Pharmaceutical and Medical Packaging News
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Originally Published March 2000
MEDICAL
Contract Sterilization: An Extension of Your Manufacturing Process
From consultation to warehousing and product shipment, contract sterilizers are partnering with their customers as an integral part of the manufacturing team.by Jenevieve Blair Polin
In the contract sterilization industry's infancy, contractors merely received manufactured goods, sterilized them, and returned them to the manufacturer. With the recent consolidation in the industry, today's biggest contractors have global networks of facilities offering total sterilization management.
In 1999, Ion Beam Applications s.a. (IBA; Louvain-la-Neuve, Belgium) purchased SteriGenics International Inc. (Fremont, CA) and Griffith Micro Science (Oak Brook, IL), forming the IBA Medical Sterilization Group (Chicago). This entity is the largest international sterilization management company, operating 37 facilities worldwide.
STERIS Corp. (Mentor, OH), another powerful North American conglomerate, acquired Isomedix Inc. in 1997, Royal Sterilization Systems in 1998, and Quality Sterilization Services in 1999. STERIS/Isomedix Services has just completed installation of a new continuous gamma irradiator at its Commerce Center facility in Libertyville, IL, and expects to open a new gamma facility in Ontario, CA, this spring.
These consolidations have changed the face of contract sterilization. Each of these companies now offers all three major sterilization technologies: ethylene oxide (EtO), gamma, and electron beam. "'Technology-neutral' is the term we use," explains Dan Carestio, director of sales and marketing for STERIS/Isomedix. "Because we offer the three technologies, we are going to put a customer's product in the right technology for the product and not just what's best for us," he adds.
Another approach to technology selection is to hire a consulting firm, such as H & W Technology LLC (West Henrietta, NY), before selecting a contract sterilizer. "Many device manufacturers don't have the staff to understand the options that are available to them in sterilization technology and, further, don't have the time to investigate and check out all of the potential contract sterilization facilities," explains Charles Hancock, H & W's director and regulatory chief.
WHO USES CONTRACT STERILIZERS?
"Contract sterilization is a godsend for the small manufacturer," explains Bill Butchee, manager of quality assurance and regulatory affairs for InnoMedica (Bloomington, MN), the medical products division of Innovex Inc., which manufactures implantable medical devices such as pacemaker leads. Huge companies, however, account for the bulk of products processed at contract sterilizers, for several reasons.
A company with an in-house gamma or electron-beam facility may develop a new product, such as a prefilled pharmaceutical syringe, that is not radiation compatible and therefore send that product to a contract EtO sterilizer. In other cases, despite capacity that may exist in-house for either gamma or electron-beam sterilization, the customer prefers to send a product to a contract sterilizer. "Often, in-house irradiators lack the inherent flexibilities designed into contract irradiators," Carestio explains. A large company may be processing a million cubic feet of one product in an in-house irradiator, but may find it inefficient and difficult to schedule processing of 100,000 cu ft of a different product with a significantly different density requiring a significantly different dose, he adds.
Contract sterilizers offer assistance when selecting sterilization methods and cycles.
Ruth Brinston of MDS Nordion (Kanata, ON, Canada), which is building new irradiators for STERIS, points out that it is difficult to compare older in-house designs with new ones. "Many of the new irradiators we are installing today are very cobalt efficient, and hence have lower operating costs and incremental dosing for easier scheduling and faster product turnaround."
Most contract manufacturers rely on contract sterilizers, partly because of the variability of product volume. Larry Rosser, president and CEO of Opportunity Medical (Highland Park, IL), a contract manufacturer of infusion delivery sets and procedure kits, says his company sometimes needs to sterilize up to 35,000 units a week, but the need is sporadic. Furthermore, a contract manufacturer needs the flexibility of different sterilization technologies. "From month to month, we are making brand new products with totally different properties and materials that dictate different sterilization methods," says Paulette Hansen, an Opportunity sales representative, "so we are definitely going to be using all of them at one time or another."
CONSULTING
Rather than considering sterilization as an afterthought, many manufacturers are benefiting by consulting with sterilization experts at the earliest point of product design. Karl Hemmrich, a materials expert now on staff at STERIS/Isomedix, often helps customers select materials, particularly plastics and resins that will be compatible with the doses that will be delivered if they intend to use irradiation. STERIS/Isomedix also has technology centers whose personnel help customers design both the actual product and packaging that will permit the free flow of gas if they intend to use EtO. Another objective often overlooked, Carestio notes, is designing a package for maximum loading efficiency of either the EtO sterilization chamber or the carrier in the case of irradiation.
Regardless of technology, the IBA Medical Sterilization Group consults on product and package design, validation, and cycle optimization as well as ongoing sterilization and process management. "This serves any company that depends on contract sterilization services," says Bruce Schullo, the company's vice president of regulatory affairs and quality assurance for North America. "We combine technology-neutral processing with laboratory and engineering consulting services. These services not only streamline processes, but also help customers reduce costs by finding the most efficient, expedient processing parameters."
VALIDATION
Many contract sterilizers are prepared to take on all responsibilities associated with designing and executing product validation. The IBA Medical Sterilization Group has a validation coordinator at each location to write the protocol for the customer. They use as a base a boilerplate protocol that complies with all international standards.
H & W Technology often writes the sterilization-related portions of premarket notifications (510(k)s) or premarket approval applications for a customer as well as smoothing the interface between the customer and FDA. "A lot of people don't speak sterilization," laughs Jonathan Wilder,
In many cases contract sterilizers have specialized tools at their disposal that ease validation. The IBA Medical Sterilization Group, for instance, within the past seven years has invested in a large supply of wireless temperature and relative humidity probes—devices set up initially through a software program. After the validation, the probes are removed from the boxes of product, and the data are downloaded and printed. "Because they are expensive, a lot of customers don't bother to buy them, but with our sterilization volume, we can justify it," explains Schullo. "A lot of customers think it's advantageous to have the structured temperature and relative humidity data printouts. They're easy to review with FDA," he says.
ELIMINATING OVERKILL
Turnaround time is critical, and contract sterilizers are constantly working on innovations that might reduce it. One possibility, they say, is to more precisely determine the amount of EtO gas necessary, instead of simply using vast quantities for several degrees of overkill. Use of less gas translates into lower cost, less residual, more-rapid cycles, and quicker turnaround time.
H & W Technology has introduced a new device to facilitate such precise determinations. They have launched the IL-series BIER (biological indicator evaluator resistometer) unit product line with a steam system, and they expect to have an EtO-based unit available by the end of this year. While BIER units were originally designed for validating the performance of biological and chemical indicators of sterilization,
The goal with this approach is to develop vessel-independent standards and eliminate a lot of the empirical, trial-and-error approaches to optimization that are currently used. "You still have to validate in the real unit, but only once, not 30 times as you're trying to optimize," Wilder explains.
The IBA Medical Sterilization Group takes a similar approach. They run statistically designed studies in pilot or R&D vessels to simulate the larger sterilization vessels and determine the optimal conditions or parameters for sterilizing a particular product. Using these more-precise methods, Schullo says that his firm "has made the ethylene oxide process, as far as turn time goes, pretty much as efficient as gamma."
PARAMETRIC RELEASE
Parametric release is another way to reduce turnaround time. The IBA Medical Sterilization Group has been offering parametric release for 2 years and currently uses it for a large medical device manufacturer. Parametric release can be compared to dosimetric release after gamma sterilization.
Some manufacturers, however, balk at the leap of faith required for parametric release. "Testing biological indicators provides positive proof that the cycle delivered conditions sufficiently lethal to inactivate the biological challenge device," reflects Richard J. DeRisio on his experience with EtO. DeRisio is vice president of clinical, regulatory, and quality affairs for Computer Motion (Santa Barbara, CA), makers of robotic, computer-assisted surgical systems for the operating room. "For companies that do not have resources for the extensive cycle development and validation studies needed to establish parametric release, testing biological indicators provides a less costly alternative that is reliable and widely accepted."
Cosmed Group (Coventry, RI) has taken parametric release a step further. The firm offers at all its nationwide facilities EO Express, a system in which all facets of EtO sterilization—preconditioning, sterilization, and aeration—occur within the chamber. In-chamber processing combines the traditional three-phase process into one continuous operation performed with the vessel, allowing for both faster and higher-quality sterilization. Using this concept, processors can reduce aeration times from days to hours. The next component, parametric release, obviates the need for biological indicators (BIs). According to Clark W. Houghtling, vice president, technical affairs, "This not only eradicates all costs associated with the BIs, but the historical sterility testing time of up to one week is gone." The last hurdle to providing the ultrafast service is getting the required documentation to the customer. "Electronic transmission of the material eliminates the time wasted by transfer of hard copy via conventional mail and allows the customer to realize the time-saving potential of EO Express."
Originally designed to compete with other EtO contract sterilizers, the new process is being touted by Cosmed as the technology with the fastest turnaround time of all types, even irradiation sterilization.
WAREHOUSING AND TRANSPORTATION
Transportation costs may exceed the actual cost of sterilization and sometimes prompt a customer to defect to a closer contractor. Reducing these costs, therefore, is an important goal of contract sterilizers.
One approach is to maximize loading efficiency. "Many customers ship us pallets that are 60 in. tall in a truck that will take 105-in. pallets, and that's not good utilization of shipping," STERIS/Isomedix's Carestio points out. In Minneapolis, where there is a high concentration of small medical device manufacturers, STERIS/Isomedix runs a truck route to pick up products for sterilization because the customers don't have full truckloads.
Titan Scan Corp. (San Diego), which sells its turnkey SureBeam electron-beam sterilization systems for in-house installations and also does contract electron-beam medical device sterilization at its San Diego, Denver, and Lima, OH, facilities, is also seeking out mini medical corridors around the world. If a company doesn't have the volume to justify the investment in an in-house electron-beam system, Titan Scan encourages them to ask, "What can I do in a partnering or strategic alliance relationship with Titan?" says Ken Carlson, vice president of sales and marketing. "They may have enough volume in the area to attract us to build a facility close or adjacent and sell services to them and others."
Most contract sterilizers will now ship sterilized product directly to a customer's distribution facilities, if desired. Some, including STERIS/Isomedix, even do case-level distribution and will also help a customer build shipments. For instance, a customer may send several different product lines to be processed and then ask us "to send two pallets of Product X, three pallets of Product Y, and seven pallets of Product Z to each of four different distribution centers; and we will load those trucks to those specifications," Carestio explains. "That is value added for them because they are not sending partial truckloads."
As another value-added option, STERIS/Isomedix will install a customer's shipping software on a terminal within the sterilization facility and act as a distribution liaison. In these cases, Carestio says, "the terminal provides a direct link directly into the customer's inventory system. Essentially one of the STERIS/Isomedix facilities appears as one of their warehouses on their system, and they just see us as an extension of their manufacturing or the beginning of their distribution chain."
The IBA Medical Sterilization Group has just completed validation of a new software system, called a manufacturing execution system or an electronic record and signature system, which will make this type of service available to all their customers. Customers are able to log on to the system via an Internet connection and see the location of their products as those products travel through the contract sterilization facility. They can then issue precise shipping instructions.
The system will also standardize all of the company's facilities. "The worst thing I remember from my days as a customer," Schullo says, "is when you deal with two or three of a supplier's facilities, and from each facility you get different paperwork, a different form in a different format, different instructions, different invoices. It's really frustrating." With the new system, IBA's operations will be "seamless—no matter where you go the total quality and service is the same," he says.
The system is debuting at IBA's Willowbrook, IL, facility. The company's six other U.S. EtO facilities will be next, and the gamma sites, Schullo predicts, will have it sometime during the next 12 months.
Another way many manufacturers save on transportation costs is to sterilize en route at a contract sterilizer located between their manufacturing facilities and their distribution centers. Jon Seulean, manager of Cobe Sterilization Services (Denver), describes just such a situation. Cobe Sterilization Services is a division of Gambro, a healthcare provider with more than 17,000 employees serving the transfusion medicine, therapeutic apheresis, stem cell therapy, renal care products and services, and cardiopulmonary care markets. Several years ago, the company moved the manufacturing of its hemodialysis product to Tijuana. They transported the product through San Diego to Denver, where it was sterilized at Cobe's in-house gamma irradiator, and then reshipped to distribution sites. The firm recently decided that IBA will process the product at its Corona, CA, facility and then ship it to Cobe's distribution centers, one of which is in California. "It costs about $1500 a truckload just one way from Tijuana to Denver," Seulean explains, "compared with only a couple hundred from Tijuana to Corona. Reducing transportation costs by as much as $1000 per truckload is significant."
Companies that want to take advantage of the efficiencies of having the contract sterilizer ship their product may need to design their packaging with that option in mind. They must design their final packs in such a way that the final assembly can be sterilized. Butchee notes that his company, in contrast, would not be able to ask for drop shipment from the sterilizer because they perform a finishing packaging process after the product returns from the sterilizer.
"When we set up the process 12 years ago, contract sterilization was still new, for this area anyway. We set it up that way so we could have another look-see at the product to make sure that no damage was done by the process of sterilizing the units," he admits.
CONTRACTOR QUALITY
Many medical device manufacturers are reassured by the vast number of audits contract sterilization facilities undergo. Schullo reports that in 1999, for example, IBA had more than 200 customer audits of its nine EtO facilities, in addition to FDA audits and international certified body audits for ISO 9000. "The audits have been very successful," he says. "With all those audits going on, I think that the confidence levels are there for most medical device companies."
Photos courtesy the IBA Medical Sterilization Group.
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