ISO 11607-1 Section 6 talks about worst case. How do I address those requirements?
ISO 11607-1 addresses “worst case” in three areas and in each case, it means something slightly different. In order to correctly interpret and apply these clauses dealing with worst case, it is important to understand the terms that are used. Specifically:
sterile barrier system – minimum package that prevents ingress of microorganisms and allows aseptic presentation of the product at point of use
protective packaging – configuration of materials designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use
packaging system – combination of the sterile barrier system and protective packaging
In clause 6.1.6 of ISO 11607-1, it states: “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.
Worst-case configuration is again discussed in 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, for example chevron pouches using the same top and bottom materials but of different sizes. To insure 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.
Additional direction regarding worst-case testing is provided in section 6.3.4 of ISO 11607-1 on packaging system performance testing, “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. Numerous reference materials exist to assist in sample size determination, and a recent article by Nick Fotis and Laura Bix discusses the subject in some detail. 1
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 (OQ) 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 package validation protocol. The choice will be dependent on corporate risk policy and economic considerations.
1 MDDI October 2006