Originally Published PMPN November
2004
Viewpoint
Demystifying Medical Device Package Validation
Answers to frequently asked questions help guide manufacturers through the validation process.
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Scott
Levy Packaging Engineer DDL Inc. |
Many medical device manufacturers struggle daily with what they need to do
to set up package shelf-life validation and what it takes to satisfy regulatory
requirements for sterile medical packaging.
Using the ISO 11607 standard as a reference guide, this article will demystify
the validation process for manufacturers by answering 10 common questions.
What is validation?
According to FDA, validation is documented evidence providing assurance that a specific process will produce a product that meets predetermined requirements and quality attributes.
Why should I validate my package?
Medical device manufacturers are required to obtain 510(k) approval on each medical device package. According to the ISO 11607 standard, the manufacturer “must ensure the product and package system combine to create a total product that performs efficiently, safely, and effectively in the hands of the user.”
What is the ISO 11607 standard?
According to Section 1.1.3 of the standard, “The intent of this international
standard is to provide designers and manufacturers of medical devices with a
framework of laboratory tests and evaluations that can be used to qualify the
overall performance of the package used to protect the device components during
handling, distribution, and storage.”
ISO 11607 considers the following attributes: selection of material, design
of the package, process validation, and final package validation.
What must I do prior to the validation process?
Before a final package shelf-life validation can be put together, specific questions need to be answered.
• What types of packages are we
validating?
• What type of expiration date do we want?
• What is the overall package
configuration?
• Which strength and integrity methods do I use?
• What are the glass-transition, melt, and heat-distortion temperatures
of the package and product?
Which kind of testing methodologies are implemented?
Package Strength. In order to produce acceptable packages on a daily basis
and throughout a determined shelf-life validation, it is important to evaluate
the strength characteristic. Not only does the strength characteristic play
a key role in a shelf-life validation, it lets medical device manufacturers
determine on a daily basis that their process for sealing packages is consistent
with their predetermined specification set in the process validation.
There seems to be some confusion in the medical device industry regarding the
strength of a package versus the integrity of a package. Package strength concerns
the force required to separate two components of the package. It could be the
force to separate two flexible components of a pouch or a flexible lid and a
thermoform tray. These forces may be measured in pounds per inch width, as in
the seal/peel test, or in pounds per square inch, as in the burst-test method.
Alone, these tests of package strength do not necessarily prove the integrity
of the entire package. In fact, the seal width that was actually measured may
be within the strength specification but may have a channel leak that could
breach the package and negate integrity.
The main culprit for poor package strength is the sealing parameters. If a proper
process validation of the sealer is not performed, the medical device manufacturer
can expect failure. Some typical package-strength testing includes ASTM F88-00,
package strength testing by seal peel testing, and ASTM F-1140-00, package strength
testing by burst testing.
Package Integrity. To maintain the sterility of an enclosed product until it
reaches its point of end use, the packaging must provide a microbial barrier
in the poststerilization environment. The manufacturer must demonstrate that,
under the rigors of distribution, storage, handling, and aging, sterile- package
integrity is maintained at least for the claimed shelf life of the medical device.
The microbial barrier properties of the package materials and design must be
evaluated after exposure to the environmental and dynamic stresses expected
for the finished package. Several methods may be used to satisfy these requirements.
They involve evaluating the material performance itself and the whole, finished
package as produced on the packaging line.
Packages may lose their integrity as a result of the dynamic-related events
that occur during processing and distribution. Physical test methods may be
used to validate that the package integrity has been maintained throughout the
package’s processing, expected shelf life, and handling. Testing includes
ASTM F1929-98, package leak testing by dye penetration; ASTM F2096-02, package
leak testing by bubble emission; and ASTM D3079-02 and ASTM D4991-94, package
leak testing by vacuum.
What is the accelerated-aging rationale?
Accelerated aging is performed on packaged medical devices to document shelf-life
and expiration times for products. Real-time aging can be performed; however,
products are often obsolete by the time a three-year expiration date is validated.
Accelerated aging is based on a thermodynamic temperature coefficient formulated
by van’t Hof that states, “For every 10°C rise in temperature,
the rate of chemical reaction will double.” However, this formula was based
on rate kinetics of a single chemical reaction, not on packages with various
kinds of materials. So, the direct extrapolation of this theory to the aging
of packaging materials must be used with caution. But the industry and FDA believe
the theory is useful in defining and justifying accelerated- aging test programs.
How is accelerated aging performed?
The temperature that avoids unrealistic failure conditions, such as deformation
due to melting, should determine temperature selection for the accelerated aging
study. Real-time aging must be performed in conjunction with any accelerated-aging
study to correlate the results found during accelerated aging.
In order to perform accelerated aging, the following information is required:
• Volume of material (the size of the individual packages that will be
placed inside the environment chamber).
• Test temperature (the temperature at which the chamber will be set).
• Expiration date (the desired shelf life of the product/package system).
• Ambient temperature (the temperature at which the product will most likely
be stored).
• Aging factor (2.0 is the most common).
The main test methodology used for accelerated aging: ASTM F1980-02.
How are packages tested for shipping and distribution endurance?
Manufacturers must evaluate the packages’ ability to adequately protect
the medical device through the handling and distribution environment. Damage,
such as material puncture, abrasion, or seal failure, may result from the dynamic
events to which packages are subjected.
Tests performed include ASTM D4169 test sequence and various ISTA procedures.
All of these test procedures address three common variables for ship testing:
shock/drop testing, vibration testing, compression testing.
Why should I develop a test protocol?
Since documentation is key to the sterile medical packaging validation process, developing a protocol is essential for satisfying the ISO 11607 requirement.
What happens after testing is complete?
A final test report must be generated to document the test results, corrective
actions, or other issues found during the validation process.
Make sure you allow adequate time to perform a thorough package evaluation validation.
The time taken to complete the validation can vary from one to nine months.
You should expect to spend $5000–$15,000 on a package shelf-life system
validation, depending on the experience and expertise of the packaging engineers.
Remember that the ISO 11607 test standard is only a framework. The final objective
of developing a safe and effective package system can be achieved by taking
many different paths.
Copyright ©2004 Pharmaceutical & Medical Packaging News
