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High-risk pharmaceutical products refer to medications and substances that, due to their nature or intended use, pose a higher level of risk to patients and the public. These products often include injectable drugs, biologics, vaccines, and other sensitive formulations that require stringent quality control measures to ensure patient safety and regulatory compliance.

The packaging of high-risk pharmaceutical products presents unique challenges due to the need for exceptional product protection, stability, and, most importantly, containment of the product to prevent contamination. As these products are often administered directly into the body, maintaining the integrity of the container closure system is critical to prevent microbial ingress, oxygen exposure, and other factors that could compromise the drug's efficacy and safety.

Container Closure Integrity (CCI) testing is a vital process within the pharmaceutical industry to verify that the packaging of a product effectively prevents any leakage or contamination. This testing is crucial in ensuring that the pharmaceutical product maintains its integrity throughout its shelf life, safeguarding patient safety and therapeutic efficacy.

MicroCurrent HVLD Technolgy for Testing Integrity of High-Risk Pharma

PTI's MicroCurrent HVLD technology represents a non-destructive and non-invasive approach to testing the container closure integrity (CCI) of various liquid-filled products, including pre-filled syringes, vials, cartridges, ampoules, blow-fill-seal (BFS) containers, bottles, and pouches. This method has proven to be highly effective in ensuring the integrity of container closures in diverse applications.

The technology employs electrode probes to scan sealed containers, aiming to detect any potential leaks. By analyzing changes in the current flow, both the existence of defects in the container and their approximate locations can be identified with precision. This makes the MicroCurrent HVLD technology particularly versatile, capable of detecting leaks in a wide range of liquid-filled products, even those with extremely low conductivity, such as sterile water for injection (WFI) and proteinaceous products with suspensions.

One notable advantage of MicroCurrent HVLD is its efficiency in terms of voltage usage. It utilizes approximately 50% less voltage compared to conventional HVLD solutions, contributing to a more energy-efficient and environmentally friendly testing process. Moreover, the reduced voltage exposure (less than 5% compared to traditional methods) minimizes potential risks to both the product and the testing environment.

Benefits of MicroCurrent HVLD:

• Deterministic, non-destructive, non-invasive, non-subjective
• High level of repeatability and accuracy
• Ideal package integrity solution for liquid filled parenteral products
• Low voltage exposure to the product and environment
• Offline and automated online inspection
• Referenced in USP 1207 guideline

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

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

Vacuum Decay Technology

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

MicroCurrent HVLD Technology

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

Force Decay Technology

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

Volumetric Imaging Technology

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

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

Blister packaging is a popular form of packaging used in the pharmaceutical, medical device, and consumer goods industries. It consists of a cavity or pocket made from a formable web of plastic or aluminum, which securely holds the product (such as tablets, capsules, or small devices) and is sealed with a lidding material.

Ensuring the integrity of blister packages is of utmost importance, especially for products that are sensitive to moisture, air, or contaminants. A leak in the blister package can compromise the quality, efficacy, and shelf life of the enclosed product, leading to potential safety risks for consumers and financial losses for manufacturers.

Leak testing is a critical quality control process that assesses the seal integrity of blister packages to identify potential leaks or weak seals. By performing leak testing, manufacturers can identify defective packages and take corrective action before products reach the market.

OptiPac Technology for Blister Package Leak Detection

The OptiPac One-Touch Tool-less system is designed for non-destructive Container Closure Integrity Testing (CCIT) of blister packages. It is a deterministic technique that utilizes volumetric imaging in vacuum together with topographic imaging to identify leaks and where they are located. The OptiPac employs controlled inputs and measured outputs using concepts similar to those used in a vacuum-based dye ingress test, but without the inconvenience and reliability difficulties of the dye ingress approach. By utilizing One-Touch Technology, OptiPac provides a quick test cycle without the need for complicated parameter modifications or changeovers, as seen with other non-destructive blister package inspection systems.

OptiPac Blister Package Inspection System which makes use of volumetric imaging technology provides high levels of sensitivity and reliability. The volumetric imaging method uses many imaging techniques with a complex deep algorithm. The test operator selects a recipe for the blister package using the HMI touch screen, then arranges it in any direction on the test plate. Vacuum is drawn to a predetermined vacuum as soon as he presses the start button. Under vacuum, the blisters enlarge, and any air leaks cause the air to be forced out of the blister. If the blister has a leak, air enters the chamber and collapses the blister cavity. To identify which blister cavities are defective, volumetric images and measurements can be acquired during the test technique. Additionally, the system shows the quantitative measurement for each product tested along with a clear pass/fail result.

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.
• No changeover to test different blister formats.
• Pre-loaded recipe library with easy recipe setup and validation of new blister formats.
• Completely tool-less.
• Identifies defective cavity.

Proper leak testing can improve production efficiency and reduce waste by identifying and resolving issues in the packaging process promptly. It enhances overall product quality and increases consumer confidence, which are essential factors for maintaining a competitive edge in the market.

As technology advances, we can expect further developments in leak testing methods, leading to even more accurate, efficient, and cost-effective solutions. Manufacturers should stay updated on these advancements and continuously improve their testing procedures to stay at the forefront of quality assurance.

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

Overview of Airborne Ultrasound Technology

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

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

Seal-Scan and Seal-Sensor Technology

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

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

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

Benefits of Airborne Ultrasound Technology

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

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

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

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

Vacuum Decay Technology for CCI Testing of Intravenous Bags

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

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

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

Benefits of Vacuum Decay Technology

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

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

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

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

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

Overview of Automated Parenteral CCI Solutions

1. E-Scan MicroCurrent RTX

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

Benefits of E-Scan MicroCurrent RTX

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

2. VeriPac LPX Technology

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

Benefits of VeriPac LPX Technology

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

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

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

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

Testing Pre-filled Syringes Using E-Scan RTX

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

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

Benefits of E-Scan RTX

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

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

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

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

What are the Challenges Associated with Tyvek Package Testing?

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

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

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

Testing Tyvek Packages Using Airborne Ultrasound Technology

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

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

Benefits of Airborne Ultrasound Technology

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

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

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

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

Overview of OptiPac Technology

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

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

Functions Offered by OptiPac's Insightful Technology

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

OptiPac Benefits

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

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

Automated Container Closure Integrity Testing (CCIT) is a process used to evaluate the integrity of containers for parenteral products, such as vials or pre-filled syringes, to ensure that they are free of defects or leaks. The goal of CCI testing is to ensure that the contents of the container remain sterile and protected from contamination.

There are several advantages to using automated CCI testing, including:

• Speed and Efficiency: Automated CCI testing is much faster and more efficient than manual operator testing, which can save time and resources for manufacturers.
• Accuracy: Automated CCI testing is less prone to human error, which can result in more accurate results and increased confidence in the integrity of the container.
• Reproducibility: Automated CCI testing is designed to be repeatable, allowing manufacturers to consistently and accurately monitor the integrity of containers.

Parenteral Products and its Advantages

Parenteral products are medical products that are administered directly into a patient's bloodstream, bypassing the digestive system. This means that the product is delivered into the body through a route other than the orally, such as intravenously, intramuscularly, subcutaneously, or through other routes. Examples of parenteral products include injectable drugs, intravenous solutions, intravenous nutrition products, blood transfusions, and others. These products are subject to strict quality control and regulatory standards to ensure their safety, efficacy, and sterility, and to maintain the integrity of their packaging to prevent contamination. The specific form of the parenteral product (e.g. solution, suspension, etc.) depends on the product and patient needs.

Advantages of Parenteral Products

Here are some advantages of parenteral products:

• Rapid onset of action: Parenteral products are delivered directly into the bloodstream, which allows for a faster onset of action compared to oral administration. This can be especially important in emergency or critical care situations.
• Measures and verifies container closure system integrity
• More effective for some conditions: Some drugs and therapies are more effective when delivered parenterally because they are absorbed more quickly or may not be well absorbed orally.
• Alternative for patients unable to take oral medications: Parenteral products provide an alternative for patients who are unable to take oral medications, such as patients with gastrointestinal issues or patients who are unconscious.

CCI Testing of Parenteral Products

CCI Testing is performed on parenteral products using a variety of methods, including vacuum decay leak testing, high-voltage leak detection, and others. The specific method used will depend on the type of product, the packaging material, and the desired level of sensitivity. The goal of CCI testing is to provide confidence in the integrity of the packaging and prevent any incidents of contamination or product failure.

The VeriPac LPX Series is a range of completely automated package quality inspection systems for container closure integrity inline testing. The VeriPac LPX has a dynamic robotic design that is customized to your production needs. To fulfil the demands of a production line, the LPX Series offers modular, scalable solutions. This adaptable platform offers a range of package forms that may be reliably automated. Flexible packaging, rigid containers, and parenteral pharmaceuticals are only a few examples of the applications for LPX automation.

The packages will be picked up and placed by a quick robotic gripper arm into the VeriPac LPX test chambers, where a quick vacuum-based test will be performed. Along with the quantitative test result data, a clear PASS/FAIL result is shown. In order to maintain continuous flow and seamless downstream processing, the packages will then be returned to the product line. Rejects are automatically taken off the production line.

Benefits of VeriPac LPX

• Automated testing enables the highest level of container quality assurance.
• Deterministic, quantitative test method.
• ASTM Test Method F2338 and FDA standard.
• Highly accurate test results - low false positives and false negatives.
• Non-destructive, non-subjective, no sample preparation.
• USP <1207> complaint.

CCI testing is used to evaluate the sealing of the product container and detect any leaks, breaches, or defects in the packaging. This is important because parenteral products are sensitive to environmental factors such as temperature and pressure changes, and any breaches in the packaging could result in contamination or degradation of the product.

Overall, automated CCI testing is an important tool for ensuring the safety and quality of parenteral products, and is increasingly being used by manufacturers to ensure that their products meet regulatory requirements and industry standards.

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

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

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

Explain MAP

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

VeriPac Series for Testing MAP Meat Packages

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

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

Advantages of VeriPac Series

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

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

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

Ensuring Dairy Products Package Integrity with VeriPac FLEX Series

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

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

Technology Overview

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

VeriPac FLEX Series Benefits

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

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

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

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

Helium Leak Detection Technology Overview

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

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

Why Use Helium as a Tracer Gas?

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

Helium Leak Detection Merits

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

Applications of Helium Leak Detection

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

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

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

Vacuum Decay Technology

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

Applications of Vacuum Decay Technology in Various Industries

• Pharmaceutical

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

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

• Medical Device

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

Vacuum Decay Technology Benefits

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

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

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

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

VeriPac Vacuum Decay Series for Snack Food Package Integrity Testing

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

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

Working Principle

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

VeriPac Inspection System Benefits

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

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

To assure the safety of pharmaceutical products, during their distribution and storage, manufacturers perform Container Closure Integrity testing (CCI testing). CCIT helps in evaluating the integrity and stability of packaging or containers till they reach their destination. Although destructive CCI techniques such as water bath, and dye tests can find leaks, they are time-consuming, inaccurate, and provide subjective test results. Furthermore, they cause considerable product loss and waste. This leads to an increase in the demand for non-destructive deterministic CCI methods such as Vacuum Decay, MicroCurrent HVLD and Airborne Ultrasound.

Vacuum Decay is a non-destructive CCI testing method that focuses on package integrity and leak path detection. Unlike manual inspection and other non-deterministic testing techniques, Vacuum Decay provides quantitative, deterministic, and accurate test results to assure package integrity. Vacuum Decay technology can handle a wide range of package types, including filled and sealed rigid, semi-rigid, and flexible packaging comprised of non-porous or porous materials.

Technology Overview

The Vacuum Decay method operates by enclosing sample packages in a tightly fitted evacuation test chamber with an external vacuum source. The test chamber is monitored using single or dual vacuum transducer technology for both the level of vacuum and the change in a vacuum throughout a defined test duration. The existence of leaks and defects inside the package is indicated by variations in an absolute and differential vacuum. This inspection method is suitable for offline laboratory testing and can be customized for manual or completely automated operations. The test cycle is non-destructive to both the product and the packaging and only takes a few seconds. It saves money by not wasting products for leak tests and produces a return on investment in less than 6 months for many products.

VeriPac Vacuum Decay Technology

VeriPac Vacuum Decay technology is the optimal non-destructive solution for determining container closure integrity in a variety of package configurations. VeriPac Series will evaluate a wide range of high-risk packaging applications and ensure that the product fulfills regulatory and consumer integrity standards. The VeriPac product line systems analyze the package in a quick, repeatable, and reproducible way, providing quantitative and deterministic test results. Vacuum Decay technologies can identify package leaks and invisible defects utilizing a non-invasive, non-subjective technique that does not need sample preparation.

The VeriPac Series is a practical alternative to destructive testing methods and can detect leaks down to sub-micron levels. An appropriate VeriPac model is chosen based on the type of package and leak test sensitivity required. Configurations can be optimized and tailored to specific applications.

• Non-destructive technology
• Defect detection down to 0.05 ccm
• Accurate, reliable, and repeatable results
• Pass/fail results backed by quantitative test data
• No tools are required to evaluate alternative package formats
• Identifies which cavity is defective
• Eliminates destructive, subjective testing methods
• Supports sustainable packaging and zero waste initiatives
• FDA recognized standard for package integrity testing

Over the years, Vacuum Decay leak testing has proven to be one of the most practical and sensitive vacuum-based leak detection technologies. Vacuum Decay technology is recognized by the American Standard Testing Method ASTM F2338 and detects leaks in hermetically sealed containers, making it useful for both the pharmaceutical and medical device industries.

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

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

What is CCIT?

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

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

Leak Testing Vials Using Various CCI Techniques

• MicroCurrent HVLD Technology

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

• Helium Leak Testing

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

• Vacuum Decay Technology

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

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

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

Food Package Integrity Testing Using VeriPac 310

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

Technology Overview

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

VeriPac 310 Benefits

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

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

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

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

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

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

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

Benefits of E-Scan MicroCurrent technology

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

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

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

Testing Package Integrity Using VeriPac 355 Series

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

Technology Overview

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

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

Advantages of VeriPac 355

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

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

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

Testing Challenges in the Medical Device Industry

There are three basic approaches to package integrity testing:

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

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

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

How Vacuum Decay and Airborne Ultrasound Technologies are Automated?

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

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

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

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

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

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

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

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

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

Technology Overview

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

Vacuum Decay (ASTM F2338)

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

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

Airborne Ultrasound (ASTM F3004)

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

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

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

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

Various CCI Services

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

Feasibility Studies for Testing Package Quality

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

Test Method Development for CCI Testing

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

Equipment and Application Support

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

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

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

CCIT also offers the following services:

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

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

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

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

Integrity Testing of Ampoules using MicroCurrent HVLD

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

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

MicroCurrent HVLD Benefits

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

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

Testing the integrity of package seals helps ensure that nutritional packaging provides required product protection. Maintaining the reliability of package seals is critical for product quality and food safety. Airborne Ultrasound and Vacuum Decay technology can be used for testing package and seal integrity of nutritional packages. These CCI technologies produce quantitative, and repeatable results, due to their deterministic nature. The primary purpose of implementing these testing methods is to ensure the safety of consumers.

Overview of Nutritional Packaging Inspection

Nutritional packaging plays a significant role in securely delivering the product. The majority of nutritional products are shelf-stable in nature, therefore package performance is typically a concern. Chemical reactions occur naturally in all nutritional products. Any break in the nutritional packing might lead to the products deteriorating due to air, moisture, and microbial exposure. Fats and other nutrients for infants might become rancid and inactive. The quality and safety of the contents that reach the customer are determined by nutritional packaging.

Package and seal integrity techniques have great expertise in the packaging industry, which helps in inspecting nutritional packages in the most efficient method in order to preserve package and product quality. For the food and nutritional packaging industries, CCIT provides a variety of technologies and solutions. The two most common nutritional package inspection technologies are vacuum decay and airborne ultrasound. While vacuum decay is utilized for applications such as filled and sealed rigid containers, dry products in pouches, and flexible packaging. Retort pouch final seal inspection can be achieved using non-destructive with airborne ultrasound technology.

Technologies to Assure Package and Seal Integrity

Vacuum Decay Technology

Vacuum decay is a package test method for vacuum-based leak detection. It is considered one of the most practical and sensitive test methods used in nutritional package inspection. When compared to destructive test procedures, this technology not only provides for a better understanding of package quality but also minimizes waste. As a result of the waste reduction, the return on investment is higher, and the operation is closer to green initiatives.

The Vacuum Decay leak testing method operates by enclosing package samples in an evacuation test chamber with an external vacuum source. The test chamber is monitored for both the level of vacuum and the change in vacuum during a pre-defined test duration using single or dual vacuum transducer technology. The existence of leaks and defects within the package is indicated by variations in an absolute and differential vacuum. Test systems can be designed to be operated manually or fully automated.

Airborne Ultrasound Technology

Pouches are the common form of packaging for most nutritional products. Hence, it is necessary to ensure the package integrity of such pouches. Airborne Ultrasound is a non-destructive and non-invasive method of inspecting seal quality. In this method, ultrasound waves are permitted to pass through the package seal, causing sound waves to be reflected. The fluctuation in the reflected signal intensity is used to detect defects.

Airborne Ultrasound technology is available in both online and offline solution options. It has been proven to be one of the most successful non-destructive testing procedures for flexible package seals. According to ASTM F3004-13, this is the standard test technique for evaluating seal quality and integrity using airborne ultrasound. This method has high applicability in the food and nutrition industry.

Vacuum Decay technology and Airborne Ultrasound technology are both ASTM test methods and also FDA consensus standards for package integrity and seal quality inspection of nutritional products. An appropriate testing method for inspecting nutritional packages is selected based on the nature of the product and its package.

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

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

MicroCurrent HVLD to assure CCI in parenteral products

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

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

What sets MicroCurrent HVLD apart from traditional HVLD technology?

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

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

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

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

An effective package integrity solution for vials will ensure:

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

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

Helium Leak Detection Technology for CCI testing of Vials

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

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

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

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

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

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

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

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

Evaluating leak test using Vacuum Decay Vs MicroCurrent HVLD Test Methods

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

Technologies Overview

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

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

Benefits of Vacuum Decay

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

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

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

Benefits of MicroCurrent HVLD

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

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

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

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

Container Closure Integrity (CCI)

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

Test methods

MicroCurrent HVLD

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

Helium Leak Detection

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

Vacuum Decay

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

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

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

Ensuring quality control with Vacuum decay technology

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

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

Benefits of using Vacuum decay technology

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

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

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

How to ensure pharmaceutical package sterility with Vacuum Decay Technology?

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

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

Advantages of Vacuum Decay Technology

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

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

Airborne Ultrasound is a deterministic test method for seal quality inspection and analysis of material types such as aluminum, foil, paper, plastic, poly, film & Tyvek. In accordance with ASTM F3004-13, airborne ultrasound is a standard test technique for evaluating seal quality and integrity. It has been proven to be one of the most successful non-destructive testing methods for flexible package seals. As per research the standard seal inspection methods are inaccurate because they fail to detect invisible defects and mistakenly reject well sealed pouches. Airborne Ultrasound technology, on the other hand, has been proven in the field of both online and offline solution options

How does Airborne Ultrasound Technology mitigate the risk of food and nutrition packaging?

Packaging has been an integral part of food and nutrition preservation in recent decades. Food is packaged with the intention of being transported and stored. Quality, brand, safety, and value of a product are all affected by packaging. To ensure the safety of their products, food producers pack their products in a way that ensures they are correctly constructed, tamper-proof, defect-free, and complete.

In Airborne Ultrasound technology, sound waves are reflected when ultrasound waves are allowed to travel through the packaging seal. Change in the intensity of the reflected signal is used to identify defects. The seal is positioned in a straight line between a pair of transducers, then moves them along the seal. Transmission and reflection of the ultrasound occur at the transition from one medium to another. When the difference in acoustic properties between two materials is greater, only less sound is transmitted, and more sound is reflected. Thickness variations have a minor impact. It is possible to identify a wide range of defects, including those that are visible and invisible, leaking and non-leaking, process-related and random.

As one of the most successful methods for non-destructive testing of flexible packaging, Airborne Ultrasound technology was awarded the ASTM Test Method F3004-13 in 2013. The flow of gas or liquid through the seal is an example of seal defect. Inability to discover non-leak defects is a basic problem with leak testing methods. However, Airborne Ultrasound technology gives a complete way to evaluating seal quality, even when a seal has a defect but may not leak.

Key benefits of Airborne Ultrasound Technology

• Deterministic inspection technique resulting in quantitative results
• Non-destructive, non-subjective, zero sample preparations
• Detects defects in the final pouch seal in real time
• This method works with any material and combination, regardless of color, porosity, surface finish, transparency, and print
• The subjective manual vision inspection procedures are no longer necessary
• Results are repeatable and reliable
• Testing the final pouch seal integrity at a low cost
• Characterizes the seal's overall quality and consistency

For sterile medical devices, seal integrity testing ensures product efficacy, shelf-life stability, and microbial sterility. Common defects that can threaten the integrity of the seal include voids, wrinkles, dust or other random particles. Hence, inspecting seals after they have been formed is important. Earlier, visual inspection or other destructive testing methods were used for seal quality inspection. However, they lacked accuracy and reliability in test results. But technology is changing. Today, the market offers a range of non-destructive inspection techniques that ensure highly sensitive and reliable seal quality inspection. Even then, the suitability depends on the type of packaging and the size of defect that needs to be inspected.

Relevance of Airborne Ultrasound Technology in Seal Quality Inspection

Airborne Ultrasound technology is a non-destructive container closure integrity testing method, capable of examining seal quality for defects. 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. It is an ASTM Test Method F3004 and FDA recognized standard for seal quality testing. 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 can identify various types of seal defects; visible and invisible, leaking and non-leaking, process-related and random.

Latest improvements in Airborne Ultrasound Technology are in the form of Seal Scan (Offline) and Seal-Sensor. Both these technologies utilize non-contact airborne ultrasonic testing technology. Seal-Scan® technology has been proven in the field by several online and offline units installed. 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.

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.

Over the last two decades, pharmaceutical industry has seen tremendous growth in the form of technological advancements and drug delivery system innovations. However, such innovations have increased quality assurance challenges for drug manufactures. For this reason, drug product manufacturers give at most importance to their quality control procedures as well as package integrity tests. All packaging forms, whether pouches constructed of porous or nonporous material, rigid thermoformed trays with Tyvek or film lids, bottles with induction-welded seals, or blister packs, need verification that their sterile-barrier characteristics are not compromised. 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 emphasized the importance of verification of microbial barrier properties of a pharmaceutical product package (i.e., CCI).

Relevance of CCIT in pharmaceutical package testing

Container Closure Integrity Testing is an assay to evaluate whether container closure systems can maintain sterile barriers against potential damage. Even a minute defect in the container can cause external elements to enter the product, thereby reducing its shelf life. Common threats that can pass through a defected container closure system include microorganisms, reactive gases, and other substances. Considering the ability of such threat to deteriorate product quality, undertaking appropriate CCI tests are beyond crucial. However, it should be noted that CCI is not a one-time process, rather an integral and comprehensive approach. It is evaluated throughout the manufacturing lifecycle of a sterile drug product -from primary package development until the products are dispatched.

Container closure systems are made up of primary packaging components and secondary packaging components. Components like vials or syringes that are in direct contact with the product are called primary packaging components. Although there are multiple CCI techniques available in the market today, regulatory guidelines have broadly classified methods into probabilistic and deterministic test methods. Under a probabilistic test method, results are generated through a series of events, each with a respective probability distribution. Thus, the accuracy of the results cannot be assured. In contrast to a probabilistic method, deterministic test methods assure quantitative results with higher level of accuracy and reliability. The United States Pharmacopeia in 2016 issued new guidelines stating that deterministic methods are preferred over probabilistic test methods. Container closure integrity testing can be performed in many different ways. All the testing methods have pros and cons. Given below is a list of non-destructive Container Closure Integrity test methods:

• Airborne Ultrasound technology
• Vacuum Decay technology
• Microcurrent HVLD technology
• Helium Leak Detection
• Pressure Decay leak testing
• Force Decay leak testing

Right from clinical trials to drug packaging, all aspects for pharmaceutical industry are subject to strict quality control regulations. The process of selecting and validating appropriate packaging for pharmaceutical products takes a significant effort. Pharmaceutical package testing is conducted to ensure the suitability of drug packaging for its intended use. It included all components containing the product, even if they are in direct contact with the drug or not. As such, containers should be capable of retaining the healing properties of the drug product throughout its shelf life or until it is administered. Even a minute breach in container closure integrity can compromise the safety and effectiveness of the drug product. This realization has prompted pharmaceutical product manufacturers to conduct appropriate container closure integrity tests to ensure product sterility throughout its lifecycle.

Why use Vacuum Decay technology for pharmaceutical package testing?

PTI’s Vacuum Decay technology is a non-destructive container closure integrity testing method, capable of evaluating both liquid and air-filled containers and detecting defects as small as below 1 micron. Non-destructive testing provides a greater understanding of package quality while also reducing waste. Waste reduction delivers a fast return on investment and brings operations closer to green initiatives. Proven to be the most practical and sensitive vacuum-based leak test method, Vacuum Decay technology is an ASTM test method, FDA consensus standard, eliminating false positives and subjective results associated with manual visual inspection. Vacuum Decay technology can identify 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 operates by placing sample packages in a closely fitting evacuation test chamber, which is equipped with an external vacuum source. Single or dual vacuum transducer technology is used to monitor the test chamber for both the level of vacuum as well as the change in vacuum over a predetermined test time. The changes in absolute and differential vacuum indicate the presence of leaks and defects within the package. Vacuum Decay technology is a practical alternative and significant improvement to destructive test methods and can precisely detect leaks as small as 5 microns, identifying process issues before they become critical, avoiding catastrophic quality deviations.

Benefits of PTI’s Vacuum Decay Test System

• Better process control - reliable and sensitive leak detection of quality critical defects.
• The advantage of test results that are both qualitative (pass/fail) and quantitative (Statistical data with each test result).
• Repeatable test results demonstrate the reliability of the instrument and test data.
• Cost savings - Eliminates product loss, waste and mess of both packaging and coffee that results from using destructive testing methods
• Using a non-destructive leak test method allows an increase in the number of products samples tested.
• Rapid test cycle and minimal training required to operate tester.
• Rapid ROI due to substantial cost savings and elimination of product loss.

Talking about medical devices, ensuring seal quality or seal strength of sterile medical device packaging are extremely crucial as well as highly regulated. Medical device package seal contains a flexible barrier which is joined to the rigid container through an advanced adhesive. A defect in the seal such as an incomplete or weak seal can initiate leaks, contaminating the product and reducing its shelf life. Hence, for quality control purposes, seal quality inspection of medical device packages is mandatory.

Historically, manual inspection was the most popular method used to inspect seal defects. Although this is covered by an ASTM method (ASTM F1886), it lacked accuracy and reliability in terms of test results. “There is a huge shift in the industry towards deterministic and quantitative test methods,” comments 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.”

Airborne Ultrasound technology is a non-destructive seal integrity test method capable of advanced seal quality inspection of pouches and flexible packaging. Seal defects can be of two types- leak defects and non- leak defects. While it is easier to detect a leak defect, detecting non-leak defects can be a challenge for manufacturers. However, Airborne Ultrasound technology allows non-destructive Container Closure Integrity testing of multiple seal defects including visible and invisible, leaking and non-leaking, process-related and random- making it a practical solution for medical device seal quality inspection.

Technology overview

Airborne Ultrasound technology 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. In the presence of a leak, the signal strength is either eliminated or reduced. Such variations in signal strength are analyzed to identify the defects. Seal scan testing is a practical solution to recognize defects, such as inconsistent seals or areas of seals that fail to meet minimum width requirement. Seal-Scan® and Seal-Sensor utilize non-contact airborne ultrasonic testing technology for advanced seal quality inspection. Seal-Scan® technology has been proven in the field by several online and offline units installed.

Benefits of Airborne Ultrasound technology

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