Change May Do You Good
Rethinking Your Sterilization Modality of Choice—or Its Process—Could Shave Days Off Delivery Time
Stacey L. Bell
Editor at Large
As these dials show, sterilization is a complicated process. Photo courtesy of Centurion Sterilization Services.
In sterilization, for example, companies are making great gains in the procedures surrounding common sterilization modalities. Not only are software and advances in the understanding of how current technology works improving turnaround times, but also, contract sterilizers are offering additional services to ease their customers’ work flow.
While sterilization cycles never came in a one-size-fits-all model, today’s diverse product mix and use of new materials are creating the need for a more innovative approach.
“As devices become more complex—for example, the growing trend to combine diagnostics and drugs within one device—sterilization is becoming especially complex,” reported Thad Wroblewski, director of sales, Eastern area for STERIS Isomedix Services in Mentor, OH. “Some newer devices require more specialized cycles. On the EO [ethylene oxide] side we’re seeing the need to use colder and less humid cycles, even though EO is more efficacious at higher temperatures and high humidity.”
Contract sterilization companies are experimenting with gassing times and cycles, wave length and strength, and are even looking at the impact of mixing different gases and sterilization methods to create cycles that will properly sterilize product in the timeliest manner possible.
“Sterilization has become more precise and specific,” noted Robert Bradley, laboratory manager for Raven Biological Laboratories in Omaha, NE. “Before, you simply brought the load to the proper temperature for the proper time until everything was dead, and you were done. Today, it’s more target specific. Medical device manufacturers want to ensure that even troublesome areas of the load are sterilized, and they are going to great lengths to ensure that this is the case. The days of ‘one BI fits all’ are long gone.”
Glenn Thibault, executive vice president and chief operating officer of BeamOne, LLC in Denver, CO, agreed. “New technologies are allowing for better process control,” he said. “Sterilizers—whether gamma, electron beam or EO—are using advances in computer technology to give better control over sterilization processes.”
Products are loaded in STERIS Isomedix Services’ San Diego, CA facility, which uses ethylene oxide in its sterilization process. Photo courtesy of STERIS Isomedix Services.
“E-beam, x-ray and hydrogen peroxide are beginning to nibble away a few percentage points of market share from EO and gamma each year, but they’re considered newer processes [and thus] still encounter some suspicion from the FDA and medical device companies,” said Mark Dott, senior consultant for Val-Pro Associates and Mark Dott, LLC in Castle Rock, CO. Dott’s companies work with medical device firms to write validation protocols, oversee validations, review the data and write final reports for submission to the FDA. “Hydrogen peroxide in particular, while accepted wholeheartedly by hospitals, is just now making stronger inroads in the medical device industry.”
Whether tried-and-true modalities or relatively young upstarts, each sterilization method continues to be refined to best serve manufacturer and market needs. Experts said that they see several overarching trends most affecting sterilization in the next few years: more precise, targeted modalities; more project management changes; and niche technologies gaining the confidence—and business—of more manufacturers.
Shorter, More Precise Cycles
“Twenty years ago, the rumor was that ethylene oxide was on its way out,” recalled Dick Malo, vice president of contract sales for Ethox International, Inc. in Buffalo, NY. “Experts said gamma was a cure-all and would be used to sterilize everything. Obviously, that didn’t happen. With advances in EO control systems and with greater sterilization science knowledge, it is likely to be here for a very long time to come.”
Indeed, EO has experienced a slight resurgence in recent years, since it is more compatible with new materials and combination devices than are other modalities, added Gary Benson, Ethox director of sales, sterilization and laboratory services.
The continued popularity of EO also can be attributed to reduced cycle times. Traditionally, products had to undergo a three-step process: preconditioning in one location, sterilization within the chamber and then aeration in a third room so that residual gas could dissipate. In addition, sterility testing with biological indicators (BIs) would add another week to the timeline.
Today, more facilities perform all three steps in one room, and some also use parametric release—which directly measures EO concentration, relative humidity and product temperature throughout sterilization. Product then is released based on meeting established cycle parameters. Time-consuming aeration periods and BI testing are eliminated, allowing loads to be sterilized and released the same day.
Of course, parametric release is not the best option for every product or company. If a device has undergone numerous changes that would require numerous validations, and for smaller volumes of product, the traditional EO precondition/treat/aerate/BI process would be more cost efficient, said Brenda Sparks, contract sales manager for Centurion Sterilization Services in Howell, MI. She also pointed out that if the product has to wait several days in queue before it is sterilized, or if the product has a one to two days’ transit time, parametric release loses some of its luster when compared with traditional processing with quick turnaround. Benson noted that “parametric release is really a moot point if EO residuals are a challenge.”
While use of parametric release is growing steadily, all-in-one processing is increasing at a more rapid pace. “EO sterilizers increasingly are moving away from using preconditioning rooms and cells prior to sterilizing and instead doing everything in the sterilization chamber,” Dott said. “They used to resist this step, but now they’ve embraced it.”
Another trend EO sterilizers are embracing is finding ways to lower residual gas levels by using reduced concentrations and dwell times. New recommended EO residual levels are expected to be released by standards organizations AAMI and ISO later this year (see “Coming Soon: New Standards” on page 42). As a result, manufacturers and their sterilization management companies are seeking ways to reduce residuals now.
“We’re looking at alternative mixtures of gas and steam to minimize EO usage while maximizing safety and lethality simultaneously,” said Jack Fitzpatrick, director of business development for Sterigenics in Oak Brook, IL. While the average EO cycle time is 12 hours, companies are experimenting with how much microbial kill can be achieved if changes are made to gas mix and levels. “We’re trying to develop a lower baseline and build from there,” Fitzpatrick explained. “By monitoring the dwell in different ways—with infrared systems or different BIs—we may be able to reduce the cycle time more.”
Fitzpatrick said that it’s becoming more common for customers to seek input on sterilization techniques closer to the beginning of a new product’s design.
“You need to continuously ask, ‘How can I reduce my cost and time to market with my sterilization?’” he said. “If you can go from a seven-day hold to a two-day quarantine period or even zero days, you’ll save money and time. Should a medical device manufacturer decide to go with a smaller Tyvek header on its pouch, would that make a difference in sterilization cycle times? What about a lighter or heavier corrugate? Or, what if you were to package 250 units in a slightly larger box rather than 200 units in a smaller one? A seemingly small change can make a significant difference.”
Experts noted that customers too often concentrate on maximizing their manufacturing processes without considering the resulting impact on sterilization time and cost.
Advances in Radiation Techniques
Of course, EO isn’t the only modality offering a more focused approach to sterilization. Gamma and E-beam sterilization have become more targeted as well. Sterigenics recently re-introduced its low-dose ExCell irradiator, which it says provides a more precise dose than any other commercially operated irradiator—maintaining delivered doses within ±10%.
Changes in the design of irradiators can save in efficiency, but MDS Nordion is finding greater gains exist around redesigning the process end to end, said Richard Wiens, product manager for sterilization for MDS Nordion in Ottawa, ON, Canada. “We’re starting to apply principles from lean manufacturing to the sterilization business. By doing a better job of scheduling, for example, you can improve throughput substantially and reduce the inventory that you keep on-hand, which is a big concern for everyone,” Wiens said.
Another challenge remains in managing Cobalt-60 supply. The isotope decays at 12% a year; thus, gamma sterilizers and suppliers of Cobalt-60 need to walk the tightrope between having enough to meet current customer needs and avoiding excess, while establishing a clear picture of future demand to allow for careful supply planning. Wiens pointed out that the growth of all sterilization modalities is driven fundamentally by the growth of the medical device industry itself, which is expanding at a rate of about 5% annually in volumes produced globally. MDS Nordion recently signed an agreement with a reactor owner in Russia and renewed its contract with a Canadian supplier to ensure its Cobalt-60 supply continues to meet growing demand.
Benson noted that while gamma used to be a low-cost alternative to EO, supply and security concerns surrounding Cobalt-60 have eradicated that advantage. “Handling, safety and security are all issues now, which may lead more companies to consider two emerging sterilization technologies: E-beam and x-ray. Both of these technologies have been around a while,” he said, “but we’re now learning more about how to control them and make the most efficient use of them as a sterilization method. As they’re proved out, they will likely gain greater market share and provide the industry with yet another option.”
At BeamOne, computer technology and advanced software allow the company to monitor just about every aspect of the sterilization process, from how fast the product is moving through the beam to how much radiation is being delivered to the product. “Our control speeds can be managed down to three significant digits now versus one significant digit 10 years ago,” Thibault noted, explaining how much more advanced today’s processors and control systems are.
When choosing a sterility modality, all other factors being equal, Wroblewski noted that manufacturers might wish to consider validation costs. “It’s not unusual to spend $30,000, $40,000 or even $50,000 on an initial EO validation, whereas a radiation validation might cost only $10,000,” he said. “You also need to figure in maintenance costs. Radiation requires quarterly audits with full loads; EO can be audited with half a cycle. Over time, the radiation maintenance can become more costly.”
Hydrogen Peroxide Makes Gains
Like E-beam and x-ray, vaporized hydrogen peroxide is still being tested in the marketplace. While its use is growing, there are still hurdles to overcome. “The hydrogen peroxide vessels can’t handle anywhere near the capacity that the contract EO and radiation facilities can. It’s more costly, as a result, since you still have to monitor each load even though less product is being sterilized,” explained Joel Gorski, PhD, director of research and development for NAMSA in Northwood, OH. He added that manufacturers also can’t use the modality to sterilize devices that contain paper or celluloid since absorption and degassing remain issues.
“Some time ago, EO had the same issues with permissible EO levels in devices,” noted Terry Langenderfer, NAMSA director of global marketing. “Hydrogen peroxide, as a fairly new methodology, is simply following the same pathway prior sterilization modalities have already addressed.”
Many OEMs prefer to outsource because they don’t want to invest in costly equipment. Photo courtesy of BeamOne LLC.
In May 2005, ASP introduced the STERRAD NX, a next-generation system that offers more concentrated peroxide for quicker cycle times and more complicated devices. Hospitals, surgery centers, research facilities and medical device companies have been drawn to the new unit’s ability to sterilize longer lumens (flexible and rigid scopes) and more complicated delivery devices, such as catheters.
Taking a Team Approach
Just as the technologies have seen some adjustments, so, too, has sterilization’s business model. Ten years ago nearly all of contract sterilizers’ medical industry customers were OEMs; today, OEMs’ outsourcing partners are composing a larger proportion of sterilizers’ business. Both the number of people involved in the sterilization project—and when they’re involved—also has changed.
Sparks said that Centurion’s customer base, which processes primarily small to medium-sized product volumes, is now seeking advice about sterilization, validation and packaging during the design phase to ensure that everyone is on board when it is time to sterilize product for clinical trials.
“We’re viewed as more of a partner now,” she said, adding that the new business paradigm translates into more communication with more people. “In the past, it was more hierarchical. R&D handed off to packaging, which handed off to sterilization. Today, the design engineer, validation and packaging experts, laboratory manager…a whole team is talking simultaneously, sharing information to create the best solution. We want to find out the customer’s situation right away. Is the device expensive? Is it difficult to obtain samples? Do we need to develop a process challenge device? What is the timeline? Sharing thoughts and information is the key to developing a successful process.”
Information exchange often is occurring among numerous companies—OEMs, their contract manufacturers and their contract sterilizers.
Need Data at 3 a.m.? No Problem
Ensuring that numerous professionals at several companies are all on the same page at any given time can be a challenge. Therefore, more companies are developing new communication tools to automate this process, too.
“In my opinion, communication between contract companies and their customers is what is changing the most,” Sparks said. Centurion currently is working on an on-line system that will offer customers real-time updates. Customers will be able to see when a shipment to be sterilized has been received, when it is scheduled for sterilization, when it will be released and when it will leave Centurion.
Within the past year, Sterigenics has introduced a subscription-based, interactive Web portal for its contract EO and gamma customers. WebVantage allows customers to perform an instant, on-line quality audit. By the end of 2006, customers also will be able to use the service to track loads, obtain answers to regulatory concerns, view electronic batch records and review account status.
“Customers can reduce sterilization costs by reducing their inventory and process times or by reducing their transportation time,” Fitzpatrick said. “By viewing their product on-line, customers can see exactly when product is going into the chamber, so they know that in some prescribed time they will need to have a truck in line to pick up their product.”
In January, STERIS Isomedix Services launched SteriLink, an interactive on-line service designed to give complete, real-time visibility into the company’s processing facilities, according to Kevin Cmiel, STERIS Isomedix Services marketing manager in Mentor, OH. Customers had noted in interviews, focus groups and STERIS’ annual client survey that they would like to be able to monitor inventory 24/7, send and receive alerts, review and retrieve historical processing documents, check performance metrics and project status as well as generate reports. SteriLink currently meets those goals for more than 50 of STERIS’ contract gamma customers; its contract EO customers will have access to their own version of SteriLink by the end of the year.
“By interacting with our processing facility through data update capabilities such as Inbound Receipt and Customer Product Release, customers will be able to shorten the time to market,” Cmiel explained. “The ability to access real-time processing information from any computer will save our customers valuable time and allow them to easily interact with our facilities, resulting in a more efficient and effective partnership.”
Experts see additional trends changing how companies will perform sterilization in the future:
• Escalating transportation costs, coupled with the need to get products to customers faster, are prompting shipping changes. More manufacturers are instructing their contract sterilizers to ship processed product directly to distribution centers or to end users. Keeping their own product warehouses low on inventory appears to be another priority for customers, some sterility experts said. “We’re seeing more movement toward just-in-time sterilization,” Thibault reported. “Companies are not warehousing products like they used to.”
• Self-contained BIs are at-tracting more interest. “There is some movement in the industrial market toward using standard, self-contained BIs, but not toward the rapid readout versions,” reported Gorski. Spore strips still top most manufacturers’ preferred validation verification methods, but parametric release is expected to dispense with the use of most BIs in time.
• Globalization will become increasingly important. “The theme for sterilization as a whole for the next several years will be globalization. Everyone in the sterilization business must have a global strategy,” Wiens said. He noted that every customer he’s spoken with about China has expressed concern about being able to remain competitive against that low-cost market. MDS Nordion and other sterilization companies have focused on creating a global reach, including developing a presence within China, so that they can help their customers succeed in that developing region.
In tandem with its global strategy, MDS Nordion is expanding its equipment offerings this year to meet the needs of companies in developing markets. The new, low-cost Epsilon is designed to sterilize lower volumes of a wider range of products than other equipment currently available.
Of course, sterilization processes and techniques will continue to evolve to better meet manufacturers’ needs to sterilize new materials and increasingly complicated devices, particularly drug/device combos, engineered tissue and other technology breakthroughs. NAMSA noted that the industry currently is working on bringing new technologies such as ozone, ultraviolet light, plasma, steam formaldehyde and chlorine dioxide to market within the next few years.
“We’re looking at technologies that offer speed, the presence of no toxic byproducts at the end of the cycle and no toxic residuals in the devices being sterilized. By continuing to optimize sterilization processes, the variety of materials used in medical devices can continue to expand,” Gorski concluded. And brilliant minds, with yet more options open to them, can continue to turn medical technology dreams into reality.