How low can you go?

A look at the sensitivity of currently available package integrity test methods may help you prepare for the findings of an ongoing Michigan State University School of Packaging study on package defect size.

As a Michigan State University School of Packaging research team looks for the smallest threat to sterility, PMP News looks at the sensitivity of today’s test methods.

Led by assistant professor Laura Bix, PhD, MSU School of Packaging aims to answer this long-standing question: What is the smallest hole that will cause a breach of sterility in sterile medical packaging? Researchers are now preparing to identify whether a 10-µm-sized or a 100-µm-sized hole results in significant ingress of microorganisms through normal Brownian motion or pressure differentials that mimic an altitude of 8000 feet. This study originally started out as a task-group study within the medical device packaging technical committee of The Institute of Packaging Professionals (IoPP) in 2002. Under IoPP member Bix, MSU researchers have managed the project.

Research is planned to take place in two phases. Phase I consists of two experiments. Experiment 1 involves testing trays with nonporous lidstock (LFK-002 paper/PE/foil/PE/HSC) using a new methodology for whole-package microbial-challenge testing. Results from this work are expected to be complete in May 2007.

The results of a preliminary run of Experiment 1 were reported to IoPP’s Medical Device Packaging Technical Committee in November 2004, and these results gave the researchers confidence that the method worked, so they have begun Experiment 2. Experiment 2 will explore the effect pressure differentials across the sterile barrier have on the penetration of microbes into the packaging. Rigid PETG trays sealed with LKF-002 paper/PE/ foil/PE/HSC lids will be exposed to an environment in which microbes are aerosolized into the air space above the package. The completion date for Experiment 2 is on or about August 15, 2006. Phase I results should dictate future research for Phase II.

Can it be done? Does it matter? Is the approach realistic? These are questions that come to mind, along with this practical one: Will it change medical package integrity testing?

“If there is no significant microbial ingress detected at the 100-µm level, this is good news,” says Hal Miller of PACE Solutions LLC. “Most every integrity test method out there can detect this level of sensitivity. However, if there is significant ingress at this level and none at the 10-µm level, then more work needs to be done to hone in on the optimum level.”

Bix acknowledges that test-method sensitivity depends upon the package and the material. “You can detect breaches in nonporous packages to much lower levels than you can when they are within packages with a porous component,” she says.

Adds Ondrea Kassarjian, who as a student was a part of Bix’s research team and now works for Lansmont Corp. (Monterey, CA): “Other variables that determine whether a particular breach presents a threat include package thickness; pressure gradients, whether there is a tortuous path through the material, such as with Tyvek; whether contaminants are airborne or liquid; and the life span of the contaminating organism. After all, even if it can get in, how long can it live without a host?”

Furthers Darrell R. Morrow, PhD, and Jeffrey Morrow-Lucas of Leak Detection Associates Inc. (Blackwood, NJ), “It is very important to distinguish between the type of fluid carrier [gas (air) or liquid (typically, aqueous)] involved in a given microbial transport situation. A given material and/or sealed package is challenged to a far greater extent by liquid-borne microbial moieties than by gas/air-borne moieties,” they explain.

Given these realities, Bix says that her team isn’t looking for a “black-or-white” answer. And even if her team does identify a hole size, it won’t necessarily end the debate—or her research. “We may come up with a small hole size—but it doesn’t consider [the effects of] secondary packaging or tertiary packaging” on sterility, she explains.

Still, identifying the “critical hole size” is the million-dollar question, says Kassarjian. “Some people are interested in the truth, while others are scared. Test equipment providers are trying to increase their sensitivities. And what if material suppliers find out that their materials aren’t performing as they should be?”

Stephen Franks, executive vice president, T.M. Electronics (Boylston, MA), is confident that testing equipment will keep pace with the research. “No matter what hole size is determined, if determined, to allow contamination in a medical package, then the instrument manufacturers will find a method to detect this hole size. At this point, if 100 µm were the size, then an operator could see it, and almost any instrument can find it. However, the caveat as always is that porous materials make the job harder.”

“It is hard to find a universal test method that will find all defects: channels, pinholes, and other defects,” says Kassarjian.

With all this in mind, we offer some industry perspective on physical test methods as they stand today to help you identify how sensitive your method is. We have also included a table on method sensitivity as described by ASTM standards. '

We acknowledge that this article may not offer a complete analysis for each test method. We also acknowledge that these stated sensitivities are potential ones and cannot be guaranteed for every testing program or for all test equipment. Finally, we realize that a discussion of test sensitivity is not a discussion of testing unit quality. According to some industry experts, commonly used testing equipment often finds defects at 100-µm sizes, and this may be sufficient.