Assessing the Waves
EtO, Gamma, Electron Beam and Hydrogen Peroxide Advances Offer Faster Cycle Times, More Confidence and Other Benefits
Stacey L. Bell - Editor at Large
Advances in BI testing and validation methods are helping OEMs get products released more quickly. Above, a lab technician with Centurion Sterilization Services performs a BI sterility test. Photo courtesy of Centurion.
When it comes to product sterilization, there is no room for compromise. While in the past, various sterilization modalities could add days or even weeks to the production process, advances in recent years and medical companies' changing mind-sets have streamlined the time frame.
"Today we're seeing companies make decisions around the sterilization modality much earlier in the design process because that decision can have such an impact on production costs," said Richard Wiens, product manager for sterilization for MDS Nordion in Ottawa, Canada. "Traditionally, sterilization was seen as a separate event in the manufacturing process. To speed products to market, companies now are automating sterilization and integrating it into the rest of the manufacturing cycle."
Due to advances in all of the modalities, medtech companies now have more factors to consider when determining which sterilization method will be most appropriate for a particular product.
Hydrogen Peroxide Gains
Vaporized hydrogen peroxide systems have been used since the early 1990s in the cGMP pharmaceutical manufacturing sector, and in recent years, more medical device companies are discovering their advantages.
"The VHP MD series sterilization system is growing in popularity due to the pressure that medical device companies feel to deliver their finished products to their customers sooner and more cost effectively; that is, improve their sterilization turnaround time compared with contract sterilization," said Larry Lachowski, sales and marketing manager for STERIS Corp. in Mentor, OH. He noted that by performing a reduced incubation time study, a user of VHP sterilization may achieve finished product release 48-72 hours after sterilization; plus, a long post-sterilization aeration phase traditionally needed with EtO is not necessary with this modality.
"In addition, device manufacturers can reduce their cost of finished goods inventory if they are able to ship products sooner," he continued. "Some companies that are using VHP sterilization have a goal to move toward parametric release with this technology to improve product release time even more."
Lachowski also noted other benefits VHP sterilization offers:
- More flexibility in product scheduling
- Low operating costs
- Broad compatibility with materials and electronics
- Environmental friendliness because it decomposes to water vapor and oxygen. In addition, the process' low operating temperature (30° to 40°C) makes it suitable for temperature-sensitive materials and devices.
Hydrogen peroxide systems were developed for in-house sterilization of medical devices. They offer medical device companies increased control and reduced inventory levels for high-value, low-volume medical devices. Class II and class III medtech companies, particularly those in the orthopedics, cardiovascular and general surgery sectors, are among the firms adopting the technology.
Sterilization services have become increasingly important to OEMs outsourcing the function. Providing validation data, filling out forms and other support services are critical components of the work. Above a lab technician at Howell, MI-based Centurion's facility examines a bioburden sample. Photo courtesy of Centurion.
Mike Valentine, director of special markets for medical devices for Irvine, CA-based Advanced Sterilization Products (ASP), said companies that spend at least $50,000 on sterilization yearly could easily make a business case for turning to ASP's STERRAD hydrogen peroxide gas plasma sterilization.
Indeed, in just the past year, ASP, a Johnson & Johnson company, has sold more than 500 units. The refrigerator-sized sterilizer is evacuated and filled with a 59% solution of hydrogen peroxide in a vapor phase. A plasma generator eliminates residual peroxide from the load at the conclusion of the cycle. Most cycles are completed in an hour or less on smaller units and in two to three hours on larger, industrial units, depending on load and product configuration.
"OEMs used to sterilize in-house with EtO (ethylene oxide), but most companies have shifted EtO to contract manufacturers due to safety concerns. With hydrogen peroxide gas plasma sterilization, manufacturers now have a choice," Valentine said. "Our business grew by 45% in 2004, and we anticipate growth topping 50% this year."
Manufacturers are turning to the process because they can sterilize a load one day and release it the next. ASP manufactures the STERRAD CycleSure BI, a self-contained, 48-hour biological indicator that offers fast turnaround, although some companies have added the parametric release option to their STERRAD units to save even more time. With parametric release, critical process parameters-including gas concentration, temperature and pressure-are redundantly monitored within the chamber to ensure they remain within pre-established parameters throughout the cycle. The product can be released as soon as the cycle ends.
While parametric release eliminates the need for BIs, manufacturers must compile enough data to validate that the process is robust, so many instead choose to continue using biological indicators. In fact, just 1% of the STERRAD-installed industrial base has decided to incorporate parametric release.
"More haven't done it because 48 hours is really pretty quick," Valentine said. He added that he expects more development to occur in this area.
"Enzymatic indicators, which give results in only 20 seconds, can offer an advantage over traditional BIs, but none has yet cleared the FDA for this process," he noted. "Integrators, which combine biological, enzymatic and fluorescent technologies, are developing new technologies in this area, which I believe is a good place for the industry to head. After all, time is money."
ASP said it plans to release the next generation of STERRAD this fall. The new version will be capable of sterilizing more complex products, including challenging lumen devices, and it will cut sterilization cycle times in half.
STERIS Corp.'s VHP system, unlike STERRAD, does not require a plasma phase. Lachowski said this means one less variable, resulting in fewer sterilizer components and a simpler cycle.
High cube All-in-One vessels at one of STERIS' facilities accomodate pallets of up to 106" in height. Each chamber holds 28 pallets. With parametric release and aeration within the chamber, products are released immediately. These facilities are typically designed with a larger number of vessels. Photo courtesy of STERIS.
Parametric release has continued to make inroads into EtO sterilization. "The concept is extremely attractive to our customers," noted Thad Wroblewski, director of sales, eastern area, for STERIS Isomedix Services. The company's EOExpress combines all-in-one processing with parametric release, allowing product release within 24 hours.
Sterigenics in Oak Brook, IL, a contract sterilization company offering EtO, gamma, e-beam, X-ray, and lab/consulting services, has also seen a dramatic increase in the number of clients interested in its CycleOne all-in-one process with parametric release. EtO is widely used because it is compatible with most materials, including plastics and resins that may find gamma sterilization too powerful.
Jack Fitzpatrick, director of business development for Sterigenics, noted that most customers have EDI (electronic data interchange) capability and expect their suppliers to have it as well, allowing transparency in the work process. He also sees an interest in RFID technology (radiofrequency identification). Tags are placed with each load of product that comes into the facility to be sterilized, and the tags send a message-for example, "lot #XYZ, 15 pallets with 40 cases per pallet, produced in ABC plant"-that can be tracked as the load moves throughout the facility. Via the web, customers can track the exact location of any particular load.
Wroblewski noted that EtO all-in-one processing tends to be geared toward large loads. Large vessels generally hold 28 to 56 pallets of material-a truckload's worth. Because so much product is being treated at once, sterilization providers have built in more redundancies and controls. For example, if one vacuum fails, a backup will take over.
"The industry has fine tuned the process to an advanced stage of process control that hasn't existed before," he said. Recently, smaller loads of 6 to 12 pallets have become economical as well.
Growth has been so strong that STERIS Isomedix has added 16 large, all-in-one vessels to its facilities over the past five years. Sterigenics has added seven chambers in North America and five chambers in Europe over the past six months.
Centurion Sterilization Services in Howell, MI has also seen healthy growth in EtO sterilization as well as interest in its R&D consulting, packaging and laboratory testing services. "The trend toward a one-stop shop continues," reported Brenda Sparks, Centurion contract sales manager.
She pointed out that while the latest buzz is about parametric release and all-in-one processing, those technologies won't work for every company.
"The validations for parametric release are a little more expensive, and if you need to wait to ship your product for any reason, there is no benefit to parametric release," she said. "Smaller volumes often are better off going the traditional BI route."
Traditional sterility testing requires the use of a BI, and Centurion, like others, tends to use a seven-day BI, for which they've validated and proven that the same results are achieved in three days.
While Minneapolis-based 3M's 4-hour BI attracted much interest and press since its debut a few years ago, "the jury is still out on the four-hour A-test," said Mike Padilla, study director in Sterigenics' SteroPro Labs Group. "That's not a hit against the test itself. It's more a matter of acceptance. Most people just aren't comfortable with it yet, so most continue to rely on a seven-day BI and do a reduced incubation time study so they can bring that seven-day BI down to three or four days."
Sparks noted that another problem small- and mid-size volume manufacturers face is the waiting times for sterilization service. At some companies, small batches are in queue until there is space. She said that's why Centurion is focused on serving the needs of small and mid-sized manufacturers. It processes all products within 48 hours of receipt, and usually it takes place within 24 hours.
Sterigenics, working closely with its customers, is addressing the issue of scheduling by instituting an advance ship notice procedure. "Customers simply send us an e-mail so we know that, for instance, in 10 days products will be at our facility, and we can schedule our equipment maintenance and work processing accordingly," Fitzpatrick explained.
Gamma Maintains Strength
More than 160 irradiators around the world process more than 240 million cubic meters of product each year, says the Gamma Industry Processing Alliance. In fact, 2004 saw record shipments of cobalt.
"Gamma continues to maintain its strength in the market, in part because it has time advantages since there is no need for a BI or for aeration, and because packaging doesn't have to be gas-permeable," Wiens said. "As regulatory pressures surrounding EtO issues in China and Europe increase, gamma is offering companies another option."
Over the next two years, MDS Nordion's customers expect to bring six more gamma facilities online, and they continue to integrate more automation into the process. Traditionally, workers would load and unload pallets; today, more companies are considering the use of robotics for some of those chores.
Wroblewski said that STERIS' gamma radiation business continues to grow rapidly. The company has expanded its offerings through the installation of high-efficiency, high-throughput irradiators with greater licensed capabilities for isotopes, providing for high-volume, lower-cost processing as well as flexible "batch" operations for special handling and expedited processing needs.
The concern about EtO residuals is also fueling electron beam's market share, said John Messick, national sales manager for E-BEAM Services, Inc. in Cranbury, NJ.
"There have been two controversies over the past year," he said. "First is whether or not EtO kills the right bacteria, and, secondly, over the residuals. About 1% of the population has some allergic reaction to the residuals, and the Europeans, especially, want to get away from that problem."
Also fueling e-beam's growth is the supply-demand balance and environmental concerns about gamma. He said gamma irradiation's nuclear source material, cobalt-60, takes a couple of years to generate, so maintaining an adequate supply can be tricky. He added that a few years ago, supply was tight, and some companies limited new customers through higher prices. Another concern is the transportation and security of a radioactive material. Electron beam can be more compatible with some polymers than gamma because many materials don't discolor as much or become as brittle after treatment, added Ray Calhoun, president of BeamOne, LLC. Lighter, less dense materials tend to be most appropriate for electron beam sterilization.
Pharmaceuticals also are driving growth. "We've been performing a lot of testing with pharmaceuticals, and with the increased body of knowledge in this area now, more pharmaceuticals are choosing electron beam sterilization," Calhoun said.
Furthermore, the technology is more gentle on active ingredients. As a result, growth in pharma applications is outpacing device use, Messick concurred.
BeamOne said many inquiries are from manufacturers seeking while-you-wait service.
"One of the biggest trends we've seen is in customers expecting rapid turnaround," said Calhoun, who explained that electron beam sterilization requires no dose grouping of product. Therefore, standard turnaround times of 24 hours or less can be achieved. Moreover, the overall time to sterilize a load can be as short as a half hour. Some customers with small volumes of high-value products can wait at the sterilizer's facility while the processing is performed.
BeamOne said it plans to add to capacity in the future. The company acquired Titan Scan in February, and it will continue to offer electron beam services exclusively to the medical device and pharmaceuticals markets. It will establish an East Coast location in addition to facilities in San Diego, Denver and Lima, OH.
Sterigenics' electron beam business is growing as well, leading the company to open a new facility in Shanghai, China this fall.
The Deciding Factors
While industry statistics note that some 60% of sterilization activity is outsourced, hydrogen peroxide is now a strong contender for in-house sterilization, and all modalities are taking advantage of new technologies and work processes to streamline their cycle times and capabilities.
Once a medtech company has chosen a modality based on compatibility with materials, speed and cost, the final deciding factor may be which supplier can offer the most value-added benefits such as shipping directly to end-users or to multiple locations, providing laboratory testing or offering real-time access to data.
Solid growth is projected for the coming years based both on the aging population's increased need for medical devices as well as continued advances in the technology.
"Looking a couple of years ahead, you never know when the next advanced process of sterilization is going to come out," said Dan Dwyer, head of healthcare sales for Raven Biological Laboratories in Omaha. "Twenty years from now, we could find that we've just been scratching the surface of what's truly possible."
Stacey L. Bell is a freelance writer who specializes in business and marketing issues. She is based in Tampa, FL.