A Standard Challenge
A perpetual flow of revisions to sterilization and packaging standards reveals the only true constant in the industry: change.
Irene Peter is not a name that is synonymous with the medical device industry. Not in the least. In fact, Peter’s name is probably more renowned in publishing circles than on cleanroom floors or in testing laboratories. And it is almost certainly unrecognizable in the boardrooms of the industry’s top device firms.
Peter may never be as well-known in the medical device world as she is in the literary realm, but her
A QTS engineer develops a tray package design. The type of sterilization method used for medical devices often dictates its packaging requirements. Some packaging materials, for example, are incompatible with certain types of radiation sterilization methods. Photo courtesy of Quality Tech Services.
Peter wasn’t referring to the medical device sector when she unleashed this sardonic gem upon the world, but her words are nonetheless fitting for an industry that is constantly evolving yet never strays far from its most basic principles.
Quality, for example, has always played a central role in the medical device industry, but the level of product quality and the systems in place to improve that quality are continuously being changed.
Peter’s paradox is perhaps most evident in the sterilization and packaging sector, where quality standards are regularly revised for device companies that rely on the same tried-and-true methods of sterilizing medical products. Frequent chan-ges to these standards can make it seem as if the sterilization and packaging sector is in a constant state of flux when it is really only the standards themselves that are changing.
Such persistent shifts in standards have made the jobs of sterilization and packaging providers more challenging in recent years as they try to keep abreast of the latest regulatory requirements. Though it is a formidable task, companies have quickly realized that staying current on industry standards is vital to survival.
“The challenge for sterilization service providers and sterilization companies is keeping up with the regulatory requirements. But it’s also about having the knowledge and the foresight to understand the regulatory agencies and their requirements years ahead of when these requirements are supposed to go into effect,” said Patrick J. Hughes, vice president of sales and marketing for Sterigenics, a sterilization services provider based in Oak Brook, Ill. “In our company we have a very large environmental and safety department so we can work with the regulatory agencies…to see what’s coming in the future. You have to be involved, and you really have to pay attention and work with the regulatory agencies to assure that you can meet future capacities and changes. It’s a big challenge.”
It’s actually more like a gargantuan challenge, particularly for smaller companies that may not have the resources to monitor all the revisions to sterilization and packaging standards. Smaller firms also may not be aware of the various organizations responsible for developing sterilization standards.
The Association for the Advancement of Medical Instrumentation (AAMI) works with the American National Standards Institute (ANSI) and the International Organization for Standardization (ISO) to develop “validation standards” for all medical device sterilization and packaging techniques. The association writes consensus standards, recommended practices and technical information reports. Its standard and recommended practices are subject to committee approval, public review and resolution of all comments.
ISO Technical Committee TC 198 (Sterilization of Health Care Products) drafts standards too. Because ISO is a worldwide federation of national standards bodies, AAMI must work through ANSI to participate in the development of any international sterilization and packaging standards.
Criteria developed by AAMI are reviewed and updated at least once every five years. But some benchmarks, such as those governing steam sterilization and sterility assurance in healthcare settings, undergo continuous maintenance.
ISO 11607 for instance, has been revised twice since its inception in 1997. The original standard (ISO 11607:1997), “Packaging for Terminally Sterilized Medical Devices,” outlined the requirements to validate and prove the performance of sterile barrier packaging, materials, processes, and systems. It was revised and updated in 2003 before being harmonized just three years later with BSI BN EN 868-1 (“Packaging Materials and Systems for Medical Devices Which are to be Sterilized”). The amended 2006 version was divided into two parts—the first detailed requirements for materials, sterile barrier systems, and packaging systems, and the second outlined the validation requirements for forming, sealing, and assembly processes.
“Standards are constantly changing, so it is critical to stay current on them,” said Bob Lord, sales and marketing director for Quality Tech Services Inc., a Bloomington, Minn.-based firm that assembles, packages and sterilizes medical devices. “For example, the EtO [ethylene oxide] and ECH [ethylene chlorohydrin] limits were recently reduced in the new edition of ISO 10993-7. Medical device companies must now figure out how to reduce their post-sterilization EO and ECH levels to comply with the new requirements.”
As if keeping abreast of standards from AAMI, ANSI and ISO wasn’t tedious, time-consuming and confusing enough, packaging and sterilization providers also must mind the steady stream of regulations handed down by the U.S. Food and Drug Administration (FDA) and its foreign counterparts. And, when the FDA is under fire from both consumers and politicians, sterilization and packaging providers feel the heat too.
A succession of highly publicized recalls involving baby food formula, pet food and the anti-coagulant Heparin over the last year or so has prompted the FDA to closely scrutinize the way companies manage their supply chains. Earlier this year, the agency instituted a pilot program to determine the feasibility of establishing a supply chain-monitoring network. The program asks pharmaceutical firms to volunteer supply chain information for drugs and active pharmaceutical ingredients.
The FDA is keeping its eye on the supply chain in the medical device industry as well, though its efforts are not as blatant. Still, the crackdown on suppliers presents a challenge to sterilization and packaging providers because they must now prove their worth to wary OEMs, industry experts told Medical Product Outsourcing.
“Recently, the FDA put a full-court press on the OEMs about supplier management. Over the last few
A Class 7 Cleanroom at Quality Tech Services Inc. Medical device characteristics can have a profound impact on the way a device is packaged and sterilized. Photo courtesy of Quality Tech Services.
years, there’s been a significant increase in the percentage of product recalls where the problem was traced back to the contract manufacturer,” said Kelly Lucenti, president of Millstone Medical Outsourcing, a contract packaging service provider based in Fall River, Mass. “That’s driven the FDA to start coming down on the OEMs. The FDA says ‘you are the ones who are sending this work to a contract manufacturer, therefore you are responsible for that product while it is being manufactured at the vendor.’ This makes OEMs much more critical about who they partner with. There is a very big consolidation effort going on right now. A lot of the large OEMs are re-evaluating which of the contract manufacturers they are going to partner with in the future.”
And this re-evaluation can take many forms. At STERIS Isomedix Services, the reassessment has come in the form of in-person audits.
“In our facilities, we’re seeing a significant increase in customer audits directed from senior management who are concerned about the increased focus on CFR 820 and management of suppliers,” said Thad Wroblewski, regional sales director for the Mentor, Ohio-based firm, which provides contract sterilization services to the medical device, pharmaceutical, consumer and industrial sectors. “Senior managers, above the typical quality/regulatory assurance groups, are taking an active role to visit our facilities. Customers are highly interested in our quality programs, particularly those that address non-conformances, and our CAPA [corrective and preventative actions] systems. It is essential to understand and assure we meet both the customer’s internal standards as well as our own. Non-conformances are simply not acceptable.”
The More Things Change ...
In a sector driven as much by change as by profit, sterilization and packaging firms can take comfort knowing that at least one thing hasn’t changed: the ways in which medical products are sterilized and packed.
The options available to medical device firms that perform this service—whether they are an OEM or a contract manufacturer—have not changed much in the last decade. EtO is still the most widely used
A product is loaded in an EOExpress chamber at STERIS Isomedix Services’ San Diego, Calif., facility. Photo courtesy of STERIS Isomedix Services.
and well-established sterilization method available in the industry, though other techniques have slowly been gaining in popularity, including gamma radiation, e-beam, gas plasma, X-ray and hydrogen peroxide.
“Changes in sterilization technologies and methodologies seem to be slow and perhaps mundane through recent years, “ Wroblewski noted. “Not much is new in terms of how we sterilize; however, what is new is an ever-increasing focus on quality and performance, supply chain management for efficiencies, supply chain visibility through web interactive services and an increased level of interest in business partnerships. Companies are realizing that sterilization is not a comodity ‘buy,’ but a service of high criticality to assure patient safety and product supply to the end user.”
This focus on quality and performance has helped make EtO a popular sterilization choice among manufacturers. Not only is ethylene oxide compatible with most device and packaging materials, it can be pro-cessed at relatively low temperatures, and it is more cost effective than some other methods, industry experts said. The cost factor is a particularly attractive advantage to customers considering using other types of sterilization methods that require more expensive equipment.
EtO also is a better sterilization method than e-beam and gamma radiation for packaged pharmaceuticals, which makes it an ideal technique for treating drug-coated devices such as stents. In addition, ethylene oxide is a good choice for plastics that may discolor or when the physical properties of the plastic may degrade with irradiation.
Despite its various advantages, however, EtO sterilization is a lengthy, complicated process, often taking as long as two weeks to complete. And, EtO is petroleum based, so when fuel prices jump, the cost of sterilizing medical devices goes up as well.
“Ethylene oxide is a chemical that comes from petroleum. When the price of crude goes up, guess what’s going up?” noted Sterigenics’ Hughes. “You try to have contracts, you try to work around that, but there are delivery charges involved too. Ethylene oxide is put into containers for us, but they have to be shipped. So, when the cost of gas goes up, the shipping costs go up. You can’t pass those kinds of costs along to your customers. You try and we do try, and most of our customers understand. It’s not us trying to get one over on someone. The costs are there.”
So are the hazards. Because it is flammable in both the liquid and gaseous state, EtO is regulated by the Occupational Safety and Health Administration and the U.S. Environmental Protection Agency. And, since it is considered toxic, medical devices sterilized with EtO must have the agent removed (aerated) before they can be used by patients, hospitals, doctors and surgeons.
Despite the potential dangers though, EtO sterilization is still the predominant method used by medical device manufacturers, and it is one that continues to undergo significant growth. STERIS Isomedix recently opened a new EtO sterilization facility in El Paso, Texas, and the firm offers its customers weekly ethylene oxide engineering runs. Operating out of the company’s Minneapolis, Minn., facility, the program allows customers to evaluate the effects of the EtO process on product components or packaging. It is ideal for material compatibility studies and new product development, the company claims on its Web site.
STERIS Isomedix also offers its customers weekly engineering runs in gamma radiation, a sterilization method that uses ionizing energy produced by gamma rays to cleanse medical devices. Gamma rays penetrate material deeper than e-beam radiation, making it an ideal method of sterilization for products with various densities and packaging types.
Though it is easy to use and has a proven track record in the sterilization sector, the gamma radiation process uses Cobalt 60, a radioactive element that must be handled and disposed of in a special way. This special handling, however, can be costly, particularly when compared with the less expensive e-beam radiation.
“We’ve seen a large movement of people going over to gamma radiation recently,” Millstone’s Lucenti said. “The biggest driver of that [movement] is to reduce cycle time. With EtO sterilization, you have outgassing that can take up to a week. The gamma sterilization doesn’t require outgassing so it takes less time. We’ve also seen people experimenting with the gas plasma system, but we haven’t seen anyone switch over large scale to that method like we’ve seen with the gamma radiation movement.”
Other sterilization methods that are growing in popularity include hydrogen peroxide, X-ray and e-beam radiation. Industry experts said e-beam sterilization is becoming more popular among medical device manufacturers due to the development of smaller scale equipment. Technological advances also have improved the e-beam sterilization process. Higher doses and shorter exposure times give e-beam radiation an advantage over gamma radiation and results in lower energy costs than other modalities. The shorter exposure time also minimizes oxidation reactions that can occur at the device surface. Manufacturers typically use e-beam radiation for high-volume, low-value products such as syringes, or low-volume, high-value products such as cardiothoracic devices.
Another type of sterilization method that is slowly gaining ground is chlorine dioxide (ClO2). This type of sterilization uses gas rather than condensation to sanitize products. “We are finding an increasing use [of ClO2] in the pharmaceutical industry as well as by medical device companies,” said Russ Nyberg, technical sales manager for Raven Labs, an Omaha, Neb.-based manufacturer of biological indicators for validating sterlization processes. “There are many advantages to using ClO2 since it is a true gas and is used under ambient temperatures. NSF International has approved the use of ClO2 for the decontamination of biological safety cabinets, where prior, one frequently had to use formaldehyde. As a BI [biological indicators] manufacturer it is a challenge to be involved with providing a certified BI for ClO2 with known resistance for use in industry as one currently does not exist.”
The Importance of Linking Packaging and Sterilization
Though it is one of the final steps in the manufacturing process, the method of sterilization is crucial to the design and packaging of medical devices. The type of sterilization method used often will determine the kind of packaging that is required, industry experts said.
“By establishing the sterilization method and level as one of the first steps in the concept phase, we can determine how robust the packaging needs to be. Over-gauging seems to happen when the needs aren’t determined prior to designing the tray,” explained Mike Anderson, manager, contract manufacturing, at OraTech, a Salt Lake City, Utah-based manufacturer of medical and dental products. “More often than not the sterilization process is determined by the medical device.”
Certainly, the kind of medical product being designed and the materials being considered to make the device can have a profound impact on the way it is sterilized and packaged. For example, a product that cannot be exposed to oxygen requires a non-permeable, vacuum-sealed package with a low oxygen count. Similarly, devices with biological coatings may be more susceptible to air and/or moisture, necessitating a need for barrier packaging materials.
It is important for sterilization and packaging providers to be involved in the product development process as early as possible in order to avoid adding time to market, experts noted. Early intervention, of course, also saves companies money.
“We are learning that sterilization processing can cost much more per unit than the packaging itself,” said Edward L. Haedt, vice president of marketing for Perfecseal Inc., an Oshkosh, Wis.-based firm that designs and manufactures medical and pharmaceutical packaging. “Anything we can do to aid sterilization processing can help reduce overall costs. We recommend that an OEM involve packaging and sterilization departments when designing new sterile barrier packaging systems.”
Sterilization and packaging providers face an onslaught of revisions to industry standards. Though keeping up with these changes is a daunting task, companies realize that it is necessary in order to survive. Working with regulatory agencies to determine the kinds of revisions under consideration and the timeline for their implementation can help companies stay abreast of these changes and work with outsourcing partners to ensure the new requirements are met.
Besides the bombardment of changes to industry standards, sterilization and packaging providers face a business environment that has been forever changed by the worldwide economic crisis. Capacity has become tighter, forcing companies to take a more cautious approach to expansion.
Sterilization and Packaging Providers Entering Disposable Instrument Market
Partnering with hospitals might appear to be a poor business decision these days, but the move has long-term growth potential for the right company.
Sterilization and packaging providers looking for ways to expand their business and secure long-term growth are turning to hospitals to help fill their coffers.
“There’s been a very strong interest out there in the packaging of disposable instruments,” said Kelly Lucenti, president of Millstone Medical Outsourcing, a contract packaging service provider based in Fall River, Mass. “I think Europe is really driving that charge because they want all of their products sterile packed in the future. There’s been a big push as a result of staph infections, Mad Cow [disease], all these other things. The industry has been driving more and more products to be sterile packed.”
The sterilization and packaging processes in hospitals has traditionally taken a different path than the system that exists in the industrial sector. Hospitals that sterilize instruments and other items with ethylene oxide (EtO) conform to standards developed by the Association for the Advancement of Medical Instrumentation (AAMI) as documented in American National Standard ST41:1999 “Ethylene oxide sterilization in health care facilities: Safety and effectiveness,” according to information from Sterigenics Inc., a sterilization services provider based in Oak Brook, Ill.
Industrial sterilization performed by OEMs or contract manufacturers is governed by International Organization for Standardization (ISO) mandate 1135, which was last revised in 2007.
Sterigenics provides hospitals with an overnight sterilization service for reusable instruments. Its SurgiCycle program uses EtO to disinfect instruments, including cameras, light cords, scopes and lumens.
“We are doing an increasing amount of reusable instruments sterilization,” noted Patrick J. Hughes, Sterigenics vice president of sales and marketing. “More hospitals, especially in California, have started contracting that service to us. There’s a couple of reasons for that. The regulations for EtO keep getting more stringent, and they change so frequently that it’s hard for hospitals to keep up and invest in it. The [EtO sterilization] becomes another cost that they don’t get back. Hospitals don’t get to charge more for sterilizing instruments because [EtO] regulations change.”