Pharmaceutical & Medical Packaging News staff

Stephen Franks, T.M. Electronics (Boylston, MA)

Over the past five years, packaging professionals in the medical device industry have moved away from biological challenge testing and toward physical testing for measuring package integrity. Package integrity is a measure of a package's sterile barrier. In ANSI/AAMI/ISO 11607, "Packaging for Terminally Sterilized Medical Devices," it is defined as "the unimpaired physical condition of the final package."

From a practical standpoint, integrity can be measured by package leakage. Leakage can result from large holes, pinholes, or cracks in materials or from disrupted seals. Either defect type represents the potential for loss of product sterility. Physical test methods, therefore, are designed to identify such material or process failures.

Currently, questions abound in industry as to what size or type of leak path can allow contaminants to enter a package. No data are currently available to support an answer.

However, prior studies by AdvaMed (formerly HIMA) indicate that high bioburden aerosol tests cannot reliably indicate leakage in a package with up to 3�8-in. gaps in the seals. (To read reports on these studies, see the articles titled "In Quest of Sterile Packaging, Part 1: Approaches to Package Testing, and Part 2: Physical Package Integrity Test Methods," in the August 1995 and September 1995 issues, respectively, of PMP News's sister publication, MD&DI.

Recent research, such as Earl Hackett's study explained in �How Pinholes Affect Packaging� in the July 2000 issue of PMP News, indicates that in flexible packages with breathable barrier materials, the nature of flow and the mobility of bacteria may in fact make penetration difficult with holes up to 50 microns. (According to Hackett, the data showed that essentially all particles that entered the hole exited on the far side. The flow through the entire package was split between the hole and the Tyvek or paper. The number of particles detected coming through the 100-mm diameter sample of barrier material was statistically the same with or without the hole until the hole reached a minimum diameter of 50 microns.)

Because physical test methods are more reliable and are more repeatable than biological challenge tests, and because they can be verified by repeatability and reliability studies, they present the best opportunity for determining package integrity.

Several physical test methods are nondestructive test does not damage package seals with pressure differentials or expose products to potentially harmful gases. For example, pressure decay tests on foil laminate pouches using T.M. Electronics� leak testers have found leaks at the 10-4 sccs level with instrument resolutions at 0.0001 psi. When used with appropriate restraining fixtures, these tests, while destructive to the package but not to the contained product, are relatively inexpensive, fast, and repeatable. To avoid stressing the seal, leak tests should be conducted after burst tests have been performed on the package. The leak test pressure should be kept below 30% of the burst seal strength. 

Tests that penetrate walls or immerse packages in fluids are generally considered destructive. While nondestructive tests may be preferred for product or package recovery, the cost of those tests may be higher, owing to slower test cycles or higher costs. 

Nonporous packages can be leak tested using a broad range of sensitivities. Maintenance of the sterile barrier is certainly required; however, a quantified leakage rate for that property may not have been defined.

Mass-spectrometer helium leak detection provides the maximum sensitivity. This test requires helium to be introduced into the package. Requirements for long-term moisture-barrier properties may demand high-sensitivity tests that mandate use of this method, while sterile barrier properties alone may require only modest sensitivities found in other, less-costly methods. Table 1 indicates relative sensitivity levels of the several methods, as well as their relative costs.

Most instrumented methods provide quantitative results. While some generate pass-fail results based on certain attributes, a functional leakage reference can be applied for qualification. Others that provide quantitative variable data can be used for statistical quality or process control.

Progress in medical package testing has been made through the use of documented physical test methods, such as ASTM methods. 

However, new methodologies need to be brought to the industry from other sciences, such as chemistry or microbiology. Such introductions may increase the confidence that manufacturers and end-users have in their sterile packages. Of course, engineering judgment must be exercised in applying the most effective as well as the most economical test methods.