The FDA would like device companies to think more about the risk of something going wrong from design to packaging and then work to minimize that risk. One way is by maintaining what the agency describes as good manufacturing practices. But as medical devices become more advanced, the demands they place on packages increases. Some say the package is as important as its contents because if a sterile package fails, the contents must be tossed. “Events and trends are making the package and its product more interdependent,” says Anthony Ahmed, product manager at Mocon Inc, Minneapolis, (mocon.com), a manufacturer of package-test equipment. “And a company that cannot demonstrate control of a new-device package is enough reason for the agency to withhold the go-ahead for production.”

Briefly, packages in this discussion span from flexible designs, such as pouches and see-through bags, to rigid packaging that includes bottles and hard plastic, and combinations such as trays with pealable lids. For each of these, a device company must show its packaging can keep contents safe from contaminants, and that is done by testing. If a test method detects so much as one hole, the package has failed. “If the leak size indicated by the equipment is off, you could be over or understating the risk for contamination based on research, says Ahmed.

Testing methods also span a range. “Simple visual tests just eye-ball the seams of a package looking for holes or discontinuities called failure paths. Tests of medium complexity examine packages with equipment that subjects them to positive pressure and then detects pressure changes or leaks. And leak-test equipment using sonic and IR methods carry price tags up to $500,000,” says Ahmed.

Of course, there are shortcomings to all of these. “There are so many ways a product can be contaminated because contaminants, such as bacteria, come in different shapes and sizes,” he adds. “The most useful figure from a test is an absolute leak area. That value determines the point at which the absolute leak area elevates the risk of product contamination. So, is the testing machine giving a relative answer, or a precise absolute answer? Ideally, the precise, absolute answer is most useful because you can relate that to an absolute hole size that tells to what degree the product runs the risk of contamination.”

Ahmed says that recent developments in middle-range testers provide an absolute hole size. The testers produce an accurate absolute-leak measurement and a total-leak area. “If there is a 1 micron hole, the system says so,” he adds. The machine is said to apply advanced technology based upon the formula of Poiseuille's Law to factor package area, volume, pressure differential and gas flow to precisely measure the absolute leak area of a package. Such accuracy lets package engineers directly relate the results of this new method to devices with certified known-leak sizes to confirm accuracy. Ahmed says older mid-range pressure-loss instruments simply calculated leak areas based upon dated and inaccurate algorithms. This made it impossible to compare results from one algorithm to results of a different algorithm. Ahmed adds that in recent tests, the new equipment produces excellent agreement between known hole size and machine reading because the reading is the result of a direct measurement rather than a calculated one.

A FEW PACKAGE TESTING STANDARDS

Those with an interest in medical-device packaging should be familiar with at least these few standards.

ISO 11607 specifies requirements for the development and validation for packaging medical devices that are terminally sterilized.

ASTM F2054 describes testing flexible-package seals using internal air pressure while restraining the package with plates.

ASTM F1140 is similar to F2054 with the omission of the restraining plates.

ASTM F2095 describes a pressure decay leak test for nonporous flexible packages with and without restraining plates.