Pharmaceutical & Medical Packaging News staff

DuPont Tyvek's research associate Earl Hackett explains how a 25-µm hole affects sterile porous medical packages. 

Whenever engineers locate defects in medical device packages, they must go back and review all package forming and sealing processes in order to locate and eliminate the cause of the defects. Because such a review is laborious, engineers often ask whether there are any defects that can be tolerated and accepted. Packaging experts have historically answered negatively, stating that any defect signals a problematic process, and locating and eliminating its cause may prevent further defects or problems.

However, just because experts have declined to qualify or quantify the type of acceptable defect, that doesn't mean that the very same experts aren't trying to find out how minute defects affect package sterility. For nearly two years Earl T. Hackett, research associate for DuPont Tyvek (Wilmington, DE), has been studying the effects of pinholes on the barrier properties of medical device packaging that uses Tyvek 1073B as its porous component. In the August 2000 issue of PMP News's sister publication Medical Device & Diagnostic Industry, Hackett, along with DuPont's Mike Scholla, Stas Rudys, Claude Michels, and John Bletsos, as well as with Alan Tallentire and Colin Sinclair, PhD, is publishing the results of their study. PMP News editor Daphne Allen caught up with Hackett before publication.

Q: What is the smallest defect that can be detected in a medical package?

A: Typically, the smallest defect that can be detected is about 50 µm. Such defects can be found using the most sensitive of tests, one of which is dye penetration.

Q: What did you set out to examine during your research?

A: We wanted to determine whether the sensitivity of the current set of physical test methods was adequate. We decided that the best way to study this was to consider the barrier characteristics of the total packaging structure, with or without a hole. If we discover that there is no significant difference in the percentage of particles penetrating the sample, with or without a defect, the barrier characteristics of the porous packaging material will not be affected by the defect. It could also be argued that the increased probability of contamination of a packaged device is proportional to the relative increase of particle penetration when a hole is present.

Q: Does the presence of such defects in the range of 25–50 µm automatically represent a threat to package sterility?

A: Our research suggests that porous packaging can be designed such that holes in this size range may not pose a significant threat of loss of sterility due to microbes being transported by air movement. One conclusion is that the porosity of the packaging material has a major effect on the degree of particle penetration through any given defect. For a given package and volume of air exchange, a more-porous barrier material will allow more of the exchange air to move through the barrier material rather than forcing it through the defect. In the test samples of the highly permeable barrier material uncoated Tyvek 1073B, small defects (measuring 25­50 µm) showed little or no discernable difference in the amount of particle penetration when compared to the same sample without the defect. Lower permeability or lower ratio of porous surface area to package volume will increase the amount of unfiltered air passing through the defect.

Q: Does that mean that such defects can be ignored?

A: At the present time we have no means of detecting 25-µm defects in porous packaging, so we really don't know if they are present or not. We cannot absolutely rule out the possibility of an event that would generate only 25-µm defects. Therefore, if defects smaller than those we could detect were proved to be a serious threat to the maintenance of sterility, we would have to develop more-sensitive test methods. As for ignoring such small defects, in the real world, I don't believe that an event that can breach a film will always stop at a 25-µm hole. It will generate larger holes that cannot be ignored.

Q: Paper is not mentioned in the research. Can any conclusions be drawn about defects 25 µm and smaller in packages that use paper?

A: We selected Tyvek 1073B for a very specific reason. Of all the available materials, it has the best ratio of barrier properties to permeability. This allows the test to be very sensitive. If I had used paper, there would have been so many particles pouring through the uncoated system that I may not have been able to detect the small increase in the number of particles allowed through the smaller holes—they would have been lost in the background noise.

Q: How does Tyvek 2FS fare?

A: Tyvek 2FS has about the same permeability as Tyvek 1073B, so the portion of the air exchange through equivalent holes would be roughly the same. Although Tyvek 2FS has excellent barrier properties, it is not as good a barrier material as Tyvek 1073B. To detect the effect of small holes in the background signal, the number of particles penetrating the barrier must be reduced to as small a number as possible. Therefore, Tyvek 1073B was selected, as it is the best combination of barrier and permeability of any material available today. If the test were repeated with a material with poorer barrier characteristics, one might conclude that larger holes were not significant, which was not the objective. The purpose of the experiment was to determine whether our current test methods were adequate for detecting defects in the best system available, which is uncoated Tyvek 1073B.

Q: Does DuPont plan to submit its test results to FDA or to any third-party testing laboratory for corroboration?

A: The tests were performed using a rather expensive system. All of the particle generation and counting equipment is off-the-shelf hardware from TSI Inc. (St. Paul, MN). The sample holder is a custom-fabricated unit designed specifically to operate efficiently at very low flow rates. If another laboratory would like to set up a test unit like this, we would be happy to help, but the cost is quite high. This equipment (or a very similar system) will likely become the international standard for defining microbial barrier properties. When that happens, several test labs will probably install them, and there will be plenty of opportunities to conduct similar studies. At the present time a similar study on seal channels is being considered.