Pharmaceutical and Medical Packaging News
Magazine
PMPN Article Index
Originally Published January 1999
MEDICAL
Standardizing Package Testing Methods
The medical device subcommittee of the American Society for Testing and Materials is working to develop consensus standards to take the guesswork and inconsistency out of package testing.
by Daphne Allen, Editor
In 1997, medical device packagers welcomed the release of ISO 11607, "Packaging for Terminally Sterilized Medical Devices." Not only did the standard clarify the responsibilities of manufacturers for package design and process validation, but it also identified a number of commonly used visual and physical tests to ensure package integrity. It explained the basic principles behind visual inspection, internal pressure, dye penetration, gas-sensing, and vacuum leak tests. With the standard packagers finally had the definition of a sterile package and knew their responsibilities for creating and maintaining one. In August of 1998, FDA recognized ISO 11607 as a consensus standard, enabling manufacturers to include a statement of conformance to the standard rather than include individual test data in some FDA approval applications.
Channels measuring 0.003 in. are detected using the dye penetration method. Tested package courtesy Earl Hackett/Dupont Tyvek.
But what the standard didn't do was give step-by-step instructions on conducting each of the integrity tests. Without standardized test methods, packagers could only follow the procedures set forth by a company's packaging department. Unfortunately, given the number of companies using these tests, significant variations exist from lab to lab, often leading to confusion and disagreement within the industry.
The American Society for Testing and Materials (ASTM) wants to change that. Several task groups within the ASTM F02.60 subcommittee on medical device packaging are working to establish standardized testing methods for the following methods: visual inspection, dye penetration testing, helium leak testing, pressure-decay testing for nonporous packaging, burst testing using restrained plates, and accelerated aging testing. "Standardizing these methods will give them validity and credibility," says Hal Miller, director of packaging technology at Johnson & Johnson (New Brunswick, NJ) and chairman of the ASTM subcommittee. "It will also help to eliminate lab-to-lab variability."
There are also efforts to develop guidelines for validating these test methods. "The goal is to show how to make sure a test is reliable, robust, and repeatable," says Miller.
Writing a standardized test method takes time, especially since ASTM subcommittees meet only twice a year and all committee members must agree on the standards. But work is already underway, so industry can expect to see a lot of activity over the next year. Following are descriptions of some of the projects planned or already underway.
VISUAL INSPECTION
ASTM has already published F-1886, "Determining the Integrity of the Seals of Medical Packaging Using Visual Inspection." According to Miller, this method "provides a qualitative approach to evaluate the characteristics of unopened, intact seals to determine the presence of integrity defects."
Miller says that round-robin studies demonstrated a 60%–100% probability of catching leaks measuring 0.003 in. Leaks this size in blisters were caught 60% of the time, while those in pouches were caught up to 100% of the time, he says. "It depends upon the amount of adhesive, lighting, and the package type."
John Spitzley, associate fellow–packaging at Medtronic (Minneapolis), says his experience using the method has yielded the same results. He adds that some packages, especially those that are opaque, may need to be opened to be evaluated.
DYE PENETRATION
During ASTM's subcommittee meeting last October, the subcommittee approved the draft of the dye penetration test method, which has since been numbered F-1929, written by Earl Hackett, a subcommittee member and also a research associate for DuPont Tyvek (Wilmington, DE).
Developing such a standard was necessary, says Hackett, because package testers often use dyes that they think are effective for packaging materials but are really meant for metal surfaces. "I developed a dye formulation using a dye that doesn't interact with the surfactant and that will wet polymer surfaces found in packaging"—i.e., not bead up. "This one wets the entire surface and allows the dye to enter defects, such as channels in seals," Hackett explains. "The challenge was to develop a dye formulation that enters the channels but doesn't enter porous materials like Tyvek during the inspection process."
A computer rendering of restrained plates for testing nonporous packages. Image courtesy T.M. Electronics.
To test the new formulation, several manufacturers made packages with known defects for a round-robin trial. Tungsten wires were sealed between the two sides of a pouch and then pulled out, creating channels. "The dye was able to penetrate 98% of the channels created by 2-mil wires," says Hackett. He also used 0.5-mil wires, but the method wasn't as successful. The next challenge, he says, is to determine what size hole contaminants can really get through.
HELIUM LEAK TESTING
In early 1998, True Technology (Newton, MA) introduced SealCheck 210, an objective nondestructive system that tests the integrity of porous packages using helium as a tracer gas. The testing system can be used for package development, validation, and routine quality inspection.
The system automatically applies a barrier tape over the porous side of the package and punches a small hole in the tape (without destroying the package) so helium gas can be introduced into the package. After the helium is introduced, a sampling probe scans the periphery of the seal and maps the concentration of helium using a mass spectrometer leak detector. The system graphically reports any leaks.
The system can identify leaks as small as a human hair (0.002 to 0.003 in. in diameter), says Eugene Achter, vice president of True Technology, who helped develop the system. Achter is working with ASTM to develop a standard for the test method.
The standard is the only one based on a new proprietary package integrity test, unlike the other methods, which have been used in industry by a number of different companies for years. But J&J's Miller sees "no reason why a special interest can't become a standard," especially if the method is valid and credible.
PRESSURE-DECAY TESTING
Pressure-decay testing involves inflating a nonporous package and measuring the loss of package pressure over a fixed period of time. If the package is intact, it should hold the inflation pressure. But if it has a leak, pressure is gradually released in relation to the size of the leak, explains Stephen Franks, executive vice president of T.M. Electronics (Worcester, MA), who is writing an ASTM standard on the method.
When using this method, testers must ensure that the port used to inflate the package does not create a path for leaks, says Franks. The standard, which is still in draft form, will help engineers use the port properly. It will also help them determine the amount of time necessary to reveal any pressure leaks. "The amount of time depends upon the internal volume of the tested package. You can use restrained plates to help keep the bag rigid and to minimize internal volume. If the volume is small, you can detect pressure leaks much more quickly," says Franks. "Everyone wants to go fast." Franks expects the standard to be available in about a year.
RESTRAINED-PLATE BURST TESTING
Franks' company, T.M. Electronics, and a second company, Test-A-Pack Systems/Carleton Technologies Inc. (Orchard Park, NY), are also helping ASTM with a draft standard on restrained-plate inflation burst testing for flexible packaging. It is not an integrity test, but a seal-strength test. According to Franks, when testing flexible, peelable packages, the restrained-plate method will identify the weakest seal location and track process sealing variations more easily than tensile seal strength tests. Tests in T.M.'s lab have shown a correlation between burst seal strength and sealing parameters in regard to nonporous pouches.
The draft currently under development will standardize the types of plates used (instead of plastic, metal, because plastic may not withstand the pressure) and help testers determine what amount of pressure to use. Franks says something may be ready for the ASTM committee to review in about six months. He also says that professor Hugh Lockhart at Michigan State University's school of packaging is studying the method for porous packages.
ACCELERATED AGING
For years, industry has relied on technical articles found in trade journals and a somewhat-related FDA guidance document to find out how to conduct accelerated aging tests. But nothing has ever been put into a true consensus document, says Patrick Nolan, technical director for DDL Inc. (Minneapolis), formerly Distribution Dynamics Labs Inc. His goal is to produce such guidance, with help from industry and FDA. "We need to get industry to use similar parameters and to use the same justifications for doing accelerated aging studies," says Nolan.
The guidance document will stress the use of practices based on the Q10 theory, known as the Arrhenius equation, which states that the speed of chemical reactions doubles with every 10°C rise in temperature. Standardizing the method for determining the temperatures at which medical packages will be stored will ensure that industry conducts aging tests consistently.
Nolan also says that it is important that engineers test the packages after aging for seal peel strength and seal and package burst strength. "You have to validate the packaging to make sure it hasn't deteriorated," he says. "Many do not understand that such tests are necessary after aging." The standard will recommend a number of tests for post- aging evaluations.
TEST METHOD VALIDATION
Standardizing these methods will help ensure that packages are being validated consistently throughout industry. But how does an engineer make sure the chosen method actually works as it is intended? You have to validate the method, too.
A draft of a "Guide for the Validation of Test Methods for Determining Integrity of Primary Medical Packages" was presented by M. Louis Arin, materials engineer at FDA's Winchester Engineering and Analytical Center (Boston). It will be a general document unlike most of the specific test methods mentioned previously. The guide will outline the general principle elements of the validation of test methods used for the integrity testing of completed sterile medical device packages.
It will also serve as a guide and educational tool that will help ensure the uniformity and effectiveness of these test methods. Arin says that the guide will be the first document of its kind to be considered by the ASTM subcommittee on medical device packaging.
CONCLUSION
ASTM's efforts to develop consensus standards for package testing do more than help manufacturers validate medical packaging. They also lay the foundation for the true worldwide harmonization of package design, manufacture, and validation practices. If these testing methods are already standardized by the time ISO 11607 and the CEN document EN 848 are harmonized, these may become international methods, says Miller. Such a worldwide consensus could only lead to one thing—a seamless international packaging community.
