Page 238 - Biomedical Engineering and Design Handbook Volume 2, Applications

STERILE MEDICAL DEVICE PACKAGE DEVELOPMENT 217

devices perform their intended function and pose no undo risk to the patient. Not only must the prod-
uct itself meet stringent regulatory requirements, but the package must also perform consistently
under variable manufacturing conditions, sterilization procedures, and distribution hazards; and per-
haps over an extended shelf life.
The development of a final package system validation protocol consists of a documented plan or
protocol to evaluate the package design and manufacturing process and ensure that it meets all of the
critical parameter and requirements of the standard (ANSI/AAMI/ISO 11607-1:2006, 4.3, 6.3, 6.4).
A comprehensive discussion of the final package system validation steps can be found in the AAMI
TIR 22:2007. A summary of the steps are
• Develop plan objectives
• Understand the packaging system design configuration
• Group packaging systems for validation
• Determine sample size
• Define acceptance criteria
• Prepare packages for testing
• Define the shipping environment
• Define product/package shelf life
• Document the results
It is generally accepted industry practice to evaluate the integrity of sterile medical device pack-
ages by subjecting a fully processed package to extremes in sterilization processes, performing a sim-
ulated shelf life or accelerated aging study, conducting a simulated distribution and handling stress
test, and then evaluating the efficacy of the package for sterility through physical test methods.
The flowchart in Fig. 7.7 shows one validation plan that has been used to gain compliance with
the requirements for the final package system validation. This flowchart should be written into a
detailed validation plan that is signed by all the parties. The written protocol will have a thorough
description of the package configuration, including a detailed description of the different levels of
packaging (e.g., sterile barrier system, carton, shelf pack, shipping container) used in the package
system being validated.
In this protocol, the accelerated aging or stability and other distribution and handling requirements
for the validation are treated as separate entities. As was discussed in Sec. 7.7, FDA requires docu-
mented evidence to support published expiration dates on medical device packages. The European
Union has required expiration dates on all medical device packages as specified in the EC Directive
93/42/EEC, which states “the label must bear . . . where appropriate, an indication of the date by
which the device should be used, in safety, expressed as the year and month.” Consequently, manu-
facturers are being forced to comply with European directives based on the ISO standards. The new
revised ISO 11607 standard has indicated that the shelf-life study should be treated as a separate entity
from performance testing. The new thinking, as stated by the AAMI Packaging Committee, is that
“Stability testing and performance testing should be treated as separate entities for (some) very
important reasons:
1. When a medical device manufacturer is selecting SBS materials for a family of devices, he or
she does not want to conduct costly and time consuming repetitions of stability testing when
nothing has changed regarding the device materials, SBS materials, or critical process parame-
ters. If stability testing and package performance testing are conducted in parallel, there is
always a risk that any failure that occurs cannot be assigned to a specific cause. Did the failure
occur as a result of distribution stresses or did aging cause the failure? Exposing package systems
to the rogors of simulated distribution testing after long exposure to elevated temperatures usually
seen with accelerated aging testing (2 to 16 weeks or more at 40 to 55°C) can result in failures
that would not normally be seen during distribution. This can lead to unnecessary, costly, and
time-consuming delays in the introduction of new product to the marketplace.