Package Integrity Testing Package integrity testing provides vital information used in determining the ability of the package to maintain the sterility and shelf life of the product. Various tests that expose the package to mechanical and environmental hazards to quantify the package’s performance: Bubble Leak Testing: Uses water submersion and air pressure to test for bubbles, which indicate a leak Dye Penetration Testing: A high precision test method that is used for locating package seal defects Real Time Aging Testing: Determines a product’s shelf life or lifespan Accelerated Aging: Uses heightened conditioning of heat and humidity to speed up the normal aging process to help expedite a product to market while real time aging studies are being conducted Vacuum Leak: Immerses the package in a liquid then draws a vacuum on it to see if it emits air bubbles Visual Inspection: Reveals and documents failures along the package surface and seal Rub Testing: Repetitively abrades an item to see if the label is damaged; determines if labels are readable after rough handling In the life sciences community, the term package integrity has many meanings. For Medical Device Manufacturers complying with ISO 11607, package integrity is synonymous with sterile barrier packaging (SBS) integrity test methods. For Drug Product Manufacturers, package integrity of parenteral packaging, the “Sterile product–package integrity” is the ability of a sterile product container/ closure system to keep product contents in, while keeping detrimental environmental contaminants out. Such contaminants may include microorganisms, reactive gases, and other substances. The product includes the pharmaceutical formulation as well as the package headspace – which may consist of ambient air or nonreactive gases with a specified water-vapor content, under full or sub atmospheric pressure levels. Sterile, parenteral package integrity is often referred to as Container Closure Integrity Testing, while medical device manufacurers refer to test methods for sterile barrier maintenance simply as Package Integrity Testing. Whitehouse Laboratories is happy to assist clients to better understand the testing requirements and the available test options. With a consultative approach, we offer a wide variety of testing options when it comes to package integrity testing- Whitehouse Laboratories is your partner in supporting the packaging development process. A few of our routine package integrity test programs are summarized below. Container Closure Integrity Testing Container Integrity Testing Laboratory offers numerous state- of-the-art options for leak testing and assessing pharmaceutical package integrity per USP <1207>. Container Closure Integrity test programs are used to optimize sealing parameters, evaluate container storage temperature impact, replace sterility tests for product stability batches, screen production lots for faulty packages and support regulatory submission applications for product commercialization around the world. ISO 11607 Package Integrity Testing In order to maintain a packaged medical device product’s sterility until it reaches the point of end use, package designs need to incorporate a sterile barrier. Medical Device Manufacturers are required by regulatory agencies to follow ISO 11607 and demonstrate that the integrity of the sterile barrier is not adversely affected by distribution, storage and handling throughout the expected shelf life of the medical device. The efficacy of the sterile barrier packaging materials and design must be evaluated after terminal sterilization and exposure to the environmental and dynamic stresses expected for the final packaging. Following environmental conditioning, accelerated aging and distribution simulation testing, which provide a controlled means to expose a package system to the anticipated environmental and dynamic stresses that the sterile products may encounter in real world distribution, package integrity testing such as whole package bubble emission by vacuum (ASTM D3078) or internal pressurization (ASTM F2096), package seal dye penetration (ASTM F1929 or F3039 for nonporous packaging) can provide the means to evaluate the efficacy of the sterile barrier packaging after exposure. Leakage and Torque Testing All containers must be able to contain the primary product. Environmental hazards such as freeze/thaw and low pressure (high altitude) exposure can influence the effectiveness of the container/closure interface. Vacuum leakage testing (ASTM D4991) and altitude simulation (ASTM D6653) can assist in the development process. For pharmacueutical containers, torque degradation studies (ASTM D2063) can help you assess how much closure retention torque may be lost after exposure to temperature cycling, compression and vibration to ensure that child-resistance and senior freindliness are maintained. Shelf Life Testing A series of walk-in and reach-in environmental chambers allow Laboratories to provide product storage programs that help ensure product integrity throughout the product’s shelf life. Labs have the chamber capacity to support materials, products and packaging systems shelf life testing e.g. Accelerated Aging (AA), Real Time Aging, Freeze/Thaw, High and Low Temperature Exposure. Packaging Materials Barrier Properties Laboratories offer numerous tests to characterize adsorption, dissolution, diffusion, and desorption of packaging materials, including Oxygen Transmission Rate or OTR via ASTM D3985 or ISO 15105-2 and Water Vapor Transmission Rate or WVTR via USP <671>, ASTM F1249, D7709, ISO 15106-2 and ASTM E96. These barrier properties tests help plan the optimal packaging material choice for specific applications to maximize preservation and prolong the shelf life of your product. Package integrity should be re¬evaluated when changes are required in package design, package materials, or manufacturing /processing conditions. Package integrity testing is important in determining the sterility and the shelf life of a medical device or product. Package integrity testing includes dye leak, vacuum leak and bubble leak testing. Visual inspection is also used as well to confirm package integrity. In order to maintain a packaged product’s sterility until it reaches the point of end use, package designs need to incorporate a microbial barrier. Medical device manufacturers are required to demonstrate that package integrity is not adversely affected throughout the rigors of distribution simulation, accelerated aging, real time aging and up to the point of the medical devices stated shelf life. The efficacy of the sterile barrier packaging design must be evaluated after exposure to environmental and dynamic stresses along with the specific expiration date (s) that the finished package is expected to see in its lifecycle. Environmental conditioning, accelerated aging and distribution simulation testing provide a controlled means to expose a package to the predicted environmental and dynamic stresses that the samples may encounter in the real world. Package strength testing and package integrity testing provide the means to evaluate the packaging after exposure. Overview of ASTM F1929 Dye Penetration Integrity Test ASTM F1929 “Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration” is a dye penetration integrity test used by package engineers that is designed to detect and locate leaks caused by channels formed between a transparent film and a porous material. The ASTM F1929 standard was first written in 1998, was reapproved in 2004, and then ASTM made a significant update to it in 2012. The latest version of ASTM F1929-12 now calls out different Test Methods (A, B, or C) that can be employed to identify an unsealed area or channel along the seal of the package.