The Changing Face of Sterilization
Advances in existing technologies and a number of emerging methods are helping manufacturers satisfy rigorous requirements.
by Daphne Allen, Editor
The majority of medical device manufacturers still use sterilization technologies that have been around for decades—EtO gas, gamma and E-beam radiation, and steam. As a result, much of the innovation taking place in sterilization involves improving cycle times, reducing cost and safety concerns, and designing affordable systems that companies can use in-house. Nonetheless, a number of emerging technologies are being presented as viable alternatives to the long-standing leaders. Device manufacturers should review their existing systems frequently to see whether they could benefit from any of these technological developments.
Used since the 1960s to sterilize medical devices, EtO currently has a large market share—according to some estimates, almost half of all devices are sterilized by EtO gas. Recent developments have helped it remain a widely used method of terminal sterilization.
EtO is popular because it is compatible with most medical materials, especially heat-sensitive plastic devices, and it is an affordable method of in-house sterilization. But safety concerns and a slow turnaround time—sometimes as long as two weeks—have frustrated both users and suppliers.
Packaged orthopedic devices are being loaded into Oratec Interventions' Sterrad sterilization chamber.
According to Brian O'Neill, group manager–sterilization for Environmental Techtonics Corp. (ETC; Southampton, PA), many EtO sterilizer suppliers are making their systems safer through automation. "EtO systems used to be more manual, but now we can use a PC to control the process," he says. "Automated doors and material handling can reduce the risk of exposure and minimize human error."
O'Neill credits the move to safer systems to the Ethylene Oxide Sterilization Association, a committee ETC helped form in order to "bridge the gap within the industry. We wanted a forum to discuss safety and current issues."
To help contract sterilizers reduce turnaround time, O'Neill says, many suppliers are moving toward using parametric release, which enables them to release product based on the verification of certain cycle parameters rather than testing or biological indicator (BI) readings. But the "onus is on device manufacturers to pay contractors to establish a protocol for their products and validate parametric release cycles," he says. "They need to put up the money now in order to save over time."
Griffith MicroScience (Oak Brook, IL), a provider of sterilization services, has come up with another way to reduce cycle time, turnaround time, gas use, and residual levels. Bruce Schullo, vice president of quality assurance and regulatory affairs, says his firm "can optimize the EtO sterilization process using various statistical studies such as those found in design-of-experiment technologies." For instance, one study reduced aeration time by 66% and another reduced cycle time from 11 to 5½ hours.
Anne Booth, a consultant based in Barrington, IL, says many companies that switched from EtO to other methods are coming back because of these and other developments. "Heated aeration, about 120°–125°F, causes the EtO to outgas rapidly. Some are using parametric release and then maximizing the EtO outgassing with heat," Booth says. Currently working with the Association for the Advancement of Medical Instrumentation (AAMI) to draft a technical information report (TIR) about parametric release, Booth says industry can expect a lot of guidance on the technique soon. "In addition to the TIR, industry can expect the related ISO standard, ISO 11135, to be reviewed in 1999," she says.
John Broad, director of microbiology at NAMSA, says that in theory, use of parametric release will eliminate the need for BIs. "If you have complete control over the sterilization process, you are capable of eliminating biological indicators."
But advances are being made with biological indicators, too, to reduce sterilization cycle release time. For instance, NAMSA has introduced rapid sterilization indicators (RSIs) for steam processes. The RSIs are biological systems derived from bacterial enzymes, says Broad; the steam's heat inactivates the enzymes, and the indicator monitors the enzymes' inactivation. After sterilization, processors just need to check the RSI for the presence of active enzymes using a colormetric substrate.
Dennis Cantoni, vice president of sales–Americas for Steris Corp. (Mentor, OH), agrees that parametric release could one day replace biological indicators, but that for now processors still need them. "It takes a while to move from current techniques, and parametric release is in the early stages," he says. In the meantime, Steris will continue to market biological indicators, including its newest 48-hour model for EtO.
Andersen Products Inc. (Haw River, NC) has developed an EtO gas diffusion technology that eliminates the need for an EtO chamber. Instead, products are placed into LDPE bags, the mouth of each bag is placed in the jaws of the processor, a preprogrammed amount of EtO is injected into the bag, and the bag is then heat-sealed. The bags are then transferred to a temperature-controlled room and exposed to a hot cell, which provides heat for both sterilization and aeration. According to the company, when compared to sterilization by means of a large vacuum pressure vessel, this system controls emissions and reduces gas use.
Gamma radiation is another well-established method of terminal sterilization and holds a market share equal to that of EtO. Device makers started using gamma in the 1960s because of its reliability and quick turnaround. Gamma-irradiated product can be released much more quickly than EtO-processed product because most dosimeters, unlike biological indicators for EtO, can be read immediately after processing.
But to use gamma, a device company must pay anywhere from $3 million to $6 million to set up an in-house operation or instead transport product to and from contract gamma sterilizers.
Wayne Gibson, manager of new product development in marketing for the industrial irradiation division of MDS Nordion (Kanata, ON, Canada), says that to help reduce costs and the amount of time product spends in the sterilizer, his firm has developed software that constantly monitors the flow of product through the irradiator. "NorTrack provides a graphical picture of where product is in the flow path," says Gibson. "An Oracle database stores tracking information. All operators need to do is to click on the boxes representing the product carriers. A screen pops up, telling what products are in each carrier, who the product belongs to, and what dose and timer setting the carrier should be receiving." MDS Nordion offers NorTrack to both irradiator contractors and in-house sterilizers.
Electron-beam sterilization uses a high-energy stream of electrons to penetrate both package and product. According to Booth, it is one of the cheapest methods of terminal sterilization. It is environmentally safe and can deliver small doses, minimizing product degradation. Recent improvements to E-beam technology include improving the beam's penetrating power and making convenient in-house systems.
In the fall of 1997 Steris acquired Isomedix (Salt Lake City) and has since planned the opening of an advanced E-beam facility. "It will be the largest E-beam sterilization facility in the United States—85 kilowatts. It will provide quick turnaround, improved reliability in terms of equipment performance, and more uptime," Cantoni says. The facility's design is from Ion Beam Applications (Louvain-la-Neuve, Belgium).
Another improvement to E-beam sterilization is automation. "We're implementing automatic loading and unloading at our facilities to reduce product damage from handling," Cantoni says.
On-line E-beam irradiators are currently being marketed by Titan Scan (San Diego). "The systems can be placed on packaging lines, so medical device manufacturers can reduce time by eliminating contract sterilizers," says Booth.
HYDROGEN PEROXIDE GAS PLASMA
Widely touted as a promising emerging sterilization technology, hydrogen peroxide gas plasma has been available for use in U.S. hospitals since 1993. But John Simmons at Advanced Sterilization Products (ASP; Irvine, CA) says his firm started receiving inquiries from medical device and pharmaceutical manufacturers shortly after the hospital models were available. So ASP developed the Sterrad 100 SI GMP, a system designed for in-house, just-in-time sterilization. The system injects and vaporizes a solution of 59% hydrogen peroxide into the chamber, killing any bacteria on any package and product surfaces the vapor can reach. Next, an electromagnetic field is created in the chamber, creating a plasma cloud that generates free radicals that kill any remaining bacteria. At the end of the process, the free radicals lose their high energy, and the hydrogen peroxide converts to water and oxygen molecules. "There are low residues and no cross-linking to destroy polymers," says Simmons, "and the cycle is about an hour."
According to Simmons, the system is designed for low-volume, high-value devices, particularly pacemakers, biological tissues, and implants. "It isn't good for high-volume disposables, so we don't expect it to take over the industry," he says. But compared to other technologies, he says, it is relatively inexpensive. "Capital costs are more than EtO—it runs $300,000–$400,000 for production equipment—but the operating costs are lower. You don't have the monitoring costs associated with EtO nor the OSHA considerations," he adds.
Simmons says that there is currently a handful of companies that have submitted 510(k)s and premarket approval applications to FDA regarding use of hydrogen peroxide gas plasma, but so far there is only one U.S. company that has approval to use it for its commercial products. Oratec Interventions Inc. (Menlo Park, CA) currently uses hydrogen peroxide gas plasma for its orthopedic and arthroscopic devices. "About one and a half years ago, we found ourselves two months away from product launch with no sterilization method," says Scott Burgess, director of quality assurance for Oratec. The company was introducing an electrosurgical device with PTFE insulation and couldn't use its then-current method, gamma irradiation. "The gamma turns PTFE into a powder. Our other option was to use EtO, but that takes about two to three months to validate." Instead, his company turned to hydrogen peroxide gas plasma and was able to validate the system in four weeks. "We have greater control over the process since it's in-house, and we can rapidly validate new devices and packaging materials," explains Burgess. His in-house experimentation even led to a discovery that ASP hadn't made. "Hydrogen peroxide gas plasma doesn't like the water-based adhesives between laminated polyethylene and polyester—it delaminates over time. You have to use a solvent-based adhesive between the laminates."
Another material packaging engineers should avoid when using hydrogen peroxide gas plasma is paper. "It can't be used with cartons," says Steris's Cantoni. "The cellulose will absorb it."
Another emerging technology not currently in wide use but still promising is the use of bright light, says Booth. Marketed by PurePulse Technologies Inc. (San Diego), the method involves using short pulses of high-intensity, broad-spectrum white light to kill microorganisms without heat, chemicals, or ionizing radiation. The light lasts for a few hundred millionths of a second and is 20,000 times brighter than sunlight, says Joe Dunn, formerly with PurePulse and now with Automatic Liquid Packaging Inc. (Woodstock, IL). "The light can go through any material that can transmit the appropriate wavelengths, such as polypropylene and polyethylene."
Pharmaceutical packagers have taken an interest in the technology, mainly because the technique works well with form-fill-seal lines. For instance, Automatic Liquid Packaging has incorporated the technology into some of its blow-fill-seal systems. "The pulsed light offers the potential to perform terminal sterilization on top of aseptic processing for injectable and parenteral fluids," says Dunn. "FDA has stated that, if possible, parenteral solutions should be terminally sterilized, and since polyethylene packaging is not compatible with autoclaving, the light seems to offer the promise of terminal sterilization."
One type of medical device that Dunn feels is suitable for bright light is the contact lens. "The system can sterilize clear products and packaging," he says.
Several developments are making terminal sterilization safer, easier, and more efficient. But the real challenge, suppliers say, is getting device manufacturers to embrace the advances or emerging techniques.
Sometimes time constraints or the devices themselves force companies to reconsider their sterilization method. That's what Oratec had to do, and the company has made history by being the first to commercialize its hydrogen peroxide gas plasma–sterilized products both in the United States and in Europe, and soon, possibly, in Japan.
Not every company has to make history. The best approach is to look continuously for ways to improve terminal sterilization, not only to save time and money, but to remain competitive as well.
See companion story, Sterilization Process Compatibility with Tyvek.