PRODUCT UPDATE
Sterilization Firms Strive to Cut Costs, Turnaround Times
Benjamin Lichtman
Bottom-line measures drive technology as suppliers work to meet changing regulatory and market needs.
Sterilization is a critical step in ensuring the safety of medical devices for final use. Whether manufacturers perform this process in-house or employ the services of a contract sterilizer, they are faced with a choice between several different technologies. Some of the most prevalent techniques are ethylene oxide (EtO), gamma irradiation, steam sterilization, and e-beam processing. All offer different advantages to medical manufacturers seeking to rid their devices of biological contaminants.
Sterilization by EtO gas is in widespread use among device manufacturers. EtO is a toxic gas that sterilizes via its action as a powerful alkylating agent. The technique, which does not deform packaging materials, has gained a strong foothold in the medical industry.
According to Lauren Andersen, managing director of Andersen Caledonia Ltd. (Strathclyde, Lanarkshire, Scotland, UK), EtO is used to sterilize more than 50% of new medical devices globally, and this figure is likely to grow. "The use of procedure packs will mushroom in Europe as it has in the US," she predicts. "The expansion of the kit packing business has led to an increase in the use of EtO sterilization over irradiation because of the mix of materials within kits," Andersen adds. Andersen Caledonia offers a variety of services to medical device manufacturers, ranging from regulatory consulting and validation to EtO sterilization and logistics.
Irradiation technologies also enjoy a strong position in the medical sterilization market. Gamma irradiation, which destroys microorganisms by disrupting their DNA stucture, offers high levels of penetration while leaving products unaffected. The technique is well suited for the treatment of disposable devices, which can be sterilized in their final packaging. Ruth Brinston, marketing manager at MDS Nordion (Kanata, ON, Canada), says "Gamma processing is extremely fast and reliable." She adds that the technology offers manufacturers process flexibility and allows for incremental dosing.
E-beam sterilization—in which products are exposed to accelerated electrons—is a promising technology that has traditionally been hampered by reduced penetration. Now, with the advent of 10 MeV and 12.5 MeV machines, the device industry is being introduced to powerful, high-throughput E-beam equipment. "The capital cost of installing such equipment has stabilized, and its reliability is improving," notes Andy Spry, marketing manager at Isotron plc (Swindon, Wilts, UK). "This may be a growth area in the coming decade."
All of these technologies are aimed at a common goal: the removal of biological contaminants from medical devices. And it comes as no surprise that this goal must be achieved at a minimum cost.
The Bottom Line
"Ours customers are asking where they can cut costs," says Jonathan Wilder, general manager at EHW Design Engineering (Rochester, NY, USA). "While we're seeing a lot of innovation and new products in the market, there is enough shareholder involvement [in device companies] that the bottom line still counts quite a bit," he adds. Wilder underscores the role that cost reduction plays in the development of his company's in-house steam sterilizers by pointing out that EHW's latest biological indicator evaluation resistometer (BIER) vessels are capable of emulating any industrial steam sterilizer process. "This offers the user an alternative to stopping production for methods development and QC testing," he says.
Andersen notes that her company's facilities were designed as a response to cost-reduction needs. "By offering both low-temperature, small-volume EtO sterilization in our gas diffusion sterilizers, and large-volume sterilization in our industrial vessels, we are able to accommodate a greater range of devices, including many items that would be damaged in traditional sterilization processes." Andersen cites intraocular lenses and absorbable sutures as examples of delicate items that are currently sterilized using the company's gas diffusion system.
Lars Jordeby, marketing manager at Scanditronix Medical AB (Uppsala, Sweden), observes the same trend. "We are seeing a demand for cost-effective systems to handle the sterilization process," he says. "I mean cost-effective in terms of saving time, space, and money." Jordeby sees in-house sterilization as a way to give manufacturers full control over quality assurance, cut production time, and lower handling and transportation costs.
Regulatory issues also play a role in increased expenses, says Cathie Deeley, marketing development manager at Puridec Irradiation Technologies (Chesham, Bucks, UK). "Plant operators need to maximize product throughput while providing more-detailed process histories to satisfy regulatory requirements," she says. Puridec's I-CON plant control software system is a response to this need, enabling contract gamma sterilizers to control and automate different aspects of their sterilization and validation processes.
The Race to Market
In addition to the direct cost of sterilization, device manufacturers must consider the turnaround time for sterilization processing, which may be a significant factor in delivering a product to market quickly. As Ken Carlson, vice president for sales and marketing at Titan Scan Corp. (San Diego, CA, USA), explains, "If your product is stalled in the supply chain for 10 days, it can make a huge difference in your bottom line." Carlson notes that Titan Scan can offer its customers same-day turnaround.
Brinston singles out efforts to reduce turnaround time as the most significant trend among sterilization suppliers. She views MDS Nordion, which supplies cobalt-60 and gamma sterilization systems, as a key player in this movement. "According to our company's studies, gamma processing generally takes about half as much time as other methods," she adds.
As time to market becomes more important, some contract sterilizers are becoming increasingly involved with their clients' supply operations. The industry, according to Spry, is moving away from the idea of sterilization as a "black-box" technology. For its part, Isotron aims to enhance its level of service by forming partnerships with its clients. "We form a part of our customer's distribution chain, reducing time and costs on shipment and logistics," he says. "It's a partnership between our company and the client to produce a sterile product."
Carlson notes that competition in the sterilization market has encouraged his company to make a thorough review of its E-beam equipment. "We are seeing increasing consolidation among sterilization companies," he says. "Given this situation, customers are increasingly sensitive to turnaround time, total cost, and possible R&D benefits that we can offer them."
One challenge that contract sterilizers and manufacturers of in-house systems alike are trying to meet is an increasingly diverse set of medical devices. "Contract irradiators need more flexibility today," says Deeley. "They need to respond to a widening portfolio of sophisticated, high-value products with varying sterilization requirements."
James Whitbourne, founder and president of STS duoTEK Inc. (Rush, NY, USA), notes the effect of this trend on hospitals, saying, "As medical devices become more complex, it becomes a challenge for hospitals to sterilize their equipment." He adds that most hospitals currently use steam sterilization to remove biological contaminants, which may not necessarily be adequate for all applications.
In a dynamic market, successful suppliers of sterilization services and equipment will have to retain a degree of flexibility. EHW's Wilder explains that his company's technological development is based on this challenge. "At EHW, we intend to develop and provide solutions to regulatory issues and to do this in a cost-effective and efficient manner," he says, adding, "Our product line will adapt to meet these goals."
To learn more about how your company can benefit from sterilization technology, review the following descriptions of some of the device industry's leading suppliers of sterilization equipment and services.
SteriGenics International Inc.
Covering less than 170 sq ft, a gamma sterilization system features many of the same components as larger irradiator systems, including a radiation shield, a product-handling mechanism, a source mechanism, and a validated control system. The steel shield is fully integrated with all other operating systems, and a specially designed door on the front of the cell permits access to the product-handling system for loading and unloading of the product containers. A key component responsible for the system's small size is the design of the cobalt-60 sealed source mechanism. When the system is in use, the source is raised vertically into position using a hoist. 
The source is fully guided and protected by a shroud to ensure system safety. SteriGenics International (Fremont, CA, USA) also offers design expertise to European firms that plan to obtain in-house sterilization capabilities, as well as to firms that require evaluations of existing in-house equipment. The company's other irradiation systems include the ExCell, MiniCell, Gemini, and 
megaCell. All units are designed to minimize turnaround time and provide processing flexibility. The company was recently acquired by Ion Beam Applications S.A. (Louvain-la-Neuve, Belgium).
EHW Design Engineering
Steam biological indicator evaluation resistometer (BIER) vessels are reportedly the first commercially available units to comply fully with ISO 11138 and ISO 11140 part 2. "In fact, the advent of these standards was a motivating factor in the creation of the company," says Jonathan Wilder, general manager at EHW Design Engineering (Rochester, NY, USA). "We saw an opportunity and knew how to meet the technical challenges." With sterilization chambers measuring 8 in. diam * 24 in. deep, the ILS 20 vessels offer increased load capacity, flexibility in operation and cycle design, computer-compatible data logging, and integral cycle record archiving. "These units provide a new level of control, accuracy, and repeatability for the validation of any steam sterilization process," says Wilder. Industrial sterilizer processes can be emulated using optional features such as subatmospheric processing, automatic air-overpressure capability, and controlled evacuation and cooling rates. The company's other products and services include a Windows-based industrial sterilizer control system, process-challenge devices to demonstrate compliance with EN 1422, as well as consulting services in sterilization, R&D, and regulatory affairs. The firm is represented in Europe by Raven Biological Laboratories Inc.
Puridec Irradiation Technologies
An integrated plant control system aids manufacturers in processing a range of products with precision dose control and high-throughput efficiency. I-CON is a PC-based control system suitable for use with all types of gamma irradiation plants. A flexible, modular design allows nearly any combination of in-cell control, automated dosimetry, and product tracking with the use of additional supplementary modules. "This enables us to tailor a control system to satisfy individual needs now, and to upgrade it as these needs grow," says Cathie Deeley, marketing development manager at Puridec Irradiation Technologies (Chesham, Bucks, UK). Traceable product documentation is automatically archived and printed by the I-CON control system. A Windows environment provides compatibility with most third-party reporting packages and databases. The programme can be installed in parallel with existing control systems to give uninterrupted processing during commissioning.
Isotron plc
Although it began by offering only gamma services, Isotron plc (Swindon, Wilts, UK) now aims to become a "one-stop shop" for sterilization, according to marketing manager Andy Spry. The firm now serves clients in the UK and Ireland with four gamma sites, two EtO sites, and one E-beam processing centre.
"We aim to be technology-neutral," says Spry. "Instead of offering only one type of sterilization service, we are able to evaluate each project individually and provide a service that is most appropriate," he adds. The company recently added a further sterilization line to its EtO facility in Thorne, Yorkshire, UK. The Thorne site is certified to EN/ISO 9002 and EN 46002.
The company is able to offer 24-hour guaranteed turnaround service for gamma processing of volumes up to one pallet load. The company's core sterilization services are complemented by laboratory service facilities. On-site laboratories at two UK sites provide comprehensive microbiological and analytical test services to manufacturers of healthcare products. Key activities include assisting with sterilization validation, biological indicator testing, residual analysis, and pyrogen testing.
MDS Nordion
A supplier of gamma sterilization systems and cobalt 60 sources, MDS Nordion (Kanata, ON, Canada) offers pallet, tote and carrier irradiation systems to device manufacturers and contract sterilizers. Pallet irradiators are engineered to process large product volumes and can result in a significant reduction in labour costs, because the product remains palletized from manufacturing until it is delivered to the customer. Tote irradiators are designed for versatile processing of different products with varying throughput needs. The multipurpose carrier accommodates product boxes of various sizes and configurations within one large container. The company has installed more than 110 sterilization units in 40 countries, and it produces more than 80% of the world's supply of cobalt 60.
"Gamma radiation has the power to penetrate dense products," says Debbie Merrithew, marketing associate for the industrial irradiation division. "When something like a surgical kit has been exposed to gamma following validated procedures, you can be confident that all the pathogens have been inactivated." Penetration is a key characteristic of gamma sterilization, and turnaround time is an advantage, she adds. Merrithew notes that gamma-processed products can be shipped immediately after treatment.
Titan Scan Corp.
A variety of turnkey E-beam solutions are provided by Titan Scan Corp. (San Diego, CA, USA). One example is the SureBeam On-Site System, which is powered by an industrial-grade RF linear accelerator. Energy levels of 10 MeV are attained, and the system's nominal dose range is 10–50 kGy. The system is compliant with ISO 11137 and EN 552 and can process up to
A material-handling subsystem loads products onto specially designed carriers that are guided through the radiation shield and onto the process conveyor. A real-time control system based on a PLC monitors and controls the flow of products throughout the system. A graphical user interface sequences and controls complex tasks, provides real-time error detection, and archives all processing data.
Scanditronix Medical AB
Designed for in-house operation, a compact E-beam sterilization system comprises an accelerator, internal radiation shielding, control and cooling subsystems, and a conveyor mechanism. The Betaline system measures
The Betaline delivers 2.5 MeV of E-beam energy, and maximum beam power is 6 kW. Products can be irradiated from two directions in order to achieve better penetration and dose homogeneity. The system is fully automatic, and no full-time operator is required. Installation time is reduced to a minimum, since the only necessary connections are electrical power and cooling water. "Betaline offers manufacturers reductions in transportation and inventory costs," Jordeby says.
Scanditronix offers its customers personnel training for regular system maintenance. The firm also provides initial validation of customer products in order to ensure suitability for E-beam processing and to calibrate dosing levels. The company, which was recently acquired by Ion Beam Associates (Louvain-la-Neuve, Belgium), is certified to ISO 9001 and EN 46001.
Andersen Caledonia Ltd.
An EtO sterilization facility provides versatility and response to individual customer requirements. The plant's mid-sized chambers are well suited to most manufacturers' needs. In addition, the company has a series of small sterilizers that use gas-diffusion technology to process small volumes, R&D work, hospital outsourcing, and short production runs. "Our facility can process loads as small as a single device and as large as nine pallets at a time," says Lauren Andersen, managing director of Andersen Caledonia Ltd. (Strathclyde, Lanarkshire, Scotland, UK).
A purpose-built laboratory has been in operation at Andersen Caledonia since 1991 and offers a range of supporting services for the device industry, including validation and cycle development, cleanroom validation, and environmental monitoring.
The company's facility is certified to ISO 9002, EN 46002, and ISO 13488, and in-house regulatory expertise is offered to assist manufacturers in approval and compliance activities. The company recently opened a facility in Lille, France.
STS duoTEK Inc.
Founded in 1979 as a provider of EtO sterilization services to medical device manufacturers, STS duoTEK Inc. (Rush, NY, USA) expanded its repertoire of services to include analytical testing, toxicology, microbiology, assembly, and packaging.
The firm's Sterilization Technical Services division is registered with US FDA and offers EtO and steam sterilization conducted in accordance with GMPs.
STS can accommodate customers' production requirements with a range of single- and multipallet sterilizers. The company also operates small EtO and steam sterilizers for testing, cycle development, and small-load processing. BIER-type vessels are used for biological indicator evaluations and related product testing. Sterilization cycles are controlled and recorded via in-chamber and in-load sensors.
"The main advantage that our firm offers is a wide variety of services including assembly, packaging, testing, and validation, as well as contract sterilization," says Jim Whitbourne, president and founder of STS. "This is very convenient, especially for smaller companies that need to outsource several processes," he adds.
