SPECIAL REPORT
The Case for In-House Sterilization
Manufacturers who bring sterilization on-site can benefit from increased flexibility and process control as well as accelerated turnaround time.
Norbert Sparrow
The development of smaller, more-affordable sterilization systems and the emergence of new technologies that use hydrogen peroxide gas or pulsed light to kill microorganisms are prompting some device manufacturers to reconsider in-house sterilization. Taking control of a key manufacturing process is one motivation. But according to many suppliers of sterilization equipment, the focus on just-in-time (JIT) production and delivery is an equally persuasive argument for bringing sterilization on-site.
"Manufacturing is conducted within a JIT framework," says Reinhard Kowatsch of Advanced Sterilization Products, J&J Medical GmbH (Norderstedt, Germany). "From the reception of raw materials to production to shipment of the finished product, everything is done according to a JIT philosophy. But then everything comes to a halt, because you need to have three pallets before your contract sterilizer can do a run. Companies put all these resources into speeding up production and scheduling JIT deliveries, but what's the point if your product is tied up for 10 days at the contract sterilization facility?" he asks.
Flexibility is another key benefit provided by in-house sterilization systems that is especially useful for manufacturers of custom devices. "Someone making a custom range of orthopaedic products," says Kowatsch, "can process different batches as required. There's no waiting around to fill a chamber—you are truly operating with a JIT philosophy."
It's all about time, and therefore it's all about money. When weighing the benefits of moving sterilization to the production facility, it's vital to look at the total cost, not just the direct cost, stresses Ken Carlson, vice president of sales and marketing at Titan Scan (San Diego, CA, USA), which supplies E-beam systems to device manufacturers worldwide. "That includes the value of the inventory that is lost in the supply chain as the product is moved around," says Carlson. "If you use a contract sterilizer, you have to ship it out and you may not get it back for 10 days. That's a huge hit to your inventory costs," he says. And when you are storing product, adds Kowatsch, you are in fact storing money.
The relocation of manufacturing sites to regions with lower labour costs may also have an impact on the use of in-house sterilization, says Carlson. "As companies set up facilities in the Czech Republic, Spain, or Portugal, they often find that there are no contract sterilizers nearby. So the options become, do I ship this product in containers, perhaps over water, to have it sterilized, or do I look at an in-house system?" asks Carlson.
When all is said and done, though, many device manufacturers will recoil at the purchase price of most in-house sterilization systems. Assuredly, it is not for everyone and contract sterilizers need not fear a mass exodus. According to one traditional rule of thumb, manufacturers who annually process a million cubic feet of product or who spend $1 million on contract services would be well advised to investigate in-house sterilization. This yardstick remains largely accurate, says Daniel Levesque, sales manager for Europe at MDS Nordion, a supplier of gamma systems, although smaller systems have brought the cost of entry down. "Tote irradiators, which can accommodate lower volumes than pallet irradiators, are a feasible investment for a company processing as little as
There are a number of benefits and limitations to each of the sterilization methods described below. To determine the one that is best suited to your particular product, you should be prepared to discuss the types of materials and packaging that need to be processed, product geometries, production volumes, and desired turnaround time. At the end of the day, you may well decide that contract sterilization remains the best
Gamma
Gamma rays can penetrate anything, making this technology suitable for the sterilization of parts with complex geometries and varying densities. It is also a fast process: product can be released for shipment the same day that it is sterilized. The installation cost of a gamma irradiation facility and maintenance expenses—the radioisotope cobalt 60 decays over time and must be periodically replaced—however, are considerable. In addition, the very notion of using radiation to sterilize products, although a known and safe technology, doesn't always sit well with people, a fact that many companies offering alternative sterilization methods tend to exploit. MDS Nordion (Kanata, ON, Canada; and Fleurus, Belgium) has been very active in educating users and the public at large on the safety of gamma sterilization as it is practiced today. In fact, says Levesque, gamma is ahead of the game when compared with the other leading sterilization method for medical devices. "I think that gamma is certainly perceived to be a safer process than EtO, where you are dealing with a gas that is explosive in nature," Levesque adds. The medical device industry has by and large accepted gamma sterilization, which has grown from three plants put into service by Ethicon Inc. in 1964 to more than 175 plants worldwide today.
Gamma sterilization can produce adverse effects in some materials. When exposed to cobalt 60, some materials exhibit embrittlement and discolouration, or they may produce noxious odours. Numerous materials have been and continue to be developed that eliminate or minimize these effects, however.
The cost of a gamma unit may decrease in the years ahead as manufacturers develop smaller systems. MDS Nordion is working on it, and Sterigenics International Inc. (Fremont, CA, USA) has developed the MiniCell, which processes product in batch sizes of approximately
EtO
Ethylene oxide (EtO) is a proven and effective technology that has been called the workhorse of medical device sterilization. Currently, approximately 50% of medical devices are sterilized by EtO gas. Many manufacturers favour this form of sterilization because it is relatively affordable and it does not degrade packaging materials. It also remains the only acceptable sterilization method for certain types of products. Environmental concerns and outgassing delays have tarnished its reputation, however. The discovery in the 1970s that the gas is carcinogenic, and restrictions placed on the use of Freon, which had been mixed with EtO to render the gas inert, have ratcheted up safety procedures and costs. Turnaround time, which can vary from 4 to 14 days, has also been a source of frustration for JIT-oriented manufacturers.
The latter point is being addressed by suppliers of EtO systems that incorporate the use of parametric release, statistical studies, and heated aeration to reduce turnaround time. Safety concerns are also being assuaged by automating EtO sterilizers to reduce the risk of exposure and minimize human error.
E-beam
E-beam systems use high-speed energy electrons as the sterilizing agent. The electrons are accelerated almost to the speed of light by means of a linear accelerator. They are scanned through the product, creating a variety of secondary particles that break the DNA chain of microorganisms on and within the package, rendering them incapable of reproduction.
One of the key advantages of E-beam over gamma radiation, notes Titan Scan's Carlson, is turnaround time. "EtO takes days, and gamma takes hours. E-beam takes about a half-hour to complete a cycle," says Carlson. Because E-beam requires less exposure time to be effective than gamma does, he adds, there is less potential for materials to become brittle or to show signs of discolouration.
E-beam is a continuous process, adds John Barnard, director of facilities at Acsion (Pinawa, MB, Canada), a firm that provides a range of E-beam consulting services. "If the system goes down, you don't lose a lot of product. With gamma or EtO, you can lose a roomful of product just from the misapplication of a batch process," says Barnard. And because E-beam uses electricity as its power source and generates no residual radiation, at the end of the day "you simply pull the plug and go home," he adds.
Nevertheless, E-beam accounts for only 10% at most of the industrial sterilization of medical devices. One reason for its limited success is its reputed poor penetration capability, although Barnard contends that this has been greatly exaggerated.
The availability of higher-voltage accelerators has made penetrability a non issue, he maintains. "There is a lot of agony over shadowing and so forth," he says, "but out of the thousands of products I've evaluated to determine their suitability for E-beam sterilization, I have only come across one or two that had to be sterilized by other means. The one thing I've found that gamma can tackle which E-beam can't is thick jars containing liquids. But even there, I'm working on a few
The cost of ownership, which reaches into the millions of dollars, has also had a damping effect on the in-house use of E-beam. Scanditronix Medical AB (Uppsala, Sweden) is hoping that smaller units it has designed to easily fit into device manufacturers' production lines will prompt companies to take a second look at E-beam.
"In the early 1990s, we came to the conclusion that there was limited demand for large E-beam systems," says marketing manager Lars Jordeby. "We began researching the development of smaller units suited for in-house use, and we are currently building a prototype." The 2.5-MeV BetaLine system comes with its own radiation shielding and can be moved from one location to another with a minimum of fuss.
Hydrogen Peroxide Gas Plasma
Sterrad sterilizers, developed and marketed by Advanced Sterilization Products, Johnson & Johnson Medical GmbH, kill microorganisms by injecting a hydrogen peroxide solution into a chamber. The vapour sterilizes those package and product surfaces it can reach, while an electromagnetic field creates a plasma cloud to generate free radicals that neutralize any remaining bacteria. The technology is aimed at manufacturers of low-volume, high-value medical devices.
"Current developments in medical technology favour high-technology products and advanced materials incorporating electronic devices that may be thermally sensitive," says Kowatsch, "so sterilization temperature is becoming a critical issue. As for gamma, there are a number of materials that are not suitable for that form of sterilization." Although the use of Sterrad in industrial environments is negligible at this point, Kowatsch believes it has a bright future within its defined application field.
Key benefits of the system, according to Kowatsch, are reduced cycle times—the recently introduced 200-L capacity chamber has a cycle time of two hours—and relatively inexpensive capital and operating costs.
The system is not suited for high-volume disposables, nor should it be used when water-based adhesive or absorbent materials are present. "Paper, linen, high-density foam, and other materials of that type will absorb the hydrogen peroxide vapour," says Kowatsch.
Pulsed-Light Systems
Using broad-spectrum pulsed light, PurePulse Technologies (San Diego, CA, USA) has developed a system that sterilizes medical products in less than a second without the use of heat, chemicals, or ionizing radiation. "Speed is the key advantage of the PureBright process," says vice president of worldwide sales and marketing Don Segal. The light lasts for a few hundredths of a second, and several pulses can be delivered each second. "The system is mounted directly on the production line," adds marketing director Roy Wallen, "providing a tremendous advantage in terms of throughput and speed." The technology is modular and can be adapted to a variety of production needs, notes Wallen. "We have a small system that allows small-batch sterilization or we can supply high-throughput units." But PureBright does have a blind spot.
"Pulsed light needs to see what it is supposed to sterilize," says Segal. "We can sterilize the surface of a pacemaker, but we can't get inside the pacemaker." The technology is suited for terminal sterilization of films, products manufactured by means of blow-fill-seal or form-fill-seal equipment, blister packs, and related items.
All Things Considered
The trend toward JIT processes and the development of more-flexible and less costly sterilization systems may stimulate some device manufacturers to explore moving sterilization processes in-house. While on-site sterilization is not a viable option for everyone, companies striving to remain competitive should continue to monitor developments within the sterilization industry. Severing ties with your contract sterilizer may not be the right decision today, but considering the rapid pace of technology, who knows what your options might be tomorrow?
