An MD&DI January 1998 Column
Two Packaging Standards Give Manufacturers the Ability to Pick and ChooseHaving two different packaging standards might appear confusing, but EN868-1 is so narrowly focused that it may be incorporated into ISO 11607, increasing industry harmonization.
There are three ways to rile a medical device executive. Make a standard so specific it eliminates any possibility of creativity. Make a standard so ambiguous it provides no clear direction. Produce two standards. The packaging community is faced with the latter, the two standards being ISO 11607 and EN868-1.
Photo by Roni Ramost
At first glance, complying with both might seem difficult given the potential for conflict and confusion. However, a closer look eliminates most fears. "The two standards have very different scopes," says Michael Scholla, PhD, medical packaging segment leader at DuPont Nonwovens (Wilmington, DE).
ISO 11607, titled "Packaging for Terminally Sterilized Medical Devices," covers the development and production of the package, laying out the fundamental requirements for selecting materials as well as developing and validating the processes that go into the package. As is the case with all ISO standards, ISO 11607 provides guidance on the particulars involved in lieu of specific requirements. "It is not a cookbook recipe," says Hal Miller, director of packaging technology at Johnson & Johnson (New Brunswick, NJ). "It allows a lot of flexibility, as long as you develop the appropriate rationale for what you do."
EN868-1, developed by the European Committee for Standardization (CEN), has a name as long-winded as the standard is tightly focused. "Packaging Materials and Systems for Medical Devices Which Are to Be Sterilized, Part 1: General
Requirements and Test Methods" deals only with the selection and testing of materials that make up the package. It does not address process development or validation.
"EN868 really deals just with materials," says Scholla. "ISO 11607 takes a much broader perspective, addressing package design issues, validation, materials, final product packagingthe whole nine yards."
The complementary nature of these two standards is their collective strength. Together they provide just about everything necessary for gaining international acceptance. There is, however, significant overlap in the area of materials and, therefore, grounds for conflict. "If you were to draw two circles, the big circle would be ISO 11607 and inside that would be EN868," Scholla explains.
For example, ISO 11607 simply states that a material's porosity must be measureda company can run whichever test it prefers. Not so with EN868-1. The CEN standard, written as a European requirement, specifies a particular test method, which is not necessarily the one most American companies would choose. In the Bendsten test specified by the CEN standard, the larger the number in the result, the more porous the material. U.S. firms commonly use the Gurley Hill test, in which lower numbers indicate a more porous material.
The CEN standard is important in the context of a European medical device directive scheduled to take effect in June. "Its goal," says Scholla, "is to provide a way of demonstrating compliance with the directive in the areas dealing with packaging." However, it is not the only way to comply. The key element is proving compliance to a notified body. "If a company decides not to comply with the strict limitations of EN868," explains Scholla, "but it can convince the notified body that it is in compliance with the medical device directive through other means, that is perfectly acceptable."
If the notified body certifies that a device meets the requirements of the medical device directive, a company is allowed to apply the CE mark to the device. "The notified body is going to set the criteria that a device will have to fulfill," says Dennis Dyke, vice president of quality and regulatory affairs at Rexam Medical Packaging (Mundelein, IL). Thus a device could be in compliance with 868-1 and maybe not satisfy some other requirements of a notified body."
CHOOSING A STANDARD
According to Dyke, many companies do not need to be concerned about these two standards because they don't relate to their products. CEN and ISO standards are applicable only for medical devices that are terminally sterilized. The packages surrounding these devices maintain their sterility.
If the two standards apply, what is the best way to choose between them? Each device exhibits a specific character, and engineers and regulatory affairs specialists should pick the standard that is most compatible with that character. Many companies continue to look for expert advice. Scholla calls such dependence on so-called experts a "checklist mentality. It's a 'tell me what to do and I'll do it' kind of thing."
The European standard focuses on materials issues. ISO 11607 is much broader (photo courtesy of DuPont Nonwovens, Wilmington, DE).
The interest in seeking outside counsel has been recognized and is being addressed by the AAMI (Arlington, VA), which plans to release a technical information report (TIR) in early 1998 regarding ISO 11607. The TIR will provide additional information on the requirements of ISO 11607 tailored specifically for U.S. companies. Written by the AAMI packaging working group, this report will explain what needs to be done to meet specific points in the ISO standard and the rationale that could be used to demonstrate compliance.
"We hope to have something that will help people understand what they are going to need to do when they're using 11607," says Joe Lewelling, AAMI senior director of standards. Scholla warns, however, not to "elevate [the TIR] to the level of a standard. You need to comply with the standard, not the guidance."
In the end, company employees make the important decisions. They select materials, develop processes, and validate those processes in ways specific to each device. No standard could possibly cover every possibility of the myriad devices that are terminally sterilized. Even if that were possible, it would not be advisable, as the packaging requirements would constrain the development of novel devices.
HARMONIZING THE CEN AND ISO STANDARDS
Arguably, the CEN and ISO standards are proof that harmonization has already taken place. ISO 11607 is the end product of negotiations of the International Organization for Standardization. EN868-1 was compiled by the European Committee for Standardization. Together they represent the majority opinion of the global medical device market. Soon, the world community may take the next step and combine the two standards into a single document.
Last September in Stockholm, the ISO working group drafted a proposal that would incorporate as much of the CEN standard as possible into ISO 11607. This proposal essentially replaces the materials sections of the current ISO standard with EN868-1. "It would amend the ISO standard to harmonize it with EN868," says Joe Lewelling, senior director of standards at AAMI (Arlington, VA).
As this article went to press, the CEN committee was scheduled to meet over Thanksgiving weekend to discuss the differences between the two standards. At that time, the proposal harmonizing the two will be put forward. "I think this is going to end up being acceptable to everybody," says Michael Scholla, co-chair of the Technical Committee 198 (TC 198) working group on packaging. "Frankly, I think it's a win-win for everybody."
The politics is almost as circuitous as the standards. The ISO working group is comprised of various technical committees. Technical Committee 198 has been given responsibility for standards on sterilization. Within TC 198 are 11 working groups assigned to specific issues associated with sterilization. Members from U.S. packaging companies collectively form an opinion that is presented as being representative of the United States.
AAMI coordinates U.S. input to the ISO standards, as well as comments on the CEN standards. "We're constantly working toward complete harmonization," says Lewelling of AAMI, which administers the international secretariats of TC 198 on behalf of the American National Standards Institute.
The idea that harmonization is a continuing process was evident in a meeting of TC 198 four years ago in Ottawa, Canada, before the two standards were formally released. Members of both packaging committeesone charged with developing the CEN standard, the other focused on the ISO standardagreed that after these standards were completed, representatives would try to consolidate them.
Whether the consolidation will come to fruition is mostly a matter of timing. Lewelling notes that certain procedural aspects of amending ISO 11607 need to be worked out. "It's not a question of what will be balloted, but at what stage within the ISO process we get to start the balloting," he says. "The ISO procedures are a little fuzzy on what you are allowed to do with regard to amendments."
STUDY THE TEXT
The challenge is to dissect the two standards, analyze the parts, and shape a response specific to the device being packaged. Understanding definitions is critical. Terms are not used lightly or interchangeably in these documents. Manufacturers package or sterilize the device. Producers make packaging materials or systems.
"We use the terms manufacturer and producer interchangeably," says Scholla, "but in 11607, these terms have very specific meanings. If you don't understand those two definitions, there will be parts of this document that you think are applicable to you that are not. As a producer you might think you've got to qualify your customers' package and wonder how you are going to do it."
Other words have specific meanings and are associated with potentially harsh consequences for getting them confused. Shall means the action is mandatory. Should denotes a recommendation or guidance.
Shall consider is a mind bender. The uses of this phrase are context specific but might, for example, be translated as requiring the company to consider certain issues involved in sterilization or transport.
"The language used in both documents is a little difficult for the American reader," Dyke says. Part of the problem is because of the use of English as it is spoken in Great Britain. But Americans may have the least troubles. "Not all the words in English translate directly into French and German," Dyke notes.
With a little work, the language barrier can be broken. "You can't run through these standards quickly and expect to pick up the meaning," Dyke notes. "You're going to have to chew on it for a while." Of critical importance is differentiating between the major appendices. The statements in ISO 11607 bearing the label normative are mandatory. Break them and surrender all hope of compliance. Of far less concern are the informative appendices, which are meant to provide guidance. They might list or describe methods that could be used to evaluate package performance, but another method can be used if it will provide similar results.
STANDARDS SHOULD REDUCE RECALLS
When choosing which standard to use, certain key points need to be kept in mind. The CEN standard addresses only packaging materials. The ISO standard also addresses package design and process validation. These two standards are not, however, mutually exclusive. There is some overlap where both standards address the same issues. For example, both require that manufacturers demonstrate and document the suitability of their packaging materials for the chosen sterilization process. Both standards also require documentation that the materials remain stable after sterilization. Consideration should be given to where the product will be marketed. In Europe, for example, compliance with EN868-1 is mandatory, whereas ISO 11607 guidelines are voluntary.
In the United States, the ISO standard is more important because FDA views it as representing the state of the art of the industry. "FDA has embraced 11607 and will be training their people in it," Scholla says. "Within the next year, they will probably start inspecting against 11607."
Miller says FDA is taking this approach because ISO documents are reviewed by packaging experts. There is a real need for quality standards in this area, according to Dyke. "Packaging and labeling are among the most common reasons for FDA recalls," he says. "Being able to establish some quality standards in the U.S. marketplace is a hot area right now."
FDA adoption of the standards would be in the best interest of the industry, Scholla says. "What's in 11607 came from industry, saying this is what we ought to have. So while ISO standards are voluntary, they can become part of the regulatory process of individual countries, because they represent the state of the art."
The ISO standard states that the properties of microbial barriers must be defined. Simply, the package must be effective, meet specified design criteria, and maintain the stated properties after being stressed environmentally. The package's permeability to air and to specified sterilizing agents must meet requirements for sterilization and removal of sterilants. Here the ISO standard is exact, providing a normative test method for the resistance of impermeable materials to the passage of air. If a material is found impermeable, no other microbial barrier testing is needed. In addition to the test for measuring permeability of materials to the passage of air, the standard's annexes address methods for evaluating performance in distribution, storage and handling, and dye penetration testing.
Among the key requirements specific to the CEN standard is the need to determine the permeability of materials, closures, and seals. To assist in this process, EN868-1 offers a decision tree for classifying packaging systems. The CEN standard has nine annexes, which are informative, offering advice on such topics as microbial barrier evaluation and the impermeability of packaging seals.
TWO IS NOT ALWAYS BETTER THAN ONE
The separability of these two standards detracts from the real opportunity they present to the packaging community. Taken together, the two standards enable manufacturers to create a total product that is efficient, safe, and effective in the hands of the user. There is, in fact, an effort to formally combine them by essentially substituting EN868-1 in place of the materials section in ISO 11607 (see sidebar). "You dump that particular standard into the ISO document and companies around the world can take the document and subscribe to it, knowing that it is a harmonized standard," says Miller.
Manufacturers and producers don't have to wait for an amended ISO standard. Such hybridization will do little except make official what everyone who has carefully examined the standards already knowsthat the rules and guidance for successfully putting together a medical device package are already available.
While expert opinion may provide insights otherwise obscured by the language in these standards, there is no substitute for the knowledge that in-house staff can bring to the process, particularly regarding the specific medical device being packaged. "No one knows your product better than you," Scholla says. "So when you sit down and read the documents, you are going to have different insights than any consultant. Don't listen to all of the things we supposed experts have to say. Get the standards and read them yourself. In order to comply with it, you have to actually read [and understand] it."