Blogs

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

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

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

Vacuum Decay Technology

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

Volumetric Imaging Technology

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

Airborne Ultrasound Technology

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

Microcurrent HVLD technology

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

Non-destructive Package Integrity Testing Method Benefits

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

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

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

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

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

Vacuum Decay Technology

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

MicroCurrent HVLD Technology

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

Force Decay Technology

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

Volumetric Imaging Technology

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

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

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.