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Demystifying
Medical Device Package Validation for Manufacturers
By Scott Levy, Package Engineer, DDL Inc.
Many
medical device manufacturers struggle on a daily basis with
what they need to do to set up a shelf-life package validation
and what it takes to satisfy regulatory requirements regarding
sterile medical packaging.
This
article will demystify the validation process for manufacturers
by answering 10 frequently asked questions, using the ISO
11607 standard as a reference guide.
1)
What is validation?
The FDA defines validation as "establishing documented
evidence which provides a high degree of assurance that
a specific process will consistently produce a product meeting
its predetermined specifications and quality attributes."
The FDA requires that all processes be validated. The manufacturer
must prove the efficacy of the product and package system.
2)
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
which performs efficiently, safely, and effectively in the
hands of the user."
3)
What is the ISO 11607 standard?
According to section 1.1.3, "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
Final package validation.
4)
What must I do prior to the validation process?
Before a final shelf-life package validation can be put
together, specific questions need to be answered to proceed.
What
type 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 utilize?
What
are the glass transition and the melt and heat distortion
temperatures of the package and product?
5)
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 characteristics. Not
only does the strength characteristic play a key role in
a shelf-life validation, it lets the medical device manufacturer
determine on a daily basis that their process for sealing
packages is staying consistent to their predetermined specification
set in the process validation.
There
seems to be some confusion within 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 values 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 are the sealing parameters.
If a proper process validation of the sealer is not performed
the medical device manufacturer can expect failure.
Some very typical package strength testing includes:
Package Strength Testing by Seal Peel Testing: ASTM F88-00
Package Strength Testing by Burst Testing: ASTM F-1140-00
Package
Integrity
In order 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 post-sterilization environment.
The manufacturer must demonstrate that, under the rigors of
distribution, storage, handling, and aging, the 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 which occur during processing and/or distribution.
Physical test methods may be used to validate that the package
integrity has been maintained throughout the packages processing,
expected shelf life, and handling.
Testing includes:
Package Leak Testing by Dye Penetration: ASTM F1929-98
Package Leak Testing by Bubble Emission: ASTM F2096-02
Package Leak Testing by Vacuum: ASTM D3079-02, ASTM D4991-94
6)
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 Von't Hof that states "for every 10 degree
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 to 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, believes the theory
is useful in defining and justifying accelerated aging test
programs.
7)
How is accelerated aging performed?
Temperature selection for the accelerated aging study should
be determined by the temperature that avoids unrealistic
failure conditions such as deformation due to melting. 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 (this is the size of the individual packages
which will be placed inside the environment chamber)
Test Temperature (this is the temperature the chamber will
be set at)
Expiration Date (this is the desired shelf life of the product/package
system)
Ambient Temperature (this is the temperature at which the
product will most likely be stored)
Aging Factor (the most common Aging Factor is 2.0)
The main test methodology utilized for accelerated aging:
ASTM F1980-02
8)
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,
and seal failure may result from the dynamic events to which
packages are subjected.
Tests
performed include:
ASTM D4169 Test Sequence
ISTA Various Procedures
All
of these test procedures address three common variables
for ship testing.
Shock/Drop Testing
Vibration Test
Compression Test
9)
Why should I develop a test Protocol?
Since documentation is key to the sterile medical packaging
validation process, developing a protocol, therefore, is
essential for satisfying the ISO 11607 requirement.
10)
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.
Closing
Advice
Make sure you allow adequate time to perform a thorough
package evaluation validation. The time taken to complete
the validation can vary from 1 to 9 months. You should expect
to spend $5 - 15,000 on a shelf-life package system validation
depending on the experience and expertise of the instructed
packaging engineers.
Remember:
the ISO 11607 test standard is only a framework. The final
objective of developing a safe and effective package system
can be achieved through many different paths.
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