Blogs

The increasing prevalence of chronic respiratory conditions such as asthma and post-COVID complications has made inhalers indispensable in healthcare. With their efficient drug delivery and ease of use, inhalers are pivotal in managing respiratory ailments. However, ensuring the sterility and stability of the medication contained within these devices is critical to their effectiveness and safety. Vacuum decay technology offers an advanced solution for detecting microscopic leaks, securing package integrity, and meeting stringent regulatory standards.

Inhalers: Applications and Challenges

Inhalers cater to diverse needs, delivering medications in dry-powder or soft mist formulations. Their applications are expanding beyond traditional respiratory treatments to manage allergies, infections, and other conditions. Despite their utility, manufacturers face challenges such as maintaining sterility, preventing contamination, and ensuring the proper functionality of container closure systems. Any compromise in these areas can affect patient safety and drug efficacy, underscoring the need for rigorous quality control measures.

Why Is CCI Testing of Inhalers Important?

Container Closure Integrity testing (CCIT) is a critical requirement for inhaler production. Regulatory authorities, including the FDA, mandate robust CCI assessments to detect potential breaches in packaging. These breaches could lead to contamination, reduced medication potency, or risks to patient safety.

For inhalers, CCI testing must confirm that the container closure system effectively protects the medication from external factors such as moisture, oxygen, and microbial ingress. The importance of this testing cannot be overstated, as the sterility and quality of each dose directly impact therapeutic outcomes.

CCI Testing Using VeriPac Vacuum Decay Technology

The VeriPac Vacuum Decay Technology, compliant with ASTM F2338 standards, is an innovative, deterministic, and non-destructive method for detecting microscopic leaks in inhaler packaging. This technology is adaptable to various packaging types, including rigid and flexible containers, making it a versatile solution for the pharmaceutical industry.

The VeriPac Vacuum decay technology operates through a straightforward yet highly effective process. First, the inhaler or its primary packaging is placed within a testing chamber, which can be designed to accommodate both rigid and flexible containers. Once secured, a controlled vacuum level is applied to the chamber. A highly sensitive pressure transducer then measures any decay in the vacuum level. This decay may occur due to gas escaping from the package or liquid vaporizing within it, both of which indicate potential leaks. This precise and reliable method can detect microscopic leaks as small as or below the industry standard of 5 microns, ensuring the highest level of package integrity.

Benefits of the VeriPac Series

The VeriPac Series stands out as a reliable solution for inhaler CCI testing, offering several advantages:

• High Sensitivity: Detects microscopic leaks with precision.
• Non-Destructive: Allows manufacturers to test without damaging the product.
• Adaptability: Suitable for both rigid and flexible packaging formats.
• Efficiency: Provides fast, accurate, and quantitative results.

Vacuum decay technology has revolutionized the approach to container closure integrity testing for inhalers. By adopting the VeriPac Series, manufacturers can ensure product safety, regulatory compliance, and patient satisfaction. As the demand for inhalers continues to grow, robust CCI testing will remain integral to delivering safe and effective treatments.

Embracing this advanced technology not only mitigates risks but also elevates the standards of pharmaceutical packaging quality, securing the trust of healthcare providers and patients alike.

Since the number of complex medical devices is rising, including implantable sensors, infusion pumps, and diagnostic instruments, package integrity becomes more important. Most of these need to be handled with utmost care in order not to get contaminated, especially if they are sensitive to moisture and oxygen. Package integrity testing would, therefore, be an optimal way for determining whether the packaging would retain a sterile barrier or not.

Challenges in Medical Device Packaging

Packaging medical devices also incurs numerous environmental challenges. Moisture-sensitive equipment presents the likelihood of being exposed to wet conditions, increasing the susceptibility to compromised product integrity and subsequent health risks. Some of the key issues are as follows:

• Environmental Exposure: Moisture, dust, and other contaminants can degrade device performance if packaging fails.
• Regulatory Compliance: Strict regulations require rigorous testing to ensure packages are sealed and sterile.
• Non-Destructive Testing Requirements: For sensitive devices, packaging tests must be non-destructive, so sample integrity remains intact.

These challenges necessitate advanced testing solutions that can provide accurate, repeatable results without harming the package.

Why is Package Integrity Testing of Medical Device Packaging Important?

Package integrity testing of medical device packaging is crucial because it verifies the packaging’s ability to maintain a sterile barrier, safeguarding the device from contamination and environmental exposure throughout its shelf life. For moisture-sensitive devices, even a microscopic breach can allow microbial ingress or moisture, compromising device safety and efficacy. This testing process helps manufacturers meet stringent FDA and ISO standards, reduce product recalls, and uphold the highest safety standards. Ultimately, package integrity testing not only protects patients but also reinforces a company’s commitment to quality, ensuring that medical devices arrive in pristine condition, ready for safe use.

Ensuring Package Integrity with VeriPac Vacuum Decay Technology

PTI’s VeriPac container closure integrity testing (CCIT) method offers a non-destructive alternative to traditional leak testing methods such as water bath, bubble leak, or blue dye tests. VeriPac systems can be used for integrity testing of Tyvek and other porous packaging, ensuring the product meets regulatory and consumer standards for quality. Introduced in 2003 as an ASTM test method, this vacuum decay technology was initially developed for testing Tyvek-lidded trays.

The VeriPac system works by connecting its leak testers to a test chamber designed to hold the package sample. A vacuum is applied to the package within this chamber, and the level of vacuum, along with any changes in vacuum over a set test duration, is monitored using single or dual vacuum transducer technology. By tracking changes in both absolute and differential vacuum levels, the system can detect leaks or defects in the package with high accuracy.

• Non-destructive test method that ensures quantitative test results
• FDA recognized ASTM test method
• Referenced in USP 1207 guideline
• Cost-effective with rapid return on investment
• Simplifies inspection and validation process

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

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

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

Understanding Deterministic CCI Test Methods

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

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

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

CCI Test Methods Offered by PTI

1. Vacuum Decay Technology

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

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

2. MicroCurrent HVLD Technology

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

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

3. Helium Leak Detection

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

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

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

In the dynamic landscape of the pharmaceutical industry, advancements in medical science intersect with stringent regulatory standards, underscoring the critical importance of ensuring the integrity of container closures for radioactive pharmaceuticals. This niche sector plays a pivotal role in the diagnosis and treatment of cancer, impacting over 5% of the U.S. population. As the demand for these life-saving products grows, so does the need for effective Container Closure Integrity Testing (CCIT) methods that guarantee safety and efficacy.

What Are Radioactive Pharmaceuticals?

Radioactive pharmaceuticals, often referred to as radiopharmaceuticals, are a specialized category of drugs that contain radioactive isotopes. These products are utilized for diagnostic imaging and therapeutic applications in nuclear medicine, enabling healthcare providers to visualize and treat diseases such as cancer. Given their unique properties and the potential risks associated with radiation exposure, ensuring their packaging integrity is essential to safeguarding both patient safety and operator health.

Packaging Challenges Associated with Radioactive Pharmaceuticals

The packaging of radioactive pharmaceuticals presents unique challenges compared to conventional pharmaceuticals. The need for leak-proof containers is paramount to prevent contamination and ensure the safe handling of radioactive materials. Additionally, packaging must comply with rigorous regulatory standards while maintaining sterility and preventing exposure to radiation. Striking a balance between robust protection and ease of access for healthcare providers is crucial.

Key Challenges Include:

• Leak Prevention: Ensuring that radioactive materials do not escape their containers is critical for both safety and regulatory compliance.
• Radiation Exposure: Packaging must mitigate the risk of radiation exposure to operators and patients during handling and administration.
• Regulatory Compliance: Adhering to stringent regulations while maintaining product integrity adds complexity to the packaging process.

Techniques to Ensure Package Integrity

1. Vacuum Decay technology

Vacuum Decay technology is a non-destructive Container Closure Integrity test (CCIT) method, widely used to detect leaks in package seals. It is recognized as the most sensitive and practical vacuum-based leak detection technique, capable of identifying leaks in sealed packaging—whether rigid, semi-rigid, or flexible, and made from porous or non-porous materials. This technology delivers reliable, accurate, and repeatable results, ensuring deterministic package integrity testing. As a non-destructive alternative to traditional methods such as Water Bath and Dye Ingress tests, Vacuum Decay is a valuable solution for leak detection in the pharmaceutical and medical device industries.

How does Vacuum Decay technology work?

Vacuum Decay operates on the fundamental physical principles of container integrity. The process begins by placing the package inside a vacuum chamber, which is tightly sealed and connected to an external vacuum source. Depending on the type of packaging and the sensitivity required, a specific vacuum level is applied. The system then evaluates the test chamber and any dead space for a designated time period. Sensitive differential pressure transducers monitor changes in the vacuum level over time. If the pressure rises beyond a pre-set pass/fail threshold, it indicates a leak in the container.

Benefits of Vacuum Decay technology

• Non-destructive package inspection system
• Accurate and reliable results
• Definite pass/fail result based on quantitative test data
• Accommodates multiple packaging formats
• Eliminates destructive, subjective testing methods
• Effective in detecting even minute leaks

2. MicroCurrent HVLD Technology

PTI’s MicroCurrent HVLD technology is a patent-pending, innovative advancement in container closure integrity (CCI) testing, offering a significant improvement over traditional high voltage leak detection methods. This non-invasive, deterministic CCI method is effective across a wide range of parenteral and biologic products, including low-conductivity liquids such as sterile water for injection. The MicroCurrent HVLD test is highly efficient at detecting pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping, and other defects in packaging formats like pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches.

One of the standout features of MicroCurrent HVLD is its use of approximately 50% less voltage, minimizing the exposure of both the product and the environment to less than 5% of the voltage used in traditional HVLD methods. PTI’s E-scan HVLD series represents a top-tier solution for robust container closure integrity testing.

Benefits of MicroCurrent HVLD Technology

• Non-destructive & requires no sample preparation
• Deterministic & non-invasive
• Offline and 100% online inspection at high production speeds
• Highly effective across all parenteral products
• Simplifies the inspection and validation process
• Referenced in Chapter USP 1207 Guidance for CCIT

Sterile packaging is a critical component in the administration of nebulizer drugs, especially given the vulnerability of respiratory medications to contamination. Nebulizers deliver medication directly to the lungs, requiring high levels of sterility to protect patients from the risks of microbial and particulate matter contamination. Any breach in package integrity can jeopardize the safety and efficacy of the drug, leading to potential health risks.

To ensure that the nebulizer medications remain sterile, rigorous package integrity testing is essential. Regulatory bodies like the FDA, USP, and EU have laid down guidelines, including FDA’s Container and Closure System Integrity Testing in Lieu of Sterility Testing (USP 1207) and EU Annex 1, to ensure that high-risk packaging like nebulizer cups and nebules meet the highest standards of sterility.

What are Nebulizers?

Nebulizers are medical devices used to deliver medication in the form of a mist that patients can inhale directly into their lungs. These devices are commonly used to treat respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis.

The effectiveness of nebulizer treatment hinges on maintaining the sterility and safety of the drug until it reaches the patient. Nebulizer medications are usually packaged in pre-filled nebulizer cups, syringes, or blow-fill-seal (BFS) packaging, often referred to as nebules. These packages must remain hermetically sealed to prevent contamination from external environments.

Package Integrity Testing of Nebulizers

Ensuring the integrity of nebulizer packaging is a complex process due to the unique characteristics of the packaging material and design. BFS packaging, one of the most common formats for nebulizer drugs, is prone to leaks in the seams and tear-off regions. Such vulnerabilities can allow gas, debris, or microbes to enter the packaging, compromising the sterility of the drug. On the other hand, egress of the medication from the packaging can occur if the integrity is compromised, leading to under-dosing or exposure to air.

To address these challenges, Container Closure Integrity Testing (CCIT) methods are employed to verify the sterility and stability of nebulizer packaging throughout its lifecycle. Traditional testing methods include visual inspection, dye ingress testing, and microbial challenge testing, but these methods often lack the sensitivity and efficiency needed for today’s complex packaging.

Package Integrity Testing Using Vacuum Decay Technology

Vacuum decay testing is a highly efficient and extensively validated method for Container Closure Integrity Testing (CCIT), recognized for its practicality and sensitivity in detecting leaks in vacuum-sealed containers. Based on fundamental physical principles, this method evaluates container integrity by providing reliable and precise quantitative results, classifying them as either pass or fail. It offers a non-destructive alternative to traditional approaches such as the blue dye test.

PTI's VeriPac system provides a non-invasive solution to conventional leak testing methods like water bath, bubble leak, and blue dye tests. VeriPac systems are specifically designed for testing the integrity of Tyvek and porous packaging, ensuring compliance with both regulatory standards and patient safety requirements. The VeriPac vacuum decay technology, codified as ASTM Test Method F2338 since its inception in 2003, was initially developed for testing Tyvek-lidded trays using PTI’s VeriPac instruments.

The technology operates by connecting VeriPac leak testers to a specially designed test chamber that houses the package sample. A vacuum is applied to the package inside the chamber, and the vacuum level, along with its variation over a predetermined test duration, is monitored using single or dual vacuum transducer technology. Changes in absolute or differential vacuum levels are analyzed to identify the presence of leaks or defects within the package.

Key Benefits of Vacuum Decay technology

• Non-destructive and non-invasive
• No sample preparation
• ASTM approved test method
• FDA Recognized Consensus Standard
• Allows for increased sampling
• Quantitative results
• Repeatable
• Rapid test time
• Eliminates cost and waste of destructive testing
• Test results can be easily validated
• SPC laboratory testing or online applications

In the medical field, patient safety is paramount, and ensuring the sterility of surgical tools is a critical part of this safety. Suture packs as well as other surgical instruments, must be maintained in a sterile condition to prevent infections and other complications during surgery. To achieve this, rigorous package integrity testing is required to confirm that suture packs remain sealed and uncontaminated until the moment they are used.

Suture packs are pre-packaged sets containing surgical sutures and occasionally other related instruments. These packs are sterilized and sealed to ensure that they remain uncontaminated until they are opened for use in surgical procedures. Sutures are crucial for closing wounds and surgical incisions, so maintaining their sterility is essential to prevent infections, promote healing, and reduce the risk of complications.

Applications of Suture Packs

Suture packs are used in a wide range of surgical procedures across various medical disciplines, including:

• General Surgery: For closing wounds and surgical incisions.
• Orthopedic Surgery: To repair torn ligaments and tissues.
• Cardiovascular Surgery: For stitching blood vessels and tissues.
• Emergency Medicine: For stitching wounds in trauma cases.

In each of these applications, the integrity of the suture pack is crucial for maintaining sterility and ensuring that the patient receives the highest standard of care.

CCI Testing of Suture Packs

The integrity of suture packs must be thoroughly tested to ensure they have not been compromised during manufacturing, shipping, or storage. Any breach in the packaging seal could lead to contamination, rendering the sutures unsafe for use. Traditional methods of container closure integrity testing(CCIT) include dye ingress testing and bubble emission testing. However, these methods can be limited in sensitivity, are highly subjective and may not detect all potential leaks, particularly those that are very small or in hard-to-detect areas.

CCI Testing using VeriPac 410

The VeriPac 410 is an advanced inspection system that utilizes force decay technology for non-destructive leak detection in blister packs, sachets, and pouches with limited headspace. This system builds on PTI’s vacuum decay technology, adding a force-based measurement component to improve detection accuracy. The force decay technology measures the force resulting from the deflection of a package’s surface during a standard vacuum test cycle. This measurement allows the VeriPac 410 to accurately identify defective packages, even in those with minimal headspace.

Technology Overview

The VeriPac 410 benchtop inspection system operates with a drawer-style test chamber that is specifically designed for the purpose. The system uses a custom package insert that adapts to the shape of the package, enhancing test sensitivity. The vacuum levels are continuously monitored throughout the test cycle, following the ASTM F2338 Vacuum Decay Leak Test Method. A drop in the vacuum level indicates that air is leaking from the package into the test chamber. After the vacuum phase, a pressure plate maps the surface pressure of the package’s lidding. The system detects defects by recognizing deviations in the pressure pattern, thus pinpointing the location of the defect within the package or cavity. VeriPac 410 technology can be scaled for fully automated inspection on the production line.

Benefits of Force Decay leak testing

• Non-destructive, non-subjective, no sample preparation
• Multiple packages can be tested in a single test cycle
• Great choice for in-process testing
• The test is operator independent and can be performed with minimal training
• The test protocol is programmed into the testing unit, hence force decay tests are repeatable

In today's healthcare and pharmaceutical industries, ensuring the integrity of packaging is paramount. This is especially true for sterile products, where the failure of packaging can lead to contamination, posing serious risks to patient safety. Among the various packaging materials available, Tyvek has emerged as a popular choice due to its durability, breathability, and microbial barrier properties.

Tyvek, a synthetic material made from high-density polyethylene fibers, is widely recognized for its exceptional properties, making it a top choice for medical and pharmaceutical packaging. It combines outstanding durability, tear resistance, and breathability with superior microbial barrier protection. These qualities make Tyvek ideal for use in sterile barrier systems, medical device packaging, and pharmaceutical packaging. However, to ensure the highest levels of safety and quality, thorough integrity testing of Tyvek packages is essential.

Why is Tyvek Package Integrity Testing Important?

Ensuring the integrity of Tyvek packaging is crucial for several reasons:

• Patient Safety: Compromised packaging can lead to contamination of sterile products, posing significant health risks to patients. Integrity testing ensures that the packaging remains intact, maintaining sterility until the point of use.
• Regulatory Compliance: Regulatory bodies, such as the FDA and ISO, have stringent requirements for packaging integrity. Adhering to these regulations is essential for market approval and maintaining the reputation of the manufacturer.
• Product Quality: Integrity testing helps in detecting defects, such as pinholes, leaks, and weak seals, which can compromise the quality of the packaged product. Ensuring robust packaging helps in preserving the efficacy and shelf life of the product.
• Cost Efficiency: Identifying and rectifying packaging defects early in the production process can save significant costs associated with product recalls, rework, and liability claims.

Tyvek Package Integrity Testing Using PTI's VeriPac Series

Vacuum decay is a highly efficient and extensively validated Container Closure Integrity testing (CCIT) method, recognized as the most practical and sensitive technique for detecting leaks in vacuum-sealed containers. This method operates on the simple physical principles to evaluate container integrity, providing dependable and precise quantitative results, categorized as either pass or fail. It has become a non-destructive alternative to conventional methods such as the blue dye test.

PTI's VeriPac package integrity testing method offers a non-destructive alternative to traditional water bath leak tests, bubble leak tests, and blue dye leak tests. VeriPac leak test systems are suitable for package integrity testing of Tyvek and porous packaging, ensuring the product meets both regulatory and patient expectations. The VeriPac vacuum decay technology, an ASTM Test Method F2338 was first established in 2003, and was initially based on tests of Tyvek-lidded trays using PTI’s VeriPac instruments.

This technology functions by connecting VeriPac leak testers to a test chamber specifically designed to accommodate the sample package. Vacuum is applied to the package within the test chamber. The level of vacuum and the change in vacuum over a predetermined test period are monitored using single or dual vacuum transducer technology. Variations in absolute and differential vacuum are analyzed to detect the presence of leaks and defects within the package.

Benefits of VeriPac Inspection System:

• Non-destructive test method that ensures quantitative test results
• FDA recognized ASTM test method
• Referenced in USP 1207 guideline
• Cost-effective with rapid return on investment
• Simplifies inspection and validation process

The safety and efficacy of injectable medications rely heavily on the integrity of their packaging. Container closure integrity testing (CCIT) ensures that vials, syringes, and other containers can effectively shield the drug product from contamination and maintain its sterility throughout its shelf life.

What is USP <382>?

Unlike its predecessor, USP, which focused on individual testing of elastomeric materials, USP <382> adopts a holistic approach. It emphasizes testing the functionality of the entire packaging system, including the elastomeric components (closures, stoppers, plungers) integrated with the container (syringe, vial, cartridge). This ensures the elastomeric components perform as intended within the specific packaging system they're designed for.

Published in December 2020, USP introduces a new set of requirements for assessing the functionality of elastomeric closures, stoppers, and plungers used in injectable drug delivery systems. These closures play a critical role:

• Protection: They safeguard the drug product from external contaminants like microbes and moisture.
• Containment: They prevent leakage of the medication during storage and transportation.
• Safe Access: They enable controlled delivery of the drug through needles or spikes without compromising sterility

USP supersedes the functionality testing portion of the previous standard, USP. This new standard places greater emphasis on ensuring that elastomeric components function as intended throughout the lifecycle of the drug product. The compliance deadline of December 1st, 2025, marks a crucial milestone, compelling pharmaceutical companies to recalibrate their practices concerning Container Closure Integrity Testing

Package integrity testing is a crucial step in the development and manufacturing of injectable drugs. These tests evaluate the ability of the packaging system to maintain a sterile barrier and prevent product contamination. USP outlines specific testing methodologies for various aspects of elastomeric component functionality, including:

• Fragmentation: This test assesses the closure's tendency to break into small particles during needle penetration, which could contaminate the drug product.
• Penetration Force: It measures the amount of force required to pierce the closure with a needle or spike, ensuring ease of access for medication administration while safeguarding against accidental punctures.
• Self-Sealing Capacity: This test evaluates the closure's ability to reseal itself after a needle or spike is withdrawn, preventing leakage and maintaining sterility.

Advanced Technologies for Enhanced Package Integrity

Manufacturers are constantly innovating and adopting advanced technologies to ensure robust CCI and meet the demands of USP. These advancements include:

• Non-destructive testing methods: Techniques like ultrasonic testing and laser-based analysis allow for evaluation of closure integrity without damaging the packaging system.
• Material science advancements: Development of new elastomeric materials with improved strength, elasticity, and resealing properties enhances the functionality of closures.
• In-line monitoring systems: Integrating real-time monitoring during the manufacturing process helps identify potential defects and ensure consistent quality of elastomeric components.

The implementation of USP signifies a significant step forward in ensuring the safety and efficacy of injectable medications. By establishing stricter guidelines for CCI testing of elastomeric components, this standard fosters the development of robust and reliable packaging systems for parenteral drug delivery. Continuous advancements in testing methodologies and materials science will further strengthen container closure integrity and contribute to the delivery of high-quality injectable medications.

In today's health-conscious world, nutraceuticals – products that bridge the gap between food and pharmaceuticals – are experiencing a surge in popularity. But ensuring the safety, efficacy, and quality of these products extends beyond the formulation itself. Proper packaging plays a crucial role in protecting these sensitive nutraceuticals from contamination, degradation, and environmental factors throughout their shelf life.

Understanding Nutraceutical Products and their Packaging

Nutraceuticals encompass a wide range of products, including vitamins, minerals, dietary supplements, herbal remedies, and functional foods. These products often contain potent ingredients susceptible to moisture, oxygen, light, and temperature fluctuations. The packaging needs to be carefully selected to create a barrier against these external threats, ensuring the product maintains its potency and quality from production to consumption. Common nutraceutical packaging formats include bottles, capsules, blisters, pouches, and stick packs.

Why is Nutraceutical CCI Testing Important?

Maintaining container closure integrity is paramount for several reasons:

• Consumer Safety: Leaky or compromised packaging can allow harmful contaminants like bacteria, mold, or moisture to enter the product, posing a health risk to consumers.
• Product Efficacy: Exposure to oxygen, light, or moisture can degrade the active ingredients in nutraceuticals, rendering them less effective.
• Shelf Life: Compromised packaging can shorten the shelf life of a product, leading to wasted inventory and financial losses for manufacturers.
• Brand Reputation: Leaky or damaged packaging can negatively impact brand image and consumer trust.

Container Closure Integrity Testing Using VeriPac Series

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.

The VeriPac SPX offers a robust container closure integrity test (CCIT) solution for nutraceutical package inspection by leveraging Statistical Process Control (SPC). This system enables automated testing to significantly increase sampling rates, ensuring comprehensive quality assurance. Its design allows for seamless technology integration as an add-on to existing production lines, facilitating easy adoption. By improving process and quality control, the VeriPac SPX helps identify defects and early deviations promptly, thereby enhancing overall product integrity and reliability.

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 inline testing.

Benefits of VeriPac Series

• Non-destructive, non-subjective, 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 operator with PASS/FAIL result
• Small footprint and modular portable design
• Referenced in USP 1207 guidance

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

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

Why is Helium Leak Testing Important for Pharmaceutical Packaging?

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

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

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

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

Helium Leak Services: Benefits of Partnering with PTI

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

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

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

The pharmaceutical and medical device industries are witnessing a surge in the development and use of combination products. These products integrate a drug, biologic, or medical device into a single entity, offering improved patient convenience and therapeutic efficacy. However, ensuring the safety and efficacy of these products requires robust Container Closure Integrity testing (CCIT) strategies. This blog delves into the world of combination products, explores the challenges associated with their CCI testing, and introduces MicroCurrent High Voltage Leak Detection (HVLD) technology as a reliable solution.

The rise of combination products is driven by several factors:

• Enhanced treatment options: Combining drugs and devices allows for targeted delivery and improved therapeutic effects.
• Patient convenience: Pre-filled syringes, auto-injectors, and inhalers offer user-friendly administration methods.
• Reduced healthcare costs: Combination products can streamline treatment processes and potentially lower overall costs.

However, ensuring the integrity of the packaging in combination products presents unique challenges:

• Complex design: Integration of different components can introduce potential leak paths.
• Material compatibility: The packaging materials need to be compatible with both the drug and the device.
• Stringent regulations: Regulatory bodies require robust evidence of package integrity throughout the product lifecycle.

Container Closure Integrity Testing of Combination products using MicroCurrent HVLD Technology

PTI's MicroCurrent HVLD technology is a non-destructive and non-invasive Container Closure Integrity Test (CCIT) method that leverages unique voltage characteristics to inspect a wide variety of parenteral products, including complex combination products. This technology is applicable to pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. The MicroCurrent HVLD test method can accurately detect the presence and location of defects such as pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping, and many others.

To ensure Container Closure Integrity, the method scans a non-conductive sealed container using electrode probes. Any defects in the package will cause a resistance differential and alter the current flow within the container. Unlike traditional HVLD technologies, MicroCurrent HVLD uses approximately 50% less voltage and exposes the product and environment to less than 5% of this reduced voltage. This lower exposure voltage not only minimizes the risk to the product but also significantly reduces ozone production during operation. As one of the most sensitive CCI technologies available, it is particularly suited for high-risk combination products.

Benefits Of 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
• Low voltage exposure to the product and environment
• Listed in USP Chapter <1207> as recommended method for parenteral liquid package integrity testing .
• Robust method and approximate 3x Signal-Noise-Ratio for a wide range of product classes and package formats
• Simplifies the inspection and validation process
• Offline and automated online inspection

In today's competitive market, maintaining the integrity of packaging systems is critical for ensuring product safety and regulatory compliance. This is especially true for industries such as pharmaceuticals, biologics, medical devices, and food and nutrition. Container Closure Integrity Testing (CCIT) is a vital process that ensures the packaging of these products remains intact and contamination-free throughout their lifecycle. PTI offers specialized and comprehensive CCIT consulting services designed to support clients through various stages of product development, testing, and production. This blog provides an in-depth overview of CCIT consulting services, focusing on the range of solutions offered by PTI, including sampling plan consulting and package development consulting.

Understanding CCIT Consulting Services

CCIT consulting services are essential for assessing the integrity of packaging systems to ensure they meet stringent regulatory standards and industry best practices. These services are critical for products that require sterile conditions and protection from external contaminants. PTI’s CCIT consulting services are designed to support clients throughout the entire product lifecycle, from research and development (R&D) to clinical trials and full-scale production. PTI's expertise spans multiple industries, providing tailored solutions that address specific needs and challenges.

Consulting Services Offered by PTI

1. CCIT Consulting

PTI's CCIT consulting services are ideal for R&D or clinical stages. The goal is to guide clients through the intricate process of component matching, production, and manufacturing. PTI’s experienced professionals assist clients in establishing robust CCIT protocols, conducting thorough testing procedures, and interpreting complex results. The service ensures that clients can maintain the highest standards of packaging integrity, ultimately safeguarding their products' quality and safety. By leveraging PTI’s extensive knowledge and proven track record, clients can trust in reliable CCIT solutions that enhance their packaging quality assurance standards.

2. Sampling Plan Consulting

Statistical sampling plans are critical for verifying compliance with relevant regulations. PTI’s sampling plan consulting service helps clients develop and evaluate these plans to ensure they meet all necessary requirements. This service is particularly important for companies that need to demonstrate regulatory compliance through rigorous testing and validation processes. PTI’s consultants work closely with clients to design and implement effective sampling strategies, ensuring that their testing methodologies are robust and reliable. This helps in minimizing risks and ensuring that the products meet the highest standards of quality and safety.

3. Package Development Consulting

Developing an optimal package design is crucial for ensuring container closure integrity (CCI). PTI’s package development consulting service assists clients in designing the best possible packaging solutions. This service involves comparing different package designs and components, providing real data on leak rates and other critical parameters. PTI’s consultants offer expert guidance on selecting materials and design features that enhance the overall integrity and performance of the packaging. By leveraging PTI’s expertise, clients can ensure their packaging systems are not only compliant with regulatory standards but also optimized for performance and safety.

Ensuring the integrity of pharmaceutical packaging is a critical aspect of regulatory compliance. Container Closure Integrity Testing (CCIT) plays a pivotal role in safeguarding product quality and patient safety. Proper training in CCIT is essential for pharmaceutical professionals to meet stringent regulatory requirements and maintain high standards in product integrity. It provides the necessary knowledge and skills to perform accurate and reliable tests, ensuring that packaging maintains its integrity throughout its lifecycle. With increasing regulatory scrutiny, understanding the nuances of CCIT is crucial for compliance with global standards such as USP 1207, Annex 1, ASTM, and ISO.

Significance of CCIT Training

Understanding and adhering to CCIT regulations is crucial for several reasons. It ensures the:

• Safety and efficacy of pharmaceutical products: Proper CCIT procedures safeguard the integrity of containers, preventing product contamination and ensuring the delivery of sterile and potent medication.
• Validity of test results: Skilled operators conducting CCIT tests following regulatory guidelines produce reliable data that upholds product quality and safety.
• Reduced risk of regulatory non-compliance: Trained personnel are better equipped to identify and address potential compliance issues, mitigating the risk of regulatory sanctions.

CCIT Training Services offered by PTI

PTI offers a comprehensive suite of CCIT training programs designed to cater to diverse needs and experience levels. Let's delve into each service:

Regulatory Requirement Training

This training focuses on the regulatory requirements pertinent to CCIT. It helps professionals navigate through complex regulations and standards such as USP 1207, Annex 1, ASTM, and ISO. Understanding these regulations is fundamental to ensuring that CCIT processes comply with legal and quality standards, reducing the risk of non-compliance.

Hands-on System Training

PTI offers hands-on training for all operator levels, from beginners to advanced users. This practical training allows participants to work directly with CCIT systems, gaining experience in setting up, operating, and troubleshooting equipment. Hands-on training ensures that operators are proficient in using the systems, leading to more accurate and reliable test results.

Test Recipe Training

Developing and optimizing test recipes is critical for different applications. PTI’s Test Recipe Training helps professionals create and fine-tune test parameters to suit specific packaging requirements. This training ensures that the tests are not only effective but also efficient, saving time and resources while maintaining high standards of accuracy.

Application Specific Training

Every package or container presents unique challenges in terms of package integrity testing. PTI’s Application Specific Training provides tailored solutions to address these challenges. By reviewing the specific issues associated with a particular package or container, PTI helps professionals find the optimal testing solution, enhancing the reliability of CCIT results.

Life-saving Pharmaceutical products, medications, particularly those in the realm of high-risk biologics and complex drug delivery systems, often require stringent storage and transportation conditions. This critical journey, known as the cold chain, ensures these temperature-sensitive drugs reach patients with their potency and sterility intact.

Maintaining a consistent cold environment throughout the supply chain is undeniably crucial. However, temperature control alone isn't enough to guarantee a drug's efficacy. Even the most minute breach in a container's integrity can have catastrophic consequences. Moisture ingress or exposure to external contaminants can compromise the sterility of the drug, rendering it ineffective or even hazardous to patients. Container closure integrity testing is crucial for this class of pharmaceuticals.

Container Closure Integrity Testing using Helium Leak Detection

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

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

The LT150 and LT80 cold chain helium mass spectrometers can test containers correctly in cold chain and cryogenic conditions and create 21-CFR Part 11-compliant reports in real-time for helium testing. The proprietary algorithm that supports these systems provide data on flow rate, gas concentration, and other variables. This helps developers in determining the exact size of a leak, down to less than 6 x 10-6-millibars-liters per second helium leak rate, which has become the industry standard for maintaining a sterile barrier.

Technology Overview

The test starts by introducing helium into the package, which is then subjected to a vacuum. The quantity of helium that escapes from the package is then measured using a helium leak detector, providing a quantitative measure known as the leak rate. In addition to leak testing, helium leak detection technology has proven to be effective for tasks such as package design, failure analysis, tooling qualification, packaging line setup and validation, and monitoring product quality. The use of helium leak detection in accordance with ASTM F2391 and USP 1207 is a widely accepted and extensively utilized method in the pharmaceutical industry.

Benefits of Helium Leak Detection

• Leaks can be measured and identified with a high degree of sensitivity.
• Because of the inert properties of the helium, no effect on the materials under test.
• Dry and temperature-independent testing procedure.
• Reduces the cost and overall processing time, since helium leak testing has a faster cycle time
• With a high-speed vacuum approach, the leak test limit can be set to 1 x 10-10 mbar L/sec, allowing for unique comparisons across components, materials, formats, and manufacturing characteristics.

 

In the ever-evolving landscape of product development and quality assurance, the role of advanced laboratory testing services cannot be overstated. These services serve as the cornerstone of ensuring product integrity, safety, and compliance with stringent regulatory standards. As industries continue to push the boundaries of innovation, the demand for comprehensive testing solutions that leverage cutting-edge technologies and methodologies has never been greater. In this context, PTI emerges as a leading provider of advanced scientific testing services, offering a diverse portfolio of solutions tailored to meet the complex needs of clients across sectors.

Overview of Advanced Laboratory Testing Services

Advanced laboratory testing services encompass a multifaceted approach to product evaluation and characterization, spanning a broad spectrum of disciplines and techniques. From initial feasibility studies to ongoing stability testing and beyond, these services are designed to address the intricate challenges inherent in product development, manufacturing, and quality control.

At the core of advanced testing services lies a commitment to precision, reliability, and regulatory compliance. By harnessing state-of-the-art instrumentation, analytical methodologies, and industry expertise, providers like PTI empower clients to make informed decisions, optimize processes, and deliver products of the highest caliber.

Testing Services Offered by PTI

PTI offers cutting-edge laboratory testing services, delivering thorough examinations customized to meet regulatory and industry requirements. Our array of science-based services encompasses feasibility studies, development of testing methodologies, stability assessments, recall and batch release examinations, as well as helium testing. These services are executed by proficient professionals utilizing state-of-the-art technologies. Our testing facilities operate within a non-GMP environment, equipped with fully calibrated instruments adhering to regulatory standards.

1. Feasibility studies

Experimental feasibility studies are the first step in evaluating the best inspection technology and test method for a specific application. They involve rigorous experimentation and thorough reporting of test data to determine the viability of various approaches. These studies guide decision-making by providing insights into the effectiveness and suitability of different inspection technologies and methods.

2. Test method development

Test Method Development Support involves documentation and testing services for creating, validating, and implementing testing methods. This includes crafting initial recipes, ensuring container suitability, and conducting system suitability tests. Overall, it streamlines method development, enhances reliability, and ensures compliance.

3. Stability testing

Stability testing ensures pharmaceutical products remain safe and effective over time. Container closure integrity testing within stability testing confirms packaging remains intact, preventing contamination or product degradation. This proactive approach safeguards quality and patient safety throughout the product's shelf life.

4. Recall & batch release testing

Recall & Batch Release Testing ensures products meet safety and quality standards before market release. It involves evaluating product quality, safety, compliance, and consistency, as well as verifying documentation accuracy. This testing safeguards public health and consumer trust.

5. Helium testing services

Helium Testing Services provides a range of testing solutions including Cold Storage Testing (-0°C to -160°C), Helium pre-filled and 100% Helium Flow Method, all conducted in accordance with USP 1207 standards. We specialize in Parenteral formats, Blister card & pouch/sachets, and many industrial applications.

Quality assurance is a critical aspect of any manufacturing process, especially in industries like pharmaceuticals and nutrition where consumer safety and product efficacy are paramount. Dry filled pouches are a common packaging solution utilized in these industries to deliver various types of products efficiently and conveniently. Ensuring the quality of these pouches is essential to maintain product integrity and meet regulatory standards.

What are Dry Filled Pouches?

Dry filled pouches are packaging solutions designed to contain and preserve dry powders, granules, or other solid forms of pharmaceuticals or nutritional products. These pouches are typically made from materials such as plastic films or laminates, which provide barrier properties to protect the contents from moisture, oxygen, light, and other external factors that could compromise their quality. Dry filled pouches come in various shapes and sizes, ranging from single-dose sachets to larger multi-dose packs, catering to different product requirements and consumer preferences.

Why is it Important to Ensure Integrity of Dry-Filled Pouches?

Package integrity testing of dry filled pouches is crucial for several reasons. Firstly, it ensures the protection of pharmaceuticals, nutraceuticals, and food supplements from contamination, moisture ingress, and exposure to light, which could compromise their quality and efficacy. Secondly, it ensures compliance with regulatory standards set by authorities such as the FDA and EMA, thereby avoiding penalties and product recalls. Thirdly, it prioritizes consumer safety by detecting potential hazards like product tampering or adulteration. Additionally, package integrity testing helps maintain shelf-life stability by identifying vulnerabilities that could affect the longevity of the enclosed products. Ultimately, it contributes to safeguarding brand reputation by demonstrating a commitment to quality and customer satisfaction.

Package Integrity Testing using VeriPac Flex

VeriPac FLEX Systems offer a powerful solution for non-destructive leak testing of pouches and other flexible packaging. Utilizing the ASTM F2338 standard (recognized by ISO 11607 and FDA), these systems deliver high sensitivity (10-20 micron defect detection) and reliable PASS/FAIL results with quantitative leak rate data.

VeriPac FLEX boasts unmatched versatility. Multiple configurations cater to diverse package formats and sizes, eliminating the need for changeovers. These streamlines testing for everything from small sachets to large bulk bags. The core technology behind VeriPac FLEX is Vacuum decay leak detection. This Container Closure Integrity Test (CCIT) method offers several advantages over destructive testing methods like water baths or dye tests. It eliminates subjectivity, reduces waste, and provides valuable insights into the packaging process itself. Additionally, Vacuum decay offers a faster return on investment compared to destructive alternatives.

Benefits of VeriPac Flex

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

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

Applications of Vials in the Pharmaceutical Industry

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

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

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

Why is Package Integrity Testing of Vials Important?

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

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

Methods to Inspect Vial Packaging

1. Helium leak testing

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

2. Microcurrent HVLD Technology

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

3. Vacuum Decay Technology

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

Oncology drugs pose significant challenges in packaging due to their potency, toxicity, and the risks of human and environmental contamination. Ensuring sterility is crucial for certain administration methods, while also safeguarding against potential harm to handlers and manufacturers. Improper packaging or material selection can result in weak seals, breaches in sterility, and product leakage, compromising both safety and efficacy.

Early-stage package development and ongoing in-process packaging checks are essential measures to guarantee effective packaging. While various tests like Extractables and Leachables (E&L) and Transportation tests contribute to product safety, they may not always detect leaks in packaging. Therefore, Container Closure Integrity Testing (CCIT) emerges as a robust and indispensable method for identifying poor packaging performance and guiding package development.

CCIT offers a comprehensive approach to assessing package integrity across a range of formats commonly used for oncology drugs, including rigid parenterals, bottles, IV bags, and blister packs. Each packaging format presents unique challenges, and CCIT offers tailored test methods for each, ensuring thorough evaluation and reliable results.

Blister packs, often utilized for oncology drugs, typically consist of a low headspace formed poly or foil tray with a flexible lid stock. For products packaged in aluminum cold form blisters, helium leak detection is employed for ultra-high sensitivity, capable of detecting leaks down to 1E-10 mBar/l*s. Additionally, force decay testing provides inline applications with sensitivity down to 15 microns, ensuring stringent quality control measures.

Rigid parenterals, another common packaging option, offer flexibility in testing methods, including Vacuum Decay and MicroCurrent High Voltage Leak Detection (HVLD). These methods can detect leaks down to 1 micron, both inline and offline, providing comprehensive assurance of package integrity.

In conclusion, addressing the unique packaging challenges of oncology drugs requires a multifaceted approach, with CCIT playing a pivotal role in ensuring product safety, efficacy, and regulatory compliance. By leveraging advanced testing methodologies tailored to specific packaging formats, manufacturers can mitigate risks and uphold the highest standards of quality assurance in oncology drug packaging.

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

Helium Leak Detection - An Overview

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

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

Helium Leak Testing Using SIMS 1915

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

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

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

SIMS 1915+ Options:

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

In pharmaceutical packaging, ensuring the integrity of containers is paramount to maintaining product safety and efficacy. Various technologies and methods are employed for package integrity testing, with MicroCurrent High Voltage Leak Detection (HVLD) emerging as a reliable and efficient solution.

MicroCurrent HVLD technology is a non-destructive container closure integrity testing (CCIT) method designed to detect leaks in sealed pharmaceutical containers, such as vials, ampoules, and syringes. Unlike traditional methods like dye ingress testing or visual inspection, which may be destructive or less sensitive, MicroCurrent HVLD offers a high level of sensitivity without compromising the integrity of the package.

The technology operates by applying a high voltage potential across the container and monitoring the resulting electrical current. When a breach or defect is present in the container's seal, the electrical current will deviate from the baseline, indicating the presence of a leak. The sensitivity of MicroCurrent HVLD allows it to detect leaks as small as microns, ensuring that even minute defects are identified.

Role of MicroCurrent HVLD Technology in Pharmaceutical Package Integrity Testing

MicroCurrent HVLD technology plays a crucial role in pharmaceutical package integrity testing by offering enhanced sensitivity, allowing for the detection of even the smallest defects in packaging to mitigate the risk of product contamination or degradation. Its non-destructive testing capability ensures that tested products remain intact, facilitating their seamless progression through the manufacturing process. Additionally, the high throughput nature of MicroCurrent HVLD systems enables efficient testing of large volumes of pharmaceutical containers, making it scalable to meet high production demands. Furthermore, its compliance with regulatory standards ensures adherence to requirements for product quality and safety, while its cost-effectiveness, despite initial investment, leads to long-term economic benefits through the prevention of product loss and reduced need for retesting.

List of E-Scan Technologies offered by PTI

1. E-Scan 605: The E-Scan 605 is an entry-level solution ideal for basic container closure integrity (CCI) testing, providing rapid PASS/FAIL test results. Featuring single-channel operation and manual loading/unloading, it offers a compact footprint suitable for low- to medium-volume testing needs.

2. E-Scan 615: The E-Scan 615 is the ideal instrument for laboratory R&D QC testing and product quality monitoring of parenteral products. Testing takes literally seconds and provides operators with PASS/FAIL and supporting quantitative data

3. E-Scan 655: The E-Scan 655 is intended for in-depth analytical container closure integrity testing of parenteral products. Location defect identification is possible along with quantitative data and PASS/FAIL.

4. E-Scan RTX: Fully automated container closure integrity testing with robotic pick & place hangling. Ideal for automation it the laboratory and production line settings.

In summary, PTI's E-Scan series offers a range of MicroCurrent HVLD solutions catering to diverse pharmaceutical packaging needs, ensuring precise integrity testing while prioritizing efficiency, safety, and compliance with regulatory standards. These advanced technologies represent a pivotal step forward in safeguarding product quality and patient safety within the pharmaceutical industry.

Tablets and capsules, the backbone of oral medication, are commonly encapsulated in blister packs. These packs, crafted from thermoformed plastic and sealed with aluminum foil or film, offer a trifecta of advantages: protection, tamper evidence, and convenience. Shielding pharmaceuticals from physical damage, moisture, and light, blister packs ensure dosing accuracy and provide tamper evidence, instilling confidence in consumers. Furthermore, their user-friendly design facilitates easy dispensing and portability of individual doses.

Package integrity testing emerges as a critical component in pharmaceutical quality control. Compromised packaging poses multifaceted risks, including product loss, contamination, and degradation. Leaking or damaged packages can lead to economic setbacks for manufacturers and jeopardize consumer safety. Exposure to external elements such as moisture, light, or oxygen can degrade the quality of medication, compromising its therapeutic efficacy.

OptiPac Technology: Pioneering Non-Destructive Integrity Testing

The OptiPac Leak Detection System is a non-destructive container closure integrity testing method specifically designed for blister packs. Employing One-Touch Technology, OptiPac ensures a swift test cycle without the need for changeovers or sample preparation. This innovative technology enables rapid detection of sub-5-micron defects, contingent on blister cavity volume. Unlike the vacuum-based blue dye test, OptiPac applies controlled inputs and measured outputs, eliminating the complications and reliability issues associated with dye ingress methods.

Technology Overview

OptiPac employs volumetric imaging technology under vacuum, coupled with topographic imaging, to identify the presence and location of leaks. The testing process involves placing the sample on the testing area, initiating a vacuum-based measurement upon pressing the start button. As the blisters expand under vacuum, air is drawn out through any leaks present. In the case of a leak, the air escapes into the chamber, causing a collapsed blister cavity. The dynamic vacuum test sequence captures volumetric images and measurement readings, pinpointing defective blister cavities. The system delivers a clear pass/fail result, along with quantitative measurements for each package test. OptiPac systems by PTI yield definitive results based on accurate and measurable quantitative data, reliably detecting leaks down to 5 microns. The interface is user-friendly, requiring no intricate parameter adjustments for new blister packaging formats, setting it apart from other non-destructive blister package inspection systems.

OptiPac’s insightful technology offers a suite of advanced functions:

• 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 the pharmaceutical industry, the safety and efficacy of products are of utmost importance, and maintaining these qualities throughout the distribution and storage chain is a critical aspect of ensuring public health. One key element in achieving this goal is the rigorous implementation of Container Closure Integrity (CCI) testing.

CCIT refers to the evaluation of the ability of a pharmaceutical package to prevent the ingress of contaminants, as well as the escape of the product, ensuring that the package maintains its integrity over time. This process is essential in safeguarding the quality and safety of pharmaceutical products, as any compromise in the packaging can lead to contamination, degradation, or other adverse effects on the medication.

Traditional Container Closure Integrity (CCI) assessment has heavily relied on destructive testing methods, such as water bath and dye tests. These approaches involve immersing packaging materials in water or applying dyes to identify potential leaks. However, these methods present significant drawbacks. They are time-consuming, requiring substantial resources for testing and result analysis, which is highly subjective and varies from operator to operator. This prolonged process can hamper production efficiency and delay product release.

Moreover, the accuracy of these methods is questionable, as they may not reliably detect all types of leaks. The subjective nature of human interpretation in analyzing results leads to potential inconsistencies and misinterpretations. Additionally, the destructive nature of these tests contributes to product loss and waste, escalating production costs and raising environmental concerns.

In the context of a growing emphasis on sustainable practices, there is a rising demand for alternative, non-destructive, and objective CCI testing approaches that can address these limitations and align with contemporary production and sustainability standards.

CCI Testing using Vacuum decay technology

To guarantee integrity and consistency of packages, the ability to precisely detect leaks and defects is necessary. Over the years industry has seen an increasing demand for non-destructive package integrity testing methods. One such method is Vacuum Decay technology.

Vacuum Decay is a test method that has been proven over decades as the most practical and sensitive vacuum-based leak test method. It is a simple test method that challenges container integrity based on fundamental physical properties. Vacuum Decay technology creates reliable and accurate quantitative results with a pass or fail determination and has been established as a non-destructive deterministic alternative method to the blue dye test. The standard vacuum decay leak test method (ASTM F2338), developed using PTI's VeriPac instruments, is recognized by the FDA as a consensus standard for container closure integrity testing. The test method is listed in ISO 11607 and referenced in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207)

How does Vacuum Decay Technology work?

Under this method, the leak testers are first connected to a test chamber that is specifically designed to hold the package to be tested. Vacuum is applied to the package placed inside the test chamber. Using single or dual vacuum transducer technology test chamber and level of vacuum are monitored along with a 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. This inspection method is suitable for laboratory offline testing and can be designed for manual or fully automated operation. The test cycle is non-destructive to both product and package and takes only a few seconds. It provides significant savings by not wasting products for a leak test and generates a return on investment in under six months for many products.

Key Benefits of Vacuum Decay Technology

• Non-destructive and non-invasive
• No sample preparation
• ASTM approved test method
• FDA Recognized Consensus Standard
• Allows for increased sampling
• Quantitative results
• Eliminates cost and waste of destructive testing
• Test results can be easily validated
• SPC laboratory testing or online applications

In the world of pharmaceuticals, the integrity of vial container closures is a matter of utmost importance. Vials are small, cylindrical containers made of glass or plastic, designed to store a wide range of pharmaceuticals, including vaccines, medications, and other sensitive compounds. Their significance lies in their ability to preserve the integrity and potency of these substances. Vials shield their contents from external factors like air, moisture, and contaminants, ensuring that the product remains uncontaminated and effective.

Package integrity testing of vials is crucial to maintain the high standards of pharmaceutical products. Any breach in the vial's integrity can lead to contamination, rendering the contents ineffective or even harmful. It's not just about preserving the product; it's also about ensuring the safety of the end-users. Therefore, advanced leak testing strategies play a vital role in guaranteeing that vials are sealed securely. Vial leak testing involves identifying leaks or breaches in the vial container closures. The main goal is to confirm that the closure system maintains an airtight seal, preserving the sterility and efficacy of the product. Vial leak testing can be performed using various methods, each with its own advantages and limitations.

1. PTI's MicroCurrent HVLD Technology

PTI's MicroCurrent High Voltage Leak Detection (HVLD) is a Container closure integrity testing method that plays a crucial role in ensuring vial integrity, for liquid fill applications including proteinaceous products and small molecule liquids. It operates on a fundamental principle: detecting breaches by applying high voltage to the vial's container closure. When high voltage is applied, if there is even a minor breach in the seal, the current will pass through the vial, alerting the system to potential defects. This technique is incredibly sensitive and can identify breaches that might otherwise remain undetected by traditional methods.

One key advantage of MicroCurrent HVLD is its non-destructive nature. Unlike destructive testing methods, this technology does not harm the vial or its contents in any way. This unique method utilizes about 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. Its ability to pinpoint even minute defects in vial closures ensures that products maintain their sterility and efficacy.

2. PTI's VeriPac Vacuum Decay Technology

VeriPac Vacuum Decay Technology is another container closure integrity test (CCIT) used for vial leak testing, for both liquid fill and lyophilized applications. This method relies on creating a controlled environment within which the vial is tested. By introducing vacuum and pressure differentials, VeriPac can identify leaks with remarkable accuracy. If there's a breach in the vial closure, the changes in pressure within the controlled environment will be detected, indicating a potential defect.

One of the standout features of VeriPac is its ability to pinpoint defects with exceptional precision. It can detect leaks in various vial types, whether they are glass or plastic, and offers a versatile solution for pharmaceutical quality control. Like MicroCurrent HVLD, VeriPac is non-destructive, ensuring that the vials and their contents remain unaltered during the testing process. This makes VeriPac a reliable choice for pharmaceutical companies looking to maintain the highest standards of quality and safety in their products.

In the pharmaceutical industry, maintaining vial container closure integrity is paramount. The consequences of compromised vials can be detrimental, affecting not only the product but also the health and safety of the end-users. Advanced leak testing strategies, such as PTI's MicroCurrent HVLD and VeriPac Vacuum Decay technologies, provide innovative solutions to this challenge. By using these cutting-edge methods, manufacturers can ensure the highest standards of quality and safety in their products.

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

Combination products can be divided into three main categories:

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

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

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

SIMS 1915+ for Leak Testing Combination Products

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

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

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

SIMS 1915+ Options

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

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

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

The integrity and safety of sterile products are critical in the pharmaceutical, biotechnology, and medical device industries. Sterile materials are essential in patient care, surgical procedures, and medical treatments because they are free of live germs. To ensure that these items stay contaminant-free throughout their shelf life and delivery to patients, thorough packaging integrity testing is required.

The sterile product package serves as the first line of defense against potential contaminants, safeguarding the product from environmental hazards, physical damage, and microbial ingress. Any compromise in the packaging can lead to compromised product quality, reduced efficacy, and increased risks to patient health. Therefore, comprehensive package testing is indispensable to validate the barrier properties, durability, and overall performance of the packaging materials.

This blog delves into the significance of sterile product package testing, shedding light on the various testing methods employed and the role they play in maintaining the integrity of sterile products.

Sterile package integrity testing methods:

1. Vacuum Decay technology:

Vacuum Decay technology is a non-destructive container closure integrity test (CCIT) capable of detecting leaks in nonporous, rigid or flexible packages. Vacuum Decay leak testing is conducted by placing a sample package in a well-fitting evacuation chamber, which is provided with an external vacuum source. The vacuum levels as well as the change in vacuum over a fixed test time are closely observed using single or dual vacuum transducer technology. Changes in vacuum level beyond a predetermined pass/fail limit indicate defects within the package. PTI’s VeriPac Vacuum Decay series can non-destructively test packaging down to sub-micron leak rates - making it an excellent alternative to destructive testing methods.

2. Microcurrent HVLD technology:

Microcurrent HVLD is a unique High Voltage Leak Detection technology, highly effective across all liquid filled parenteral products. Its applications include liquid-based products ranging from extremely low conductivity sterile water for injection (WFI) to large molecule-based proteinaceous products with suspensions. Its ability to detect small pinholes, micro cracks and seal defects makes it an ideal choice for testing high risk pharmaceutical and parenteral products.

In conclusion, sterile product package testing is a cornerstone of product quality assurance, safety, and regulatory compliance. By meticulously examining packaging materials, seals, and integrity, manufacturers can safeguard product sterility, extend shelf life, meet regulatory expectations, and instil confidence in their consumers. As industries continue to advance and consumer expectations rise, investing in robust sterile product container closure integrity testing methodologies remains a fundamental necessity for any organization producing and distributing sterile products.

Ensuring the integrity of container closures is a critical aspect of pharmaceutical and biotechnology industries. Maintaining the integrity of containers, such as vials, syringes, and cartridges, is essential to preserve the quality, efficacy, and safety of products throughout their entire lifecycle. Traditionally, blue dye testing has been a widely used method to detect leaks and potential breaches in container closures. However, with the ever-evolving landscape of technology and scientific advancements, it is essential to explore and embrace alternative methods that offer higher sensitivity, reliability, and efficiency.

In this blog, we will explore cutting-edge container closure integrity testing methods that go beyond the limitations of blue dye testing. While blue dye testing has served as a valuable tool for detecting gross leaks, it may not be sufficient to detect micro-leaks or hairline cracks that could lead to potential risks during storage, distribution, and administration of pharmaceutical products.

Non-destructive CCI testing methods offered by PTI:

1. Microcurrent HVLD Technology

High Voltage Leak Detection (HVLD) is a non-destructive and non-invasive container closure integrity test (CCIT) used to assess the closure integrity of parenteral product packaging, such as pre-filled syringes, vials, cartridges, ampoules, BFS, bottles, and pouches. By employing quantitative electrical conductivity measurements, this technique allows for non-destructive testing of packages.

The HVLD method involves passing micro-current signals through the sample packages. If there is a leak in the package, the electrical resistance of the sample decreases, leading to an increase in current flow. The newer MicroCurrent HVLD technology operates using approximately 50% less voltage and exposes the product and surrounding environment to less than 5% of the voltage compared to traditional HVLD solutions. This makes it a more efficient and safer option for evaluating packaging integrity in pharmaceutical and medical applications.

2. Vacuum Decay technology

Vacuum Decay has proven to be an exceptionally effective technology for detecting leak paths and ensuring the integrity of packages. One of its key advantages is the ability to provide quantitative, deterministic, and reliable test results without causing any damage to the containers being tested. The process involves placing the packages in a meticulously fitted evacuation test chamber connected to an external vacuum source. Throughout the testing, the vacuum levels are constantly monitored to detect any deviations from the predetermined target vacuum level. If a package has defects, air will escape, leading to a noticeable change in the chamber vacuum level. Conversely, non-defective packages will retain the air, ensuring the chamber vacuum level remains constant. The versatility of this method is remarkable as it can accommodate a wide range of packaging formats, including filled and sealed rigid, semi-rigid, and flexible packages made from both non-porous and porous materials.

3. Helium Leak Detection Technology

Helium leak testing is the method of locating leaks in various enclosed or sealed systems by using helium as a "tracer" gas and measuring the concentration of the gas as it escapes due to a leak. Helium is used as a tracer gas because it is non-toxic, non-flammable, and non-condensable, and its atmospheric concentration is less than 5 ppm. Helium, as the second-smallest molecule in the periodic table, can flow through practically any defect or openings. Furthermore, because it does not react with other compounds, helium is relatively safe to use. To find and measure the leak, a mass spectrometer leak detector (MSLD), also known as a helium leak detector, is used.

4. Volumetric Imaging Technology

The OptiPac One-Touch Tool-less technology is intended for non-destructive leak detection of blister packages. To identify leaks, the OptiPac uses volumetric imaging technology to measure the motion of a blister package under vacuum. With new blister package formats, the interface is practical and straightforward to set up, requiring no tooling changeover or extensive parameter modifications as seen with previous non-destructive blister package integrity testing systems. The system collects volumetric data from each cavity, responding to variable cavity shapes, sizes, and configurations of various blister pack forms.

In conclusion, as the pharmaceutical and biotechnology industries strive to ensure the highest standards of container closure integrity, it is evident that traditional blue dye testing alone may not be sufficient to detect all potential risks. Fortunately, cutting-edge container closure integrity (CCI) methods offer superior sensitivity, reliability, and efficiency, surpassing the limitations of blue dye testing.

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

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

Testing Integrity of Vials using Helium Leak Detection Technology

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

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

Why is Helium used as a Tracer Gas?

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

Technology Overview

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

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

Packaging is a crucial aspect of the nutritional product industry, as it not only protects the product but also serves as a means to attract customers and communicate important information about the product. The packaging of nutritional products should be designed to preserve the quality, freshness and integrity of the product, while also being visually appealing, informative, and convenient for the consumer.

Nutritional product packaging can vary greatly depending on the type of product, its intended use, and the target market. Packaging materials can also play a significant role in the nutritional product industry, as they must be compatible with the product, safe for consumers, and sustainable. Some common packaging materials include plastic, glass, metal, and paper, each with its own advantages and disadvantages.

Most nutritional products are shelf-stable in nature; therefore, package performance is typically a concern. Chemical reactions occur naturally in all nutritional products. Any break or breach in the nutritional packing might lead to the products deteriorating due to air, moisture, and microbial exposure. Container closure integrity testing (CCIT) of nutritional products is vital to eliminating packaging defects and the possibility of product degradation. Read on to understand how PTI's VeriPac Flex Series guarantees the integrity of packaging for nutritional products.

Nutritional Package Inspection using VeriPac Flex System

VeriPac FLEX Systems are non-destructive inspection solutions for flexible packaging that deliver a clear PASS or FAIL as well as quantitative data that correlates to a leak rate. VeriPac FLEX Systems are available in several configurations for both the leak test instrument and the test chamber capacity to accommodate a wide range of package specifications and test sensitivity requirements, with solutions ranging from small format sachets and stick packs to very large bulk size pouches and bags.

They provide unparalleled sensitivity, reliability and practicality in testing a wide range of flexible package formats and is recognized by the FDA as a consensus standard for package integrity testing. The VeriPac tester is used to detect leaks in packages and is connected to the appropriate FLEX chamber based on the package size. There are several VeriPac configurations available with different leak detection capabilities depending on the application. The integrated flexible test chamber (IFC) is used for sachets or stick packs with low headspace, while the Drawer Style test chamber (D-Series) is available in sevearl standard sizes for other package sizes. Automated platforms for the VeriPac FLEX technology are also available for automated robotic handling of the pouches.

The VeriPac FLEX systems are unique in that they use a flexible membrane that conforms to the package shape and size, preventing stress and damage to the film materials. Multiple packages can be tested at once in a single test cycle. Custom designs can also be manufactured for large package formats and bulk products.

Benefits of VeriPac Flex Series

The test method is deterministic and quantitative.

It is non-destructive, non-subjective, and requires no sample preparation.

The method can test multiple packages in a single test cycle.

It is a cost-effective method that offers a rapid return on investment.

The method supports sustainable packaging and zero waste initiatives.

It simplifies the inspection and validation process.

The results are accurate and repeatable.

The method conforms to ASTM test method and FDA standard

Medical device package inspection is the process of evaluating the quality and integrity of the packaging of medical devices to ensure that they are safe for use. The packaging of medical devices is critical, as it protects the device from damage during shipping and handling, prevents contamination from external sources, and maintains the sterility of the device until it is used.

The package inspection process involves examining the packaging for any defects or damage that could compromise the integrity of the device. This includes checking for punctures, tears, or holes in the packaging material, as well as inspecting the seals and closures to ensure that they are secure and intact.

Medical device manufacturers are required to adhere to strict regulations and standards to certify that their packaging meets the necessary quality and safety requirements. Package integrity testing is an essential part of this process, as it helps identify any potential defects or issues with the packaging before the device reaches the end user.

Destructive vs Non-destructive Package Integrity Testing

Destructive package integrity testing involves damaging the package in some way to evaluate its integrity. This type of testing is typically more invasive and may not be suitable for products that need to be sold intact. An example of destructive package integrity testing is burst testing, where the package is subjected to internal pressure until it ruptures.

Non-destructive package integrity testing, on the other hand, involves evaluating the package's integrity without damaging it. This type of testing is typically less invasive and is more suitable for products that need to be sold intact. An example of non-destructive package integrity testing includes pressure decay testing, where a package is subjected to a pressure change and any leaks are detected by measuring the change in pressure.

Package Integrity Testing using Vacuum Decay Technology

Vacuum Decay is a non-destructive Container Closure Integrity Test (CCIT) that provides a definite pass/fail quantitative data along with dependable, reproducible, repeatable, and accurate results. The basic idea underlying Vacuum Decay technology is to question the integrity of containers based on their basic physical characteristics. Sample packages are first put into an evacuation test chamber that is tightly fitted and has an external vacuum source. A predetermined vacuum level is selected for the test based on the test sample and required level of sensitivity. The next step is to evacuate the test chamber and test system dead space for a certain amount of time. Differential pressure transducers are used to track changes in vacuum level over time. A pressure increase above the specified pass/fail limit indicates that the container is leaking.

Benefits of Vacuum Decay technology:

• Non-destructive, non-subjective, no sample preparation.
• Accurate, reliable, repeatable results.
• Definite pass/fail result based on quantitative test data.
• Accommodates multiple packaging formats.
• Eliminates destructive, subjective testing methods.
• Effective in detecting even minute leaks.

Packaging is an essential aspect of the meat snack product industry. Proper packaging helps maintain the quality, safety, and freshness of meat snack products, which is important for both consumer satisfaction and safety.

Modified Atmosphere Packaging (MAP) Tray Packs are a popular packaging method for fresh beef, pork, and poultry products, as well as for many other processed meats. Modified Atmosphere Packaging is a packaging technique that involves altering the composition of the atmosphere inside a package to extend the shelf life of the product. The goal of MAP is to slow down the natural degradation process of food by reducing the amount of oxygen inside the packaging and increasing the number of other gases, such as nitrogen or carbon dioxide. MAP has been widely used in the food industry for many years and is particularly useful for fresh fruits, vegetables, and meats. By reducing the amount of oxygen in the package, the growth of bacteria and fungi is slowed down, which helps to preserve the quality of the product for a longer period of time.

Advantages of MAP include:

1. Extended shelf life: MAP can significantly increase the shelf life of perishable foods, reducing the risk of spoilage and food waste.

2. Improved food safety: By creating an environment that inhibits the growth of microorganisms, MAP can reduce the risk of foodborne illnesses.

3. Reduced need for preservatives: With a longer shelf life, there is less need for the addition of chemical preservatives, which can be harmful to health.

4. Maintained food quality: MAP can help maintain the color, texture, and flavor of the food, which improves customer satisfaction.

How to Ensure Package Integrity of Meat Products.

The integrity of meat snack products can be tested using various methods including visual inspection, microbiological testing, or other non-destructive Container Closure Integrity Test (CCIT) methods. In this blog we will discuss how Vacuum Decay technology can be used to test the integrity of meat products

Vacuum Decay is a test method that has been proven over decades and further improved with new technological innovations. It involves drawing vacuum on a package within a test chamber and monitoring the vacuum level for decay, which would indicate a leak. The method established itself as a non-destructive replacement to the water bath leak test. It provides significant savings by not wasting product on a leak test and generates a return on investment in under six months for many products.

Vacuum Decay's acceptance as a regulatory tool is evident, and continued development optimizes the technology so that it can do more, perform better, and perform faster. PTI’s next generation of improvements are not incremental improvements, but rather foundational shifts in how the technology will serve the food, pharmaceutical, and medical device industries.

The next generation of VeriPac test systems has undergone a technology overhaul across the product line, improving each model to better perform for their respective applications. Innovation in the field of vacuum decay has often been focused on improving the practicality and sensitivity of the test method. The next generation of VeriPac systems combine both technological innovation and practical adjustments to current technology to make it the most sensitive and versatile vacuum-based leak detection technology to date. Through the introduction of unique test cycles, pneumatic controls, and processing algorithms, the VeriPac Vacuum Decay Technology is establishing itself as the foremost vacuum-based leak detection technology.

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 .
• Accurate, reliable, repeatable results.
• ASTM test method F2338

PTI is a group of researchers, engineers, and professionals who are dedicated to enhancing the overall package quality experience over the course of the packaging lifecycle. To ensure container closure integrity, PTI has created and developed a number of inspection technology platforms. Each technology is based on the principle that there cannot be a test method without a valid test method. The technology solutions provided by PTI are centred on container closure integrity and give a deterministic measurement of package performance needed by critical applications. By delivering package performance data from the development stage to in-production online package inspection, the solutions are widely utilized to address a variety of packaging design and material difficulties.

List of CCI and Package Integrity Techniques Offered by PTI:

1. Vacuum Decay Technology

Vacuum Decay is one of the most practical and sensitive vacuum-based leak detection techniques. This test provides the most accurate, repeatable, and reliable quantitative results, along with a pass/fail determination. The ASTM F2338 standard vacuum decay test method was developed using PTI’s VeriPac instruments. Additionally, it is recognized in the United States Pharmacopeia Chapter on CCI and classified in ISO 11607. The non-destructive container closure integrity testing (CCIT) method from VeriPac can use a differential pressure or absolute pressure transducer leak test device to find package leaks and undetectable defects.

2. Microcurrent HVLD Technology

PTI packaging and inspection systems transformed the traditional HVLD method and offered a new technology for assessing the integrity of all parenteral and biological products, including low conductivity liquids such as sterile water for injection (WFI). When compared to standard HVLD solutions, this innovative technology, known as Microcurrent HVLD, uses approximately 50% less voltage and exposes the product and environment to less than 5% of that voltage. The Microcurrent HVLD test method may detect and locate pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping, and a variety of other defects.

3. Helium Leak Detection Technology

Helium leak testing is the process 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 escapes as a result of a leak. Because it is non-toxic, non-flammable, non-condensable, and its atmospheric concentration is less than 5 ppm, helium is utilized as a tracer gas. Helium can pass through almost any cracks or openings since it is the second-smallest molecule in the periodic table. Additionally, helium is relatively safe to use because it does not react with other substances. This method uses a mass spectrometer leak detector (MSLD), also known as a helium leak detector, to locate and measure the leak.

4. Airborne Ultrasound Technology

PTI's proprietary Airborne Ultrasound technique is a non-destructive, non-invasive seal quality inspection method. Airborne Ultrasound technology offers thorough seal quality studies and is applicable to a wide range of packaging materials, including: Tyvek, paper, foil, film, aluminium, plastic, and poly. Defects of many forms, visible and invisible, leaking and non-leaking, process-related and random, can be detected. Airborne Ultrasound technology is an ASTM Test Method F3004 and an FDA-approved standard for testing seal quality.

5. Volumetric Imaging Technology

The OptiPac One-Touch Tool-less technology is intended for non-destructive leak detection of blister packages. To identify leaks, the OptiPac uses volumetric imaging technology to measure the motion of a blister package under vacuum. With new blister package formats, the interface is practical and straightforward to set up, requiring no tooling changeover or extensive parameter modifications as seen with previous non-destructive blister package inspection systems. The system collects volumetric data from each cavity, responding to variable cavity shapes, sizes, and configurations of various blister pack forms.

6. Force Decay Technology

Force Decay is a quantitative package integrity testing approach that is well-suited for low-headspace packaging. Non-porous materials, such as films, laminates, or foils, can be used in packaging formats. It does not harm or modify the sample packages because it is a non-destructive test method. When the test is finished, the packages can be returned to the batch without being discarded. The 410's force decay technology can measure force from a package's surface deflection during a conventional vacuum-based test cycle. VeriPac 410 force decay technology has been validated on a variety of package types, including: blister packs, transdermal patch sachets, and low headspace suture packs.

PTI’s continuous technology development has brought more technology and measurement solutions to market under one brand. Whether it be helium leak detection, high voltage leak detection, airborne ultrasound, or a vacuum-based solution, PTI - Science of Quality is the think tank you can rely on to provide the highest level of technology solutions for package quality. PTI continues to build on our journey, and we look forward to supporting you on yours.

PTI - Packaging Technologies & Inspection - is a group of scientists, engineers, and packaging professionals who are working to improve the overall package quality experience throughout the packaging lifecycle.

To ensure container closure integrity, PTI has designed and developed seven different inspection technology platforms. Each technology is based on the idea that there cannot be a test method without a valid test method. The technology solutions provided by PTI are centred on container closure integrity testing and give a deterministic measurement of package performance needed by critical applications. By delivering package performance data from the development stage through to in-production online package inspection, the solutions are widely utilized to address a variety of packaging design and material difficulties. PTI offers services and consulting in package inspection technologies, container closure integrity and test methods for most of the package types.

List of Services Offered by PTI:

1. Feasibility Studies

The first step in assessing and choosing the optimal CCI technology and test technique for a particular application are feasibility studies. To examine and verify the performance and quality of a package, various test methods are available. The main goal of the feasibility study is to assess the client's application and identify the best inspection technology that will deliver the most precise, sensitive, and reliable data for conclusive package integrity verification.

Clients receive a clear report of a quantitative test technique from PTI's feasibility studies for container closure integrity testing (CCIT) and package quality inspection, which confirm the suggested strategy as it applies to a particular package format. Both positive control samples with certified defects and tested good test samples are used. The technology solution, a specific leak test technique, test settings, test result information, and acceptance criteria are all detailed in the report. The report on PTI's feasibility studies outlines a clear path from the client's problem description to the quantitative test methodologies and findings, as well as how to guarantee package integrity by validating a suggested strategy in relation to a particular package format.

2. Test Method Consulting

Engineers, scientists, and other specialists on PTI's staff are experts in developing test methods, consulting on them, and conducting feasibility studies for a range of applications. The report on PTI's feasibility studies outlines a clear path from the client's problem description to the quantitative test methodologies and findings, as well as how to guarantee package integrity by validating a suggested strategy in relation to a particular package format.

3. Technical Support

PTI service specialists offer remote help via a variety of virtual channels in addition to on-site service. Installation, calibration, training, and upgrades are among the remotely offered services of PTI. The GTS staff can adapt to your demands regarding service schedule. Installations, validation, and after-sale support and maintenance are all skills, our staff have received training in. This network provides services to a varied range of markets around the world.

The ability of container closure systems to maintain a sterile barrier against potential contaminants that could lower the quality of the finished product can be understood as container closure integrity. External contaminants may enter the product through even the smallest leak or breach of the sterile barrier, impairing its capacity to perform as expected. Despite being popular leak testing techniques, dye ingress and microbial ingress have been shown to produce results that are often inaccurate and subjective. Deterministic test methodologies that can be controlled, calibrated, and provide a firm determination of CCI have therefore been encouraged by regulatory bodies.

Vacuum Decay is a non-destructive container closure integrity testing (CCIT) method for detecting leak paths and package integrity. The test method is simple in principle and challenges container integrity based on fundamental physical properties. This test provides a quantitative result that is accurate, repeatable, reproducible, and reliable with a pass/fail determination.

Our line of non-destructive VeriPac package testing equipment is backed by the tradition of excellence and performance reliability that PTI brings. The FDA acknowledges the standard Vacuum Decay leak test method (ASTM F2338), which was created using PTI's VeriPac instruments, as a consensus standard for testing container closure integrity (CCI). The test method is referenced in the United States Pharmacopeia Chapter on CCI and listed in ISO 11607 (USP Chapter 1207). The test is conducted by drawing vacuum on a package inside of a test chamber, and the vacuum level is checked for any decay that might signify a leak. The technique has established itself as a non-destructive substitute for the water bath leak test. By avoiding product waste for a leak test, it offers significant savings and, for many products, achieves return on investment in less than six months.

Industry Applications:

1. Pharmaceutical Industry

Pharmaceutical manufacturers prioritize quality control and package integrity because defects in pharmaceutical product manufacturing can directly affect drug quality. Even minor defects in the packaging or container may allow outside elements or contaminants to enter the drug. A manufacturer prioritizes implementing the proper container closure system because it affects both the product and the patient. CCI testing is a non-destructive package inspection technology for detecting leaks and avoiding potential contamination. The regulatory bodies take CCI's negligence very seriously. The guidelines support deterministic, dependable test methods for measuring industry-wide quality standards.

2. Food and Nutrition Industry

Packaging is crucial to today's food and nutrition industry. Packaging serves a variety of purposes, including product safety, brand awareness, product promotion, product protection and product delivery. Food and nutrition products are packaged so that they stay fresh for the entire shelf life. However, the challenges associated with packaging food and nutrition products have increased due to frequent innovations in packaging formats and the move towards sustainable packaging materials.

In order to ensure that the products are free from any type of contamination or defect, manufacturers are encouraged to perform appropriate package integrity tests. Various Container Closure Integrity Testing techniques are now available on the market to guarantee the quality and sterility of packages for the duration of their shelf life or until they are delivered to the consumer. Vacuum Decay technology and Airborne Ultrasound technology, among other methods, are very useful in food and nutrition package inspection.

Benefits of Vacuum Decay Technology

• Non-destructive, non-invasive, no sample preparation
• Accurate, reliable, repeatable results
• Supports sustainable packaging and zero waste initiatives
• FDA recognized standard for package integrity testing
• ASTM test method F2338

A combination product may be defined as 'a product composed of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product.' In simple words, a combination product is a combination of at least two product categories such as drug, device and/or biological products. Best-known examples of combination products include prefilled syringes, pen injectors, auto-injectors, inhalers, transdermal pumps and patches, and kits containing drug administration devices or components. Often termed as high-risk medical devices, combination products host various challenges for manufacturers, demanding in-depth testing and evaluation. Read on to know how manufacturers can test the integrity of combination product packages using helium leak detection.

Package Integrity Testing using Helium Leak Testing

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

Why is Helium used as a Tracer Gas?

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

How Does Helium Leak Detection Technology Work?

The test procedure begins by filling the package with helium, which is then subject to vacuum. Then, the amount of helium escaping from the package is quantitatively measured using a helium leak detector. This is then stated as the leak rate. Apart from leak testing, helium leak detection technology is also suitable for package design, failure analysis, tooling qualification, packaging line setup and validation, and product quality monitoring. Helium leak detection per ASTM F2391, is a well-established method recognized and widely used in the pharma industry.

Applications of Helium Leak Testing

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

Evaluating the ability of the container closure system to provide a sterile barrier and prevent leaks resulting from contamination is a crucial step towards maintaining the safety and suitability of primary packaging. United States Pharmacopeia (USP) and Food and Drug Administration (FDA), the driving forces behind container closure systems in the US, enforce strict regulations for Container Closure Integrity Testing (CCIT).

Traditionally, Dye Ingress and Microbial immersion were two popular methods to evaluate container closure integrity. However, they were probabilistic methods that lacked accuracy and provided subjective test results. In 2016, USP issued guidelines that they preferred deterministic test methods over probabilistic test methods. Examples of deterministic test methods include Vacuum Decay technology, Airborne Ultrasound technology, Helium Leak Detection etc. In this blog, we will discuss the role of VeriPac 355, which is a Vacuum Decay technology in testing container closure integrity.

CCI Testing Using VeriPac 355 Technology

The VeriPac 355 is a non-destructive technology based on the ASTM vacuum decay leak test method (F2338-09) and is recognized by the FDA as a consensus standard for package integrity testing. This micro leak detection system is applicable across a wide range of packaging formats and is specially designed to test containers for gas leaks for dry products (lyophilized vials, powder-filled) as well test for liquid leaks (non-protein based liquid-filled vials, prefilled syringes). The non-destructive nature of the technology allows it to be incorporated into protocols at any point in the handling process. VeriPac 355 technology's capability of detecting leak rates as low as 0.2 cc/min makes it an optimal quantitative test method for many pharmaceutical and food applications.

VeriPac 355 Working Principle

The VeriPac 355 leak tester is connected to a test chamber designed specially to hold the package being tested. Vacuum is then applied to the package inside the test chamber. Using a high-resolution absolute transducer technology, the test chamber is monitored for the level of vacuum as well as the change in vacuum over a predetermined test time. Although the test cycle takes only a few seconds, it produces accurate and non-subjective test results. 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 semi-automatic operation. This inspection method is suitable for laboratory offline testing and QA/QC statistical process control.

Inspection Criteria

• Measures seal integrity of entire container or package
• Tests for gas leaks for dry products (lyophilized vials, powder filled)
• Tests for liquid leaks (liquid filled vials, prefilled syringes)

Benefits of VeriPac 355 Series

• Non-destructive, non-subjective, no sample preparation
• Deterministic, quantitative test method
• Measures seal integrity of entire container or package
• Tests for gas leaks for dry products (lyophilized vials, powder filled)
• Tests for liquid leaks (liquid filled vials, prefilled syringes)
• Measures and verifies container closure system integrity
• Defect detection down to 0.2 ccm
• 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

Most powder dairy products (milk powders, infant formula, protein-based powders, etc.) require process monitoring, production control and modified atmosphere packaging (MAP) to retain their quality throughout its shelf-life or until it reaches the end-user. However, products that use MAP often have high risks of deficiencies in package quality control. Most MAP applications use Nitrogen flushing, and testing package quality involves sampling package gas content days after the product has been packaged. The protein based content of many products will allow bacteria to consume the majority of the O2 content before the increase in O2 is detected by gas testing equipment. Leaks as small as 10-20 microns will only increase the oxygen content to levels below 3%, the typical pass/fail threshold, passing defective product. Although packaging integrity testing can be conducted using traditional methods like water bath, they are only sensitive to 25-micron leaks at best. Therefore, dairy product manufacturers should use testing methods that offer highly sensitive leak testing along with the highest level of quality assurance.

Package Testing using VeriPac Test System

Vacuum Decay has been verified as the most practical and sensitive vacuum based leak test method. It is capable of creating reliable and accurate quantitative results and a pass or fail determination. The standard Vacuum Decay leak test method (ASTM F2338), developed using PTI's VeriPac instruments, is recognized by the Food and Drug Administration (FDA) as a consensus standard for container closure integrity (CCI) testing. The test method is listed in ISO 11607 and referenced in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207). VeriPac series are a practical alternative to destructive testing methods that provide subjective test results and variable test standards.

PTI brings a tradition of excellence and performance reliability to our line of VeriPac non-destructive package testing equipment. PTI's VeriPac Series has the capability to non-destructively test packages at the production line with high levels of accuracy and sensitivity. Non-destructive testing not only reduces wastage, but it also allows operators to have a greater understanding of package quality. Moreover, it can accommodate multiple package formats and requires non changeover when testing different size packages.

Technology Overview

Under this technique, the VeriPac leak tester is connected to a test chamber that contains sample packages. Vacuum is applied to these packages and a dual 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.

VeriPac Inspection system:

• Non-destructive, non-subjective, 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 operator with PASS/FAIL result.
• Small footprint and modular portable design.
• ASTM test method and FDA standard.
• Referenced in USP 1207 guidance.

Finding the appropriate packaging for perishable foods can be quite challenging for manufacturers. Apart from considering factors such as vulnerability and freshness, a food package must ensure safety throughout its shelf life or until it reaches the end-user. To ensure that the contents are not exposed to any foreign contamination, manufacturers should conduct regular tests that can evaluate the ability of the packaging in maintaining seal integrity. Package integrity testing can pinpoint the exact location of leaks which helps operators identify the problematic area and make necessary adjustments. As a result, manufacturers can be sure of the packaging quality and ensure that the customers enjoy their products in the freshest possible state.

For inspecting package integrity of food products, PTI has developed VeriPac 310 series, a non-destructive, non-invasive Container Closure Integrity Testing (CCIT) system for highly effective leak detection. It is an ASTM approved patented vacuum decay leak test method F2338-09 recognized by the FDA as a consensus standard for package integrity testing. The VeriPac 310 provides quantitative measurements for identifying package defects before critical process issues get out of control. The tests can be performed in any sequence with real-time results.

VeriPac 310 series was developed using VeriPac leak test instruments. The next generation of VeriPac systems combines both technological innovation and practical adjustments to current technology to make it the most sensitive and versatile vacuum-based leak detection technology to date. Through the introduction of unique test cycles, pneumatic controls and processing algorithms, the VeriPac technology is establishing itself as the foremost vacuum-based leak detection technology. VeriPac systems reduce waste and provide operators with a clear understanding of package quality.

Technology Overview

Under this method, VeriPac leak testers are connected to the test chamber designed to hold the sample packages. Vacuum is then applied to the package being tested. 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. VeriPac 310 test systems are suitable for manual or automatic operation and are designed for laboratory offline testing and production applications for QA/QC statistical process control. Testing is more reliable, sensitive and efficient than destructive methods such as the water bath or burst test.

Benefits of VeriPac 310 Series

• Non-destructive, non-subjective, no sample preparation
• Deterministic, quantitative test method
• Repeatable, rapid and reliable testing
• Cost effective and economical
• Simplifies the inspection and validation process
• ASTM test method and FDA standard

Ensuring the integrity of product packages is of utmost priority to snack food manufacturers. On-the-go snack products like wafers, chips, jerky,and coffee are vulnerable to deterioration by organic components such as moisture or air. Such foreign contaminants can enter the product through defective packages and accelerate the food decomposition process. In fact, mold, oxidation, flavor degradation, and spoilage are often the direct result of compromised package integrity. These factors can create a negative impact on consumers’ perceptions of a product and brand.

It is vital for manufacturers to ensure that packaged products are properly tested for integrity to insure that products remain fresh until they reach the consumer. Today, the market offers a wide range of leak testing that is both destructive and non-destructive. However, manufacturers should realize that a method applicable for one is not ideal for another. The leak testing method chosen should be based on the specific package specification and defect rate detection. Read on to know in detail about snack food packaging integrity testing method offered by PTI.

Package testing using PTI VeriPac Vacuum Decay Series

PTI's VeriPac inspection systems are ASTM approved vacuum decay leak test method (F2338) recognized by the FDA as a consensus standard for package integrity testing. This test method was developed using VeriPac leak test instruments. Vacuum Decay technology is a container closure integrity test (CCIT) method, referenced in the new USP <1207> Chapter Guidance as a deterministic test method for package integrity testing. This method is also listed in ISO 11607.

VerIPac test systems have a proven capability to non-destructively test a wide range of packaging formats without requiring any changeover when testing different size packages. Additionally, it is also possible to test multiple packages in a single test cycle. VeriPac provides a qualitative result (PASS or FAIL) as well as quantitative data that correlates to leak rate and leak size. Being a non-destructive method, the test allows non-defected packages to be returned to the production line, thereby reducing waste and improving testing capabilities. This makes it a practical alternative to destructive testing methods like water bath and dye ingress.

Technology Overview

The process begins by connecting VeriPac leak testers to a test chamber specifically designed to hold the sample package. Vacuum is applied to the package being tested. Using a single or dual vacuum transducer technology, vacuum levels, as well as changes in vacuum over a predetermined test time, are monitored. The changes in absolute and differential vacuum indicate the presence of leaks and defects within the package. VeriPac test systems are suitable for laboratory offline testing and can be designed for manual or fully automated operation. The test cycle takes only a few seconds, is non subjective, and non-destructive to both product and package.

VeriPac Inspection system:

• Non-destructive test method that ensures quantitative test results
• FDA recognized ASTM test method
• Referenced in USP 1207 guideline
• Cost-effective with rapid return on investment
• Supports zero waste initiatives

Medical devices are available in a variety of forms with complex geometric attributes such as valves, tubes and others that can complicate the medical device testing process. Hence, medical device leak testing equipments are expected to provide high levels of sealing effectiveness and test result sensitivity to narrow down the complexities.

Medical Device Package testing using Seal Scan technology

Seal-Scan® is a deterministic, quantitative, high-resolution method based on is an Airborne Ultrasonic Technology (ABUS). It is highly effective in non-destructively inspecting and analyzing pouch seals for defects and seal integrity for consistency. Seal-Scan systems utilize the ASTM Test Method F3004-13, which is a non-destructive test method for evaluating seal quality and integrity using Airborne Ultrasound technology. The test procedure is simple, quick and requires no sample preparation. Additionally, Seal-Scan® provides advanced digital imaging software tools for process control which offers in-depth seal quality analysis.

Seal-Scan features two scan modes:

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

Technology Overview

The test beings by scanning the pouch seal or package material between two focused ultrasonic sensors. Ultrasonic waves propagate through single or multiple layers of bonded materials. As the ultrasonic waves propagate through different mediums, it causes reflections of sound waves, which reduces/eliminates signal strength. The level of signal passing through the seal is a function of the quality of the seal. Various types of defects; leaking and non-leaking, process-related and random are detectable.

Seal scan has two scan modes (L-Scan and C-Scan) that is capable of producing Opto-Acoustic images as well as detailed statistical analysis. 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 online inspection. C-Scan produces multiple scans (along X and Y-axis of seal area) that provide a high-resolution ultrasonic image of the seal structure. This technology can be integrated into a pouch production line via the Seal-Sensor for 100% fully automated on-line seal defect detection.

Benefits of Seal Scan Technology

• Deterministic inspection method producing quantitative results.
• Works for any material and combinations, regardless of color, transparency, print, surface finish and porosity.
• Produces high resolution Opto-Acoustic image of seal.
• Characterizes overall quality and uniformity of the seal.
• ASTM Test Method F3004 and FDA recognized standard for seal quality inspection.

Medical devices and pharmaceuticals products are manufactured with zero tolerance to defects. For this reason, manufacturers give top priority to quality control procedures and regulatory standards. This is to make sure that products maintain the quality standards required for their intended use.

Packaging plays an important role in maintaining product quality and ensuring the product reaches consumers defect-free. While selecting the right packaging material is important, testing integrity of packages also holds high relevance. Traditionally, destructive testing methods like Dye Ingress and Water Bath were popular Container Closure Integrity Testing (CCIT) techniques. However, in recent years, the industry has moved towards deterministic methods to achieve more precise, reliable results.

How PTI's VeriPac Series ensure package integrity?

PTI 's VeriPac series are non-destructive, non-subjective test systems ideal for leak testing high-risk applications that require extreme levels of test reliability and accuracy. This technology uses an ASTM approved vacuum decay leak test method F2338, which is listed in ISO 11607, USP <1207>. It is an FDA recognized consensus standard for package integrity testing. Using cutting-edge innovation, VeriPac inspection systems provide repeatable, sensitive, and more robust detection of defects. 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 including flexible, rigid and semi-rigid packaging. Apart from package integrity testing, VeriPac technology can also be used for stability studies, clinical trials, quality assurance testing and statistical process control (SPC).

Technology Overview

The test method is initiated by connecting VeriPac leak testers to a test chamber that is specially designed to contain the package being tested. The package is placed inside the test chamber to which a vacuum is applied. Using a single or dual vacuum transducer technology, the level of vacuum as well as the change in vacuum over a predetermined test time are monitored. The variations in absolute and differential vacuum indicate the presence of leaks and defects within the package. The sensitivity of a test is a function of the package design, the package test fixture and critical test parameters of time and pressure. 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.

Benefits of VeriPac series

• Deterministic, quantitative test method.
• Defect detection down to 0.034 cc/min.
• Highest level of repeatability and accuracy.
• Cost-effective with rapid return on investment.
• Simplifies the inspection and validation process
• Results proven superior to dye ingress.
• ASTM test method and FDA standard
• USP <1207> Compliant.

Maintaining quality requirements and ensuring package integrity are important criteria for pharmaceutical product manufacturers. As such, the shift to more automated processes and digital measurement systems have systematically become a greater part of pharmaceutical manufacturing. In this blog, we will discuss automated package inspection techniques offered by PTI.

1. Vacuum Decay technology

Vacuum Decay technology is a non-destructive Container Closure Integrity Test (CCIT) used for leak detection in nonporous, rigid, or flexible packages. It is an ASTM-approved, FDA-recognized test method with proven capabilities to provide reliable, reproducible, repeatable and accurate quantitative results. This method involves drawing vacuum on the sample package kept in the test chamber and analyzing the vacuum level for any defect, indicating a leak.

Vacuum Decay technology is applicable across a wide range of pharmaceutical and medical devices with the capability of detecting leaks in single digit micron range while accommodating multiple packaging types. PTI has made further advancements in Vacuum Decay technology with its PERMA-VAC technology and VeriPac FLEX Series.

PERMA-VAC technology that addresses vacuum decay detection at the very core of physical test measurement, controlling the test system volume and maximizing the SNR between good and defective samples. It is a a single or dual vacuum transducer technology, which has higher test sensitivity for providing accurate and reliable results.

The VeriPac FLEX series, designed specifically for dry filled pouches and flexible packaging are available in several configurations with the ability to accommodate various package specifications. Each model achieves a specific range of test sensitivity and various test chamber sizes are available depending upon the package size and characteristics. The VeriPac FLEX series offer defect detection to the 10 to 20 micron range.

2. MicroCurrent HVLD Technology

PTI's MicroCurrent HVLD technology is a unique High Voltage Leak Detection Technology for container closure integrity testing. It is found to be highly effective across a wide range of high-risk pharmaceutical products and medical devices. 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. Being a non-invasive technique it requires no sample preparation and has a high degree of reproducibility and accuracy throughout.

The Microcurrent HVLD test method can detect the presence and location of pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping and many other defects. It assures product CCI by scanning a non-conductive sealed container with electrode probes. Any defect in the packaging results in resistance differential and change in current flow in the container as well as the approximate defect location.

Such automated platforms would provide the same 100% testing capability with an accurate inspection that includes quantitative test data and a pass/fail result. Proper sensory measurement requires time to capture a result. However, these new automated technologies can still reliably inspect containers at a much higher rate than was possible before, with a more sensitive leak detection capability.

According to USP1207, the headspace inside a sterile pharmaceutical or medical device packaging is an important part of a product. Therefore, it should comply with corresponding quality-relevant attributes. The attributes may vary depending on the product. For instance, the residual oxygen concentration is one of the attributes for oxygen-sensitive formulations. Testing low headspace packages like sachets and blister packages can be quite challenging for manufacturers. Read on to know how PTI's VeriPac 410 ensures package integrity of low headspace packages.

Leak testing using VeriPac 410 series.

Over the years, manufacturers of multi-cavity blister packs and low headspace packaging have been using destructive test methods to evaluate the integrity of such packages. However, such traditional test methods lacked accuracy and produced subjective, and unreliable results. In order to overcome the limitations of destructive test methods, PTI has developed VeriPac 410 inspection system - a non-destructive seal and leak detection technology for blister packs, sachets, and pouches with low headspace.

The VeriPac 410 employs a mix of vacuum decay technology and differential force measurement to identify defects in packages. Multiple packages can be tested in a single test cycle, depending on package specifications. The non-deterministic nature of the test produces accurate and reliable results, removes subjectivity and the operators can get a definite pass/fail outcome. Additionally, being a non-destructive test method, the VeriPac 410 allows tested packages to be returned to the production line and eliminates the cost and waste associated with destructive leak test methods. This test method has a wide range of applications including low volume flexible and semi-flexible package leak testing.

Technology Overview

The VeriPac 410 tester is connected to a specially designed drawer-style test chamber. A custom package insert that conforms to the package shape increases test sensitivity. Certain types of packages can be tested in multiple during a single test cycle. The location of the defective package or cavity is identified. Vacuum levels are monitored during the test cycle to evaluate the package using the ASTM F2338 vacuum decay leak test method. Decay of the vacuum level indicates that air is leaking from the package into the test chamber.

Once the vacuum testing phase is complete, a pressure plate maps the surface pressure of the flexible package lidding. The pressure plate system recognizes the pressure pattern exerted by the package when it is not defective, and the lack of pressure exerted on the pressure plate by a defect, allowing for both defect detection and location of the defective package or cavity.

Benefits of VeriPac 410 system

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

Supports sustainable packaging initiatives

ASTM test method and FDA standard

Cost effective with rapid return on investment

Package integrity is of paramount importance in ensuring that sterility is maintained over a product’s entire shelf life. It is also a critical factor in preventing penetration of microorganisms throughout the distribution process. International Organization for Standardization defines package integrity as "the unimpaired physical condition of the final package."

Flexible pouches are extensively being used in the pharmaceutical and food industry as a primary packaging component. Even a minute breach in the sterile condition of the product is often considered a serious risk, resulting in the disposal of valuable products. Therefore, manufacturers give utmost importance for package integrity testing. Today, the market offers a host of techniques that can evaluate packages both destructively and non-destructively. In this blog we will discuss how VeriPac Flex system effectively evaluates integrity of a wide range of flexible packages.

Flexible package inspection using VeriPac Flex Series

Designed specifically for pouches and other flexible packaging with dry-filled products, VeriPac FLEX series are innovative non-destructive container closure integrity testing (CCIT) systems. Applicable across a wide range of flexible packaging formats, this technology provides unparalleled sensitivity, reliability and practicality in testing without requiring change-over of settings or tooling.

Utilizing the ASTM method for Vacuum decay leak testing (F2338), VeriPac inspection systems provide quantitative data and definitive PASS or FAIL results. PTI offers VeriPac FLEX Systems in several configurations to accommodate various package specifications and test sensitivity requirements. Such configurators for both the leak test instrument and the test chamber capacity enable evaluation of small format sachets and stick packs, up to large bulk size pouches and bags.

Because it eliminates subjectivity, reduces the waste and cost associated with traditional test methods, they are perfect alternatives to destructive package inspection techniques. Infact Vacuum decay leak testing technology has proven to provide a short return on investment when compared to destructive methods, such as the water bath or blue dye leak test. Listed in ISO 11607 and recognized by the FDA as a consensus standard for package integrity testing, VeriPac test systems detect critical packaging failures reliably and reveal valuable information on the packaging process.

Understanding the working of VeriPac FLEX systems

Depending on the size of the package, the test operator first connects VeriPac tester to the appropriate FLEX chamber. There are two VeriPac systems namely, integrated flexible test chamber (IFC) and drawer Style test chamber (D-Series) that can be paired with the FLEX chamber to provide different leak detection capability depending on the application. While the integrated flexible test chamber is for sachets or stick packs with low headspace, drawer style test chamber features two standard sizes, the Small (D) or Large (DXL) depending upon the package size and specifications. Customs designs can be manufactured for large package formats and bulk products. The unique difference with VeriPac FLEX systems is how the package is tested. PTI utilizes its flexible membrane that conforms to the package shape and size, eliminating any stress and damage to the film materials.

Benefits of VeriPac FLEX systems

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

Container closure integrity testing (CCIT) or leak testing is an important process in the manufacturing phase of a pharmaceutical drug product in particular parenteral products. CCIT is performed to evaluate and maintain sterility over the shelf life of a product as well as to prevent contamination of the product from moisture, reactive gases, or micro-organisms. In earlier times, dye ingress, microbiological ingress and other probabilistic test methods were being used in the industry. However, the results produced by such methods lacked accuracy, reliability and were highly subjective. Therefore, manufacturers are now replacing probabilistic test methods with deterministic methods, which reduce the needs for sample preparation and validation and provide more accurate detection of leaks and defects.

Why is VeriPac 465 effective in highly sensitive micro leak testing?

PTI's VeriPac 465 is a deterministic, quantitative inspection technology that is non-destructive and non-invasive to the package being tested. This technology requires no sample preparation and performs leak detection based on the basic principles of physics. The VeriPac 465 is an ASTM approved, FDA recognized package integrity testing method which is based on vacuum decay leak test method (F2338). This test method was developed using VeriPac leak test instruments. Unique test cycles, pneumatic controls and processing algorithms are certain features of VeriPac 465 system that make it the foremost vacuum-based leak test for parenteral products.

This inspection method is suitable for laboratory offline testing and QA/QC statistical process control. The test cycle takes only a few seconds, results are non-subjective and testing is non-destructive to both product and package.

 

Technology overview

The test begins by connecting VeriPac 465 leak tester to a chamber that is specially designed to contain the package to be tested. Vacuum is then applied to the test chamber in which the package is placed. Using dual transducer technology, the test chamber is monitored for both- level of vacuum and 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 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. VeriPac 465 technology reduces the baseline measurement for good samples and amplifies the test result for defective samples. This technology is geared towards detecting leaks in the MALL range for parenteral packaging and can also be applied to flexible and semi flexible package formats

Inspection Criteria

• Measures seal integrity 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)

Benefits of VeriPac 465

• Non-destructive, non-subjective, no sample preparation
• Defect detection down to 0.002 cc/min
• Highest level of sensitivity, repeatability and accuracy
• Results proven superior to dye ingress
• Deterministic, quantitative test method
• Supports sustainable packaging and zero waste initiatives
• ASTM test method and FDA standard

As pharmaceutical products leave the laboratory for distribution, they may be exposed to certain conditions that put their integrity at risk. Product quality deterioration and economic losses may be caused due to extreme temperatures or shocks during transportation. Pharmaceutical package inspection is vital to identify and control materials that may alter the protective capacities of packaging. Container Closure Integrity Testing of pharmaceuticals is performed with the purpose of guaranteeing the safety of the products during its distribution and storage lifecycle until delivery to the patient. CCIT helps in determining the integrity and stability of packaging or container until the point of delivery.

CCI testing using Vacuum decay technology

To guarantee integrity and consistency of packages, the ability to precisely detect leaks and defects is necessary. Although destructive Container Closure Integrity Testing (CCIT) methods like water bath, dye tests, peel and burst tests can detect leaks, they are time-consuming, unreliable and produce subjective test results. Additionally, they generate significant product loss and wastage. Over the years industry has seen an increasing demand for non-destructive package integrity testing methods. One such method is Vacuum Decay technology.

Vacuum Decay is a test method that has been proven over decades as the most practical and sensitive vacuum-based leak test method. It is a simple test method that challenges container integrity based on fundamental physical properties. Vacuum Decay technology creates reliable and accurate quantitative results with a pass or fail determination and has been established as a non-destructive deterministic alternative method to the blue dye test. The standard vacuum decay leak test method (ASTM F2338), developed using PTI's VeriPac instruments, is recognized by the FDA as a consensus standard for container closure integrity (CCI) testing. The test method is listed in ISO 11607 and referenced in the United States Pharmacopeia Chapter on CCI (USP Chapter 1207)

How does Vacuum Decay Technology work?

Under this method, the leak testers are first connected to a test chamber that is specifically designed to hold the package to be tested. Vacuum is applied to the package placed inside the test chamber. Using single or dual vacuum transducer technology test chamber and level of vacuum are monitored along with a 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. This inspection method is suitable for laboratory offline testing and can be designed for manual or fully automated operation. The test cycle is non-destructive to both product and package and takes only a few seconds. It provides significant savings by not wasting products for a leak test and generates a return on investment in under six months for many products.

Key Benefits of Vacuum Decay technology

• Non-destructive and non-invasive
• No sample preparation
• ASTM approved test method
• FDA Recognized Consensus Standard
• Allows for increased sampling
• Quantitative results
• Repeatable
• Rapid test time
• Eliminates cost and waste of destructive testing
• Test results can be easily validated
• SPC laboratory testing or online applications

Medical device packaging plays a fundamental role in safeguarding the product and retaining its quality throughout its shelf life. A package containing medical devices should not only reach the hospital defect free, but it also must withstand sitting on a shelf, possibly for years, without breaking down. Therefore, medical device packaging should be in line with international regulations and quality standards. In order to ensure quality of medical device packages, manufacturers reply on package integrity and seal quality test methods. Although the market offers a complete range of inspection techniques, it is important for manufacturers to choose the appropriate one based on packaging material used and sensitivity levels required.

The ideal solution is a non-destructive method for inspecting the physical properties of the seal and a non-subjective analysis to determine the seal quality. PTI’s Airborne Ultrasound technology (ASTM Test Method F3004-13) uses a transmission of 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 be addressed and corrected immediately, which significantly reduces the quantity of defective packages produced.

Package inspection using Seal-Scan technology

PTI's Seal-Scan® is a non-destructive Airborne Ultrasonic technology (ABUS) that inspects and analyzes pouch seals offline. Seal-Scan® is a semi-automatic inspection system with x-y drive, used for the detection of seal defects, seal characterization and material analysis. This technology utilizes the ASTM Test Method F3004 for seal quality and integrity evaluation. .Seal-Scan® is a deterministic, quantitative, high-resolution method that inspects pouch seals for defects and seal integrity for consistency. Testing using a Seal-Scan® is non-destructive, non-invasive, and requires no sample preparation. Seal-Scan® provides advanced digital imaging software tools for process control which offers in-depth seal quality analysis. PTI has designed several configurations of SEAL-SCAN® for both offline inspections to accommodate various package specifications, test sensitivity and package handling requirements.

Technology overview

Under this method, the pouch seal or package material is scanned between two focused ultrasonic sensors. Ultrasonic waves pass through single or multiple layers of bonded materials. Ultrasonic propagation through different mediums causes reflection of sound waves and reduces/eliminates signal strength. Seal Scan technology can detect different types of defects including leaking and non-leaking, process-related and random are detectable. This technology can produce Opto-Acoustic images as well as detailed statistical analysis by either of two scan modes (L-Scan and C-Scan). 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 online inspection. C-Scan produces multiple scans (along X and Y-axis of seal area) that provide a high-resolution ultrasonic image of the seal structure. This technology can be integrated into a pouch production line via the Seal-Sensor for 100% on-line seal defect detection.

Benefits of Seal Scan Technology

• Deterministic inspection method producing quantitative results
• Works for any material and combinations, regardless of color transparency, print, surface finish and porosity
• Produces high resolution Opto-Acoustic image of seal
• Characterizes overall quality and uniformity of the seal

Blister packs are common packaging formats for solid dose drugs in the form of tablets and capsules. Such packages not only preserve the quality of the drug, but also ensure ease of use to the consumer. Blister packages are commonly used by drug manufactures to ensure protection of the product from oxidation, moisture or other atmospheric pollutants which may lead to product degradation.

However, in recent years, the industry has seen a tremendous increase in the number of high-risk medicines, which are more sensitive to environmental condition than other tablets or capsules. This has further increased blister package integrity challenges. Although the number of environmental contaminants that can enter a package depends on leak size, with blister package, even minute leaks can become troublesome. Therefore, Container closure Integrity Testing (CCIT) of blister packs is extremely crucial.

OptiPac inspection system for non-destructive blister package testing

The OptiPac Leak Detection System is a deterministic non-destructive package integrity testing method created specifically for blister packs. Designed and engineered with One-Touch Technology, OptiPac achieves a rapid test cycle without requiring any changeover or sample preparation. This unique technology can provide rapid detection of sub-5-micron defects depending on blister cavity volume. Although OptiPac system uses similar principles applied in a vacuum-based blue dye test, it applies controlled inputs and measured outputs without the hassle and reliability issues of the dye ingress method. OptiPac uses volumetric imaging technology to measure the motion of a blister package under vacuum to detect leaks. The interface is practical and simple to setup with new blister package formats, requiring no complex parameter adjustments experienced with other non-destructive blister package inspection systems.

Technology overview

OptiPac utilizes volumetric imaging under vacuum with topographic imaging to detect the presence and location of leaks. The test begins by placing the sample on the testing area for vacuum-based measurement. After pressing the start button, vacuum is pulled to a defined vacuum. The blisters expand under vacuum, and air is drawn out of the blister through any leaks present. In the presence of a leak, the air escapes into the chamber causing a collapsed blister cavity. A volumetric image and measurement reading is taken during the dynamic vacuum test sequence, that determines which blister cavities are defective. A definitive pass/fail result as well as the quantitative measurement associated with each package test is also displayed. PTI's OptiPac systems provide a definitive result based on accurate and measurable quantitative data, reliably detecting leaks down to 5 microns.

OptiPac’s insightful technology offers a suite of advanced functions:

• 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

The rapidly increasing preference towards combination pharmaceutical products continues to fuel innovation, while presenting unique challenges in implementing a container closure integrity (CCI) testing strategy. Common examples of combination products include prefilled syringes, pen injectors, inhalers, and drug-eluting stents, orthopedic products, infusion pumps and more. The packaging for combination products can be just as complex as the products themselves. Hence, container closure integrity testing in line with current USP <1207> guidance and regulation is critical to ensure package integrity.

Techniques to ensure CCI: Helium leak testing & Microcurrent HVLD technology

1. Helium leak testing

Helium leak testing refers to the process of finding leaks in some type of enclosed or sealed system using helium as a “tracer” gas and measuring its concentration as it escapes due to leakage. Apart from being an ideal solution for ensuring Container Closure Integrity, the technology is also applicable in package design, monitoring product quality, failure analysis and line set up and validation.

Under this method, a helium leak detector otherwise known as Mass Spectrometer Leak Detector (MSLD) is used to identify and calculate size of the leak. The test part is first connected to a leak detector and then the tracer gas, helium is introduced. In the presence of a leak, helium escapes from the test parts and this partial pressure is measured and results are displayed on the meter. Helium Leak Detection per ASTM F2391, has long been recognized by the FDA as a consensus standard for package integrity evaluation. The test method is also referenced in the United States Pharmacopeia (USP) Chapter on Container Closure Integrity (CCI) – USP <1207>.

2. Microcurrent HVLD technology

PTI’s MicroCurrent HVLD technology is a non-destructive, non-invasive container closure integrity test method that is found to be highly effective across applications such as pre-filled syringes, vials, cartridges, ampoules, BFS, bottles and pouches. This technique can precisely detect any leak in a wide range of liquid-filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. Under this method, the sealed container is scanned using electrode probes to detect the presence of any leak. Defects in the container as well as its approximate location can be identified by analyzing a change in the current flow. MicroCurrent HVLD technology utilizes about 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. It is one of the most effective CCI technologies for all parenteral and biologic products.

Benefits of PTI’s MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation
• Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Ensure higher levels of accuracy and reliability in results
• Offline and 100% online inspection at high production speeds
• Simplifies the inspection and validation process
• Referenced in USP 1207 Guideline

Over the years, there has been a steady increase in the demand for pre-filled syringes for injectable drug products that can be self-administered. However, considering the complex nature of pre-filled syringes, Container Closure Integrity assurance can be quite challenging. Container Closure Integrity is understood as the ability of containers to maintain a sterile barrier against possible contamination. A leak or breach in the sterile barrier can rapidly convert a lifesaving drug into a threat for patients. Parenteral products are the highest risk of all packaging formats. Vials, ampoules, and pre-filled syringes have the highest potential for microbial growth, and the risk to the end patient amplifies the focus needed on CCI for these applications.

High Voltage Leak Detection (HVLD) has been in the market for decades. However, PTI’s MicroCurrent technology has revolutionized HVLD. MicroCurrent HVLD  aims to achieve a high level of CCI assurance across the entire range of parenteral products. High Voltage Leak Detection is a deterministic test method included in USP 1207, and is an established and reliable solution for all liquid filled parenteral products.

Pre-filled syringe testing using HVLDmc (E-Scan 655) technology

The E-Scan 655 is a Microcurrent HVLD technology-based leak test instrument used to inspect vials, syringes, and other liquid filled parenteral products. It is a non-destructive conductivity test method, exposing the package and product to lower voltage than other conductivity-based solutions.

The E-Scan 655 features a fast test cycle and simple operation. It can accommodate a wide range of applications and products, including low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. The technology uses a non-contact, non-invasive test method that requires no sample preparation. Additional benefit include ability to migrate from laboratory to 100% inline testing applications at high production speeds.

Technology Overview

The E-Scan testing process uses a set of electrode probes to scan a non-conductive container that is sealed. The container material can be glass, plastic, or poly laminate. The container or package must contain liquid (minimum fill 30%). In the presence of a pinhole, crack, or other defects, there will be a resistance differential and change in current flow, indicating a breach in the container. The approximate defect location can be identified.

Benefits of 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

Container closure integrity may be understood as the ability of container closure systems to maintain a sterile barrier against possible contaminants that can deteriorate the quality of the final product. Even a microscopic leak or breach of the sterile barrier can cause external contaminants to enter the product and compromise its healing properties. Parenteral products are at the highest risk of all package formats. Vials, ampoules and prefilled syringes have the highest potential for microbial growth, and the risk to the end patient amplifies the focus needed on CCI for these applications. Although dye ingress and microbial ingress are common leak testing methods, they are proven to provide subjective results that lack accuracy. Hence regulatory bodies have instructed a shift towards more deterministic test methodologies that can be controlled, calibrated and provide a definitive determination of CCI.

High Voltage Leak Detection (HVLD) is an effective Container closure integrity technique for non-destructive package inspection of non-porous pharmaceutical and parenteral products. This technology operates on the simple property of electrical current. The latest evolution of HVLD, PTI’s patented MicroCurrent HVLD technology , aims to achieve a high level of CCI assurance across the entire range of parenteral products. It can precisely detect any leak in a wide range of liquid- filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. The MicroCurrent HVLD reduces voltage exposure to the product to less than 5% of the voltage exposure experienced when testing with comparable HVLD solutions. Reducing exposure voltage not only reduces any risk that the voltage poses to the product, but also greatly reduces the production of Ozone during operation when compared with traditional HVLD solutions.

How does MicroCurrent HVLD technology work?

Under this method, the container is scanned by the high voltage probes. High voltage is applied to one side of the container and a ground probe on the opposing side. If the package has 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 vial. If there is a micro-leak or crack in one of the container walls, the break-down resistance is reached and the current passes through. HVLD is the only leak detection technology that does not require mass to pass through a defect site, requiring only the passage of electricity through a crack. This characteristic makes HVLD sensitive to leaks in which most leak test solutions cannot identify. Applications of High Voltage Leak Detection Technology include testing of the following package formats:

• Pre-filled syringes
• Ampoules
• Drug product cartridges
• Liquid filled vials

Benefits of MicroCurrent HVLD:

• Deterministic, non-destructive, non-invasive
• High level of repeatability and accuracy
• Ideal package integrity solution for parenteral products
• Low voltage exposure to the product and environment
• Offline and 100% online inspection at high production speeds
• Referenced in USP 1207 guideline

The pharmaceutical industry is crucial to the health care system as they assure treatments that were unimaginable a few years ago. As the industry grows in importance, the techniques of primary packaging for pharmaceutical products, especially high-risk medicines have taken on new prominence.

Since many high-risk pharmaceutical products are filled and sealed in combination devices, it’s critical for manufacturers to ensure that the components function well together. Hence, design and distribution considerations are critical to both the drug and the container. Manufacturing inconsistencies and tolerance differences in packages containing multiple components are primary contributors to distribution issues. Often, such inconsistencies result in container closure failure, causing serious implications down the supply chain. For instance, glass vials and pre-filled syringes may not seal properly at critical fill-finish closure points. Such a failure can cause oxygen or other environmental contaminants to enter the product and compromise the efficacy of the drug in the barrel. At this point, it is critical to use the most precise leak testing method possible.

Why Container Closure Integrity testing is important?

As per the FDA- Food and Drug Administration, A container and closure system refers to "the entirety of packaging components that together contain and protect the product". In simple words, Container Closure Integrity testing can be understood as a leak detection test. CCI solutions include non-destructive package inspection technologies to ensure product sterility throughout the product’s lifecycle. CCIT plays a vital role in ensuring that the products are free from any possible contamination. Conventionally, probabilistic test methods like bubble tests, dye ingress and microbial challenge were extensively used in pharmaceutical package testing. Since it was found that such test results lacked accuracy and reliability, the United States Pharmacopeia (USP) released guidance in 2016 stating that deterministic methods are preferred over probabilistic test methods. With this new USP <1207> chapter guidance, manufacturers today rely on non-destructive alternatives like Vacuum Decay technology and Micro Current HVLD technology that ensure highly sensitive package integrity solutions.

1. Vacuum Decay technology: Vacuum Decay technology is a non-destructive container closure integrity solution capable of detecting leaks in nonporous, rigid or flexible packages. Vacuum Decay leak testing is conducted by placing a sample package in a well-fitting evacuation chamber, which is provided with an external vacuum source. The vacuum levels as well as the change in vacuum over a fixed test time are closely observed using single or dual vacuum transducer technology. Changes in vacuum level beyond a predetermined pass/fail limit indicate defects within the package. VeriPac Vacuum Decay series can non-destructively test packaging down to sub-micron leak rates - making it an excellent alternative to destructive testing methods.

PTI’s VeriPac 465, the latest addition to the vacuum decay series is a robust and reliable solution for testing pharmaceutical containers and parenteral products, achieving highly sensitive sub-micron leak detection. The VeriPac 465 is the most sensitive vacuum based technology on the market to-date.

Benefits of Vacuum Decay Technology:

• Non-destructive, non-subjective, no sample preparation
• Deterministic test method that provides quantitative results
• Multiple package testing in a single test cycle
• Economical with rapid return on investment
• ASTM Test Method, FDA standard and USP 1207 Guidance

2. Microcurrent HVLD technology: Microcurrent HVLD is a unique High Voltage Leak Detection technology, highly effective across all liquid filled parenteral products. Its applications include liquid-based products ranging from extremely low conductivity sterile water for injection (WFI) to large molecule-based proteinaceous products with suspensions. Its ability to detect small pinholes, micro cracks and seal defects makes it an ideal choice for testing high risk pharmaceutical and parenteral products.

Benefits of PTI’s MicroCurrent HVLD technology:

• Non-destructive, non-invasive, no sample preparation
• Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Ensure higher levels of accuracy and reliability in test results
• Simplifies the inspection and validation process
• Offline and 100% online inspection
• Referenced in USP 1207 Guidelines

Often described as the driving force of pharmaceutical industry, biologic drugs have the ability to address chronic diseases, unmet medical needs and comprise of more than half of the drugs in development. These are generally large complex molecules, derived from human, animal, or microorganisms through biotechnology. Examples include blood components, cells, vaccines, tissues, and recombinant proteins. The ability of biological drugs to treat life threatening diseases coupled with aging population has lead to tremendous growth in the global biological drugs market. However, the rapid growth of biological products has also increased packaging challenges to deliver safe and effective products.

Drug contamination is a serious concern in any medical industry; however, for biologics, it amplifies several folds because they are used to treat serious illnesses and chronic conditions. Contamination has a direct impact on product stability resulting in reduced shelf life and efficacy. Along with maintaining an acceptable shelf-life, there are other challenges too. Another important factor that can affect the quality of a drug is environmental conditions. For example, if a product is exposed to extreme temperature during transit, the product quality may be compromised. A biologic can also lose its stability if it’s unable to withstand variations in light and chemicals that it might encounter. Therefore, in order to cover packaging challenges associated with biological products, ensuring its container closure integrity is crucial.

Ensuring package integrity with PTI’s MicroCurrent HVLD technology

PTI’s MicroCurrent HVLD technology is a non-destructive, non-invasive container closure integrity test (CCIT) method that is found to be highly effective across applications such as pre-filled syringes, vials, cartridges, ampoules, BFS, bottles and pouches. This technique can precisely detect any leak in a wide range of liquid-filled products including extremely low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions. Under this method, the sealed container is scanned using electrode probes to detect the presence of any leak. Defects in the container as well as its approximate location can be identified by analyzing a change in the current flow. MicroCurrent HVLD technology utilizes about 50% less voltage and exposes the product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. It is one of the most effective CCI technologies for all parenteral and biologic products.

Benefits of PTI’s MicroCurrent HVLD technology

• Non-destructive, non-invasive, no sample preparation
• Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
• Ensure higher levels of accuracy and reliability in results
• Offline and 100% online inspection at high production speeds
• Simplifies the inspection and validation process
• Referenced in USP 1207 Guideline

The World Health Organization (WHO) has stated that healthcare associated infections pose the highest risk in the delivery of healthcare services globally. This causes a serious threat to millions of patients worldwide every year. Therefore, ensuring sterility of medical devices is an important way to reduce the risk associated with faulty medical devices in hospitals and other healthcare settings.

Appropriate packaging and packaging materials are crucial to help preserve sterility of medical devices. Conventionally, medical device manufacturers relied on manual visual inspection as a method for assuring quality. However, such methods lacked accuracy and reliability in test results. To overcome the limitations of traditional test methods, manufacturers moved towards deterministic Container Closure Integrity testing (CCIT) methods that ensured quantitative and accurate test results.

PTI’s Airborne Ultrasound technology is a seal quality inspection test method, capable of non-destructively examining seal quality for defects. It is an ASTM Test Method F3004 and FDA Recognized Standard for seal quality testing. Such tests are mainly conducted to provide enhanced seal quality inspection of pouches, flexible packages and tray seals. Airborne Ultrasound technology ensures in-depth seal quality analyses and is applicable for multiple packaging materials Tyvek, paper, foil, film, aluminium, plastic and poly. According to Oliver Stauffer, CEO of PTI-Packaging Technologies & Inspection, “Ultrasound is one of the only technologies that are telling us what the quality of that physical bonded nature of the seal materials are.”

Under this technology, ultrasound waves are passed through the package seal which causes reflections of sound waves. The signal strength is reduced or eliminated in the presence of a leak/ defect. Such variations are closely observed to identify the leak. Inability to detect non-leak defects is a common challenge faced by most leak test methods. However, with Airborne Ultrasound technology, users are able to identify various types of seal defects; visible and invisible, leaking and non-leaking, process-related and random.

PTI has redefined seal integrity testing with its latest improvements in the form of Seal Scan (Offline) and Seal-Sensor. Both these technologies utilize non-contact airborne ultrasonic testing technology. With the advancements in form of Seal Scan and Seal-Sensor, Airborne Ultrasound technology has been 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.

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.

Blister packs also known as press through packs are common packaging formats for drugs in the form of tablets and capsules. Such packages not only preserve the quality of the drug, but also ensure ease of use to the consumers. Blister packages are commonly used by drug manufacturers to ensure protection of the product from oxidation, moisture or other atmospheric pollutants which may lead to product degradation.

However, in recent years, the industry has seen a tremendous increase in the number of high-risk medicines, which are more sensitive to environmental condition than other tablets or capsules. This has further increased blister package integrity challenges. Although the amount of environmental contaminants that can enter a package depends on leak size, with blister packages, even minute leaks can become troublesome. Therefore, ensuring blister package integrity is extremely crucial.

Earlier traditional destructive methods such as the dye ingress method was used to test blister packages. But these methods were subjective, probabilistic and lacked accuracy in test results. This encouraged manufacturers to use non-destructive Container Closure Integrity test (CCIT) methods that were accurate and produced quantitative results with measurable result data.

PTI’s VeriPac Universal Blister Verification (UBV) system is a reliable and hassle-free technique to ensure blister package leak detection. These are deterministic non-destructive solutions specifically designed for multi-cavity blister packs. PTI’s VeriPac UBV utilizes volumetric imaging under vacuum to identify the presence and location of leaks.

Under this method, sample packages are placed inside the test chamber. After pressing the start button, vacuum is pulled to a pre-determined level. If any leaks are present, the packages expand under vacuum, and air escapes into the chamber causing blister packages to collapse. Volumetric measurement readings are taken during the vacuum test, that analyzes which blister cavities are defective. It is a rapid test that allows operators to get quantitative measurements associated with each package test in addition to definitive pass or fail results.

The UBV technology offers leak detection down to 10 microns with minimal test time, averaging 10-30 seconds depending on blister cavity volume. Test system requires no tooling changeover or other complex adjustments with simple interface for testing various blister package formats. This technology is specifically useful for tiny blister cavities which are quite difficult to detect using standard vacuum systems due to its low headspace.

Benefits of VeriPac UBV technology:

• Non-destructive package inspection system
• Accurate and reliable results
• Definite pass/fail result based on quantitative test data
• Accommodates multiple blister packaging formats with no tooling changeover
• Eliminates destructive, subjective testing methods
• Effective in detecting even minute leaks

Seal integrity plays a vital role in ensuring the quality of packaging products. Even a minute defect in the seal can initiate a leak, which can compromise the quality of the product and directly affect its shelf life. It can also result in huge financial losses to the manufacturer. That being said, manufacturers give considerable importance to conducting appropriate seal integrity tests to ensure package integrity at every stage of its lifecycle.

Seal integrity testing methods can be classified into two- Destructive testing methods and Non-Destructive testing methods. Since under Destructive methods, the packages may get destroyed, its popularity has steadily declined over the past few decades due to this waste and high cost. “There is a huge shift in the industry towards deterministic and quantitative test methods,” says Oliver Stauffer, Chief Executive Officer at PTI - Packaging Technologies & Inspection. “This includes vacuum decay and airborne ultrasound for medical device applications. The industry is currently moving away from dye ingress and manual visual inspection because there are so many blind spots in applying them and there’s a huge false sense of assurance.”

Seal quality inspection techniques offered by PTI:

Vacuum Decay technology is a non-destructive Container Closure Integrity test (CCIT) method, used for seal quality inspection in nonporous, rigid or flexible packages. With the ability to detect leaks down to the sub-micron level, , Vacuum Decay technology is identified as one of the most practical vacuum-based leak detection methods. Its ability to provide quantitative, reliable and repetitive test results make it ideal solution for seal quality inspection in Pharmaceutical, Medical Device and Food and Nutrition industries.

Under this method, the sample packages are first placed in a close fitting evacuation test chamber that contains an external vacuum source. The vacuum levels and changes in vacuum over a pre-determined time are closely monitored. 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 the absolute and differential vacuum indicate the presence of leaks and defects within the package.Over the past few years, Vacuum Decay technology has seen great advancements in the form of PTI’s PERMA-VAC technology and VeriPac FLEX Series.

The next generation PERMA-VAC technology is a single or dual vacuum transducer technology that has made the VeriPac line of test systems the most sensitive vacuum-based leak tests available in the market. It has higher test sensitivity for providing accurate and reliable results and can be applied to rigid and semi-flexible packages alike. PTI’s PERMA-VAC technology ensures the most stable test measurement ever achieved through vacuum decay.

VeriPac FLEX series is an ideal package inspection solution for dry filled pouches and flexible packaging. To accommodate different package formats and test sensitivity requirements, VeriPac FLEX series is available in several configurations with multiple test chamber sizes.

 

2.Airborne Ultrasound technology:

Airborne Ultrasound technology is yet another seal quality inspection technique, 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.

 

Ensuring pharmaceutical package integrity has always been a priority for drug product manufacturers. However, over the past few decades, innovations in health care sector have also accelerated pharmaceutical package integrity challenges. Although testing package quality of all healthcare products is important, in the case of parenteral products it is amplified significantly. Parenteral products are defined as injectible products that can be either liquid or powders. Solutions can contain suspensions, emulsions and be proteinaceous in nature. ”. Since these drugs are directly administered into human bodies, ensuring complete integrity of such packages is crucial. Common packaging formats for parenteral products include Liquid-filled containers such as vials, ampoules, syringes, BFS and auto injectors; Lypholized (powder) products are often packaged in vials. Even a minute breach in the package can cause microbial contamination leading to product deterioration. Hence ensuring container closure integrity is a critical process in the life cycle of parenteral products.

What is HVLD Methodology?

High Voltage Leak Detection (HVLD)) is a non-destructive Container Closure Integrity Test (CCIT) method used primarily to evaluate closure integrity of parenteral product packaging. HVLD technology makes use of quantitative electrical conductivity measurement principles. This method operates by passing high voltage micro current signals through sample packages. Under the presence of a leak, the electrical resistance of the sample declines, causing an increase in current. Applications of High Voltage Leak Detection Technology include testing of the following package formats:

• Pre-filled Syringes
• Ampoules
• Drug Product Cartridges
• Liquid Filled Vials
• Blow-Fill-Seal (BFS) Container

PTI’S MicroCurrent HVLD technology has revolutionized the conventional HVLD method. MicroCurrent HVLD is a non-destructive, non-invasive CCI technique that can be applied to a wide range of liquid filled products including low conductivity sterile water for injection (WFI) and highly proteinaceous drug products within suspensions. PTI’s E-scan HVLD, a highly sensitive CCI testing process uses electrode probes to scan sealed non-conductive containers. Under the presence of a leak, there will be a change in current flow indicating a defect in the container along with its approximate location. This unique technique uses about 50% less voltage and exposes the product and environment to less than 5% of the voltage. An important feature of E-scan HVLD is its ability to easily shift from the laboratory offline to 100% inline testing applications. With the capability to accommodate multiple packaging formats including glass, plastic or poly laminates, it is an ideal solution for parenteral package testing.

Benefits of MicroCurrent HVLD:

• Deterministic, non-destructive, non-invasive
• High level of repeatability and accuracy
• Ideal package integrity solution for parenteral products
• Low voltage exposure to the product and environment
• Offline and 100% online inspection at high production speeds

Medical device industry is crucial to health care system as they play a vital role in the delivery of many health care services. Over the past few decades, tremendous developments in medical technologies have challenged the medical device packaging industry to ensure quality and reliability in packaging. Although testing package quality of all medical devices is critical, in case of Class III medical devices it amplifies several folds. Class III medical devices are understood as devices that sustain or support life, are implanted, or present potential unreasonable risk of illness or injury. Examples include pacemakers, breast implants, and respiratory ventilators. Since these devices are directly placed into human bodies, proper packaging is required to ensure the quality of the product until it reaches the patient. Any breach in the packaging can cause contaminants to enter the device, thereby making it more of a threat to the patient than a treatment. Hence appropriate CCI technologies are needed to ensure standardized packaging quality.

Container Closure Integrity Testing(CCIT) is a leak detection test conducted using a non-destructive package inspection system to ensure sterility and product quality throughout its shelf life. Earlier, probabilistic test methods such as bubble test, dye ingress and manual visual inspection were used to test package quality of medical devices. However, these traditional methods lacked accuracy and provided uncertain and subjective results. In order to overcome the shortcomings of probabilistic methods, industries are now moving towards deterministic methods that assures a higher level of accuracy with quantitative results. According to Oliver Stauffer, Chief Executive Officer at PTI - Packaging Technologies & Inspection “ There is a huge shift in the industry toward deterministic and quantitative test method. This includes Vacuum Decay and Airborne Ultrasound for medical device applications. The industry is currently moving away from dye ingress and manual visual inspection because there are so many blind spots in applying them and there’s a huge false sense of assurance.”

Packaging Technologies & Inspection-PTI’s VeriPac Vacuum Decay Technology and Airborne Ultrasound Technology have revolutionized automated CCI Technologies.

Vacuum Decay Technology is a CCI testing method that detects leaks in nonporous, rigid or flexible packages. Such tests are conducted by placing a sample in an evacuation test chamber, drawing vacuum and monitoring vacuum level for any decay, indicating a leak. Such tests are known to provide reliable and quick results. PTI’s VeriPac Vacuum Decay Technology is a non-destructive package inspection system based on the ASTM vacuum decay leak test method (F2338-09) and accredited by the FDA for package integrity testing. Its applications include empty and pre-filled syringes, liquid-filled and lyophilized vials and other flexible and rigid liquid-filled packaging. PTI’s PERMA- VAC technology, known to provide consistent and reliable results is the latest development in the VeriPac line of test systems. The VeriPac Universal Blister Verification (UBV) system designed for non-destructive blister package leak detection uses a volumetric imaging technology to measure the motion of a blister package under vacuum to detect leaks.

PTI’s Airborne Ultrasound Technology is a non-destructive Seal Integrity Test used to examine seal quality for defects. “Ultrasound is one of the only technologies that are telling us what the quality of that physical bonded nature of the seal materials are,” says Oliver Stauffer, CEO of PTI. Under this method, high-frequency sound waves are passed through the pouch seal area, causing the reflection of sound waves. Variations of the reflected signal strength are used to reflect defects if any. PTI’s Airborne Ultrasound Technology for 100% Inline inspection of pouch seals has been extremely helpful in verifying final pouch seal quality. Any defect in the pouch seal including voids and delamination, foreign materials and inclusions, incomplete seals and misaligned seals can be detected using a Seal-Sensor scan and are automatically rejected from the production line.

Vacuum Decay Method (VDM) is used by manufacturers of packages for the food, beverage, industrial and pharmaceutical industries in order to detect leaks in rigid or flexible packages.

Both methods are established ASTM test methods: Vacuum Decay ASTM F2338 and Airborne Ultrasound ASTM F3004.These technologies are non-destructive methods and can be chosen depending on the characteristics of the product to be tested.

Today’s healthcare industry assures treatments that were unimaginable a few years ago. As pharmaceutical industry grows in importance, the techniques of primary packaging for healthcare products, especially parenteral products has taken on new prominence. Common parenteral packaging methods include Liquid-filled containers such as vials, ampoules, syringes, blow-fill-seals and auto-injectors and containers filled with lyophilized products. Since these drugs are directly administered into human bodies, high sensitivity integrity tests are required to ensure product quality throughout its shelf life. For reasons of safety, packaging material, integrity and design are regulated by Food And Drug Administration as strictly as the product itself.

Container Closure Integrity Testing is a leak detection test conducted using a non-destructive packaging inspection system to protect the drug from any possible contamination. It is a crucial step in evaluating safety and integrity of the primary packaging so as to maintain a sterile barrier and to avoid leakage resulting in contamination of the drug. Packaging components like bottles, vials, syringes that are in direct contact with the product are called primary components while aluminum caps, cardboard boxes are secondary components as they are not in direct contact with the product. Proper packaging should be a priority for all drug products, but in case of parenteral products, these concerns amplifies several folds as they are directly injected. Hence initiating a proper container closure system is vital for product and consumer safety.

Although Container Closure Integrity Testing(CCIT) can be performed in many different ways, it can be broadly classified into Probabilistic methods and Deterministic methods. Probabilistic test methods including Microbial Challenge by Immersion, Tracer Liquid Tests (e.g. Dye Ingress), Bubble Tests etc. are traditional test methods where result accuracy may be uncertain. On the other hand, Deterministic test methods like Electrical Conductivity and Capacitance Test (HVLD), Laser-based Gas Headspace Analysis, Mass Extraction, Pressure Decay provide quantitative results with high accuracy. The United States pharmacopeia released guidance in 2016 stating that deterministic methods are preferred over probabilistic test methods.Packaging Technologies And Inspection (PTI’s) Microcurrent HVLD technology and vacuum decay technology are the latest inventions in package integrity testing of parenteral products.

1. Microcurrent HVLD Technology: Microcurrent HVLD is a unique High Voltage Leak Detection Technology, highly effective across all parenteral products. Its Applications include liquid-based products ranging from extremely low conductivity sterile water for injection (WFI) to proteinaceous products with suspensions. Its ability to detect small pinholes, micro cracks and seal defect detection down to single-digit microns makes it an ideal choice for testing parenteral products.

2. VeriPac Vacuum Decay Technology: VeriPac Vacuum Decay Technology, based on the ASTM vacuum decay leak test method (F2338-09) and accredited by the FDA for package integrity testing, is a non-destructive inspection system, capable of defect detection down to 0.002 cc/min. This system is applicable for empty and pre-filled syringes, liquid-filled and lyophilized vials and other flexible and rigid liquid-filled packaging. Depending on the package type and leak test sensitivity needed, appropriate VeriPac model can be selected.

PTI’s next generation PERMA- VAC technology addresses vacuum decay detection at the very core of physical test measurement by controlling the test system volume and maximizing the SNR between good and defective samples. This makes PERMA-VAC the most reliable vacuum-based leak test available in the market.

The global pharmaceutical industry has seen tremendous growth over the last few decades. The complex nature of the industry coupled with frequent breakthroughs has made it a favorite subject of scrutiny. Since any defect in the packaging of drugs can have serious consequences, assuring the quality of the packaging is of prime interest for every manufacturer. Pharmaceutical products are expected to be free from microbial contamination and safe to use right from production throughout their shelf-life. The drug’s stability can be adversely affected through contamination in the form of oxygen, humidity or microbiological ingress. In order to prevent such risks, integrity tests with high sensitivity are required.

Previously, only sterility testing was conducted on pharmaceutical packaging. However, when it was realized that sterility testing alone is not sufficient to hold the integrity of the medical products, the US FDA published Guidance for Industry for Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products. This emphasised the importance of verification of microbial barrier properties of a pharmaceutical product package (i.e., CCI). FDA defines Container Closure Integrity Testing (CCIT) “as the sum of packaging components that together contain and protect the dosage form”.

Container Closure Integrity Testing is a method of leak detection using a non-destructive packaging inspection system to prevent possible contamination. Such a test is essential since any defect in the container can cause external particles to enter the product, thereby reducing its shelf life. Implementing right Container Closure System has been of prime importance for a manufacturer as it affects both the product and the patient. Hence, the relevance of CCI Testing in the pharmaceutical industry has steadily increased over the years. Contaminants that can enter a product include micro-organisms, reactive gases, and other substances. CCIT ensures product quality is maintained from the point of manufacture throughout its distribution and use. Container closure systems include primary packaging components and secondary packaging components. Components such as a glass vial or syringe, which come into direct contact with the product, are primary packaging components. On the other hand, components that are crucial to ensure correct package assembly, such as aluminum caps, over stoppers etc. are the secondary packaging components

CCI Testing Methods

Container closure integrity testing can be performed in many different ways. Each method has its own merits and demerits. A number of factors have to be considered while selecting appropriate testing methods. These factors include, but are not limited to; the reliability of the test method, material of the primary package and inline versus an offline testing requirement. CCI testing methods can also be selected depending on specific desired outcomes. Examples of desired outcome include: identifying the presence of leak paths, understanding leak path’s location, evaluating leak rate for the whole package, and measuring potential for microbial ingress. The United States pharmacopeia released guidance in 2016 stating that deterministic methods are preferred over probabilistic test method.

1. Probabilistic methods: Here, the testing methods are more traditional, and the accuracy of the result is uncertain. The probabilistic methods include the following:

• Microbial Challenge by Immersion
• Tracer Liquid Tests (e.g. Dye Ingress)
• Bubble Tests
• Tracer Gas (Sniffer Mode)

2. Deterministic methods: Such methods provide quantitative results with a higher level of accuracy. The chances of errors are also minimal. The deterministic methods include the following:

• Electrical Conductivity and Capacitance Test (HVLD)
• Laser-based Gas Headspace Analysis
• Mass Extraction
• Pressure Decay
• Tracer Gas (vacuum mode)
• Vacuum Decay