Defining Worst Case
|Return to Article: Complying with ISO 11607: What Will TIR 22 Do for You? Part II|
There has been much discussion and even confusion centered on meeting the worst-case requirements of ISO 11607. What makes this particularly challenging is that ISO 11607-1 addresses worst case in three areas. In each case, it means something slightly different. Correctly understanding and applying these clauses is necessary in order to fully comply with ISO 11607.
Clause 6.1.6 ISO 11607-1:
“When similar medical devices use the same packaging system, a rationale for establishing similarities and identifying the worst-case configuration shall be documented. As a minimum, the worst-case configuration shall be used to determine compliance with this part of ISO 11607.”
Within product families (i.e., devices that are similar but not identical), a common sterile barrier system may be used to protect a variety of medical devices. The worst case is established by identifying the device(s) that apply the most stress to the packaging system. The worst-case configuration may be the bulkiest or heaviest item in an otherwise common group of medical devices or an item with the greatest number of fitments or other product features such as with an IV or fluid transfer tubing set. Often, the determination of the worst-case configuration is clear. However, in some cases it may be necessary to test more than one device (e.g., the heaviest device as well as the device with the most fitments) to ensure that the packaging system has been fully challenged. Properly characterizing and evaluating the worst-case configuration will ensure that the other devices in the product family will be appropriately protected by the packaging system. It’s important to draft a written rationale statement documenting the worst-case chosen and make it a part of the testing protocol.
Clause 5.1.5 of ISO 11607-2:
“When similar preformed sterile barrier systems and sterile barrier system manufacturing processes are validated, a rationale for establishing similarities and identifying the worst case configuration shall be documented. As a minimum, the worst case configuration shall be validated to determine compliance with this part of ISO 11607.”
In this case, worst-case configuration applies to the sterile barrier system manufacturing processes not to the device itself. When validating manufacturing processes, the (preformed) sterile barrier systems may be grouped into families, such as chevron pouches using the same top and bottom materials but of different sizes. To ensure that the validation is meaningful for the entire sterile barrier system family, the worst-case configuration(s) for the (preformed) sterile barrier family must be identified. In our chevron pouch example, the worst case could be the largest pouch and the smallest pouch.
Clause 6.3.4 of ISO 11607-1:
“Performance testing shall be conducted on the worst-case sterile barrier system at the specified process limits of forming and sealing and after exposure to all the specified sterilization processes.” There are two predominant approaches to addressing the requirements of this section.
The first and most common approach utilizes sourcing preformed barrier systems or producing sterile barrier systems in a fully validated process. Sterile barrier systems that have been produced as lots run at typical operating conditions within the validated window are tested and evaluated. By choosing an appropriate sample size from multiple lots (typically three), one can be assured, at a given confidence level, that the full range of package characteristics (e.g., seal strength) have been represented. Hence, sample size selection and number of lots to be evaluated are important components of the documented rationale.
The second approach involves producing sterile barrier systems at the worst-case conditions of manufacture, generally the extremes of the validated window. For example, sterile barrier systems may be produced at the lowest validated temperature, the lowest validated pressure, and the shortest validated dwell to yield sterile barrier systems with the low-end worst-case seal strength. Typically, the parameters used to establish the operational qualification are used to produce the sterile barrier systems needed to assess the packaging system performance. This approach can be costly as specific and separate production runs will need to be performed to create the sterile barrier systems at the worst-case conditions of manufacture.
The approach to achieving compliance to ISO 11607 will vary between medical device manufacturers, but in each case the approach chosen should be supported by an appropriate rationale, to be included in the documented packaging system validation protocol. The choice will be dependent on corporate risk policy and economic considerations.