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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.