For the right approach to package testing, rely on ISO 11607 and FDA consensus standards.
Stephen Franks, T.M. Electronics Inc. (Worcester, MA)
The release of a terminally sterilized medical device to the marketplace is the culmination of monumental design and development efforts. Once the product has met its own design criteria, it and the package in which it is enclosed must form a single functional entity that performs efficiently, effectively, and safely.
Package testing enables engineers to ensure that packaging holds up its end of the bargain. Testing also supports documentation of ongoing conformance to specifications. Such evaluations help ensure the maintenance of the sterile barrier around the product.
All packaging forms, whether pouches constructed of porous or nonporous material, rigid thermoformed trays with Tyvek or film lids, bottles with induction-welded seals, or blister packs, need verification that their sterile-barrier characteristics are not compromised.
It is incumbent on you to obtain FDA approval of the protocol you use to validate your packaging system. Guidance in determining your course of action can be found in ANSI/ AAMI/ISO 11607-1997, "Packaging for Terminally Sterilized Medical Devices," and the related guidance document from the Association for the Advancement of Medical Instrumentation (AAMI), "Guidance for ANSI/ AAMI/ISO 11607-1997, Packaging for terminally sterilized medical devices," TIR 22:1998. ISO 11607 is an international standard that provides a guideline for designing, manufacturing, and testing final packages as well as the development of documentation necessary to demonstrate the validation of a package design and its conformance to specifications. FDA considers ISO 11607 to be the paradigm validation protocol for medical device packaging.
The package validation protocol must be approached in stages, each of which becomes an issue when designing your package test systems. The first consideration involves the selection and qualification of the materials to be used in the package.
Depending upon the application, specific performance requirements are considered essential for sterile-barrier packaging materials. For example, a package with peelable seals, in addition to having minimum physical properties such as tensile strength, porosity, and burst strength, must demonstrate a minimum specified seal strength (4.1.5.c). Formed packages have additional requirements for specifications for seal width and burst and/or seal strength (22.214.171.124), and packages suitable for sterilization must conform to tolerances appropriate to the sterilization method utilized (126.96.36.199.4).
Once your package has been subjected to a formal material qualification, objective evidence is needed that your package forming and sealing processes consistently produce results (5.0) that meet specifications. The golden rule of all testing—if you can't measure it, you can't control it—applies here.
To qualify your manufacturing process, it is necessary that verifications include the establishment of upper and lower processing limits, that valid test methods for quality attributes (such as seal strength) are in place, and that procedures have been established to ensure process control. These verifications are obtained through careful, well-designed package-testing procedures.
Furthermore, the same test methods used for packaging manufacturing control can be used before and after performance testing of the package (188.8.131.52) to ensure that the packaging materials and seals are strong enough to maintain package integrity throughout manufacturing, sterilization, distribution, and storage. Transportation and handling test performance protocols can be invaluably enhanced with the use of quantified seal strength and integrity test data.
READY, SET, TEST
The objective of package testing is twofold: first, to ensure the integrity of the sealed package, and second, to ensure that no weaknesses develop during sterilization, normal handling, transportation, and storage. Terminally sterilized medical packaging must provide a microbial barrier between the medical device and the external environment, and this barrier must be maintained against physical, chemical, or microbial challenges. The sterile package must be able to maintain the integrity of both the seals and the materials under stress. This implies, and ISO 11607 confirms, that a validatable package-testing process must include both package-integrity testing and seal strength testing, two complementary but very different procedures.
Package integrity is defined as the "unimpaired physical condition of a final package" (3.12). This attribute may be thought of as a "leak test" of the package. Seal-strength testing, on the other hand, measures the mechanical strength of the seal.
Seals must bond properly to maintain package integrity throughout the life of the package. Identifying seal strength also allows you to adjust the package's peelability. ISO 11607 refers to two methods that may be used to determine seal strength and burst or creep pressure resistance (inflation testing):
- Seal-strength testing (ASTM F88) uses a defined-width sample of a package perimeter seal. A moving jaw pulls the sample apart at a constant speed while measuring the resistance force during seal separation. The test is particularly suited to peelable packages. A significant advantage to this test is its sensitivity, and a disadvantage is that in the majority of cases, a perimeter seal is sampled only at several locations and a total package seal-strength measure is not obtained.
- Inflation seal-strength testing (ASTM F1140 and ASTM F2054) includes burst, creep, and creep-to-failure testing. Burst testing pressurizes the entire package and captures the peak rupture pressure. This test provides a whole-package minimum seal strength, and is equally applicable to peelable and nonpeelable seals. In a creep test, the package is pressurized to a predetermined level (less than that required to burst the package) and held over a defined time period, resulting in a pass/fail attribute test result. In the creep-to-failure test, the creep pressure is held until the seal fails. The variable here is the time to failure, a variable that like the burst pressure can be quantified and used to monitor the process of seal manufacture.
Flexible packages under pressure will deform and transmit stress to the seal in addition to the pressure forces. These added stresses may affect the location of seal rupture. Restraining plates can counteract these wall stresses, leaving only the pressure forces around the seal perimeter (ASTM F2054), and can generally indicate the weakest seal. In Figure 1, a foil pouch is held in a restraining plate fixture for seal strength testing.
Package integrity testing involves physically testing the total package to ascertain whether the package will protect its contents from damage and maintain sterile package integrity (6.4.3). ISO 11607 indicates the use of microbial challenge tests to confirm the ability of the package to prevent the ingress of microorganisms.
Examples of these tests include materials property tests and whole-package biological aerosol challenge tests. Although in fairly common use, microbial challenge tests on whole packages are not always the most appropriate test of package integrity.
A study published by the Health Industry Manufacturers Association (now known as AdvaMed) in the August and September 1995 issues of Medical Device & Diagnostic Industry titled "In Quest of Sterile Packaging, Parts 1 and 2," indicates that microbial challenge tests are not reliable measures of whole-package integrity and that physical test methods reliably find defects when properly applied. Examples of physical test methods reviewed in ISO 11607 include internal pressure testing (bubble test), dye penetration testing (a visual test), gas sensing (trace gas pressurization and detection), and vacuum leak tests (blue dye test).
When considering whole-package physical integrity tests, the engineer must consider material issues, package design, and the attributes of the en-closed medical device. Of primary importance is whether the barrier materials are in whole or in part porous. Another issue is whether a destructive or nondestructive test is appropriate for your package. Equally important is your budget for test equipment.
FDA allows manufacturers to essentially self-certify conformance to certain consensus standards. According to the FDA Modernization Act of 1997, manufacturers can declare that their packaged product conforms to test methods produced by consensus organizations. If the standards are recognized by FDA, test data may not need to be included when submitting 510(k)s, PMAs, IDEs, etc.ASTM F88: 1999Standard Test Method for Seal Strength of Flexible Barrier MaterialsASTM F1140: 2000Standard Test Methods for Internal Pressurization Failure Resistance of Unrestrained Packages for Medical ApplicationsASTM F1327: 1998Standard Terminology Relating to Barrier Materials for Medical PackagingASTM F1886: 1998Standard Test Method for Determining Integrity of Seals for Medical Packaging by Visual InspectionASTM F1929: 1998Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye PenetrationTable I: A partial list of consensus standards pertaining to medical device package testing as recognized by FDA.
Following consensus standards is voluntary, but it might save manufacturers considerable effort in identifying valid test methods and in submitting applications to FDA. A list of recognized consensus standards for testing medical packages is shown in Table I and can also be found at www.fda.gov/cdrh/ost/321.html. Even though device engineers only need to declare conformity to FDA, they still must validate these methods in their own laboratories and demonstrate test-method sensitivity.
Shelf-life testing (sterile package integrity maintenance) is a final consideration for the test designer. Once your package has proved to maintain a sterile barrier, it is essential that your materials and seals do not deteriorate over time or become weakened by normal transport and storage stresses. According to ISO 11607, the same functional tests you have put in place—both seal strength tests and package integrity tests—can be used to evaluate the package's ability to maintain sterile package integrity over time (6.4.3).
Assurance that your package will provide an effective, consistent sterile barrier for your medical device requires a well-designed, thoroughly documented test protocol evaluating both seal strength and package integrity testing. ISO 11607 provides a guideline, but tailoring your testing program to your particular product and package requires understanding of your package and of the way various seal and package tests function.
Future articles will examine both seal-strength testing and package integrity testing. Various test methods will be discussed in great detail. We will also look closely at fixtures designed to adapt certain test methods to your products, including restraining plates, methods of access to sealed packages, and techniques to test seal strength of pouches before they are filled and sealed.