Six Myths about ISO 11607
The contributors to ISO 11607:2006, Parts I and II, address some misconceptions about the new document.
by Nick Fotis
Cochair, AAMI TC198, WG7
Jackie Daly Johnson
Cochair, AAMI TC198, WG7
Curtis L. Larsen
Past Cochair, AAMI TC198, WG7
Past Cochair, AAMI TC198, WG7
Michael H. Scholla
Global Convener, ISO TC198, WG7
Past Cochair, AAMI TC198, WG7
Publication of ISO 11607: 2006, “Packaging for Terminally Sterilized Medical Devices,” Parts I and II, truly is a milestone in medical packaging history. The document represents a new era of global harmonization and understanding for medical packaging around the world. It has taken more than five years of discussion and work to prepare a document that all the countries of the ISO community have unanimously adopted.
Harmonization of ISO 11607 and EN 868-1 has been a goal since work began on both standards in the early 1990s. Because of several impediments too numerous to discuss, the process has unfortunately taken much longer than expected. But with contributions, cooperation, and hard work from several countries around the world, we have achieved our goal. The recent publication of the standard has been met with universal, global acceptance.
As is always true with the introduction of new or revised documents, some questions have recently arisen and should be addressed. This article will discuss these so that medical device industry professionals can make even better use of this harmonized standard.
Test data will only be accepted from validated test methods (with precision and bias statements) as found in the appendix of ISO 11607. Is this a new
All versions of ISO 11607 state and have stated that all test methods must be validated. The previous two versions of ISO 11607 had the same requirement (see section 4.4 of ISO 11607:2000).
Test methods that have been subjected to interlaboratory studies (ILS) to determine precision and bias (P&B) cannot be considered validated. Acceptable ILS results prove that the method can be validated in the hands of a given laboratory and what degree of precision can be expected. The laboratory conducting the testing will have to do additional internal testing to demonstrate that in that lab, results are similar to those published in the P&B statement. It is entirely possible (and demonstrated several times in our experience) that a laboratory can run an ASTM test method, but the result is incorrect because that laboratory never validated the method itself.
Compliance responsibilities are no longer clear. Weren’t they better outlined in previous versions?
Assigning responsibilities has, in fact, led to problems. For example, a manufacturer of SBS (sterile barrier system) materials may not be aware or capable of addressing all interactions between device and package or all end-user requirements for package design when providing materials to a medical device manufacturer (MDM). Assignment of responsibilities to various parts of the supply chain has been eliminated under new rules from both ISO and CEN. The rationale for eliminating them is 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 packaging 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 which party did the work.
Isn’t physical proof of sterile barrier integrity sufficient to demonstrate medical device sterility?
The standard does not state that proof of sterile barrier integrity is sufficient to demonstrate sterility of the medical device. Demonstrating device sterility is covered by many ISO sterilization standards. Once the device is sterile, it is the package’s role to maintain that sterility until the time of use. ISO 11607 indicates that sterility maintenance can be demonstrated by physical testing of sterile barrier and microbial barrier testing of any porous component. This was also part of ISO 11607:2000 (see clauses 5.2.4 and 7.3.2).
The document requires that the worst-case packaging configuration be determined and used for testing. Does this mean that testing is performed on packages produced at the lower limits of the process parameters established during process validation?
No, don’t confuse worst-case process parameters with worst-case design configurations. The requirement for a worst-case process is discussed in ISO 11607-2:2006, clauses 5.3 and 5.4. The worst case may not be the lower limits. The use of worst-case SBS does not necessarily require MDMs to acquire from sterile packaging manufacturers (SPMs) special lots of preformed SBS made at worst-case conditions specifically for design performance qualification. It means that when an MDM is placing a closure seal on a preformed SBS or is sealing a lid to a blister tray, for example, he or she should seek out the process variables that produce the weakest SBS and test samples made under those conditions.
When addressing the design configuration worst case, one approach is to evaluate the worst-case configuration for the device and package family. Using IV sets as an example, these products can range from simple tubes with fittings to a complex system of tubes, ports, and valves. If you wish to classify IV sets as a family that can be packaged in, for example, a specified header bag, you must identify the family, determine the worst-case example (the one with the most tubes, ports, and valves, for instance), and use it for design qualification performance testing.
Process validation has not always been seen as necessary for final packaging system validation, so many MDMs used to figure out the optimum process parameters and ignore upper and lower extremes of the process. The new standard now emphasizes package system validation. Isn’t this a new requirement?
The notion that an MDM can ignore the upper and lower extremes of the process contradicts ISO 11607:2000, clause 6.2.1. This is not a new requirement, and validation of a critical packaging process has always been an FDA requirement for a number of years. If you demonstrate that the packaging system protects the sterile barrier system and its contents until the point of use, but the packaging process is not validated, you may ask yourself, “What has been achieved except for a single data point?” If an SBS is manufactured outside optimum process parameters, will it pass package performance testing?
Stability testing and dynamic testing should be performed on the same test samples. Is this a good approach?
Stability testing and performance should be treated as separate entities for two very important reasons:
- When an MDM 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 device materials, SBS material, or critical process parameters.
- 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 rigors of simulated distribution testing after a long exposure to the 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 a new product to the marketplace.
The working group’s (TC198/ WG7) rationale was that when the Q10 equation is applied, there is no component for freeze-thaw cycles or humidity. When a package fails a test that incorporates these dynamics, it tells you nothing about shelf life. When treated separately, the packaging engineer can determine whether the failure was related to shelf-life testing or dynamic testing. If cumulative stresses are a concern, the dynamic testing can be after exposure to aging conditions.
Of course, the ISO 11607 document allows for these to be done together, if a particular company wants to do this for a specified reason. But the better approach is to keep the two tests separate based on the discussion outlined above.
Overall, the revised 11607 document has been well received by the technical community and has generated few questions. An extensive revision to the existing Technical Information Report (TIR 22) has been assembled and is available to the public through www.aami.org. This document will help engineers new to sterile medical packaging adopt the standard into their companies as well as provide specific guidance for applying the standard within FDA’s framework. The TIR document is meant to address the questions raised above, as well as provide some fundamental background and detailed lists of requirements of sterile packages. It is hoped that this will help packaging engineers and others involved with sterile medical packaging benefit from the combined years of experience of the entire packaging working group members of AAMI. It is also hoped that the TIR will be as well received and frequently consulted as the recent 11607 revisions.
The authors are active past and present cochairs of the AAMI Sterilization Standards Committee, Working Group 7, Packaging, which is the U.S. technical representation to ISO/TC198, WG7. Larsen, Miller, Scholla, and Spitzley explain ISO 11607 during the AAMI Webinar, “New Global Standard for Sterile Medical Device Packaging,” presented in three parts. To view the Webinar, which was to be held in early May, visit www.aami.org. Fotis, Larsen, Miller, Scholla, and Spitzley are all members of PMP News’s Editorial Advisory Board.