Originally published August, 1996
For packaging engineers, meeting the demands of an increasingly globalized device industry brings a wide variety of challenges. Faced with conflicting regulatory requirements, device packagers are actively engaged in efforts to create internationally recognized test methods and harmonized standards that will make their packaging acceptable anywhere in the world. At the same time, cost pressures in the medical marketplace are compelling materials suppliers and packaging engineers to explore new materials and package configurations that can reduce the expense of packaging without compromising device safety.
To examine these and other issues, MD&DI invited a panel of experts in the field of medical packaging to participate in a roundtable discussion. Brought together in conjunction with the MD&M East Conference and Exposition in New York City last June, the panel was moderated by MD&DI executive editor Steven Halasey.
The seven participants were Paul Fielding, regulatory affairs manager for Rexam (Bristol, UK); Joyce Hansen, director of the Sterilization Science Center for Baxter Healthcare (Round Lake, IL); Curt Larsen, principal packaging engineer for SIMS Deltec (Minneapolis); Hal Miller, director of packaging technology for Johnson & Johnson (New Brunswick, NJ); Barry Page, consultant and North American representative for mdc Medical Device Certification, a notified body that is headquartered in Memmingen, Germany; Mike Scholla, Tyvek medical packaging segment leader for DuPont Nonwovens (Wilmington, DE); and John Spitzley, associate fellow of packaging for Medtronic, Inc. (Minneapolis).
Questions posed by MD&DI are in bold, with the participants' answers following.
THE SUPPLIER'S ROLE
With the acceptance of international standards such as ISO 11607, compiled by the International Organization for Standardization (ISO), is the device industry on the verge of having harmonized requirements for packaging?
Page: A lot of work is being done in this area by ISO, going beyond what was done by CEN [the European Committee for Standardization] in Europe. When standardization first became a concern for manufacturers, FDA made a move to examine expiration dating of packaged devices on the basis of their ability to maintain sterility. One of the first articles that the HIMA Sterile Packaging Working Group put together raised questions about whether this was a realistic goal.
Larsen: According to early statistics, the number of recalls and problems resulting from packaging problems was horrendous. Industry has come a long way since 1974 or 1975 when people really started implementing good manufacturing practices [GMPs], but gathering the data and doing the testing needed to make dating claims is a laborious process.
I would like to see more of that work done by materials suppliers. Right now, they say they can't do it because they don't know what kind of machinery the material will be run on, how the material is going to match up with other materials that will be added to it, or what kind of processing it'll go through. I agree that that's a huge area of concern, but even data that were limited in scope could be useful in answering technical questions or dealing with regulatory issues.
Miller: It would certainly be a service to the medical device industry if materials suppliers would perform broad-based stability and long-term aging studies on their materials with different sterilization methods. When suppliers want to sell me a particular product, many times my first question is "What's in it for me?" The fact is that I would have to put a lot of resources to work in order to test and evaluate the product, and that's expensive. However, if the supplier has already done some of that testing, it becomes an extremely valuable service to manufacturers.
Fielding: Rexam certainly does some materials testing, but there's not a formal procedure. We target the characteristics that are critical to us and consider a range of sterilization procedures. Some such testing is a lot better than nothing, and it gives some degree of confidence. But it's inhibiting knowing that, if we test for several years, the materials will have changed by the time we're halfway done. The big questions are how the testing is done and for how long. If you're talking about real-time testing for periods as long as five years, then chances are the materials would've changed anyway.
Miller: Well, your material may have changed, but device manufacturers would still be using it. We still conduct the five-year shelf study and the accelerated aging study. If nothing else, suppliers could perform the accelerated aging testing so we can at least get to market. Any testing we can do to shorten the lead time from development to getting that product to market--whether through our suppliers or within our own organization--is a benefit.
Hansen: Part of the problem with real-time versus accelerated aging studies is that there's not a standard industry procedure for aging materials. A technical information report is being compiled by the AAMI [Association for the Advancement of Medical Instrumentation] Radiation Sterilization Working Group, which could potentially be accepted as a standard for accelerating aging procedures. While it's only guidance information, it would be beneficial in that people would use similar methods and could share data and give continued guidance on how to perform these studies.
Miller: From what I've seen of the AAMI document, it will give some credibility and substantial background for using the Q10 theory for accelerated aging, and for using a Q10 value of 2.0 as a very conservative approach to accelerated aging.
Hansen: At the very least, it would be a guidance document that people could refer to. And if materials manufacturers were to follow suit, it would be even easier to compare data.
Spitzley: But if a company were to take an aggressive approach, and later the standard became more conservative, would the materials that were evaluated using a faster accelerated regimen have to be retested?
Miller: That's an individual company judgment. The document will also outline boundary limitations for temperature, and manufacturers must look at their material characteristics and compositions to judge whether they've exceeded those boundaries. If the boundaries haven't been exceeded, then the earlier evaluations should be fine.
Will FDA accept that kind of generic test when a company wants to switch a material? How refined is the agency's demand for a material's characterization?
Scholla: ISO 11607 outlines certain information that must be supplied by a material manufacturer. As a result, our company is developing a manual that shows how its material meets the ISO standards and that includes technical data to support that information. FDA will expect that, if I supply device manufacturers information about the microbial properties of Tyvek, it's not going to change unless there's an interaction between the rest of the packaging materials or the device in the material.
However, we can't test every conceivable combination. So our plan is to generate data on the stability of a select number of package types, using various sterilization methods, in order to provide information that will be useful to the device industry in reducing the amount of work it needs to perform.
But presumably, if someone wanted to shift to a material that wasn't Tyvek, that material's manufacturer would have to be supplying similar information.
Spitzley: Yes, but it's not only materials. In a lot of cases it's an adhesive, and the same situation applies. If, under a broad range of parameters, an adhesive supplier can demonstrate that he's tested his material and it remains relatively stable over time, then the manufacturer just has to demonstrate that any processing he's doing doesn't interfere with that stability. Such a procedure would make it a lot easier for everybody. Currently, however, users must generate all those data for themselves, and that's time-consuming and expensive.
Larsen: And those data aren't shared between companies--each company performs the same tests. It's certainly a duplication of effort. If testing results were available from materials manufacturers, it would reduce the workload industrywide.
Miller: Often the types of materials used aren't as extensive as manufacturers think. While there are a lot of adhesive coatings on films and papers, there are certain films that are fairly standard. Data on these films would be a great benefit, because companies wouldn't have to continually reinvent the wheel.
Who would put together that sort of packaging materials compendium?
Miller: Device manufacturers aren't really looking for one packaging materials compendium. Instead, they would like suppliers to focus on selecting materials to create the overall package, not just one part of the package. Suppliers are the ones who really control the formulations for their particular product line. Maybe they don't want to share that information with other competitors, but they could still share it with device manufacturers.
Spitzley: It would be helpful if suppliers provided a guideline sheet that outlined their material, testing procedures, equipment it was sealed on, sterilization processes, sealing parameters, and so on. Then, if a manufacturer's packaging fell within those ranges, the company wouldn't have so much testing to do. If it chose to go outside those ranges for a particular application, it could provide that gap in the data without having to repeat the entire testing procedure every time.
Larsen: Believe me, if two companies come through my door and only one has this sort of guideline sheet, the one that makes it available to me will be the primary candidate to get its materials in-house. So such information is certainly a valuable marketing tool for these materials manufacturers. Of course, manufacturers want to be able to compare the data from vendor to vendor to make sure they're comparable.
In the area of test methods and sterility barriers, what's the next step? Has FDA made some moves to accept physical testing?
Hansen: Medical companies have used many test methods, some of which have not gone through the qualifications and validations necessary to ensure they can detect the maintenance of a sterile barrier. Improving, qualifying, and validating those test methods will be the push for the future. One recently published ASTM [American Society for Testing and Materials] test method allows researchers to rank the ability of materials to maintain sterility, but each company must then determine what level is acceptable for it, and these acceptable levels are likely to vary.
Spitzley: FDA has indicated orally that it's open to accepting physical testing, although it hasn't elaborated on what conditions would apply to such testing. However, I doubt there's ever going to be one method for evaluating the integrity of sterile packages because packaging systems can be complex. What's more important than trying to establish one worldwide standard is ensuring that such testing is documented and validated.
Who would actually be carrying out the testing you're talking about? Is it the manufacturer of the materials, the device manufacturer, or both?
Larsen: Both. People who are manufacturing and shipping the materials have certain requirements they must meet, based on their customers' specifications. When the customers get the material, they then perform tests and evaluations to make sure the requirements were met. So there need to be standardized systems at both ends of the pipeline to evaluate the materials. There's currently an effort at the ASTM F2.6 subcommittee level to standardize such methods.
How refined is the system now for characterizing materials? Can you distinguish between different blends of materials, or is there a need to so?
Miller: There's no real need to distinguish between different blends of materials. Each company has a specific material that it needs to perform a specific function. Depending on the physical or chemical properties of the product or its sterilization process, manufacturers may need to look at tensile, tear, or seal strength, or at puncture or impact resistance, and so on. These factors are more important than whether the material is a certain kind of coextrusion blend.
Hansen: I agree, but with the ASTM test method researchers can rank and compare materials. The method is sensitive enough to determine how well materials perform as barriers. But, as others have said, industry will still be faced with deciding what is acceptable.
Scholla: It will be impossible to agree upon a value, regardless of how many test methods there are, because the devices on the market, their distribution channels, and how long they last in the life cycle vary. Some products have a 3-month shelf life and probably don't need the same microbial barrier that is needed for products that have a 10-year shelf life. If that material will maintain the sterility and package integrity as well as the sterility of the device inside it and it meets the needs of the customer, that's great. However, the difficult part is judging what's acceptable in each instance. It may be impossible to establish a final value that is acceptable unless studies are conducted that demonstrate a correlation between microbial barrier properties and sterility over time, and that's expensive.
Is anyone suggesting that if you had a ranking of materials and a set of devices, and you knew that a device was going to have a shelf life of 5 or 10 years, you should necessarily use a material of a certain rank?
Spitzley: Jack van Asten from the Netherlands is putting together a test to rank materials and evaluate intact packages. He suggests that there will be some materials and systems that won't meet the requirements of that particular test and that would consequently be abolished. That's where there's going to be a lot of contention.
Scholla: It's up to each company to decide what materials it uses. If a company chooses a high-end material with excellent microbial barrier properties, it generally means less risk and greater ease in bringing a product to market. However, if a company is completely cost-driven, it may choose a low-end material that has greater risks associated with it. It doesn't matter what kind of standard you put out there. If a company can prove its system works, it's going to use it.
ISO 11607 and EN [European Norm] 868 have prompted a need for more-standardized test methods, as well. But because of the vast array of devices that are packaged and maintained in a sterile environment, it's difficult to say one material is good and one isn't. What people would really like is to have a checklist they could go through item by item. That may be fine for the device manufacturer who understands his product and can establish the criteria for it, but for an international organization to say, "This will work for every device out there," there's no way.
Miller: Most materials on the market have been around for a long time and have been accepted by use. What comes into play is cost. Companies are increasingly cost-driven and are looking at source reduction to keep materials costs down. My company's going to use the material that's most effective for its product and the package. If that happens to be a 21-lb paper, that's the way we'll go. If it happens to be the high end of a rugged Tyvek material, that will be our choice.
What is the status of European Union environmental standards for medical packaging, and where does the United States stand with regard to them?
Fielding: Regulations are being drawn up in Europe that affect medical packaging as well as packaging in general. While the regulations are expected to be implemented throughout the European Union at the end of June, the problem is that they will be implemented in various ways, according to each member state. Trade associations representing the medical device and packaging industries in Europe, EUCOMED [European Confederation of Medical Devices Associations] and ESPA [European Sterilization Packaging Association], are trying to have medical primary packaging in Europe eliminated from that legislation, but whether this will happen is still unknown.
Miller: In the United States, each of the individual states is trying to implement its own environmental regulations. The federal government has been stalled for years, except for what the Federal Trade Commission has set for guidelines. California and Oregon are probably the leaders in consumer packaging, setting the pace for reducing, reusing, and recycling. Consequently, it's tougher for companies to comply when doing business in those states.
Page: In the United States this is a local issue. Some sort of uniformity would be helpful, but with the shrinking of the federal government it's less likely to happen, and the matter will continue to be addressed at the local level in various states.
Larsen: A good example of the work toward recycling has been the international effort within the plastics industry to design a numeric or alphanumeric system for identifying materials and their constituents. It's been on the docket for years and sure, we've got the chasing arrows symbol, but what we do in the United States is not the same as what is done in Europe and around the world, so we need to work toward an international methodology.
Is there a need for industry to take the lead in this area? Presumably manufacturers are the ones who are most harmed if they need to satisfy 50 different sets of regulations.
Page: The trouble with that is whom you identify as manufacturers. Many manufacturers of other products have bigger packaging problems than the device industry does. The device industry is a relatively small part of all manufacturing and packaging.
Miller: It's also a sheltered industry. As Paul Fielding noted, the European industry is attempting to get exemptions from the European Packaging Waste Directive for regulated products such as pharmaceuticals and medical devices. And so far, whenever the American states have implemented environmental laws, they have exempted FDA-regulated materials because of the restraints that companies have. So from a primary package standpoint, the medical device industry is pretty well sheltered and, as a result, hasn't paid as much attention to the issue as perhaps it should.
OPTIMIZING PACKAGING DESIGN
What are the key challenges facing the designers of medical packaging?
Larsen: One challenge designers face every day involves making conversions to existing packaging systems, evaluating different materials, and gaining confidence that those materials will perform as needed. Making changes to packaging materials and designs has been laborious in the medical device industry, and now our marketplaces are requiring packaging engineers to do it more quickly.
Scholla: The key challenge facing packaging engineers is designing packages that protect the device and meet the needs of the customer--while also keeping in mind the increased pressure to lower costs.
Spitzley: Increasingly, single-barrier packages are being used instead of double barriers because of cost and environmental pressures. Strangely enough, most of the resistance to these changes comes from within a company, not from outside. Internal regulatory people often think they're violating some statute that requires a double barrier, but I am not aware of any requirement stating that a sterile medical device must have a specific number of barriers. Consequently, industry needs to intensify its efforts to educate people about single-barrier packaging and its performance.
Scholla: When switching from a double-package design to a single-package design, do you need to reengineer your primary package?
Spitzley: It doesn't really involve a lot of engineering changes, but manufacturers have to consider how the product is used by the end-user. Obviously, a manufacturer can't just decide to remove the outer barrier and give customers a package that doesn't allow them to be comfortable with the way it's handled.
Miller: Primary packages don't always need to be reengineered. If a company decides to remove the outer pouch of a general-purpose medical device that was formerly packaged in a double pouch, for instance, the primary package doesn't need to be reengineered. However, if a company chooses to eliminate a tear-open outer pouch and instead use a peelable foil, then reengineering is needed because of the design and material changes. In still other instances--as with sutures that have historically been packaged in a foil tear-open pack and peelable outer pouch--reengineering may not be required but may be done to improve the efficiency of internal operations.
Then there's the area of orthopedic implants, in which no company wants to be the first to eliminate the double package for fear that doing so could put it at a competitive disadvantage. In such a case, however, where the inner and outer packages were designed primarily to prevent the product package from opening during handling and distribution, the elimination of the outer package would likely require a major redesign.
When a package is reengineered or its process is reengineered, what's the magnitude of savings that you're looking at?
Spitzley: Most of the advantages a company gains by changing to single-barrier packages are not in materials savings but in manufacturing savings realized by not having two seals to inspect, two pieces of equipment, two separate lines, and so on. Companies may have to switch their materials because they're now using a single-barrier configuration, but that's not where the cost savings commonly occur.
Larsen: Obviously, a portion of the packaging cost is eliminated, but the extent of the savings depends on the materials used. Cost savings are also achieved because auditing and inspection in the processing and quality assurance steps are virtually eliminated. But companies must do their homework in evaluating the closures for the maintenance of sterility, in performing proper testing to ensure that they'll have the barrier they need, and perhaps in reengineering outer shelf containers or multiple containers to keep these devices in usable condition.
Miller: Johnson & Johnson has had an internal source reduction program since 1992. Our overall goal is a worldwide source reduction of 10% by 1997, and that will probably be reached fairly easily. Our goal for the year 2000 is 25%.
Spitzley: Is that by volume?
Miller: That's by weight. And in 1995 we had an annual worldwide source reduction of about 12%, which is a fair amount when you consider that's on roughly 400 million pounds worth of packaging at savings of probably a dollar per pound.
THE CHANGING GLOBAL MARKET
To what degree is globalization changing the way companies approach their packaging?
Spitzley: Companies must be prepared to manufacture at sites around the world as they become larger, and those changes frequently need to be made rapidly. They also need to take into account not only the regulations of the various countries, but the various cultures of those who will be working on their products. Manufacturing abroad may be more difficult and lengthen the time of implementation, but in the end a company has a manufacturing line that can move around the world fairly rapidly.
Miller: A lot depends on the type and size of the company. Larger companies may have multiple manufacturing facilities around the world and may have the luxury of assigning a specific site for a designated country or region. Then those specific sites can adapt to the regulations of that area.
Smaller companies have to supply the world from only one area, and for them, the challenge lies not just in adhering to regulations, but also in distribution and ensuring that customers receive what they're used to. For instance, we may typically sell a device in threes, sixes, or twelves in the United States. In many countries, however, customers want singles because that's what they're used to. In such a case, a company then needs to look at redesigning to unit packaging to meet the demands of a specific market--and this redesign may be only for that market.
Hansen: Awareness of the standards outside the United States has increased. In the past, manufacturers looked only at U.S. standards and operated with the idea that if products were manufactured in accordance with U.S. standards, others would accept them. Now manufacturers wanting to sell to the international market must examine the requirements of various countries and then manufacture in accordance with those requirements. If that means doing something extra, companies will often do it because they want to sell there. Consequently, device manufacturers are looking for standards that can be applied globally to any packaging line or manufacturing operation.