Medical Device Link.

Originally Published September 2000

SPECIAL REPORT

Sterilization Meets New Demands

by Annie Lubinsky

Pressured to keep costs down, meet stringent regulations and standards, and get products to market quickly, medical device makers are leaning on sterilization service and equipment providers a bit more these days. As a result, equipment manufacturers and contract sterilization companies are increasing their products' and services' value by broadening their range of offerings, inventing new processes, and taking advantage of electronic communications. The results have helped pharmaceutical and medical device companies remain competitive. Among other benefits, these companies can obtain 24-hour turnaround, have their products shipped from the sterilizer directly to the distributor, and find a custom process suitable for highly specialized new products.

WIDER RANGE OF SERVICES

By continuously responding to customers' requests, sterilization companies have become providers of a broad range of services. They look for ways to carry out sterilization more quickly and cost-effectively, as well as ways to increase the number and types of services. For example, some sterilization companies have become technology neutral in their stance, either because they feel it is in their best interest to refer a customer to the most appropriate process for their product, or because they have the ability either to provide or to find a range of sterilization processes.

A technician reads doimeters after products have exited the irradiator.

One such firm is North American Sterilization and Packaging (NASP; Franklin, NJ), which focuses on the assembly, packaging, and sterilization of medical devices. NASP can help design the device, source components, manufacture the device, package it, and sterilize it using EtO. They can also source gamma or steam sterilization. "We provide customers with control of the entire process," says Ed Gumpy, senior sales executive. "Accountability comes from one source rather than many; there is less transportation time required, and thus less cost and quicker turnaround."

Contract sterilizers are expanding their services.

Gumpy's office is in a three-year-old facility, which may soon be working to capacity—next year the company is planning to build a new facility in order to expand its volume of operations.

IBA (Louvain-La-Neuve, Belgium) also maintains a technology-neutral stance. IBA has acquired five additional companies within the past two years, enabling the organization to serve a wide variety of customer needs. The acquired companies include Griffith Micro Science (formerly headquartered in Chicago), which provides contract EtO sterilization as well as laboratory services such as microbiological and chemical testing and consulting; SteriGenics International (formerly headquartered in Fremont, CA), which offers contract gamma and electron beam (E-beam) sterilization as well as the design, development, and installation of complete gamma irradiation systems; RDI (formerly of Long Island, NY) and Scanditronix (formerly of Sweden), which provide in-house sterilization capabilities through the design, development, and installation of E-beam sterilizers; and Wellhöfer (formerly headquartered in Germany), which provides personnel dosimetry systems. "Of particular interest to the medical industry is IBA's acquisition of Griffith Micro Science and SteriGenics. These companies were acquired to combine multiple technologies and to offer medical device manufacturers a broad range of solutions," says David E. Meyer, president of North American operations (headquartered in Chicago), which includes IBA's Medical Sterilization & Analytical Labs division. "Through IBA's acquisition and merger of these established companies, we are able not only to offer more services but also to maintain an unbiased position with medical device and pharmaceutical manufacturers."

RESPONSIVE TO NEW NEEDS

Ideas about sterilization have been changing, according to Jonathan Wilder, president and general manager at H & W Technology LLC (Rochester, NY). "While product safety has always maintained primary importance, sterilization has now moved into the manufacturing process, which means that speed and cost have become increasingly important," Wilder says. It also means that companies connected with sterilization have been more responsive to customers' unique or emerging needs, whether these occur before the sterilization process, during it, or after the cycle is completed.

Product-specific studies. Chris Dwyer, marketing and sales manager at Raven Biological Laboratories Inc. (Omaha, NE), a manufacturer of sterility assurance products, says that Raven has had increased requests for resistance studies of inoculated products and for studies of materials. The company will test materials to be sure they do not protect contaminants in some way, which would allow micro-organisms to survive sterilization.

ASP provides the Isodox gas generator for sterilizing barrier isolators.

Biological indicators (BIs). Raven also helps companies by designing BIs for product-specific requirements. "For example, in a device with a long lumen, such as a catheter, you need to be sure the sterilization cycle can penetrate the entire length of the device," Dwyer explains. To this end, Raven has developed small BIs that fit inside a medical device without impeding the sterilization process. "We are also designing a BI specifically for use with the new technology created by Advanced Sterilization Products (ASP; Irvine, CA), hydrogen peroxide gas plasma sterilization," says Dwyer.

More help with compliance. Healthcare companies are asking for assistance in complying with regulations. H & W Technology provides solutions to regulatory issues in sterilization and disinfection, from training to consulting to manufacturing controls and validation equipment. "A great influence on the packaging for reusable medical devices is ISO regulations regarding BIs and chemical indicators," says Wilder. "As a manufacturer of biological indicator evaluator resistometers (BIERs), we can say from experience that it is a challenge to comply with standards. If a company wants to say that an indicator is compliant with worldwide standards, they can validate that claim with our machine."

Increased expertise. Sue Duensing, regulatory affairs manager at Opportunity Medical (Highland Park, IL), a contract manufacturer of disposable medical devices, says: "Over the past couple of years, our customer requirements have changed. In the past, it was common for a customer to require assembly and packaging of a device but specify the sterilization service to use. Customers would provide their own sterilization expertise to perform a sterilization validation on the product. Now, many of our customers contract with us to assemble, package, and sterilize the device and to provide them with the finished product. In this case, we are actually performing the sterilization validation with the contract sterilizers, which requires more in-house expertise to offer these services."

Opportunity Medical put this newly developed expertise to good use recently when the company helped a customer solve a sterilization problem. "In this case," says Duensing, "it was a matter of switching the process from ethylene oxide [EtO or EO] to gamma irradiation, which was more appropriate for their product. Their product had a thin film of silicone applied to it during the production process. The silicone encapsulated the anaerobic organisms and prevented the gas from penetrating and providing the necessary kill we needed. We have since recommended using gamma to sterilize the product, and we are currently performing sterilization validation for our customer."

New equipment. Opportunity Medical is looking at the possibility of installing a steam sterilizer. In addition, they may broaden their marketing approach. "We have never marketed our ability to perform a customer's sterilization validation process. Since we find we are doing this more and more often, we may decide to promote this in the future as an additional service. We have upgraded our in-house technical expertise in the regulatory affairs and quality assurance areas to provide this type of value-added service for our customers," Duensing says.

Raven's spore suspension helps show whether materials will protect microorganisms.

Raven Biological Laboratories will acquire a new BIER, allowing the company to expand its testing capability, especially for parenterals. "The unit has more capabilities, such as air-over-pressure and spray cooling, which prevents the bursting of small pouches and ampules during the cool-down phase," Dwyer explains.

DISTRIBUTION

Distribution has become another area in which contract sterilizers continue to expand their services. Jonathan Wallace, quality assurance manager for Sterilization Services Inc. (Atlanta), says that in addition to providing EtO sterilization for the medical device industry, the company aims to include distribution when the customer requires it. "This is something that saves the customer money if we do it," says Wallace. "In general, if a manufacturer sterilizes its product close to its distribution center, this saves travel time and money. Many times transportation costs more than sterilization."

Sterilization Services has been helping its customers distribute product for about five years and has seen distribution as a growing need. "Now, instead of waiting until the customer inquires about distribution, we ask if they need it. Sometimes they don't know they can rely on us for that service," Wallace says.

Titan Scan, a division of Titan Corp. (San Diego), has also responded to customers' requests for warehousing and distribution services. "We have offered these services on a limited basis for one and a half years," says Titan Scan's vice president of operations, Harry Shaffer. "As the need for warehousing and distribution has grown, we've increased our attention to this need, particularly in one of our locations."

Titan Scan, which builds and installs E-beam and x-ray sterilization chambers for its customers, also provides contract E-beam sterilization for medical devices. "We have seen a heightened sensitivity to turnaround time in our customers," says Shaffer. "It's a high selling point that Titan Scan can offer a premium service—we can complete sterilization in 12 hours if the client requests it. Our standard turnaround is less than 72 hours for most projects. The number of customers using the premium service has increased over the past year."

RESEARCH SERVICES

Not only do healthcare companies want a quick turnaround, they also want the right process. These companies are increasingly asking for assistance in finding the appropriate sterilization method for their new products and in validating the process.

IBA's Analytical Labs business is increasing its services to healthcare companies. "Our Analytical Labs operation provides research and development services to review the effect of x-rays on materials," says Meyer. "The company has been testing a number of products during the past year and plans to begin sterilization testing for medical devices within the next two months."

IBA's Analytical Labs offers these consultative services in its SteriPro program. "This is a scientific platform in which we analyze and optimize the sterilization process. With respect to EtO processing, we are able to reduce cycle times and perform the studies necessary to enable a company to carry out parametric release," says Meyer. SteriPro can also assist customers with packaging validation, process validation, material compatibility, product sterilization, residual testing, and equivalency studies.

SteriPro has another goal, however. Currently, IBA has helped it's customers manage their supply chain cost-effectively by offering distribution services at many of its contract sterilization locations. "We have already consolidated volumes and helped customers manage their inventory. That was the easy part," Meyer says. "We now need the creativity of consultative services like SteriPro to examine the sterilization process and find additional areas where we can cut costs or add value." He believes that through research, scientists can continue to find better and less expensive ways to sterilize products.

FASTER CYCLE TIMES

Once a sterilization method has
been determined, healthcare companies look for ways to cut cost and increase speed without sacrificing safety. Several solutions have been developed to accomplish this, particularly with EtO sterilization.

Wallace points out that there are two new processes; one is reduced incubation time release. A validation study of the laboratory recovery methods reduces the incubation time from 7 days to 3 or 4 days. The second method is parametric release, a process that allows products to be released as quickly as they can be processed. Wallace says that Sterilization Services is currently working with firms on both of these approaches for releasing their product to the market faster.

In addition to making bacterial spore test strips, Raven is developing BIs for ASP's hydrogen gas plasma sterilization technology.

Perhaps the most significant time-saver for sterilization in recent years is Cosmed Group Inc.'s (Coventry, RI) quick turnaround for EtO sterilization. According to Clark Houghtling, vice president of technical affairs for the firm, the 24-hour turnaround on EtO sterilization, called EO Express, "allows customers to have their products sterilized and released to the market in one day. In these days of just-in-time delivery and reduced inventory, it is a valuable service."

For a long time, Houghtling says, radiation sterilization held two advantages over EtO: it was a quicker process (2 to 4 days compared with standard EtO's usual 7 to 10 days), and there were no residual concerns. While EO Express eliminates these two advantages of radiation, it adds one important advantage not shared by radiation—EtO sterilization has no material incompatibility. "Often, a company is using two methods of sterilization," Houghtling explains. "They use gamma for quicker turnaround time, then use EtO for anything not compatible with radiation. That means a company is dealing with two processes, two loads, two validations, and in many cases two suppliers. It is more cost-effective to do only one method of sterilization."

Raven's industrial-use BIs are designed to fit specific applications.

EO Express saves time by using what is called "all-in-one processing." The company eliminates the lengthy preconditioning and aeration processes that take place before and after sterilization. Instead, conditioning, sterilization, and aeration all occur within the chamber. In addition, Cosmed uses parametric release, which eliminates BIs and the time needed to test for bacterial viability.

Eliminating BIs also saves money for the customer, Houghtling says. "There is no need to buy BIs, pay someone to place them into and retrieve them from the load, pay for shipping to the laboratory, or pay the laboratory to test them."

EO Express has been used for about two years. "During that time, the process has withstood rigorous regulatory scrutiny by FDA and ISO," Houghtling says, "and it has achieved complete acceptance."

COOLER TEMPERATURES

While speed is greatly valued in healthcare manufacturing, other concerns can become more important. For example, some products are so sensitive to heat that finding a relatively cool but still effective sterilization process is the first priority.

Sterilization Services Inc. offers sterilization at relatively cool temperatures, which are better for plastics, wovens, cottons, and heat-sensitive materials. "We have recently seen bioabsorbable materials in the healthcare market," says Wallace. "Examples are orthopedic screws that hold broken bones together for a certain period of time, then are absorbed slowly by the body. These materials dissolve at high humidity and at temperatures around 100°F, the conditions found in the human body. These bioabsorbable materials cannot withstand high heat during sterilization. Therefore, we have developed what we call Cold Cycle Processing for heat-sensitive product. We have made the hardware and software changes possible to accomplish this; however, the cycle may take longer." Wallace explains that pharmaceuticals may also need a cooler temperature, a need that is filled by contract sterilization providers.

EMERGING TECHNOLOGY

A relatively new sterilization process, low-temperature hydrogen peroxide gas plasma can be used for the sterilization of surgical instruments and medical devices. ASP, a division of Johnson & Johnson, builds and installs Sterrad sterilizers, which use the hydrogen peroxide gas plasma technology. Originally designed as a safer alternative to EtO for the company's internal use, the gas plasma process quickly attracted interest from medical device manufacturers. "The Sterrad process is targeted to highly invasive, high-cost products where lower residuals and two-hour cycle time are especially beneficial to the medical device manufacturer," says John Simmons, worldwide business director of scientific and industrial markets at ASP. "Medical device manufacturers can use this technology to save costs and bring the sterilization process back in-house, allowing them to control this key element of manufacturing."

Medical products undergo sterilization in the JS 10000 irradiator.

The Sterrad gas plasma technology addresses supply-chain issues, bringing improvements in cycle times and lead times. Small product batches are sterilized as needed for just-in-time processing.

While gas plasma technology is designed for safety and speed, there are some limitations. "No sterilization method is for everything," Simmons says, "and gas plasma is incompatible with powders, liquids, and cellulosic materials such as linen." Sterrad is not for high-volume commodity products; however, the Sterrad 200 and 800 GMP units are appropriate in size for such items as implants, pacing devices, cardiovascular products, and ophthalmic products.

On the pharmaceutical product side, ASP offers the Isodox gas generator, which uses chlorine dioxide gas. This technology is appropriate for sterilizing barrier isolators and large room-decontamination for the pharmaceutical and biotechnological industries.

MORE INTERNET

Like all businesses, sterilization companies are increasing their use of the Internet to speed communication and provide better service to their customers. IBA, for example, has been working with its customers to provide real-time tracking of products through their sterilization facilities, an offering the company expects to make available late this year or early next year. NASP plans to make greater use of the Internet by creating an enterprise resource planning (ERP) system to streamline the ordering process.

Cosmed, in order to further expedite its EO Express sterilization process, has developed the Steri-Link manufacturing execution system. Steri-Link, an electronic data interface (EDI) between Cosmed and the device manufacturer, allows all necessary documentation to be transmitted immediately to
the customer via a secure, password-protected e-mail. This, in turn, means there is no "hold" time for sending the processing records to the customer. Once products are removed from Cosmed's sterilization unit, they're ready to be distributed. According to Houghtling, Cosmed intends to improve Steri-Link even further by providing customers with information 24 hours a day, 7 days a week, via an EDI.

A STREAMLINED PROCESS

The result of constant scrutiny and attempts at improvement is that sterilization processes can be customized to fit each pharmaceutical or medical device company. In effect, sterilization can be streamlined just like any other manufacturing process. Sterilization systems can be adapted to accommodate new and never-before-sterilized products, they can be faster, and they can better enable a manufacturer to verify and validate cycle times. Contract sterilization services truly function as an arm of a company's business, accepting the roles of product designer, process validator, and distributor in addition to sterilization service provider. Increased speed and improved processes mean that healthcare companies can continue to provide safe medical and pharmaceutical products in a timely, cost-effective manner.