Page 206 - Biomedical Engineering and Design Handbook Volume 2, Applications

STERILE MEDICAL DEVICE PACKAGE DEVELOPMENT 185

“Primary package” replaced by “sterile barrier system”(SBS). This is defined as the “minimum
package that prevents ingress of microorganisms and allows aseptic presentation of the product at
the point of end use.”
“Final package” replaced by “package system.” This is defined as “(the) combination of the ster-
ile barrier system and protective package.” This combined package could include the second sterile
barrier, or outer package, in a dual pouch or tray; a paperboard carton or shelf box; and the shipping
container. These all may combine to form the “package system.”
The elimination of “package integrity.” This was defined as “unimpaired physical condition of a
final package.” Now it is implied that package integrity is lost if the sterile barrier system is breached
or does not “prevent the ingress of microorganisms to the product.”
Test Method Validation Test data will only be accepted from ISO 11607 validated test methods,
which may include a precision and bias statement and is based on round-robin testing of the test
method itself by several labs. However, a test method validation is not complete until it is actually
performed in a specific test lab with standard materials to show that the lab can produce data equal
to that shown in the precision and bias statement. This is not to say that a test method developed by
an individual company could not be used to test a specific attribute of the material or package.
However, the method must be validated by determining its precision and bias against a “standard.”
The validation must be documented and retained as evidence that the repeatability and reproducibil-
ity were determined and are within acceptable tolerance as those shown in the precision and bias
statement. In addition, the sensitivity of the method must be determined. This would apply in the
case of a package leak test to demonstrate package integrity.
Compliance Responsibilities Compliance responsibilities that were clearly outlined in Sec. 4.4 of
the old standard have been omitted from the new ISO 11607-01. Therefore, some confusion may
arise over certain areas of responsibility such as
• Who should test the packaging suppliers’ seals?
• Who is responsible for validating package sealing equipment?
• Who is responsible for evaluating the biocompatibility or other material characteristics such as
microbial barrier properties?
However, members of the Standards Revision Committee from AAMI, TC198, WG7 stated that
the rationale for elimination of assignment of responsibilities was that under the old standard when
an auditor assessed compliance to the standard, and a device manufacturer handled an aspect that
was “assigned” to a package supplier, the auditor would have to determine that compliance with
the standard was not achieved. The important point is whether the requirement is met, not who did
the work.
Ultimately, the medical device manufacturer must take care up-front with contractors and ven-
dors to determine roles and responsibility in the entire package development and validation process.

Worst-Case Packaging The revised standard places additional emphasis on the concept of testing
the “worst-case” package configuration. More on this concept later.

Stability Testing (Accelerated Aging) as a Separate Entity Another significant change was to
separate performance testing (distribution and transportation) from stability testing (shelf life) in the
final package system validation. Previous studies had combined these effects of aging with extreme
environmental conditions and dynamic events inherent in distribution in a sequential test method.
The new thinking as stated by the AAMI Committee was “Stability testing and performance testing
should be treated as separate entites.” More on this concept in later.
The FDA has recognized this standard for product reviews in its 1997 Guidance for Recognition
and Use of Consensus Standards: Availability. This standard specifies the basic attributes that mate-
rials must have for use in packaging for terminally sterile medical devices. In addition, it provides
the producer or manufacturer the guidance to conduct a formal qualification and validation of the