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Maintaining the container closure integrity of vials stands as a paramount concern within pharmaceutical manufacturing, crucial for upholding product quality, efficacy, and ensuring patient safety. Conventional vial leak testing methodologies possess inherent limitations in detecting microleaks, posing a potential risk to product sterility. In response to this challenge, the advent of MicroCurrent High Voltage Leak Detection (HVLD) technology presents a groundbreaking solution, boasting unparalleled sensitivity and precision in vial leak detection.

Overview of Vial Leak Testing

Vial leak testing constitutes a pivotal stage in pharmaceutical manufacturing, serving to pinpoint any potential breaches in vial integrity that could culminate in contamination or compromise product stability. Established techniques encompass visual inspection, dye ingress and other destructive methods. Nonetheless, these methods may fall short in identifying microleaks, characterized by minute defects capable of facilitating the ingress of contaminants. Hence, manufactures are now moving towards more deterministic technology that offer quantitative and reliable test results.

Vial Leak Testing using MicroCurrent HVLD Technology

MicroCurrent HVLD is a non-destructive method for assessing the integrity of container closures in non-porous pharmaceutical and parenteral products. This technique relies on the principle of electrical current to detect any leaks in a range of liquid-filled products, including those with extremely low conductivity such as sterile water for injection (WFI) and products containing proteins or suspensions.

Compared to conventional HVLD technology, MicroCurrent HVLD significantly reduces product voltage exposure to less than 5%, thereby eliminating any potential risk to the product and reducing Ozone formation during testing.

In this method, the container is scanned using high voltage probes. One side of the container is subjected to high voltage, while a ground probe is attached to the other side. If the container is intact, both sides offer complete electrical resistance, and no significant current passes through. However, if a micro-leak or fracture is present, breakdown resistance occurs, allowing current to flow through the defect.

HVLD is unique among leak detection methods as it does not require mass to pass through the defect site; instead, it transmits electricity through the crack. This sensitivity enables HVLD to detect leaks that other conventional leak test solutions may miss.

Benefits of MicroCurrent HVLD Technology

• Scalable from the R&D Laboratory to production line
• 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 <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

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.

In today's fast-paced world, businesses across various industries are constantly seeking ways to streamline their operations, enhance productivity, and deliver innovative solutions to their customers. To meet these demands, many companies turn to Comprehensive Integrator and Original Equipment Manufacturer (OEM) solutions. These versatile services offer a range of benefits, from reducing development time to ensuring product quality and scalability.

PTI's Integrator and OEM Solutions are designed to help manufacturers automate their package integrity testing processes. PTI offers a variety of sensory technologies, including Airborne Ultrasound, Vacuum Decay, Microcurrent HVLD, and Force Decay, that can be integrated into existing packaging lines or used to create new PIT systems. PTI also works closely with OEMs to integrate its technologies into their equipment.

PTI's Integrator and OEM Solutions offer a number of benefits, including:

• Increased productivity: By automating package integrity testing, manufacturers can free up operators to focus on other tasks, such as production or quality control.
• Improved product quality: Automated package integrity testing can help to identify and remove defective products from the production line, preventing them from reaching customers.
• Reduced costs: It can help to reduce the cost of labor and materials, as well as the risk of recalls.
• Compliance with regulations: PTI's solutions can help to ensure that products meet regulatory requirements for package integrity.

If you are a manufacturer who is looking to automate your package integrity testing process, PTI's Integrator and OEM Solutions can help. PTI has a team of experienced engineers who can help you to select the right sensory technology and integrate them into your production line. PTI also offers a variety of services, such as training and support, to help you get the most out of your PIT system.

Here are some of the specific solutions that PTI offers:

• Airborne ultrasound technology is used to inspect and analyze seals non-destructively. PTI's Seal-Scan® and Seal-Sensor products use airborne ultrasound to provide real-time seal quality inspection on the production line.
• Vacuum decay technology is used to leak test packages and containers. PTI's VeriPac platform uses vacuum decay to provide a deterministic method for leak testing that is repeatable and reliable.
• MicroCurrent HVLD technology is a CCIT test used to inspect packages for defects such as pinholes and cracks. PTI's MicroCurrent HVLD technology is non-destructive and can be used to inspect a variety of package materials.
• Force decay technology is used to measure the force required to open a package. PTI's Force Decay technology can be used to detect counterfeit products or to verify the integrity of packages.

If you are interested in learning more about PTI's Integrator and OEM Solutions, please visit our website or contact us for a consultation.

Automated Container Closure Integrity Testing (CCIT) of pre-filled syringes is a critical quality control process that ensures the product inside the syringe remains safe and effective during its shelf life. Pre-filled syringes are used to package and deliver various injectable drugs, such as vaccines, insulin, and other biologics.

The container closure integrity of pre-filled syringes can be compromised due to various factors such as: microcracks, defects in the rubber stopper, or improper sealing. To detect any potential defects in pre-filled syringes, automated CCI testing is done. This testing involves subjecting the pre-filled syringe to multiple conditions to check for any leakage or breakage in the container or closure.

Automated CCI testing of pre-filled syringes can be done utilizing techniques such as vacuum decay, high voltage leak detection, and tracer gas detection. These methods involve the use of specialized equipment to subject the pre-filled syringe to certain conditions including vacuum, high voltage, or exposure to a tracer gas. Any potential leaks or breakages in the container or closure can be detected by monitoring the pressure or electrical conductivity changes, or by the presence of the tracer gas

Automated CCI testing is crucial to ensure the safety and efficacy of pre-filled syringes. It is a reliable and efficient way of detecting potential defects in pre-filled syringes and ensuring that only products which meet the required quality standards are released to the market.

CCI Testing using E-Scan RTX

The E-Scan RTX platform is PTI’s fully automated, modular container closure integrity testing solution for pre-filled syringes. The RTX is a practical and reliable CCI solution that features a dynamic robotic design, tailored to fit your production requirements. This robust, adaptable platform utilizes MicroCurrent HVLD technology, a revolutionary form of HVLD that is the ideal CCI solution for high-risk, delicate biologic liquids. It provides a rapid PASS/FAIL result – its test cycle is only seconds – and is suitable for batch release testing, in line on production or in the lab.

PTI’s MicroCurrent HVLD technology uses a unique mode of DC voltage, applying no more than 50% of the voltage used on conventional high-voltage technologies. The nature of the PTI solution allows for the detection of leaks in packages with liquids of extreme low conductivities, including packages containing sterile water. The low voltage and current applied to the container also reduce the voltage the product is exposed to during the test. This technological advantage makes it the ideal solution for all parenteral and biologic solutions.

Benefits of E-Scan RTX

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

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.

Biological drug products are complex, large-molecule drugs that are derived from living organisms or their components. They are designed to mimic, augment or replace the function of naturally occurring molecules in the body. These drugs are often produced through biotechnology, which involves manipulating living cells to produce specific proteins or other molecules.

Examples of biological drug products include monoclonal antibodies, recombinant proteins, vaccines, and gene therapies. These drugs are used to treat a wide range of diseases, including cancer, autoimmune disorders, and genetic diseases.

Biological drug products are often more expensive than traditional small-molecule drugs because they are more complex to manufacture, require specialized facilities, and are subject to rigorous testing and regulatory requirements. However, they can also provide more targeted and effective treatments for certain conditions.

Package integrity testing is an essential part of ensuring the safety and efficacy of biologics. Any damage or compromise to the packaging of biologics can lead to degradation or contamination, which can impact their efficacy and safety. The choice of method depends on the specific biologic being packaged, the type of packaging used, and the regulatory requirements. It is important to perform Container Closure Integrity tests (CCIT) solutions. at multiple stages of the manufacturing process to ensure that the biologic remains safe and effective from production to patient use.

CCI Testing of Biologics using E-Scan MicroCurrent HVLD

The E-Scan 655 is a revolutionary deterministic offline micro leak test instrument that utilizes a new class of HVLD technology to inspect vials, syringes, and other liquid filled parenteral products for container closure integrity. The E-Scan 655 technology is a MicroCurrent conductivity test method, HVLDmc, that is completely non-destructive to the container and product; exposing the package and product to lower voltage than other conductivity-based solutions.

The E-Scan MicroCurrent HVLD technology is often used in the pharmaceutical industry for detecting leaks in parenteral drug products, such as vials and syringes. E-Scan MicroCurrent HVLD technology is considered to be a reliable and efficient method for leak detection, ensuring the integrity of the drug product and patient safety.

The technology uses a non-contact and non-invasive test method that requires no sample preparation. The E-Scan 655 features a fast test cycle and simple operation. Additional benefits include quick changeover and easy recipe setup to accommodate a wide range of products and applications. E-Scan MicroCurrent HVLD technology can be migrated from laboratory to 100% inline production applications.

Benefits of E-Scan MicroCurrent HVLD

• 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 <1207> 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.

The ability to evaluate the possibility of the container closure system to maintain a sterile barrier or to prevent leakage is a vital step in determining the safety and suitability of primary packaging. The United States Pharmacopeia (USP) and Food and Drug Administration (FDA) implement strict guidelines for container closure integrity testing (CCIT) as the driving factors behind safety examination of materials and closure systems in the US.

Historically, the two most common procedures for testing container closure integrity were dye immersion and microbial immersion (both probabilistic tests). In 2016, USP provided recommendations stating that deterministic methods are favored over probabilistic methods for CCIT because they produce reliable and predictable findings at low detection limits.

Non-Destructive CCI Test Methods Offered by PTI

1. Vacuum Decay Technology

Vacuum Decay has been substantiated as one of the most practical and sensitive vacuum-based leak detection methods. This test provides a quantitative result that is reliable, reproducible, and accurate, as well as a pass or fail judgement. PTI's VeriPac equipment was used to produce the ASTM F2338 standard vacuum decay test procedure. It is also recognized in the United States Pharmacopeia Chapter on CCI and is classified in ISO 11607. Using an absolute pressure or differential pressure transducer leak test device, VeriPac's non-destructive technology can detect package leaks and unseen defects.

2. Volumetric Imaging Technology

The OptiPac One-Touch Tool-less technology is intended for non-destructive leak detection in blister packages. To identify leaks, the OptiPac employs 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.

2. MicroCurrent HVLD Technology

PTI packaging and inspection systems transformed the traditional HVLD method and offered a game-changing 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 the 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 faults.

PTI provides package leak testing, seal integrity testing, and container closure integrity testing systems (CCIT). Our technologies eliminate subjectivity from package testing and employ ASTM-compliant test methodologies. The inspection technologies developed by PTI are deterministic test procedures that generate quantitative test result data.

Parenteral preparations are defined as solutions, suspensions, emulsions for injection or infusion, powders for injection or infusion, gels for injection and implants. They are sterile products intended to be administrated directly into human bodies. Parenteral drug products are expected to be free from microorganisms, pyrogenic substances as well as other visible particles. Contaminated parenteral drug products can cause serious health concerns to the patient. Hence, sterility assurance and package integrity testing are of paramount importance in parenteral drug manufacturing. Read on to know more about parenteral products package testing methods offered by PTI.

Parenteral products package testing methods:

1. Vacuum Decay technology

Vacuum Decay technology is a non-destructive Container Closure Integrity test method primarily used to detect leaks in package seals. Proven to be the most practical and sensitive vacuum-based leak test method, Vacuum Decay technology is capable of identifying leaks in sealed rigid, semi-rigid and flexible packaging made of non-porous or porous materials. It provides reliable, accurate and repeatable test results that ensure deterministic package testing and leak detection. Vacuum Decay technology has established itself as a non-destructive alternative to traditional test methods like Water Bath and Dye Ingress, making it a practical solution for leak detection in the Pharmaceutical and Medical Device industry.

How does Vacuum Decay technology work?

The principle behind Vacuum Decay technology is simple and it challenges container integrity based on fundamental physical properties. The test begins by placing sample packages in a closely fitting evacuation test chamber, which is equipped with an external vacuum source. Based on the test sample and level of sensitivity required, a pre-determined vacuum level is chosen for the test. The next step involves evaluating the test chamber and test system dead space for a pre-determined period. Differential pressure transducers are used to monitor changes in vacuum levels for a specified period. A pressure increase beyond the predetermined pass/fail limit indicates container leakage.

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
• ASTM Test Method F2338, FDA Consensus Standard and USP 1207 compliant
 

2. MicroCurrent HVLD Technology

PTI’s Microcurrent is patent-pending unique CCI technology that has revolutionized the conventional high voltage leak detection method. It is a non-invasive and deterministic container closure integrity testing method that is effective across all parenteral and biologic products including low conductivity liquids such as sterile water for injection. The Microcurrent HVLD test method is highly effective in detecting the presence and location of pinholes, micro-cracks, stopper/plunger leaks, non-visible leaks under crimping and many other defects across applications like pre-filled syringes, vials, cartridges, ampoules, BFS, bottles and pouches. A unique mode of Microcurrent HVLD uses about 50% less voltage and reduces the exposure of product and environment to less than 5% of the voltage when compared to conventional HVLD solutions. The E-scan HVLD series is a leading solution of sturdy container closure integrity test equipment.

Benefits of MicroCurrent HVLD technology

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

Packaging is an essential part of the pharmaceutical industry, given the sensitive nature of the contents. High-risk medications and lifesaving drugs need utmost care and protection until they reach the patient. As such, stringent industry standards apply to pharmaceutical packaging. Manufacturers give high priority to safety and quality while selecting packaging materials for a drug or healthcare product. The packaging should be able to act as a barrier against external contamination and chemical reactions. Exposure to reactive gases can alter the physical, chemical and biological attributes of the products. This makes Container Closure Integrity Testing of pharmaceutical packaging a regulatory requirement.

Role of MicroCurrent HVLD in ensuring pharmaceutical package integrity

Often referred to as the conductivity and capacitance test, High Voltage Leak Detection (HVLD) is a test method found to be highly effective in detecting the presence and location of leaks in a wide range of pharmaceutical and parenteral applications. It can be used for leak testing in nonporous, rigid or flexible packages, as well as packages containing liquid or semi-liquid products. High Voltage Leak Detection test is conducted using electrical conductivity and resistance principle. 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. Compared to other leak detection methods that rely on flow of gas or liquid, HVLD technology relies on “flow” of current. This reduces challenges with defect clogging compared to flow-based analysis.

The latest evolution of HVLD, PTI’s patent pending MicroCurrent technology, aims to achieve a high level of CCI assurance across the entire range of pharmaceutical products. 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. Ozone in the headspace of a container can be detrimental to the product, and in the operating environment can affect respiratory health.

Benefits:

Non-destructive Container Closure Integrity Test (CCIT)

Requires no sample preparation

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 testing may be understood as a set of techniques used to protect the contents of a package from potential physical, chemical and microbial threats. It plays a crucial role in determining and maintaining sterility and shelf life of pharmaceutical products, medical devices, and food and nutrition products. Since such products are extremely sensitive to external environmental conditions, even a minute breach in the package can cause micro-organisms, reactive gases or other harmful substances to enter the product. This can result in serious health issues to the end user and affect brand loyalty of manufacturing companies. As such, testing for leaks is an important aspect of the manufacturing process.

Historically, manufacturers relied on destructive testing methods like Water Bath or Dye Ingress as well as other unreliable methods such as Visual Inspection to test integrity of packages. However, such tests lacked accuracy and reliability in test results. Moreover, being destructive testing methods, it caused damages to the package being tested making it unfit for use. These limitations of destructive techniques prompted manufacturers to opt for non-destructive testing methods that do not harm the product and provide reliable, repeatable and quantitative rest results. Reduction in waste coupled with material cost advantage gives non-destructive methods an practical edge over destructive test methods. Examples of non-destructive testing methods include Vacuum Decay technology, Airborne Ultrasound technology and Microcurrent HVLD technology.

VeriPac test systems for precise and reliable package integrity testing

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

Technology Overview

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

Benefits of VeriPac series

• Non-destructive, non-subjective, no sample preparation
• Deterministic, quantitative test method
• Defect detection down to 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

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

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.