Medical Packaging: Achieving a Single Global Standard

Originally Published MDDI January 2004

Cover Story

A harmonized medical packaging standard will alleviate confusion and provide a single document that will ensure worldwide conformity.

Michael H. Scholla

Quality packaging systems for sterile medical devices are essential for ensuring that the global healthcare marketplace receives safe and efficacious products. Contaminated products cannot be used, so it is imperative that the systems designed to protect them are adequate to the task. Many national and international standards have been developed to address packaging sterilization and validation of the sterilization process for both industry and hospitals. In the last 10 years, efforts have focused on continuing to harmonize global standards to ensure that medical packaging meets performance requirements.

Recently, activities have been initiated to harmonize the International Organization for Standardization (ISO; Geneva) and the European Committee for Standardization (CEN; Brussels) standards for medical packaging. This article reviews the history of the harmonization effort and the impact of global harmonization on medical packaging suppliers, hospitals, and medical device manufacturers.

Background of Standards Development

Harmonization of the ISO and CEN packaging standards has been a goal since the development of these standards was initiated more than 10 years ago. Unfortunately, many factors prevented harmonization from being an obtainable goal at that time. Standards and standards development were new to this industry, and many concerns focused on how such standards would be applied. Europe needed a standard that met the essential requirements of the medical device directives, and ISO needed one that was voluntary and applicable globally. The strategy within CEN was to develop a horizontal standard (EN 868-1) along with several vertical standards to address specific performance requirements for various types of products used in medical packaging (EN 868 Parts 2–10). Conversely, the ISO strategy was to develop a single standard that addressed the required performance attributes of medical packaging without establishing specific performance criteria.

Although many of the European experts participated in the development of both the ISO and CEN standards, it was clear that development of a globally harmonized standard was initially unattainable. At the meeting of ISO Technical Committee (TC) 198 in Ottawa, ON, Canada in 1993, a resolution was passed that basically said: ISO would develop its standard (ISO 11607), CEN should develop its standards (EN 868 series), the two should be independent, and when it came time to revise these standards, efforts should be made to harmonize the ISO and CEN documents. CEN affirmed this approach by passing a resolution with the same strategy. After that, both committees were able to finish and publish their respective standards.

ISO published ISO 11607-1997: “Packaging for terminally sterilized medical devices” in 1997 and also adopted verbatim the Association for the Advancement of Medical Instrumentation (AAMI) and American National Standards Institute (ANSI) ANSI/AAMI standard. In the United States, an AAMI Technical Information Report (TIR 22-1998), “Guidance for ANSI/AAMI/ISO 11607—1997 Packaging for terminally sterilized medical devices,” was developed and adopted as well. This TIR addressed the issues surrounding how device manufacturers and medical packaging manufacturers would implement ANSI/AAMI/ISO 11607 and what test methods are typically used to show compliance with various requirements in the standard.

EN 868 Part 1 was published in 1997 and serves as the normative reference for medical packaging in Europe. The rest of the EN 868 series (Parts 2–10) was finalized and published over the next few years. These standards have specific performance requirements and test methods for various materials, such as coated paper and pouches, used in medical packaging (for a list of the parts' subject matter, see the bibliography included with this article). Although these specific requirements are not mandatory, compliance with the ones in the applicable standard can be used to demonstrate compliance with EN 868 Part 1.

After these standards were published, the next year or so was a period of assessment and implementation. The medical packaging industry was asking plenty of questions. What were the requirements of these standards? How is compliance with these standards demonstrated? What test methods should be used? What differences exist between the ISO and CEN standards? Are these differences in conflict? In addition, several Asian countries were developing regulations for medical packaging and were investigating the adoption of either the ISO or CEN standard as their national requirement.

Lessons Learned

Looking back, what did the medical packaging industry learn from the first round of standards development and implementation? First, the requirements of the ISO and CEN standards were very similar and were not in conflict. There were philosophical differences in some areas (such as whole-package microbial challenge testing versus physical testing for package integrity), but these areas were worded in each of the two documents to ensure the requirements were not mutually exclusive.

Clearly there was more philosophical agreement than difference. For example, both sets of standards apply to medical devices that are packaged and terminally sterilized in the hospital or healthcare facility. The expectation of both the ISO and CEN medical packaging committees was that, unless required by specific regional regulation, these standards should be applicable to hospitals on at least a voluntary basis. A packaged, terminally sterilized medical device should be held to the same expectations of performance and safety regardless of the location of the packaging process. Both committees have reaffirmed this principle on several occasions.

The medical packaging industry also realized that it lacked a critical element for consistent standards: the availability of robust test methods that had been subjected to formal round-robin testing, adoption by consensus-standards organizations, and validation in individual laboratories. Within the United States, these gaps resulted in the development and adoption of several ASTM test methods under the leadership of Hal Miller of Johnson & Johnson (New Brunswick, NJ).

The development of standardized test methods to assess the performance of medical packaging has had a significant effect on the U.S. industry. Standardization of test methods allows laboratories to reduce the number of specific methodologies while retaining the overall capability. In addition, standardized test methods allow individual laboratories to assess their own capabilities against the stated intralaboratory variability. Several areas still present opportunities for standardization of test methodologies (i.e., how many different ways can a seal strength test be run and the results interpreted?). However, at least one standardized test method can be used to demonstrate compliance with every “shall” statement in the medical packaging standards.

Initially, formal demonstration of compliance with ISO 11607 and EN 868 was really limited to the EN 868 series. In reality, most products placed on the market in Europe demonstrate compliance with EN 868-1 by demonstrating compliance with the specific requirements in the applicable EN 868 Parts 2–10 standards. However, in the United States, the passage of the FDA Modernization Act of 1997 had a significant influence on all standards related to medical devices, including the medical packaging standard. One component of the legislation was to codify the ability of FDA to recognize standards and enable device manufacturers to declare conformity to recognized standards in their premarket notification (510(k)) applications. Since then, more than 600 medical device standards have been recognized, including ISO 11607 and AAMI TIR 22, and declarations of conformity are becoming more common.

Following implementation of the act, a significant outcome was that industry and FDA became more comfortable with standards and the process of using them to show conformity. The vernacular and acronyms (such as CD, CDV, TC198WG7) are about as user-friendly and understandable as log tables were before calculators. Overall, the medical packaging industry has developed a level of comfort with standards, and many of the initial concerns about limiting market access and competition have proven to be unfounded. This is a relatively normal cycle associated with industries as they mature.

Harmonization Hurdle

It also became evident that there was one major hurdle to future attempts at harmonization. ISO 11607 covers materials, package design, and process. EN 868 primarily addresses materials with some forays into design in Parts 2–10. The packaging process is outside the scope of the EN 868 series. This difference is still an obstacle to complete harmonization. To address this issue, a strategy has been developed that requires splitting the ISO standard into two parts. This strategy will be discussed in more detail later. As an interim step, ISO developed the second edition of 11607, which was approved and published in early 2003. This revision includes notes that identify differences in specific clauses between the ISO and CEN standards. An example can be found in clause 4.3.2:

Unless otherwise specified in the test methods for materials, test samples should be conditioned in accordance with ISO 187 at (23 ± 1)°C and (50 ± 2)% relative humidity.

NOTE 1—For compliance with EN 868-1, the above becomes a requirement (EN 868-1:1997, 5.2).

The second edition was adopted by ANSI and AAMI in 2000. Unfortunately, there was a delay in getting the document through the ISO editorial system. Those editorial differences were overcome, and the standard was adopted and published. Because of the differences in timing for approval, ISO 11607 2nd ed. had a publication date of 2003 while ANSI/AAMI/ISO 11606 2nd ed. had a publication date of 2000. Such minor differences impede the user-friendliness of the documents and could easily confuse users who wouldn't know that the two standards are identical. 

A Global Standard

In 2002, working groups began the required five-year revision of EN 868-1. A working group of ISO TC 198, Sterilization, met in Kyoto, Japan, in May of that year. The primary discussion for this medical packaging working group (WG 7) concerned formally initiating development of a single document that would be adopted by both ISO and CEN as the global medical packaging document.

The group discussed differences between the current ISO and CEN documents and considered the scope of work assigned to both the ISO and CEN medical packaging committees. After considering document CEN/BT N 6287, “Product Standards and Conformity Assessment,” as well as ISO/IEC Guide 7, “Guidelines for drafting of standards suitable for use for conformity assessment,” the group determined that the harmonization project should be split into two parts. One document would address materials, design, and package performance; the second would address validation of the packaging process. The technical committee approved preliminary titles and scopes, and the work items were formally affirmed by CEN.

A task group was formed and chartered to develop the two drafts that would be submitted for adoption by both ISO and CEN as global medical packaging documents.

The task group included Tim Galekop (chair of the CEN medical packaging group) and Jimmy Van Veen of the Netherlands; Hans-Ulrich Plenio, Gerd Herfurth, and Stefan Manhart of Germany; and Hal Miller, John Spitzley, Cathy Nutter, Curt Larsen, and Paul Fielding of the United Kingdom.
The task group met twice (London in late October 2002 and Arlington, VA, in January 2003) and developed two draft documents. These were submitted as working drafts to the technical experts of ISO/TC198/WG7 and CEN/TC102/WG4 for comment. Working drafts are documents that are under review by the committees and distribution is limited to their technical experts. It is not necessary for mirror groups in member countries to develop an official comment or position on comittee draft (CD) documents; however, many countries did so to ensure that there would be input from as many members as possible. Comments were resolved at a meeting of the working group in Frankfurt, Germany, in June 2003.

The revised drafts were then sent for ballot in the committee-draft-with-vote (CDV) stage. Sixteen participating member countries responded to the ballots and all countries voted to approve both standards. Comments to the ballot were resolved at a meeting of TC 198 in New Orleans in December 2003. The documents will progress to the next stage and will be balloted as draft international standards. This stage requires translation into French and German by the ISO central sectretariat. Translation can take up to two months. After translation (or if two months have passed and the translations are not complete), there is a five-month ballot period. Comments to the ballots will be compiled and distributed to national mirror groups. The mirror groups then typically meet to develop national positions on the comments. The working group will meet in late 2004 or early 2005 to resolve the comments and revise the documents for submission as final draft international standards. A two-month ballot period will follow for a vote of yea or nay, with only editorial comments allowed.

Voting stages will be conducted within both ISO and CEN. Both organizations must affirm the documents for them to be accepted as harmonized international standards. At any stage from CD onward, the documents can be moved forward to the next step or reballoted at the same status, 
depending on the significance of the revisions made after consideration of the comments. 

The Need for Two Documents

Two documents are necessary because the differences between ISO and CEN standards involve validation of a specific process. There is a high probability that the first document (ISO 11607-1: CDV, “Packaging for terminally sterilized medical devices—Part 1: Requirements for materials, sterile barrier systems and packaging systems”) can be developed into a standard that will be adopted as both an ISO and a CEN standard because it does not include the packaging process. However, the probability that CEN will adopt the second document (ISO 11607-2 CDV, “Packaging for terminally sterilized medical devices—Part 2: Validation requirements for forming, sealing and assembly processes”) is lower because it deals with validation of a specific process. If ISO adopts both, and CEN adopts only the first, it ensures that at least materials, design, and performance will be harmonized. If CEN adopts both, the industry ends up with global harmonization of medical packaging including the process. Affirmative votes from 10 CEN member countries at the CD stage is certainly encouraging.

Key Differences in the Documents

It is important to understand the major differences and requirements contained in the latest drafts.

Terms Defined. The first major difference is the definition of four key terms: sterile barrier system, preformed sterile barrier system, protective packaging, and packaging system. The term sterile barrier system was introduced in these drafts to eliminate confusion. In the past, terms such as package, final pack, product package, etc. were used to describe the package around a medical device.

Unfortunately, diverse interpretations of what these terms encompassed caused confusion. For example, consider a device packaged in a rigid lidded tray that is then placed inside a header bag. This is then placed in a shelf pack, and 10 of these are placed in a shipping carton. Does final pack or package include just the tray, or the tray and header bag, or the shelf pack too? What about the shipping carton?

When analyzing the issue of sterile packaging versus any other type of packaging, it is clear that there are many common attributes and functionalities, but there are also some attributes and functionalities unique to sterile packaging. 

All packaging—from appliance packages to food packages—should identify the contents of the package, maintain the contents in an acceptable form for use, and protect the contents of the package from the environment. Sterile packaging has the added unique requirements of allowing sterilization processing, maintaining the sterility of the contents, and opening in such a way to allow for aseptic presentation. In the draft documents, sterile barrier system is defined as “the minimum packaging configuration that provides a microbial barrier and allows aseptic presentation of the product unit at the point of use.”

In the above example, this definition would include the lidded tray and the header bag. It could also be only the lidded tray, if the header bag were intended to be a dust cover rather than a sterile barrier. A preformed barrier system is a “partially assembled sterile barrier system prior to filling and final closure and sealing” and would include pouches, header bags, and opened reusable sterilization containers, among others. Protective packaging is the “packaging configuration designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use.” This definition would include the shelf pack and shipping carton and any other packaging used to protect the sterile barrier system. Packaging system is the “combination of the sterile barrier system and protective packaging” and could include all packaging through a cargo container. Sterile-fluid-path products such as tubing sets used for administration of IV fluids have been designed with closure systems that constitute a sterile barrier system by keeping the interior of the catheter sterile and allowing aseptic presentation. A pouch containing an IV tubing set that is labeled as having a sterile fluid path would not be considered a sterile barrier system but rather a dust cover.

There are expanded sections in Part 1 for reusable container systems and reusable textile products used mainly in hospitals. The focus of these areas is to ensure that performance is demonstrated throughout the usable life of the sterile barrier system.

Validated Processes for Preformed Sterile Barrier Systems. Another potential major impact of the draft of ISO 11607-2 is the requirement that preformed sterile barrier systems be produced using validated processes. For many sterile packaging manufacturers in the United States and the European Union, process validation is already a requirement of many of their customers, but this requirement could have a significant impact in undeveloped countries.

Test Methods. Two new annexes are currently included in the draft of Part 1. The first is an extensive list of test methods that can be used to fulfill the requirements of the standard. The list is informative and not normative, which means that other test methods can also be used if they are properly validated. The second annex is a medical packaging primer that should be useful to nonpackaging professionals with minimal understanding of medical packaging.

EN 868 Parts 2–10. The ISO committee has determined that these documents meet the needs of CEN. It is expected that CEN will retain them and begin their revision as these documents approach the five-year mark. ISO has adopted these documents as informative references within the drafts.They can be used to demonstrate compliance with applicable parts of the ISO drafts, which is how they are currently used to show compliance with applicable parts of EN 868-1. There are no plans to move the authority of these documents into ISO from CEN.

Industry Impact

If these draft standards are adopted, they will certainly affect medical device manufacturers, sterile packaging manufacturers, and hospitals in various regions of the world. If a device manufacturer is selling a sterile medical device in Europe, it must be shown to comply with the Medical Devices Directive. Compliance with the sterile packaging clauses of the directive can be demonstrated by complying with EN 868-1. If the packaging used is covered by one or more of EN 868 Parts 2–10, compliance with EN 868-1 can be shown by demonstrating conformance with these parts. If either of the draft standards is approved as an EN document, compliance with the device directive would then be demonstrated by complying with this new ISO/EN standard. 

If the draft of 11607-2 is adopted as an EN standard, manufacturers of preformed sterile barrier systems sold in Europe will be required to validate their processes for making the seals and closure systems on pouches, header bags, reel goods, etc. If Europe chooses not to adopt Part 2 (and only adopt Part 1), this requirement would not be in effect in Europe. Validation of all of the processes is a primary reason for the adoption of both parts of the standard in Europe. Why should the final seal on a pouch be produced using a validated process when all the other seals are not? In the United States, preformed sterile barrier systems sold to hospitals are considered medical devices by FDA and, therefore, validation of the packaging process is required by the quality system regulation (QSR). 

European hospitals are not mandated to comply with the Medical Devices Directive unless they sell sterilized products into the marketplace. They can, however, voluntarily choose to comply with EN 868-1. If the 11607 drafts are adopted, they will be able to voluntarily comply with 11607-1 or 11607-2 or both. If a hospital sells sterilized products into the marketplace, it is treated as a device manufacturer and would have to demonstrate compliance with the directives and the standards as outlined above. 

Compliance with ISO 11607

In the United States, medical device manufacturers do not have to comply with ISO 11607. However, because FDA has recognized the first edition, manufacturers can choose to declare conformity in their 510(k) submissions. The second edition has been nominated for recognition in the FDA process and should be published in the Federal Register as a recognized standard in the near future. If the new drafts are approved as ISO standards, they will be nominated for FDA recognition and published in the Register once they are recognized.

If the new drafts are approved, they will also likely be balloted as ANSI/AAMI standards for approval as American national standards. The content of the new drafts of 11607 contain no requirements that are not already addressed in the current edition of 11607. U.S. device manufacturers have mainly used 11607 as guidance, with few retroactively demonstrating compliance. However, several manufacturers have used declarations of conformity on submissions for new devices, and this trend should continue. 

Sterile packaging manufacturers that produce preformed sterile barrier systems for sale in the United States have implemented process validation to varying degrees. Some converters validate everything. Some only validate their process if their customer requires it. If they also manufacture pouches and reel goods for sale to hospitals, the process must be validated to comply with the QSR. If drafts of both ISO 11607-1 and 11607-2 are adopted, then there will be further impetus toward validation of all processes. 

Applicability of the proposed drafts of 11607 to hospitals in the United States is essentially the same as in Europe; they can adopt 11607 as a voluntary standard if they choose. The issue that arises with hospitals everywhere seems to be associated with Part 2, which addresses validation of the packaging process. For example, consider a medical device that has been wrapped in central supply room (CSR) wrap prior to sterilization. Some hospital representatives contend that this type of packaging process in the hospital can never really be validated. Others maintain that it can. At issue is the ability to demonstrate that the folding pattern used creates a closure that maintains sterility of the product and that the procedure for this proven folding pattern is actually performed by the people in the CSR area, according to the specification. It may not be easy but it can be done. More importantly, because the process for manufacturing preformed sterile barrier systems must be validated, it makes sense that the final seal and closure system should also be validated. Unless the closure process is validated, it is too difficult to demonstrate that product sterility is maintained to the point of use. 

Depending on the regulatory approach in each country, countries outside of North America and Europe use the current EN 868 and ISO 11607 for conformity in ways that are similar to those used in Europe or the United States. Several Asian countries are considering adoption of either EN 868 or ISO 11607 as regulatory requirements. The harmonization of the documents would eliminate the need for these nations to choose which standard to use.

Conclusion

Packaging systems for sterile medical devices represent a critical component in delivering safe and efficacious products into the global healthcare marketplace. A long list of standards addresses sterilization and validation of the sterilization process for all the types of sterilization in both 
industry and hospitals.

It doesn't really matter how well a sterilization process works if the packaging system does not perform. Marketing sterilized product in packages that are inadequate either by design, material choice, or faults in the process results in further problems. The product becomes contaminated and is unusable. Today, there are two normative standards for medical packaging, and the relevant ISO and CEN committees are diligently working to gain global concurrence on a single normative standard. 

Bibliography

AAMI TIR 22 (1997), “Guidance for ANSI/AAMI/ISO 11607–1997, Packaging for terminally sterilized medical devices.”

EN 868-1, “Packaging materials and systems for medical devices which are to be sterilized—Part 1: General requirements and test methods,” 1997.

EN 868-2, “Packaging materials and systems for medical devices which are to be sterilized—Part 2. Sterilization wrap—Requirements and test methods,” 1999.

EN 868-3, “Packaging materials and systems for medical devices which are to be sterilized—Part 3: Paper for use in the manufacture of paper bags (specified in EN 868-4) and in the manufacture of pouches and reels (specified in EN 868-5)—Requirements and test methods,” 1999.

EN 868-4, “Packaging materials and systems for medical devices which are to be sterilized—Part 4: Paper bags—Requirements and test methods,” 1999.

EN 868-5, “Packaging materials and systems for medical devices which are to be sterilized—Part 5: Heat- and self-sealable pouches and reels of paper and plastic film construction—Requirements and test methods,” 1999.

EN 868-6, “Packaging materials and systems for medical devices which are to be sterilized—Part 6: Paper for the manufacture of packs for medical use for sterilization by ethylene oxide or irradiation—Requirements and test methods,” 1999.

EN 868-7, “Packaging materials and systems for medical devices which are to be sterilized—Part 7: Adhesive coated paper for the manufacture of heat-sealable packs for medical use sterilization by ethylene oxide or irradiation—Requirements and test methods,” 1999.

EN 868-8, “Packaging materials and systems for medical devices which are to be sterilized—Part 8: Re-usable sterilization containers for steam sterilizers conforming to EN 285—Requirements and test methods,” 1999.

EN 868-9, “Packaging materials and systems for medical devices which are to be sterilized—Part 9: Uncoated nonwoven materials of polyolefines for use in the manufacture of heat-sealable pouches, reels and lids—Requirements and test methods,” 2000.

EN 868-10, “Packaging materials and systems for medical devices which are to be sterilized—Part 10: Adhesive coated nonwoven materials of polyolefines for use in the manufacture of heat sealable pouches, reels and lids—Requirements and test methods,” 2000.

ISO 11607 (1997), “Packaging for terminally sterilized medical 
devices,” 2nd ed., 2003.

ISO 11607-1: CDV, “Packaging for terminally sterilized medical 
devices—Part 1: Requirements for materials, sterile barrier systems and packaging systems,”2003.

ISO 11607-2 CDV, “Packaging for terminally sterilized medical 
devices—Part 2: Validation requirements for forming, sealing and 
assembly processes,” 2003. 

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