Medical Package Testing: It’s Come A Long Way, Baby

Originally Published MDDI August 2004

Package Testing  



A series of significant events provided the impetus to shift the importance of package testing and package quality much closer to that of the device itself.

Stephen Franks

Modern package testing dates its birth to the passage in 1976 of the Medical Device Amendments to the Food, Drug, and Cosmetic Act and the institution of industry good manufacturing practices (GMPs) in 1978. Although established in 1931, it was not until 1976 that FDA was given regulatory oversight of medical devices. Even with the passage of the amendments, package testing barely existed as a concept or a discipline before the 1980s.

At that time, the package itself was considered secondary to the product; any testing was qualitative and arbitrary, designed and used at the sole discretion of the medical device manufacturer. “Much of the package testing consisted of no more than a visual inspection and whatever seemed the right thing to do,” say experienced package engineers John Spitzley of Medtronic Inc. and Curt Larsen, now with the DuPont Medical and Industrial Packaging Group. Ron Pilchik, an independent consultant since 1978, recalls that the medical device industry adapted some test techniques, such as the Gurley porosity test and the Elmendorf tear test for paper-barrier packages, from the paper industry, but few tests were available to determine the seal strength or integrity of the medical package.

A series of significant events over the next 20 years provided the impetus to move package testing and package quality to the significantly higher level required today. These events were: 

•The development of Tyvek as a dominant barrier packaging material used in the industry.
•The development of physical test methods (e.g., burst and tensile seal-strength tests and bubble or dye leak integrity tests).
•Recognition by FDA in regulations that packaging requires the same quality standards as the medical device itself.
•The development of ASTM's flexible medical package subcommittee to bring the industry together on significant testing needs such as physical methods and microbial challenge methods.
•The development and evolution of ANSI/AAMI/ISO 11607 and other consensus standards that are unifying and standardizing testing requirements in medical device packaging.

In the early 1980s, two factors influenced medical device companies to develop their own test methodologies. First, FDA had expressed concerns about product failures in the field that were apparently packaging related. Reaction to this concern contributed to the 
development of two primary physical test methods: seal-strength testing (generally as a tensile test) and leakage integrity testing (bubble or dye test). These tests represented the beginning of the concept we refer to today as packaging process control.

During this evolution of testing methods, some in industry encountered the difficulties involved in developing new methods. Don Barcan, who started his consulting career in the 1970s, recalls the development of the B-D carbon recontamination test, which used carbon dust. One major drawback of the test, he says, was the explosive nature of the dust. “Much like the old flour mills of the 1800s, a mere spark could set off a real explosion of the dust, and there was a lot of it,” Barcan says.

Curt Larsen remembers the smoke test, which, he says, was as good at “plugging the holes you were looking for as finding them.”

But there was some good news, too. In the early 1980s, the burst test was introduced by ARO Corp. As a physical test of the whole package, it gave device manufacturers a new piece of information on the quality of seals.

Later, in 1987, TM Electronics improved the basic method with the introduction of the first electronic burst tester, the BT-100. Digital, quantitative, and operator-independent results were available from this tester, providing another step toward improved process control.
The second factor pushing device manufacturers toward new package test methodologies was the emergence of the use of Tyvek in medical packaging in conjunction with ethylene oxide (EtO) sterilization methods. FDA's Ana Placencia questioned how to measure the effectiveness of the existing and new sterile barrier materials such as Tyvek. These biological sterility issues led to the development of whole-package microbial challenge tests that became widely used by the mid- to late 1980s. In fact, FDA took the position that package testing must be validated with a microbial challenge test. 

Scientific Methods

The effort to establish stated means and methods for package forming and testing was led by the HIMA Packaging and Sterilization Committee. In 1993, the Health Industry Manufacturers Association (HIMA, now AdvaMed) published the first industry guide, HIMA Reference on Sterile Packaging. Before this, recalls Hal Miller, retired director of packaging technology at Johnson & Johnson, “it was every man for himself in integrity testing.”

The factors underscoring the need for process control and the concern about maintaining barrier sterility led to the first acknowledged awareness that package testing must consist of both seal-strength testing and package integrity testing. At the same time, it became obvious that some kind of industrywide guidance was needed to evaluate the test methods being used.

In the early 1990s, the ASTM Medical Device Packaging Subcommittee F2.6 established itself as a major resource for medical device manufacturers. Formal test methods were written defining existing test methodologies such as the burst test (F1140) and the porous sterile barrier microbial ranking test (F1608). ASTM's disciplined formalization of test methods established the concept of harmonized and uniform testing standards and anticipated the paradigm shift in the mid-1990s to the exploration of the science behind package testing issues. 

Industry groups such as HIMA and AAMI began to examine the science of medical packaging and testing. A major effect of the application of scientific analysis was the reevaluation of the ability of microbial challenge tests to confirm whole-package sterility. A seminal paper published by John Spitzley in MD&DI in 1993 titled “How Effective is Microbial Challenge Testing for Intact Sterile Packaging?” resulted in a major industry study.⁶¹  The study was the basis for a two-part article published in MD&DI in August and September 1995 (“In Quest of Sterile Packaging”).^2-3
 
The study resulted in a shift of opinion among device manufacturers and testing professionals away from whole-package microbial challenge tests toward physical integrity test methods as a more reliable measure of package sterility. This shift was supported by a group of materials and instrument suppliers meeting together in ASTM F2.6, who also concluded from intensive and scientific study that physical test methods are more effective. This is one of the first, and certainly most important, examples of the emphasis beginning to be placed on the scientific analysis of package testing.

Along with this development was the introduction of a new package tester, TM Electronics' BT-1000 (see Figure 1). This instrument tested both the seal strength and the whole-package integrity of the item under test, a critical recognition of the necessity for both of these testing streams. The BT-1000 also provided graphic analysis of the test. It stored and statistically analyzed test results so that manufacturers could convert their processes to statistical process control (SPC) methods for quality control. 

Scientific study also led to an improved method for dye penetration testing (ASTM F1929). Developed by Earl Hackett of DuPont Corp., the new method formalized the dye materials and defined the sensitivity of the method by defect size.

Standardized Test Methods

The work of industry groups and FDA resulted in recognition of the need for physical test methods and FDA's requirement for industry to define their sensitivity and repeatability. In 1995, FDA added to its regulations the requirement that packaging meet the same quality and process control standards as the medical device itself, in that both testing and process validation procedures were now required.

This new orientation and the growing awareness of device manufacturers of the need for harmonized and uniform testing standards, beginning with the publication of F1140-88 and F1608, culminated in the publication of ISO 11607 in 1997.⁴  Formulated by representatives of the European medical device industry and HIMA and AAMI, this standard provided directed methodology for both seal-strength testing for process control and package integrity testing for sterile-barrier packaging. It was accepted internationally and, for the first time, medical device manufacturers worldwide were speaking the same language when they discussed package testing. 

ISO 11607 also heralded the next major milestone in package testing, known to many as the golden rule: If you can't measure it, you can't control it. This golden rule became the guiding principle for ASTM in the standardization and evaluation of package test methods.

Hal Miller, as chairman of the ASTM F2.6 Medical Device Packaging Subcommittee, led an industry group drawn from the medical device manufacturing community in an effort to document and quantitatively verify the repeatability, reproducibility, and sensitivity of test methods. Miller recalls that the then-new ISO 11607 could only refer to common test methods, most of which were undocumented. He made it his goal to “identify and document all the methods mentioned in the ISO document with sensitivity and repeatability data.” 

After 1997, industry groups began to encourage FDA to use physical rather than microbial challenge testing for validation. This resulted in FDA's acceptance of industry consensus standards—test methods that had been scientifically evaluated and quantitatively defined for uniform and consistent use industrywide. The acceptance of consensus standards by FDA was essential not only for domestic medical manufacturers, but also for device manufacturers internationally who intended to market products in the United States. The effect of FDA's adoption of industry consensus standards was to unify and harmonize package testing for all medical device manufacturers under its jurisdiction. 

The Packaging Future

I have focused on the evolution of package testing over the past three decades from the earliest questions faced by packaging engineers: Why test? How to test? What needs to be tested? These queries led to the identification of test methods and the beginning of the standardization of test equipment and methods (see Figure 2). It also helped establish that package testing consists of two distinct and essential branches: seal-strength testing and package integrity testing.

Today, package test methods—as well as test equipment—are rigorously defined and quantitatively evaluated before being used by manufacturers. With the focus shifting in this direction, medical device manufacturers have effectively transferred the development of package testing equipment and test methods to highly specialized and sophisticated test equipment companies.

Test equipment has evolved from simple, operator-dependent, qualitative setups to highly sophisticated, repeatable, reliable instruments such as the TME BT-1000 package tester, which addresses both essential aspects of package testing (seal strength and leak integrity) in a single instrument. 

The qualification of new testers and integrity test methods for Tyvek lidded trays by Mocon and PTI has been recently published under ASTM F2.6 guidance, indicating the rigor now being applied both to new instruments and newly developed test methods. Because of the importance of continuing and expanding the quantification of test data and their correlation to package quality and consistent packaging process control, the newest testing equipment provides users with electronic transmission of data via Ethernet or Internet to process control centers where manufacturers can monitor output continously. 

The same basic medical packaging tests have now been in use for the past 20 years. With this in mind, when asked whether this indicates that medical package testing has not changed significantly during that time, Spitzley, Larsen, Miller, and Barcan all agree emphatically: “Not true.” While many foundational concepts originated in the 1980s, the science and methodology needed to use those basic tests effectively has developed greatly.

Barcan notes the importance of the change in identification and qualification of the ASTM F88 seal-strength method. The method was changed from measuring forces at peak, which can vary considerably, to sustaining force, which provides consistency to the method.

Consultant Pilchik notes that the “one pound force per inch” rule of thumb in tensile seal-strength testing should now pass to oblivion. Barcan concludes in his recent article, “Exposing the Myths of Tensile Seal Strength Testing” that today's control of materials and processes and correct test methods provide a truly scientific understanding of what is being measured.⁵  Consider the distance from the original whole-package burst tester, a mechanical, single-analog-gauge instrument that was operator controlled and provided only qualitative data (pass or fail), to today's sensitive, repeatable, quantitative package tester. We have come a very long way.

Where is the future of package testing to go? There has been a great deal of increased sophistication, but very little change in the philosophy of physical testing, in the past 25 years. New areas of study and test methods not yet conceived will certainly come along. A study is currently under way headed by Laura Bix, PhD, of the Michigan State University School of Packaging, under the auspices of the IoPP Medical Packaging Technical Committee. That study considers the actual size of the leak required to render a sterile barrier ineffective against contamination. This information will enable test designers to ensure that test methods are not only repeatable, reliable, and sensitive, but also appropriate for the product under test.

Although seal-strength testing for process control will always be required, test equipment is being developed that will use optical indicators, chemical indicators, or electrophysical techniques to define an entirely new way to examine package integrity. A major step in the development of package testing is also now under way. In the past year, Mocon and PTI have introduced nondestructive tests for leak integrity for Tyvek lidded trays, as has TM Electronics for nonporous packages. These first steps are opening the door to new testing methods and 
approaches.

How should medical device manufacturers, test equipment manufacturers and designers, and packaging engineers react to the continuing evolution of package testing? The credibility of new test equipment is now being established up front, rather than by designing equipment for already-existing methods.

The next generation of packaging engineers and the designers tasked with the development of new instrumentation and methods must maintain this approach. Medical device and test instrument manufacturers must be willing to devote their people resources, time, and determination to make the evaluation of new test methods and instruments using international standards a universal practice.

As Miller notes, “If you want to be a market leader, you must take a leadership position.” You, the medical packaging engineer, must keep current with trade literature and participate in ASTM, ISO, AdvaMed, AAMI, IoPP, and other professional organizations that contribute to the body of knowledge and the development of the standard test methods. This will ensure that reliable, high-quality medical device packaging is delivered for the health benefit of those who need it most.

References

1.John Spitzley, “How Effective Is Microbial Challenge Testing for Intact Sterile Packaging?” Medical Device & Diagnostic Industry 14, no. 8 (1993): 44–46.
2.Joyce Hansen et al., “In Quest of Sterile Packaging, Part 1: Approaches to Package Testing,” Medical Device & Diagnostic Industry 16, no. 8 (1995): 56–61.
3.Joyce Hansen et al., “In Quest of Sterile Packaging, Part 2: Physical Package 
Integrity Test Methods,” Medical Device & Diagnostic Industry 16, no. 9 (1995): 81–85.
4.ANSI/AAMI/ISO 11607-2003, “Packaging for Terminally Sterilized Medical Devices”(Geneva: International Organization for Standardization, 2003).
5.Donald S. Barcan, “Exposing the Myths of Tensile Seal Strength Testing,” Pharmaceutical & Medical Packaging News 12, no. 4 (2004): 26–28.

Bibliography

Franks, Stephen. Package Testing 201. 
(Boylston, MA: TM Electronics, 2002); Available from Internet: www.tmelectronics.com.

Franks, Stephen. “Strength and Integrity, Part 1: The Basics of Medical Package Testing.” Pharmaceutical & Medical Packaging News 10, no. 1 (2002): 28–33.

Franks, Stephen. “Strength and Integrity, Part 2: The Basics of Seal-Strength Testing.”Pharmaceutical & Medical Packaging News 10, no. 6 (2002): 52–53.

Franks, Stephen. “Strength and Integrity, Part 3: Physical Package Integrity Testing.” Pharmaceutical & Medical Packaging News 11, no. 1 (2003): 41–43.
Franks, Stephen H. and Barcan, Donald S. “Comparing Tensile and Inflation Seal-Strength Tests for Medical Pouches.” Medical Device & Diagnostic Industry 20, no. 8 (1999): 60–67.

Larsen, Curt et al. “HIMA Reference on Sterile Packaging.” Report 93-7. (Washington, DC: Health Industries Manufacturers Association (HIMA), 1993).

Parisi, Anthony et al. “Toward a New Consensus on Sterile Device Packaging.” Medical Device & Diagnostic Industry 14, no. 1 (1993): 84–87, 119.

“Recognition and Use of Consensus Standards; Final Guidance for Industry and FDA Staff.” (Rockville, MD: FDA, 2001); Available from Internet: www.fda.gov/cdrh/ost/321.html.  

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