A gamma cobalt rack, pictured here submerged in water, is used to sterilize medical products. Photo courtesy of Steris. |
Once again, ethylene oxide (EtO) sterilization has resumed its starring role in medical device sterilization. For decades, EtO was the sterilization modality of choice for OEMs due to its reputation for excellent material compatibility, but in the 1980s and 1990s, gamma unseated EtO from the top spot because it offered much faster turnaround times. The equation began shifting again during the past few years as advances in EtO technology have reduced and even eliminated time-consuming steps from the EtO process.
Today, ethylene oxide holds a market share of about 54%, followed by gamma radiation at 36%, electron beam (or e-beam) radiation at 6% and other niche-specific sterilization methods, including steam, vapor phase hydrogen peroxide, gas plasma, at 4%, said Clark Houghtling, vice president of technical affairs for Cosmed Group, Inc. in Queensbury, NY. Houghtling said the data are from several sources, including Arc Chemical, a division of Balchem Corp.
“During the last five years, EtO use probably has increased by 4-5%,” Houghtling noted, attributing the increase to several factors. First and foremost, the growth of the custom kit business has meant that manufacturers have flocked to EtO because a kit often contains one or more materials not compatible with radiation.
Indeed, material compatibility is one of OEMs’ initial considerations when developing new products. After all, assembling a device only to discover that it will need to be unassembled because a component is not gamma compatible adds unwanted delays and expense. Material compatibility is the main determinant for choosing which sterilization modality to use, some sterilization providers say.
In part, products today are significantly more complicated, said Dan Carestio, vice president of sales and marketing for STERIS Isomedix Services in Mentor, OH. “Often times, devices contain a pharmaceutical component, coating or a microelectronic device—all of which can be difficult to sterilize or restrictive in determining which modality to use. As products have become more complex, sterilization has become more customized to specific products,” he added.
Niki Fidopiastis, SteriPro manager at Sterigenics’ sterilization validation consulting and laboratory group in Corona, CA, added that while OEMs often are more familiar with one type of sterilization, they should not “limit themselves to one sterilization method if they offer a range of products.” Often, a method that works well for one category of products isn’t appropriate for another, and advances in technology may mean that another method may now be more suitable.
Photo courtesy of MDS Nordion. |
EtO Speeds Up
EtO has been a popular choice for sterilization for many years for several reasons. First, it is compatible with a wide range of device materials. Its low-temperature process, which usually occurs in a range of 120-125F°, won’t alter the composition or functionality of most materials. As a result, EtO often is used to sterilize plastics and other materials that may weaken under the stresses of radiation.
In fact, the only materials that can’t be EtO-sterilized are liquids, such as those contained in pre-filled syringes or water cups, or devices enclosed in gas-impermeable packaging such as foils. These products comprise less than 2% of the medical products offered on the market, Houghtling estimated.
Traditionally, EtO consisted of a three-phase process. Products are first preconditioned and then moved to a vessel for sterilization, followed by aeration in a third location to dissipate residual gas. A rule of thumb is that the softer the material, the more it outgases; porous products outgas more quickly than dense materials.
Following the process, a biological indicator (BI) release for sterility testing is performed. BIs are placed in different locations in the sterilization load, and the death of these agents indicate sterilization efficacy.
The problem with this method is sterility testing traditionally takes seven days, so the entire EtO process may take 9-14 days—an eternity when rushing to beat a competitor to market.
The industry has worked to shorten the cycle times as well as to streamline the process to alleviate several other associated problems such as concerns about environmental and worker exposure to EtO gas and its residuals. Gary Benson, manager of sterilization laboratory sales and service for Ethox Corp. in Buffalo, NY, noted that residual gas continues to be a main focus for his customers.
“In some parts of the world, particularly products distributed in Japan, the idea of residual gas has become almost a barrier of entry into its marketplace,” he said, noting improvements in sterility methods. “The difference today is the understanding of technology that allows optimal microbial kill while minimizing the EtO residual content at the end of the cycle. In some cases, the concentration of gas has been reduced in addition to reducing cycle time. We, like so many others, are just improving the processes that already exist.”
All-in-one processing technology is increasingly being embraced by sterilization companies. This approach differs from traditional EtO processing because preconditioning, sterilization and aeration all occur in one chamber. Sterigenics has created CyclEOne to help its customers speed the release of product to market. This single-chamber sterilization results in efficient outgassing, which in turn leads to earlier release of product to market, Fidopiastis reported.
Parametric release, a technology first used in the contract sterilization industry by the Cosmed Group a few years ago, directly measures EtO concentration, relative humidity and product temperature—three parameters not routinely monitored when using a BI release, noted Houghtling. “It involves a more comprehensive validation of the process upfront combined with additional requirements for routine monitoring that allow you to release the load for sterility based on meeting the established parameters of the cycle rather than on biological indicators,” he said.
The real power of parametric release is in combining it with other methods, which has led to a new process known as EOExpress. This all-in-one processing incorporates electronic data transfer to allow sterilization and release to market of goods in one day. The concept is that sterilization which takes place under a tightly controlled and monitored process is ensured of its efficacy. By eliminating the testing step, products are released right after aeration.
Control Quality
“You can inspect quality in—which is very expensive—or you can control the processes that impart quality,” said Rob Michaloski, an account manager at Harmac in Buffalo, NY. “Also, the tighter the control of the process, the more freedom an OEM has in development with material selection and product design. Parametric release offers significant potential value to OEMs considering the duration of post-processing testing that is common today in EtO cycles.”
While industry experts believe that parametric release will become increasingly common in the near future, Anne F. Booth, president of Booth Scientific in Hendersonville, NC, noted that some companies may delay employing the technology because their chambers are older and will have to be retrofitted. Additional requirements such as equipment for direct EtO gas detection and more powerful recirculation systems must be incorporated within the chambers, which means a larger capital investment. More comprehensive validation requirements for such a process also may serve as a barrier.
Houghtling stated that contract sterilization companies may be reticent to employ these combined technologies that can lead to one-day turnaround.
“Instead of using their sterilizer to process two or three runs a day, now they may only be able to put in one load,” he said. “EOExpress is more capital intensive for contract sterilizers to install because they literally need to have twice as many machines to do the same amount of product, but the huge advantage to customers in turnaround time will likely spur them to make this change. After all, customers get a lot more value when they’re getting a sterilized product back in one day, rather than 14, for the same cost.”
Still, other options exist. For example, seven-day BIs soon may be a thing of the past because manufacturers increasingly have used a test that takes only three days instead. It optimizes growth conditions for biological indicators and reduces the wait time.
Twenty-four and 48-hour versions are becoming increasingly popular as well, and the FDA approved a four-hour BI about 18 months ago. But because sterilization is critical to OEMs, they appear to be taking a cautious approach to the most recent innovations.
“We will use this type of BI in customer validations when asked; however, Sterigenics will not use four-hour BIs in its current in-house cycle development programs,” Fidopiastis said.
Another company not sold on four-hour BIs is B. Braun. “We use a three-day biological indicator, but it depends on what you validate to,” said Steve Stancick, environmental health and safety manager and sterilization technical adviser for B. Braun in Bethlehem, PA. “Rather than go to a four-hour BI, I think it would make better sense to eliminate BIs altogether and go to parametric release.”
On the other hand, gearing up for parametric release can be costly, noted Benson, who noted that BIs and conventional testing costs are much lower than an extensive parametric release study. “However, potential changes in the industry standards may make parametric release not only more affordable but more manageable for both customer and vendor.”
Growing Compatibility
For several years, some in the industry expected gamma to displace EtO as the dominant sterilization modality.
“Gamma’s advantage has always been its turn time,” noted Benson. “There was no need for preconditioning of the product load, no need for aeration or removal of residuals.” The process could be completed in three to five days—faster if OEMs were willing to pay for express service.
While in the past materials compatibility was a huge problem—some Teflon and other plastics tended to yellow, crack or emit odors when exposed to radiation—companies have responded by refining materials and making polymers and other composites that can withstand radiation. These changes have caused an incremental increase in material costs.
Further, gamma technology has become more efficient over the past years, according to Gord Ashfield, vice president of sales and service at Ion Technologies for MDS Nordion in Ottawa, Ontario. Ashfield pointed to design changes and increased equipment automation as key factors fueling improved efficiency.
“We’re retrofitting a major facility with new equipment that will result in 40% more throughput,” he said. “Irradiators being built today are 25-30% more efficient than the ones built 10 years ago. Facilities are being built larger and with increased flexibility to take advantage of economic efficiencies. They can increase capacity just by adding more cobalt, which can be done at incremental costs.”
E-Beam: A Brighter Future?
Gamma’s market share may not have stabilized, some observers say.
“I believe we may start to see some market shift from gamma to e-beam and X-ray as the technology improves and throughputs improve costs,” Benson said. “In the long term, the potential exists to see explosive growth of a third series of sterilization capabilities in X-ray.”
B. Braun’s Stancick agreed that e-beam may be able to make inroads against gamma in the future. “If you have a choice between a radiation source you can turn off and one you can’t, you’re going to choose the one you can better control,” he pointed out, noting that cobalt 60 is always giving off radiation. When it is not being used, it must be placed under a pool of water. Electron beams, on the other hand, can be shut off.
Some others disagree that e-beam will pull market share from gamma in coming years. “I see direct evidence that it’s quite the opposite,” said Ashfield, noting that one company in the industry has removed its e-beam equipment while another has gone bankrupt.
Fidopiastis said Sterigenics has successfully advanced the gamma process to improve sterilization compatibility with pharmaceuticals and tissues as well as the more-difficult-to-gamma-sterilize vaccines.
Nevertheless, gamma sterilization companies may gain a competitive edge in their own sector in another way.
“Gamma sterilization service providers have an opportunity to differentiate in their market through innovation by developing ideal chamber designs so that OEMs can cost effectively achieve consistent dosing throughout the chamber,” Michaloski said.
Unfolding Trends
Certainly, OEMs tend to be most concerned with ensuring a product is thoroughly sterilized. Next, cost and turnaround time factor into the equation. EtO and gamma cost roughly the same, and with recent advances in the former, it now can sterilize devices in the same amount of time—and possibly even more quickly—as gamma. By many estimates, the shift from gamma to EtO has already started. However, there are other trends unfolding as well.
• | OEMs are considering sterilization earlier in the product development process. “There is higher sensitivity in the industry for engineers, quality control and regulatory affairs professionals to institute requirements for sterilization at the beginning of design input,” Benson noted. “There’s an increasing awareness that material selection is contingent on the type of sterilization process used and vice versa, and how a device is subsequently packaged and marketed.” |
• | Contract manufacturer and sterilization companies are offering consolidated, expanded services. Companies reported that customers increasingly value their ability to provide laboratory, testing, distribution and fulfillment services in addition to sterilization capabilities. OEMs appreciate companies that offer one-stop shopping, which streamlines the supply chain and results in greater control over all the processes while reducing transportation costs and time. |
• | Outsourcing will continue. While the outsourcing of sterilization has been an ongoing trend for the past 15 years or so, companies that haven’t outsourced the process may do so soon. “Companies have been outsourcing due to tightening regulations, including stricter emissions controls outlined in the Clean Air Act,” Carestio said. Further, sterilization equipment is expensive so it often makes sense for manufacturers to devote their financial and human resources to revenue-generating activities such as research and development and distribution and sales channels, not sterilization. “Unless you have volume in the millions of cubic feet, it’s difficult to justify in-house sterilization on a cost basis,” explained Carestio. “However, if a product is very complicated and high-cost, then in-house sterilization becomes an option because it gives you more control.” |
• | Sterilization validation will shift from OEMs to outsourcers. OEMs increasingly are relying on outside consultants and companies to provide guidance and expertise in sterilization in addition to performing the process. |
• | OEMs will continue to look for shorter sterilization cycles. “Companies want their products sterilized in hours, not days, because otherwise they’re tied up in inventory,” noted Michaloski. “Time is money, and the longer your product is locked up in your supply chain, the slower the cash flows in your business model.” |
Gamma sterilization technology is becoming more compatible with different materials. Above, products in carriers are staged before being sterilized in a gamma irradiator at a Steris plant. (Photo courtesy of Steris.) |
While most OEMs have focused on EtO and gamma as their top sterilization choices, other options may soon make headway. “Hydrogen peroxide seems to be the up and coming source,” noted Stancick. “When you’re done with it, it converts to water vapor and oxygen so there are no disposal problems. As far as being environmentally friendly, that’s the answer, but its load sizes are limited. If they can’t do 8, 10 or 24 pallets at a shot, the bigger companies don’t want to be bothered.”
Gas plasma also is on companies’ radar screens, said Fidopiastis. He pointed out, however, that the chambers of these sterilizers are small. Several sterilizers would be needed to handle any sizable volume.
“I think we’ll see a lot more technological changes in all the modalities to keep up with the times—to sterilize more products, more quickly,” she said. “Both technology and regulations are moving together to streamline the entire sterilization process. Regulations are requiring that fewer products be tested and are leaning more toward the overall value of sterilization. Everything is coming together to give customers more choices in accepted modalities, and that’s a good thing for medical device companies and consumers alike.”
About The Author
Stacey L. Bell is a Tampa, FL-based freelance writer who specializes in business and marketing issues.