Liquid-filled containers, such as ampoules, syringes, and vials are the most prevalent forms. Microbial infection, exposure to gases, and water vapor can all lead to product degradation if the packaging is breached. Pharmaceutical products that save lives might lose their effectiveness or even cause adverse effects. As a result, container closure integrity is an important factor of the lifetime of a sterile pharmaceutical product.

Ensuring quality control with Vacuum decay technology

Vacuum decay is a test technique for determining closed container integrity (CCI) for high-risk packaging applications that provides quantitative and deterministic quality assurance with rapid, consistent, and reliable test results. The Vacuum decay method provides non-destructive and non-invasive leak detection in hermetically sealed containers. This is actually a simple test method and it tests container integrity using basic physical characteristics. It entails drawing vacuum on a package inside a test chamber and checking for any deterioration in the vacuum level, which would indicate a leak. As a non-destructive alternative to the water bath leak test, the approach has gained popularity. It saves money by not wasting items during the leak test.

This technique is applicable to a wide range of packaging formats. The Food and Drug Administration (FDA) has designated the standard vacuum decay leak test technique (ASTM F2338) as a consensus standard for container closure integrity testing. The test technique is mentioned in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207) and is listed in ISO 11607.  It may be used to evaluate rigid or flexible packaging, as well as plastic, glass, or metal containers, making it useful in the pharmaceutical and food and beverage sectors.

Benefits of using Vacuum decay technology

• Non-destructive, non-invasive, no sample preparation
• Cost effective with rapid return on investment
• ASTM test method and FDA standard
• Pass/fail results backed by quantitative test data
• Capability to test multiple packages in a single test cycle
• Non-subjective, accurate and repeatable results

CCIT.s.a are leading providers of various CCI test methods including Vacuum Decay, MicroCurrent HVLD, and Helium Leak Detection, manufactured by our affiliate PTI Inspection Systems in the United States. We specialize in test method development for all container closure integrity of pharmaceuticals, medical device and nutritional products and package quality testing projects. Our aim is to provide customers with deterministic non-destructive technologies for container closure integrity and then provide full support in the complete implementation of CCI systems.

The ability to resist microbiological ingress and the entrance or escape of substances is necessary for the packaging of sterile pharmaceutical products to maintain their quality. Pharmaceutical package integrity standards are quite strict since any packaging defect might have a direct influence on the health and safety of patients. USP 1207 explains how to ensure the integrity of non-porous containers used to transport sterile pharmaceuticals. Syringes, cartridges, flexible bags or pouches, plastic or glass ampules, capped vials or bottles, and containers for drug/device combination products are examples of pharmaceutical packaging.

How to ensure pharmaceutical package sterility with Vacuum Decay Technology?

The most feasible and sensitive Container Closure Integrity test method has been proven to be vacuum decay. The test measurement yields a quantitative result that is both dependable and accurate, as well as a pass/fail determination. Vacuum Decay technique works by enclosing sample packages in a tight-fitting evacuation test chamber with an external vacuum source. The test chamber is monitored for both the level of vacuum and the change in vacuum during a set test duration using single or dual vacuum transducer technology. The existence of leaks and defects within the package is indicated by variations in absolute and differential vacuum.

As it is a non-destructive test method, it saves money by not wasting product during leak tests and produces a return on investment in under 6 months for most of the products. Vacuum Decay has shown to be a non-destructive alternative to the blue dye leak test. Vacuum Decay is an ASTM Test Method F2338, which is also recognized by the FDA as a Consensus Standard for Package Integrity Testing. It is referenced as a deterministic test method for container closure integrity testing in the new USP 1207 Chapter Guidance.

Advantages of Vacuum Decay Technology

• Non-destructive, non-subjective, no sample preparation
• Pass/fail results backed by quantitative test data
• Cost effective with rapid return on investment
• Deterministic, quantitative test method
• Identifies which cavity is defective
• ASTM test method and FDA standard
• Repeatable, rapid and reliable testing

Package integrity must be evaluated as part of a sterility program in order to determine the risk of new leaks occurring during pharmaceutical storage. After understanding the mechanism and the rationale for guaranteeing no contamination, it is recommended that test techniques with detection ability as near as feasible to the maximum permitted leakage limit be utilized.

Container Closure Integrity (CCI) is primarily intended to ensure parenteral bio-pharmaceutical sterility and product quality throughout its shelf-life and usage. Guidelines for initial qualification and standards for validation have been set out and are available in chapter 1207 of the US Pharmacopeia (USP<1207>) (1). Any common CCI testing (CCIT) approach can be used to obtain a method that is suitable for its intended application within an end-use cycle. the principles outlined in USAP<1207>. CCI is an integrative and comprehensive process.

Common challenges faced by the pharmaceutical packaging

Pharmaceutical packaging plays a very important role in ensuring protection and maintaining the quality of pharmaceutical products. As a result, a great number of challenges are faced by pharmaceutical packaging. Let us see some of the challenges.

1. Preserving the medical quality of products

The medicines may lose their therapeutic properties, which is one of the biggest challenges faced by the industry, owing to a continuous exposure to heat and moisture. Pharmaceutical materials must be carefully selected and must not be allowed to alter the product by external elements or the product may become totally waste.

2. Ensuring safe transportation of liquid medications and injections

The other big challenge faced by pharmaceutical packing involves ensuring the safe shipping of non-solid medications such as liquids medications and injections. Due to it’s fluid nature, these non-solid medications are considerably harder to handle, especially with glass packaging. There is a high chance of breaking down. In order to avoid this problem, modern technologies like foam packaging and roto molding cases are integrated into the pharmaceutical packaging industry so that the glass packaging does not break down.

3. Proper information of medicine and dosage

The specified dose consumption of medicine is very much important. Also the package must provide information on the required dose, and information about the medicine it is composed of, expiry date and the serial number in order to avoid any misunderstanding.

Role of CCI testing in reducing pharmaceutical package problems

CCI testing helps mitigate pharmaceutical package issues to a great extent. The capacity to describe elements and chemicals which are able to move through container closure system components and contaminate the therapeutic product is a crucial stage in knowing the biological safety and appropriateness of a container. The US Pharmacopeia (USP) and Food and Drug Administration (FDA) are the main forces behind the safety assessment of materials and container closure systems in the United States. These are complying with high Container Closure Integrity Testing criteria (CCIT).

Many damaging procedures were considered suitable to guarantee that container closures preserve the sterility of devices. Basically blue dye or water bath are the procedures. These procedures were actually time consuming, inaccurate and unreliable. Moreover, test operators may not be able to control some test aspects and the resultant findings may be subjective. As a result, the FDA led the industry to shift away from the probabilistic test techniques in favor of deterministic technologies that make it possible for variables to be checked better, performed in consistent circumstances and reliably detect major leakages. Until the emergence of new technologies such as Vacuum Decay and MicroCurrent HVLD, a proper balance between sensitivity and reliability was a difficult factor. These new technologies can successfully scan containers with a greater sensitive leak detection capacity at a much faster speed than ever before.

Vacuum Decay technology: A non-destructive Container Closure Integrity(CCI) testing method which measures leak by vacuum decay. This technology is usually used for sealed packages. In nonporous, stiff or flexible packaging the vacuum decay test identifies leaks. The vacuum decay leak test method is used to check the packages after they are filled to verify the integrity of the product. This method is mainly used by the food package manufacturer, beverages and pharmaceutical industries. This approach minimizes the number of precious completed medicines needed to evaluate stability because the test is not destructive of the samples. After the vacuum decay test, the same samples may be utilized for additional laboratory tests normally necessary for stability studies.

MicroCurrent HVLD technology: MicroCurrent HVLD is a non-invasive Container Closure Integrity(CCI) technology applicable for a broad variety of parenteral filled liquid goods, including exceptionally injecting low conductivity sterile water and protein-filled products. The test procedure assures CCI by scanning a container that is non-conductive and sealed with electrode samples to identify pinholes, micro cracks, leakage of stoppers/plungers, invisible leaks, etc. The resultant difference of resistance and change in current flow indicates a breakdown in the container. Thus a defect is detected with exact defect location.

In addition to offline laboratory systems for leak detection and package quality testing, CCIT offers configurations that provide the capability of fully automated inspection. These technologies do not compromise the reliability of test measurement and automatic inspections take the perfect time to manage and monitor expensive final goods. Automated inspection platform provides best in class CCI testing with no compromise within the parenteral process. PTI’s technologies provide the reliability and accuracy in test measurement, while the automation platform provides the flexibility needed to not compromise on quality.

Package integrity testing of medical devices is important to ensure safety and security of the product throughout its shelf life. Medical device packaging aims to protect the product from physical damage, biological contamination, or any other external disturbance. Technological advancements have offered a wide range of sustainable as well as economical packaging materials and formats to the medical device industry. However, irrespective of whether the devices are packed in rigid thermoformed trays with Tyvek or film lids, or in pouches of porous or non-porous materials or sealed bottles or even blister packs, pharmaceutical package testing is critical to verify that their sterile barrier characteristics are not compromised. Today, the market offers a complete range of technologies that can non-destructively inspect medical device packages for container closure integrity.

Package Integrity Solutions for Sterile Medical Device

1. Airborne ultrasound Technology

Airborne Ultrasound technology is a seal quality testing method, which is capable of non-destructively conducting advanced seal quality inspection of pouches and flexible packaging. It is capable of accommodating multiple packaging materials like Tyvek, paper, foil, film, aluminum, plastic and poly and is also proven to provide deterministic, reliable and accurate test results.

As the name suggests, this method utilizes ultrasound waves to detect defects in package seals. Ultrasound waves are passed through the material as the package seal moves along the sensor head. This causes reflections of sound waves. Such signal strength variations are closely monitored to identify defects if any. Its ability to evaluate seal quality even under conditions where the defect may not result in a leak, makes Airborne Ultrasound technology a practical choice for seal quality inspection across different industries.

PTI’s Seal-Scan (Offline) and Seal-Sensor (Online) are the latest advancements to the ultrasound test series. Both these technologies make use of non-contact airborne ultrasonic testing technology and have been established as one of the most effective methods for inspection of flexible package seals. Airborne ultrasound is also an ASTM Test Method F3004 for seal quality inspection.

Benefits of Airborne Ultrasound technology:

• Deterministic seal quality inspection technique that assures quantitative and reliable results.
• Applicable for multiple material types and combinations regardless of color, transparency, print, surface finish or porosity.
• Eliminates subjective manual inspection methods.
• Non-destructive, non-subjective, no sample preparation
• Technology can be integrated for 100% online defect detection of the final pouch seal.

2.Vacuum Decay Technology

Vacuum Decay is a non-destructive Container Closure Integrity test method focused on package integrity and detection of leak paths. Compared to manual inspection and other non-deterministic test methods, Vacuum Decay offers quantitative, deterministic and reliable test results to ensure package integrity. Vacuum decay technology is capable of accommodating a wide variety of packaging formats including filled and sealed rigid, semi-rigid and flexible packaging made of non-porous or porous materials. This test operates by placing packages in a well fitted evacuation test chamber, which has an external vacuum source. The vacuum levels are continuously monitored to identify any variations from a pre-determined targeted vacuum level. A defect in the package will cause air to escape from the package into the test chamber. On the other hand, packages without any defect hold in the air, maintaining constant chamber vacuum level. Vacuum Decay technology has been proven over years to be one of the most practical and sensitive vacuum-based leak detection solutions.

Benefits of Vacuum Decay technology:

• Non-destructive, non-subjective, no sample preparation.
• Capable of detecting defects down to 0.05 cm.
• Accurate, reliable, repeatable results.
• Supports sustainable packaging and zero waste initiatives.
• FDA recognized standard for package integrity testing.
• ASTM test method F2338.

What is Container Closure Integrity Testing?

Container Closure Integrity Testing can be understood as a leak detection test conducted using non-destructive package inspection systems to ensure product stability throughout its shelf life. CCIT plays a major part in ensuring that the products are free from possible contamination. While there are multiple ways to conduct a CCI test, it can be broadly classified into probabilistic and deterministic test methods. Traditional test methods like bubble test, dye ingress and microbial challenge by immersion come under probabilistic test methods. However, upon realizing that such tests lacked accuracy and reliability, The United States Pharmacopeia released guidelines in 2016 stating that deterministic methods ae preferred over probabilistic test methods. Vacuum Decay technology and Airborne Ultrasound technology are among the most preferred deterministic test methods.

VeriPac Test Systems for Effective CCI Testing

The VeriPac test methods are non-destructive, non-invasive inspection system for CCI and package integrity testing. They utilize the ASTM approved patented vacuum decay leak test method recognized by the FDA as a consensus standard for package integrity testing.

This ASTM method was developed using VeriPac leak test instruments and has proven its capabilities under GMP regulatory guidelines. Applications for VeriPac technology include stability studies, clinical trials, quality assurance testing and statistical process control (SPC). VeriPac testers feature the patented PERMA-Vac manifold system and dynamic test modes that provide the ability to test a wide range of package formats. Leak detection of high-risk applications requires the highest level of test measurement reliability. The VeriPac series have redefined the reliability and accuracy of test measurement systems.

How do Veripac Test systems Operate?

VeriPac leak testers connect to a test chamber that is specially designed to contain the package to be tested. The package is placed inside the test chamber to which vacuum is applied. The single or dual vacuum transducer technology is used to monitor the test chamber for both the level of vacuum as well as the change in vacuum over a predetermined test time. The changes in absolute and differential vacuum indicate the presence of leaks and defects within the package. Test systems can be designed for manual or automatic operation. This inspection method is suitable for laboratory offline testing and production applications for QA/QC statistical process control. The test cycle takes only a few seconds, is non-invasive and non-destructive to both product and package, making it an ideal choice for CCI inspection across industries.

Inspection Criteria

• Seal quality testing of entire container or package
• Measures and verifies container closure system integrity
• Tests for gas leaks for dry products (lyophilized vials, powder filled)
• Tests for liquid leaks (liquid filled vials, pre-filled syringes)

Blister packs are popular packaging options for pharmaceuticals and consumer goods. A wide range of pharmaceutical products are packed in blister packs, ranging from capsules and tablets to high-risk hormone-based drugs and steroidal treatments. Commonly made of thermoformed plastic, these are quite useful in guarding products against external factors like heat, moisture and humidity.

However, concerns over integrity of blister packaging have increased over the years. Even a minute breach in the packaging can result in compromised package integrity. Hence, pharmaceutical manufacturers concerned about quality and shelf life of their products make Container Closure Integrity testing a crucial part of their manufacturing process. There are several methods available to test blister packs, and each has its own merits and demerits. For instance, the most common method to test blister packs remain dye ingress. However, this method is subjective, probabilistic and lacked accuracy in test results. This encouraged manufacturers to use non-destructive CCI test methods, that were accurate and produced quantitative results with measurable result data.

Blister Package Inspection with VeriPac UBV Technology

The VeriPac UBV Leak Detection System is a deterministic, non-destructive technology designed specifically for multi-cavity blister packs. The VeriPac UBV utilizes volumetric imaging under vacuum to detect the presence and location of leaks. It is a rapid test requiring no changeover or sample preparation. Operators simply input the number of blister cavities, place the blister pack on the inspection plate and press the START button. Within seconds, the operator sees a definitive pass/fail result, along with a volumetric measurement reading. The location of the defective cavity is presented to the operator with an image of the tested package. The intuitive and simple method makes it a practical solution giving rapid feedback to production line operators.

The UBV technology can provide rapid detection of defects as small as 10 microns with a fast test time, averaging 10-30 seconds depending on blister cavity volume. Test system requires no tools or test parameter changes for different blister formats. This technology is particularly advantageous for small to tiny blister cavities that are notoriously difficult to detect with a standard Vacuum Decay technology due to the very low headspace.

Technology Overview

Under this method, the sample is first placed inside the hinged test chamber. After pressing the start button, vacuum is pulled to a defined level. The blisters expand under vacuum, driving air out of the blister through any leaks present. If there is a leak in the blister, the air escapes into the chamber leaving a collapsed blister package. During the dynamic vacuum test sequence, a volumetric measurement reading is taken which determines which blister cavities are defective.

Benefits of VeriPac UBV Technology

• Non-destructive technology
• Accurate and repeatable results
• Pass/fail results backed by quantitative test data
• Completely tool-less
• No changeover to test different blister formats
• Identifies which cavity is defective
• Eliminates destructive, subjective testing methods

Medical device quality control inspection is considered to be highly significant in ensuring safe delivery of medical devices from their place of origin to the market. However, tremendous development in medical technologies have challenged the medical device packaging industry to ensure quality and reliability in packaging

Adding to that, drug contamination is a serious concern in any medical industry- specifically for Class III medical devices. Class III medical devices are understood as devices that sustain or support life and are implanted, or present potential unreasonable risk of illness or injury. Since these devices are directly placed into human bodies, proper packaging is required to ensure quality of the product until it reaches the patient. Any breach in the packaging can cause contaminants to enter the device, causing major health risks. Hence, appropriate package integrity testing and seal quality inspection of Class III medical devices are required so as to ensure seal quality and sterile barrier integrity are maintained.

Initially, manufacturers heavily relied on visual inspection or other probabilistic test methods to inspect seal quality and integrity. However, such methods lacked accuracy and reliability in terms of test results. Hence, manufacturers are now shifting towards non-destructive method for evaluating seal quality and inspecting physical properties of a seal. One such technique that is increasingly becoming popular among medical device manufacturers is Airborne Ultrasound technology. It is an ASTM test method F3004 and FDA recognized standard for seal quality integrity testing. These tests are primarily conducted to provide advanced seal quality inspection of pouches, flexible packages and tray seals. The test is conducted by transmitting high frequency sound waves through the pouch seal area, providing a simple pass or fail result of seal quality. A linear scan analysis of the seal area will detect channel defects, misaligned seals, incomplete and missing seals immediately after the package has been sealed. If the system detects a package defect, the product can immediately be removed from the packaging and reworked. Process related defects can also be addressed and corrected immediately, which significantly reduces the quantity of defective packages produced

Airborne Ultrasound technology variants, namely Seal-Scan® and Seal-Sensor provide both, offline and online inspection of packages and accommodate various package specifications, test sensitivity and package handling requirements. Seal-Scan® offline systems offer in-depth seal quality analysis and seal characterization. Seal-Sensor online inspection systems for automated 100% inline scanning of pouch seals can be integrated into pouch production or pouch handling line. They provide a quick analysis of the seal area without tampering with the packaging to identify defects, such as incomplete or missing seals, wrinkles, channel defects and so on.

Advantages of Seal Scan and Seal Sensor method

• Deterministic seal quality inspection method that produces quantitative results.
• This method works for any material type and combinations regardless of color, transparency, print, surface finish or porosity.
• Non-destructive and non-subjective test method that requires no sample preparation.
• Technology can be integrated for 100% online defect detection of the final pouch seal.
• Repeatable, reproducible and reliable results for seal quality inspection.
• Cost-effective solution for seal integrity testing and seal analysis that characterizes overall quality and uniformity of the seal.