What Is A Vacuum Decay Leak Test?
What is a vacuum decay leak test, and why is vacuum decay leak testing important for parenteral products?
Vacuum decay is a nondestructive packaging leak test method that evaluates an entire product-package system. Vacuum decay leak testing has grown in popularity over the past 20 years. Vacuum decay leak testing evaluates a package’s ability to preserve gas headspace and the packaged product’s integrity under pressure. As many parenteral products are packaged in liquid form, vacuum decay testing can accurately determine any weaknesses in a product’s integrity or product’s packaging integrity under pressure. Thus, issues with product-package integrity during air freight shipping can be avoided. Vacuum decay leak testing is particularly important for companies that produce therapeutics overseas and ship them to the United States or other countries, where products may experience multiple pressurization cycles during shipping.
ASTM F2338-09 is the standard test method for detecting leaks in packages by the vacuum decay method. ASTM F2338-09 is recognized as the standard for vacuum decay testing by the United States Food & Drug Administration.
Which product-package systems can be tested with vacuum decay leak testing?
Packages that can be tested by vacuum decay are rigid non-lidded trays, semirigid non-lidded trays, trays or cups sealed with porous barrier lidding materials, rigid nonporous packages, and flexible nonporous packages. Vacuum decay testing is a nondestructive testing method. Thus, these tests can be performed on parenteral products or medical devices that are sterilized and packaged.
How is vacuum decay leak testing performed?
First, the test package is put in a vacuum test chamber. The chamber door is then closed, and a vacuum is drawn to a target pressure level (such as the pressure a package might experience during air freight transport). After establishing the vacuum, the package test system is isolated from the vacuum source and monitored. Any subsequent pressure rise (vacuum decay) inside the test chamber is observed and recorded. A pressure rise above the vacuum baseline indicates that the package headspace gas leaks or vaporized liquid product. In some instances, a liquid product can vaporize and plug leak paths, impacting testing accuracy. The vacuum decay cycle time is traditionally less than 30 seconds. However, the test system, the product-package, and the desired vacuum sensitivity level result in differences between testing cycle times. Indeed, each vacuum decay testing cycle is unique to each product-package system, and testing parameters are specified based on the package’s contents. Variances in package contents include liquid products, gas products, solid products, little gas headspace, and lots of gas headspace. The shape of the package (package morphology) also plays a role in vacuum decay test design. Package morphology includes package size, as well as package rigidity, flexibility, and porosity. Note that highly porous packages may have difficulty retaining pressurized air.
Vacuum decay test chambers are designed to enclose packages being tested snugly. The snug fit minimizes test chamber dead space and maximizes testing sensitivity. In special cases, features may be added to the vacuum decay test to limit package movement or expansion during the test.
Special cases include:
- Prefilled syringes
- Flexible bags
- Pouches
- Other similar products
Features may also be added to mask gas flow through porous packaging materials such as paper or Tyvek®. Vacuum decay leak systems can be setup to detect leaks in packages filled with liquids or to detect leaks in packages containing gases, solids, or a combination of both. Small leak pathways can be clogged with packaged liquids. Thus, packages testing for liquid leaks will need to undergo a higher vacuum during testing. Specifically, the test conditions will need to be below the liquid’s vaporization pressure so that the vaporized liquid yields a measurable rise in pressure. In contrast, gas leaks from packaging materials are detectable under lower vacuum settings.
Most vacuum decay instrumentation relies on a single 1000 Torr gauge or absolute transducer for pressure when it comes to equipment. A few instruments use a dual transducer system for pressure with either a 1000 Torr gauge or absolute transducer coupled with a more sensitive, higher resolution 10 Torr gauge transducer. Fancier equipment can continually readjust the “leak-free” baseline pressure to account for atmospheric pressure changes. Equipment functionality checks use either a calibrated fixed orifice leak or a NIST calibrated airflow meter for artificially introducing leaks into the test chamber containing a leakproof (negative control) package. When determining the sensitivity of the vacuum decay setup, the lowest airflow rate that triggers a rise in pressure above background noise level is the limit of detection for the leak test. Note that both negative control and positive control leak packages should be evaluated along with test packages. Further positive control (leaky packages) and negative control (leak-free packages) should be used to understand how the test chamber pressure rise compares for various sizes of leak paths positioned in multiple package locations. Evaluating different leak paths before testing package samples supports accurate vacuum pressure and vacuum hold times for multiple packaging types and leak sizes. For example, a large leak in a package with low gas headspace may not be detected if the time allotted for the initial vacuum is so long that all of the headspace gas is evacuated before the pressure rise testing phase. Conversely, a plastic bottle with a cap pinhole leak may require additional vacuum time to detect trapped air flowing out of the cap’s screw threads. Controls are essential for more than evaluation of different leak paths. Negative controls with product-filled, leakproof packages are important to ensure the validated baseline represents all package-to-package variations.
Leaks simulated using a calibrated flowmeter can only represent packaging gas leaks and not liquid-plugged leak paths. Often liquid-plugged leaks volatilize once the test pressure falls below the liquid’s vaporization pressure. Vaporization of the liquid leads to a rapid rise in test system pressure and the leak’s detection. The pressure rise due to liquid vaporization stops once the vaporized liquid’s saturation point is reached. This liquid vaporization is the reason that testing parameters for fluid leaks vs. gas leaks are different.
What are the limitations to vacuum decay leak testing?
Recent research suggests that vacuum decay is limited in its ability to detect leaks in packages containing proteinaceous liquid products (e.g., peptides, antibodies, or other therapeutic biologics). Experiments have found that proteins in liquid formulations can irreversibly clog laser-drilled holes in glass vials. Thus, vacuum decay testing may not determine if the integrity of the glass vial packaging is intact when protein formulations are being assessed. For this reason, vacuum decay leak testing is not recommended for proteinaceous liquid products.
Summary
Overall, vacuum decay leak testing is a package integrity test that evaluates a package’s ability to preserve gas headspace and the packaged product’s integrity under pressure. Vacuum decay leak testing is particularly important for companies that produce liquid therapeutics overseas and ship them to the United States or other countries. Indeed, parenteral products produced overseas often experience multiple pressurization cycles during shipping. Product-packaging systems should be able to stay intact after experiencing these pressurization cycles reliably. All in all, ensure you choose a contract testing organization that can support you with appropriate package integrity testing for your unique parenteral product, medical device, or product needs.
MycoScience is a contract manufacturing organization that specializes in filling sterile syringes and vials for parenteral products. MycoScience also offers Package Integrity Testing, Sterilization Validations, Bacterial Endotoxin Testing, Preservative Efficacy Testing, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, Cytotoxicity Testing, EO Residual Testing & Environmental Monitoring services for medical device companies, and allied industries. MycoScience is an ISO 13485 certified facility.
References
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
