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Emory Establishes Center for Device Innovation

Originally Published MX March/April 2006

BUSINESS PLANNING & TECHNOLOGY DEVELOPMENT

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Harnessing Academic Innovation

Emory University's Woodruff Health Sciences Center (Atlanta) in January announced that it is establishing the Emory Center for Device Innovation (CDI), a new initiative that will prepare medical technology projects for outside investment, product development, and commercialization.

Emory reports the center will also guide promising projects through the proof-of-concept stage of development, as well as help Emory faculty protect their ideas as patentable intellectual property.

Guidant Stent Found to Infringe Medinol Patent

Last September, Boston Scientific Corp. (Natick, MA) ended a 10-year contentious relationship with Israeli stent manufacturer Medinol Ltd. (Tel Aviv, Israel) after paying $750 million to settle a long-standing patent dispute. But now, with its acquisition of Guidant Corp. (Indianapolis) a near certainty, Boston Scientific finds itself embroiled with Medinol yet again.

In late February, a federal court in the southern district of New York ruled that a coronary stent manufactured by Guidant infringes on a Medinol patent. Although many industry analysts say Medinol's case is not particularly strong, patent infringement cases in the coronary stent sector have historically been protracted, costly struggles.

If Medinol's claim holds up, the company is expected to seek royalty payments representing as much as 20% of all infringing stent sales. Neither Guidant nor Medinol issued a public comment on the dispute, but Paul Donovan, Boston Scientific's senior vice president for corporate communications said, “We intend to fight this vigorously.”

The dispute with Medinol is yet another fire on Boston Scientific's doorstep as it scrambles to gain shareholder and regulatory approval to close the Guidant deal while moving to resolve its manufacturing quality issues with FDA.

Declaring War on Wear in Pumps and Valves

Cover Story: Pumps & Valves

The small size of this valve by Parker Hannifin reduces the travel distance of moving parts.

Pumps and valves do vital work in many different medical devices and manufacturing operations. Of course, their work wears them down—and eventually wears them out. But in many cases, they're able to fend off wear and tear for many years and millions of cycles.

What's being done to extend the lives of these crucial components? Using innovative designs and hardy materials, manufacturers are equipping pumps and valves for lengthy battles against wear and tear. For their part, users are promoting component longevity by making the work that pumps and valves do less damaging and less stressful. And when they work together, manufacturers and users of pumps and valves can come up with long-lasting solutions for even the most wearing fluid- and air-moving problems.

Wear-Fighting Valve Designs

This valve, by I&J Fisnar Inc., applies seals to housings of medical devices. Designing valves with only one or two moving parts can reduce wear.

Ask valve manufacturers how they minimize product wear and you get a variety of answers. One technique is to shorten the travel distance of moving parts. Inside the miniature valves made by Parker Hannifin's Pneutronics Div. (Hollis, NH), parts usually move no more than 0.02 in., reports market development manager Mark Garland.

Another wear-reducing strategy is to use simple designs. For example, most of the dispensing valves made by I&J Fisnar Inc. (Fair Lawn, NJ) have only two or three moving parts, says Vladimir Siroky, president of the company. These products are primarily used in device manufacturing operations.

In addition, some valve makers try to minimize the number of parts that come in contact with the medium flowing through the valve. These wetted parts are particularly prone to wear, according to Jim Victoria, application development manager for EFD Inc. (Lincoln, RI), which also makes dispensing valves used in medical device manufacturing. In EFD's diaphragm valves, Victoria notes, only the diaphragm and sealing head come in contact with the fluid being dispensed.

Like these EFD valves, Parker Hannifin's Liquid X valve has only two wetted parts. Pneutronics designed this miniature valve so that the diaphragm protects the stainless-steel actuator from the medium. The diaphragm isolation design helps the valve last for 10 million cycles, according to Garland.

Some of EFD's valves include packings that separate the fluid and air chambers. Made of soft Teflon material, the packings form a tight seal around the piston to prevent leakage from one chamber to the other. Teflon is compatible with more chemicals than most plastics, Victoria adds, lessening the risk of deterioration when the material is exposed to fluids in dispensing operations.

Wear can also be minimized by a valve design featuring tight tolerances and carefully balanced loads, says Ralph Buck, electrofluidic systems product manager for The Lee Co., a valve and pump manufacturer in Westbrook, CT. Valves that use a lot of force to open and close can overcome high levels of friction, so the design does not have to be highly engineered, Buck explains. But valves wear faster when excessive force is used to drive the valve seat into
the elastomer seal. “It's like hitting a nail with a sledgehammer,” he says.

The Right Material

Electronically commutated dc motors by KNF Neuberger Inc. provide speed control, allowing the pumps to be brought up to speed slowly.

A key tool in the battle against wear is material selection. Manufacturers can use a variety of metals, plastics, and rubbers to make valve components. In part, the choice depends on which material holds up best when exposed to a particular medium. For example, Siroky notes, manufacturers might choose ultra-high-molecular-weight plastics for the diaphragms of valves used to dispense aggressive cyanoacrylates, or so-called crazy glues.

Or an application may involve anaerobic fluids, which crystallize or harden when they come in contact with metal ions. Valves used to dispense such fluids must have wetted parts made of plastic, Siroky says.

Then there are UV resins, which are used in the manufacture of a number of medical devices. According to Siroky, these resins cause a reaction if they contact aluminum, so they're often dispensed using valves with stainless-steel bodies.

Polycarbonate is a popular choice for many medical device components. But lipids take a toll on many polycarbonate formulations, warns Jim Pisula, vice president of marketing for Value Plastics Inc. (Fort Collins, CO), which makes plastic tubing connectors. So for applications involving lipids, valve manufacturers must be sure to use a lipid-resistant version of polycarbonate. Another alternative, Pisula notes, is to eschew polycarbonates in favor of acrylics or other materials characterized by native resistance to lipids.

For many valves, leakage is a common failure mode. Valve leakage can often be traced to the seal, says Buck. So to lengthen valve life, manufacturers can opt for a durable seal material. For example, they might select Viton rather than silicone.

Manufacturers can also boost seal durability with a coating. Halkey-Roberts Corp. (St. Petersburg, FL) makes valves that go into sterilizers for colonoscopes. These valves are exposed to peracetic acid, which makes silicone seals sticky and gummy over time, explains Lew Lecceardone, the company's vice president of medical marketing. So the seals are coated with a special oil that protects them from peracetic acid. This helps to keep the valves operating efficiently in sterilizers for years.

Some EFD valves also have coated components. For example, Victoria notes, the company reduces corrosion inside its spool valve by coating wetted parts with titanium. Similarly, Garland says, Pneutronics uses passivation treatments to prevent corrosion of stainless-steel valve components.

In addition to valves, some suppliers offer extras that help OEMs reduce wear in fluid- and air-carrying systems. For example, EFD provides feed lines and fittings made of materials that are compatible with customers' media. The company has also introduced a device that controls the temperature inside dispensing equipment to minimize fluctuation of fluid viscosity. According to Victoria, the ProcessMate 6500 reduces the frequency of manual valve adjustments to compensate for viscosity changes, thereby reducing valve damage and wear caused by operator handling of the components.

KNF Neuberger Inc. uses stainless-steel or aluminum heads to make corrosion-resistant pumps.

Pump Makers Battle Wear

Like valve manufacturers, pump makers use a variety of techniques to battle wear. Inside WOB-L pumps made by Rietschle Thomas (Sheboygan, WI), the longer the stroke, the more a pump's connecting rod will wobble. This makes the pump work harder, which increases wear and tear on the piston seal, explains David Droege, the company's miniature-products support manager. Most pumps manufactured at the firm's Sheboygan facility are custom made. So, depending on the application, the company could design a WOB-L pump with a shorter stroke length to reduce wear, Droege says.

At KNF Neuberger Inc., based in Trenton, NJ, pump diaphragms are designed using finite-element analysis. The computer program “helps us develop the most robust design possible,” says David Vanderbeck, the company's business development manager. For example, Vanderbeck says, the program showed designers where to add structural elements on the underside of a diaphragm to boost strength without too much of an effect on the flexibility of the component.

Reinforced diaphragms are also used in miniature pumps made by Parker Hannifin's T Squared Pumps unit (Fairfield, NJ). In some cases, the firm molds webbing or matting into rubber diaphragms to boost their resistance to tensile loads. In high-pressure applications, the reinforced elastomer diaphragms last longer than a standard diaphragm would, notes Len Prais, engineering manager at T Squared Pumps. But in low-pressure applications, he adds, a standard diaphragm might last just as long as a reinforced one and also operate more efficiently because it would produce less internal friction.

Besides reinforcing diaphragms when necessary, Prais and his colleagues try to eliminate restrictions in their pumps that cause parasitic losses. These losses can add loads to the diaphragm and other components, thereby shortening pump life. According to Prais, one way to reduce harmful restrictions is to use special valve designs that minimize backpressure inside the pumps.

In many cases, pump life can also be lengthened by effective cooling. This is true in oxygen concentrators that use Rietschle Thomas WOB-L pumps. Enclosed in a case, these WOB-L units are cooled by two fans, one on either side of the pump. Each application is different in how and where the pump is mounted, as well as in the amount of room available to move air around the pump. So Rietschle Thomas engineers work with each OEM to produce a cooling design that will maintain the proper ambient temperature around the pump, Droege says.

Rietschle Thomas can work with OEMs to design a pump, like this miniature diaphragm dc compressor, that will maintain the proper temperature to avoid wear.

Material Considerations

In addition, Droege notes, the company's engineers pay attention to the material used to make piston seals in the pumps. The seals include a Teflon substrate that can be supplemented with proprietary polymer materials that lessen wear and boost seal life.

To make pump heads, KNF uses a variety of materials, with the choice depending in part on the medium. Stainless steel is fine for many applications, but others might call for a plastic material. KNF has had good luck with Ryton, an expensive plastic that offers good chemical compatibility, Vanderbeck says.

According to Droege, heat generated by pumps produces moisture that will quickly degrade aluminum pump heads and valve plates. So many manufacturers treat these parts with dichromate. However, Teflon-impregnated parts last longer in high-humidity environments than those treated with dichromate, Droege explains. So sometimes the company impregnates metal components with Teflon. Some firms also use Teflon to help preserve pump diaphragms. For example, diaphragm pumps are used in diagnostic equipment that handles many different reagents. To prevent these reagents from attacking rubber diaphragms, Vanderbeck says, the elastomeric components can be coated with a protective Teflon layer.

The User's Role

Broadly speaking, there are two major factors that affect the life span of pumps and valves: how they're made and how they're used. No matter how well a component is made, its life will be short if users don't do their part to minimize wear and tear.

For starters, Victoria says, users should read all manuals and instructions that come with a component and follow the manufacturer's recommendations. This may seem obvious, but many users simply don't do it, Victoria maintains. Failing to follow instructions “is probably one of the major reasons for wear and tear in our equipment,” he says. In many cases, he notes, rapid and excessive wear is caused by easily avoidable mistakes such as incorrect setup and inappropriate use.
Some users who don't read and follow instructions make disastrous mistakes even when they are trying to do the right thing. For instance, Victoria points to people who try to clean a valve used to dispense cyanoacrylate by flushing it with water. Instead of cleaning the valve, Victoria says, flushing with water causes the glue to harden inside the component.

Although improper maintenance can lead to disaster, proper maintenance can be crucial in extending component life. In silicone-dispensing systems, for example, small amounts of material may get cured inside a valve. Eventually, Siroky says, this buildup of cured material will impede the action of the valve. So he recommends that users periodically take the valve apart, clean it, and make sure all the components are moving freely before reassembling it.

As for pneumatic systems, air containing rust or dirt particles will eventually break down valve seals. To prevent such problems, Siroky recommends filtration of air flowing into pneumatic components. Filters should be installed at several points along a pneumatic line, including the point just before air flows into a valve.

According to Garland, filtration is particularly important in systems that include miniature valves because of the vulnerability of the small components and sealing surfaces in these valves. Generally speaking, Pneutronics recommends a minimum 40-µm filtration level at the source. But Garland says that a micron rating of 10 or less is even better at reducing the risk of contamination, which is one of the main causes of valve failure. On the downside, he notes, a 10-µm filter may have to be significantly larger than its 40-µm counterpart to prevent unacceptable flow restriction in a system.

In liquid-moving systems, debris can get trapped between the valve seat and seal, Buck says. To prevent this and the resulting valve leakage, Lee provides last-chance safety screens that filter liquids flowing into valve components. Besides harming valves, Buck says, liquid-borne debris can scratch the seal or piston inside a pump, causing leakage. So users must also filter the liquid flowing into pumps. The filters must be changed regularly to prevent dirt buildup on them that will add to the load on the pump, Vanderbeck notes.

Another way pump users can reduce wear and tear is to pay careful attention to mounting. For example, Droege says, some Rietschle Thomas pumps should only be mounted in a horizontal plane. Vertical mounting of these pumps adversely affects the motion of the internal components, which can result in damage that will shorten pump life.

In many cases, pumps are mounted on shock mounts that lessen the vibration of the unit. According to Droege, the type of shock mounts a user selects can have a major effect on how much a pump will shake while in operation. So Rietschle Thomas helps customers through the process of determining which shock mounts are right for their applications.

System Issues

Temperature control units, like the ProcessMate from EFD Inc., can reduce valve wear and tear by keeping a material at optimum dispensing temperature.

To minimize pump and valve wear and extend component life, users should look beyond the components themselves and consider other issues. For instance, what type of fluid is in the system? If it's prone to crystallization, it's important not to let the system dry out, Buck warns. Drying can result in the formation of crystals that lodge in components and damage them. In pinch valves, for example, crystals can make small cuts in the rubber, creating weak spots that will be prone to failure, Buck says.

To prevent damaging crystallization, Buck recommends that OEMs either keep fluids in these systems at all times or flush them out with water or some kind of cleaning solution following each use. Systems can remain dry once the crystal-precipitating liquids are cleaned out of them, he says. But don't make the mistake of trying to clean out a system with air. This will evaporate the liquid, but leave behind the
mischief-making crystals.

Another issue to consider is how an air- or fluid-moving system is powered. According to Vanderbeck, one option worth considering is voltage shaping. As the name implies, this involves shaping the profile of the voltage applied to the motor. Voltage shaping requires a logic-control device that varies the supplied voltage, which in turn changes the speed of the pump.

Instead of turning on the system voltage all at once, Vanderbeck notes, voltage shaping allows users to ramp up the voltage from zero to a maximum operating level, so pumps can be brought up to speed slowly. Voltage shaping also allows control of pump speed so that output matches the requirements of the system in a particular situation. “If you don't need the full output of the pump, you can slow it down so you're just putting out what the system requires—no more,” he explains.

Since the pump isn't constantly running at full speed, the pump and other components are subjected to less pressure and flow, thereby reducing wear and tear throughout the system. As a result, Vanderbeck says, voltage shaping can result in a “tremendous increase” in component life.

William Leventon is a freelance writer who contributes frequently to MD&DI.

Copyright ©2006 Medical Device & Diagnostic Industry

FDA Unable to Regulate Devices Sold on Auction Sites

NewsTrends

FDA has no way to track or regulate devices sold on eBay or similar auction sites.
Although selling devices over the Internet is common, there is often no way to ensure that the buyer is qualified to use the product or that the seller is offering a legitimate product. Safety and liability issues can occur with such transactions. Some of these issues were raised in a December Washington Post article. The article focused on refurbished single-use devices (SUDs) for sale on eBay.

What can device manufacturers do to prevent unauthorized Internet sales? Apparently not much, other than alert FDA.

“There's a real concern on behalf of many of our members,” says Mark Leahey, executive director of the Medical Device Manufacturers Association. “The underlying patient safety issue has been compounded now that we've found out that these products are being sold online or at sites like eBay. Once the product is out of the manufacturers' [hands], they can't guarantee that when it gets to the hospital, it hasn't been doctored, or that something has happened to it.”

Leahey also questioned the trustworthiness of some products sold on eBay, as well as how the site validates who buys products that require a prescription. “When dealing with healthcare, there has to be a hypersensitivity. EBay is a great platform for certain transactions, but certainly I don't think it is appropriate for medical devices.”

According to Larry Spears, FDA cannot and does not have a way of tracking or regulating devices sold on eBay or similar auction sites. “EBay isn't subject to our requirements, because it is only a middleman,” says Spears. “We have no authority to regulate eBay.” The Web site doesn't take ownership of products, nor does it transfer products, he explains. Spears is deputy director for regulatory affairs in CDRH's Office of Compliance.

FDA has been working with eBay on screening advertisements before they are posted or on having inappropriate ones removed after they appear. FDA also tries to monitor high-risk products, such as those that require a prescription or are implanted in the body.

“If we see [advertisements] once they've gone up and get them taken down, that's about the best that we can do,” says Spears. He adds that pursuing an individual would be nearly an “impossible task.”

“We typically regulate companies. If it's a company that's selling its products on eBay, we can follow up with it,” says Spears. “With individuals, it's very hard to track down a person who is selling out of his or her home. We're just not going to do that—it's not the way we operate.”

Ultimately, the seller is held responsible. “But the question is, are we going to be able to find out who the sellers are?” asks Spears. “And depending on who they are, we have to decide whether it's worth going after them. We have to prioritize. If we're talking about a high-risk device, then clearly we're going to be interested. If it's a pair of clamps that one person is selling, we may not.”

If a product is sold illegally, the seller is subject to the same legal requirements as any manufacturer. “That's a violation, and as a company, they would be subject to a warning letter,” says Spears. “For an individual selling one product that doesn't have a 510(k) but should, we're not likely to try to find out who he or she is.” Spears says having the advertisement removed is usually enough action. So far, eBay has been responsive in removing ads that FDA has indicated were inappropriate.

Some sellers place a disclaimer in their eBay ads. They usually state that the items are subject to FDA regulation, and that the seller will verify that the buyer is authorized to use the item before it is shipped.

“It would be our preference to not have [any devices sold] on eBay, but eBay isn't going to go that far,” says Spears. “We've just tried to work out the best agreement we can with them, recognizing that they don't have to do any of this. They could put us in a situation where they say, ‘FDA, you just go after everyone if you want; we're not going to do anything.'”
Copyright ©2006 Medical Device & Diagnostic Industry

IBS to Manufacture Safe Syringes

OUTSOURCING NEWS

Legislation in the United States requires healthcare employers to select safer needle devices and to involve staff in identifying those devices that meet the safety requirements.

Integrated BioSciences Inc. (IBS), based in Lewisberry, PA, has signed two memorandums of understanding (MOUs) with syringe engineering company Unilife Medical Solutions (Sydney, Australia). The MOUs enable IBS to manufacture syringes that are in compliance with this legislation.

Unilife has created a platform technology for syringes called Unitract, which is designed to reduce the risk of needlestick injury and to prevent reuse. Ed Paukovits, president of IBS, said in a release, “I am confident that the Unitract technology has significant potential to help revolutionize the global syringe market.”

One MOU states that IBS will establish the first automated assembly line for the Unitract Clinical line of safety syringes. The Unitract Clinical syringes feature an automatic retraction mechanism that controls retraction speed of the needle. An interchangeable needlemount allows for the use of common luer-slip and luer-lock needle products.

IBS will be the exclusive manufacturer of the clinical syringes in the United States. West Pharmaceuticals has agreed to provide assistance with design and development. Alan Shortall, chief executive officer of Unilife, said, “Unilife recognizes that the preexisting relationship between IBS and West Pharmaceutical Services adds great value to our capacity to rapidly commercialize the Unitract portfolio of safety syringes.” Production is scheduled to begin in late 2006, once IBS has completed and validated several Class 8 cleanrooms.

The second MOU establishes that IBS will create a production center for the Unitract Safe Syringe at its headquarters in North America. In exchange, IBS will contribute 50% of all capital expenditure associated with the development of the assembly line. The outsourcing company will be the sole manufacturer to North American markets, as well as to China, the UK, and other markets as they emerge. Unilife has already received orders for 30 million units in China and the UK. As with the clinical syringes, production of the Safe Syringe will begin in late 2006.

IBS is a full-service contract manufacturer with ISO 9001:2000 certification. The company is CGMP compliant and FDA registered for Class I and Class II devices.

Copyright ©2006 Medical Device & Diagnostic Industry

Editorial Advisory Board

Originally Published MX March/April 2006

EDITORIAL ADVISORY BOARD

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Business Savvy

Throughout 2006, MX will be announcing members of an editorial advisory board that will help to guide the overall direction and content of the publication. Members of the board will include a variety of experts drawn from industry, government, finance, legal affairs, and academic organizations, each with specialized expertise in the business of medical technology. In addition to the members named in the accompanying article, the previously announced councils are listed below.

Information Technologies Reimbursement Affairs
   
Janet Dillione
Chief Operating Officer,
Healthcare Information Technology,
Siemens Medical Solutions USA
Robin R. Bostic
Vice President,
Reimbursement,
Thoratec Corp.
   
Tim Gee
Principal,
Medical Connectivity Consulting
Ted R. Manen, JD
Member,
Epstein Becker & Green
   
Harvey Rudolph, PhD
Global Program Manager,
Medical Devices,
Underwriters Laboratories Inc.
Jo Ellen F. Slurzberg
Vice President,
Reimbursement and Health Policy,
Almyra Inc.

Copyright ©2006 MX

Milestones

Originally Published MX March/April 2006

MILESTONES

St. Jude Medical Inc. (St. Paul, MN) has completed its acquisition of privately held Savacor Inc. (Los Angeles). The acquisition, completed for an initial cash payment of $50 million and undisclosed milestone terms, complements St. Jude's development efforts in managing congestive heart failure. Savacor has heart failure diagnostic and therapy guidance products and technologies under development and in clinical evaluation, reports St. Jude.

As part of an ongoing restructuring process, Medical International Technology Inc. (Denver), which specializes in needle-free injectors for both humans and animals, is forming two divisions: a human medical technology division and an animal medical technology division. Concurrently, the company is proceeding with its acquisition of ScanView (Montreal), a manufacturer of portable ultrasound technology that also has animal and human applications.

Michigan Economic Initiative Targets Medtech Manufacturers

Saginaw Future Inc., a Michigan-based economic development agency, has launched a medical devices and technology initiative designed to attract, retain, and assist medical device, diagnostic, and life sciences firms in the central region of the state. To date, the agency has raised nearly $700,000 for the initiative and is applying for a $2 million grant from a state fund designed to promote job growth and new investment in the state.

Sevrain

Sevrain: Guiding Michigan's medtech future.

Christophe Sevrain, former head of Delphi Medical Systems Corp. (Troy, MI), has been contracted to lead the new initiative. “Pharmaceuticals, medical devices, instrumentation, diagnostics, and biotech research are growing faster in Michigan than in any other state,” he says. “The Saginaw Valley's role will help keep that momentum going.”

Last fall, Saginaw Future received $100,000 in grants to develop strategy recommendations for regional development and job growth in the medical device and diagnostics industry. The funding was provided by the Michigan Economic Development Corp., Saginaw Community Foundation, and Saginaw County Revolving Loan Fund. Working with a medical device and technology committee, which included representatives from regional medical device companies, Saginaw Future formulated a strategy for developing start-up and corporate spinout medtech companies, as well as supporting existing companies transitioning to medical manufacturing. The initiative will target the regional area of Saginaw, Bay, and Midland counties.

According to Sevrain, Michigan's historically strong presence in the automotive industry has built the infrastructure necessary to support medical device companies. “The Saginaw region understands advanced manufacturing and has a highly skilled workforce in place, which are key advantages to transitioning into medical manufacturing.”

Crary

Crary: Sparking change in mid-Michigan.

JoAnn Crary, president of Saginaw Future, says Sevrain's involvement in the initiative represents a significant opportunity for the mid-Michigan region. “Sevrain is an agent of change with extensive experience in start-up companies, which is what we will be creating with the initiative.”

Steam: Uses and Challenges for Device Sterilization

Table I. (Click to See Full Table) A sampling of time-temperature relationships for steam sterilization.
The use of steam for sterilization is fairly widespread; however, steam is seldom used as a sterilization method by the medical device industry. Most disposable plastic devices are terminally sterilized by ethylene oxide (EtO) or radiation. These processes provide low temperatures that most plastics can tolerate. Steam, however, is the most commonly used sterilization method in many healthcare facilities.

Despite its use of high temperatures, steam is a simple and inexpensive sterilization method with many benefits. It yields little waste (entropy is its only by-product). It is also efficacious in terms of its ability to kill microbial organisms.

With the growing complexity of medical device and drug combinations, it is essential to consider steam. These combination devices, such as drugs in syringes, drugs on catheters, and drug-eluting stents, often require steam sterilization because EtO cannot sterilize liquids and irradiation breaks down many drug compounds.

Risks and Challenges

Steam sterilization has long been used in hospitals as well as in the pharmaceutical, aseptic processing, and food industries. In many ways, it has been a victim of its own successes. For example, steam is most often characterized by its overkill. It uses extremely high temperatures to inactivate highly resistant nonpathogenic thermophile spores and, more recently, extremely resistant prions, that other sterilization methods cannot destroy. Its simplicity and low capital cost make it an inexpensive, attractive, and viable sterilization method. Typical steam sterilization equipment costs less than one-third as much as an EtO chamber system and controller. It costs less than one-fourth as much as gamma or E-beam equipment and facilities.

Sterilization exposure times can range from as short as 3 minutes at 134°C to as long as 3 hours at 101°–111°C, depending upon the bioburden (see Table I). Hospitals use steam at 134°C for 3 minutes for flash sterilization in emergency situations and 121°C for 15 minutes on a routine basis.

Design Considerations for Steam

Table II. (Click to See Full Table) A sampling of time-temperature relationships for steam sterilization.

In order to consider steam as a sterilization method, manufacturers must account for the influence and effects of temperature when they are designing devices (see Tables II and III). As devices become more complicated and sophisticated, there is an urgent need for plastics that are more heat stable. There is also a need for a reasonable bioburden approach without concern for thermophiles, thermotolerant spores, and anaerobes.

If a bioburden approach were applied to steam sterilization, as it is toward radiation methods (without looking at thermophiles, thermotolerant spores, and anaerobes), low-temperature steam (e.g., 90°–100°C) would likely be sufficient to achieve 10–6 sterility assurance for ultraclean (low bioburden), environmentally controlled manufactured devices. With compatible adjuncts (e.g., pH <4.5, formaldehyde), steam cycles could be as low as 65°–75°C. A combination of steam (for heating) and dry heat (for inactivation) may provide another means of effectively sterilizing materials that are otherwise difficult to sterilize.

Table III. (Click to See Full Table) Materials that can be sterilized using dry heat.

The number of healthcare products that can be steam sterilized has always been high. Healthcare products that can be steam sterilized include drugs, fluids, surgical instruments, metal containers, implantables, and reusables. By contrast, the use of steam for presterilizing medical devices or for sterilizing disposables or devices for use in controlled environments is relatively small compared with EtO and radiation methods. Steam sterilization, however, is being used more frequently to sterilize combination products. Steam is sometimes the only means to effectively terminally sterilize combination devices without adversely affecting the drugs incorporated into them.

Processing and Materials

Steam sterilization is generally carried out at 121°C (250°F) for 15 minutes or at 134°C for 3–4 minutes. Temperatures can be reduced to 115°C, and even as low as 105°C, depending upon the bioburden, integrity, heat resistance, and characteristics of the material being sterilized. Low-temperature steam processes (65°–80°C) have been used (e.g., steam-formaldehyde); however, other combinations could also be used. Now that ethylene glycol has been deemed no longer a significant toxic residue, a combination of steam and EtO is an option for sterilization of pyronema domestication on cotton sponges. Steam-propylene oxide, which is less effective and less toxic, should also be considered. Although steam-formaldehyde is not used in the United States because of safety concerns, it is used in Europe, India, and elsewhere.

Steam (water vapor) is a ubiquitous compound. Steam delivers high heat condensation, and it is an activating agent. Before a dormant spore can begin germination and outgrowth, it must be activated. However, at higher temperatures, steam becomes sporicidal. Sterilization, by definition, destroys or eliminates resistant microbes, including bacterial spores such as anthrax.

More-resistant microorganisms (e.g., prions) cannot be eliminated using most standard methods. Extended and high-steam sterilization, however, can at least reduce the effectiveness of these organisms. Using the classical definition of sterilization, it is an absolute criterion. A method has to be capable of destroying or eliminating all forms of life. In practice, however, sterilization is best defined as a process that is capable of delivering a certain probability that an exposed or treated product or material is free from viable microorganisms, including resistant microbial spores, such as Bacillus anthracis and smallpox, and prions.

Limitations

No sterilization method sterilizes all healthcare products and materials without some damage or destruction.

Consequently, sterilization methods must be selected after much consideration, evaluation, and review of their parameters and effects.

Heat, for example, can damage some materials. It can melt acrylics and styrene, distort PVC, and corrode some metals. A product that is wet after steam sterilization can also be a problem. Moisture also can adversely affect electronics and can cloud some materials or leave water mark stains on them. Wet products or packages can be a source for recontamination. To alleviate issues caused by moisture, changes to the loading and processing procedures may be needed or a drying step may be required to remove moisture and dry the product.

Sterilization agents that kill all microorganisms are not without complications and limitations. Heat can seriously deform, melt, or degrade parts. Radiation can alter, cross-link, deteriorate, discolor, offgas, and damage some materials. Chemical sterilants can leave toxic residues. Many sterilization methods may not penetrate certain plastics and mated surfaces. Steam is the only means of sterilizing prions with high-intensity temperature. It is a viable option for sterilizing and decontaminating neurosurgery and ophthalmic instruments, for example.

Government Use of Sterilization

More than three decades ago, the U.S. Department of Defense (DoD) took on the task of improving the war against germs with improved sterilizers for its field hospital units. Originally, the military used steam autoclave systems. For the DoD evaluation, the initial principal candidates evaluated were steam, steam-EtO, steam-formaldehyde, and electron-beam (E-beam) irradiation. Steam-EtO processes have been used for sterilization of cotton sponges and salt-encrusted spores.

In 2003, large x-ray machines were used to eliminate possible anthrax germs sent through the U.S. mail. X-ray systems, however, may not be effective against small viruses or prions. These machines are sufficient for treating paper and cellulose materials, but their ionizing irradiation can degrade materials and thus possibly start fires. In addition, they may be unable to inactivate some small germ viruses. X-ray irradiation can destroy drugs and high-tech electronics. It also produces diminutive toxic offgassings, and thus poststerilization aeration of the mail was required.

The Future of Steam

For combination products, steam or steam combined with other methods should be considered. For example, dialyzers can be steam sterilized in place on carousels and released via process control or parametric release on a routine basis. Dialyzers can also be sterilized with water at high temperatures. Some sutures can be steam sterilized, and some polypropylene films and Tyvek (spunbonded polyolefin) packages can be autoclaved. Some plastic containers and syringes that contain liquids can also be steam sterilized. These include containers and syringes made from materials such as high-density polyethylene, polyvinyl chloride (PVC), and polyallomer (copolymer of propylene and polyethylene). Items such as syringes, catheters, or drug-coated stents can be steam sterilized at low temperatures (i.e., <121°C).

Improvements to plastics, such as copolymerization and the addition of heat stabilizers, are making them more suitable for steam sterilization. The reduction of sterilization temperatures also helps make plastics more suitable for steam. The consideration of steam sterilization is also important in the context of developments in sterilization technology. Improvements in computer controls, microprocessors, monitoring devices, biochemical and chemical indicators, and the integration of lethality for parametric release all affect the viability of steam sterilization. Because of environmental considerations, some contract facilities in Europe are replacing EtO sterilizers with autoclaves as an acceptable alternative.

A Look at Dry Heat

Dry heat processes cannot produce heat as effectively as steam methods can. However, dry heat at lower temperatures has been found to be effective for materials and electronics that cannot be sterilized using steam or irradiation (see Table III). Given that steam can heat 12 times faster than dry heat, steam can be used to heat packaged products, which can then be sterilized with dry heat. Dry heat can sterilize electrical components without damaging them, and it can sterilize metals without producing corrosion.

Given sufficient time, dry heat can penetrate surfaces that steam and chemicals cannot. Considering the EtO process overall—including preconditioning, sterilization, and poststerilization aeration—dry heat times of 4–7 days would be equivalent to the overall EtO process release. Sterilization at lower temperatures (e.g., 105°–135°C) allows even more materials (polypropylene, high-density polyethylene, polysulfone, etc.) and items (instruments, nonaqueous embolics, etc.) to be sterilized by dry heat.

There are many materials that can be damaged by low-temperature dry heat, including acrylonitrile butadiene styrene, acrylics, styrene, polyethylene, and PVC. However, unlike radiation, dry heat is a possible option for heating materials such as acetal, polypropylene, and Teflon.

Polyurethane can be hydrolytically attacked by steam but not by low-temperature dry heat.

Dry heat processing uses no other agent (e.g., steam or chemical humidification) as a means of sterilization. Therefore, it should be a good candidate for process control and parametric release. The same principles of calculating lethality by steam sterilization apply to dry heat.

The combination of steam and dry heat may provide a means to effectively sterilize products that might not otherwise be sterilizable by either method alone. And, if a product might be contacted by both moist and dry heat, it may be beneficial to combine both methods in sequence. Using steam followed by dry heat would enable the dry heat to dry the load after the moist heat had destroyed most microorganisms. Spores resistant to moist heat are not typically resistant to dry heat and vice versa, so some sterilization may occur with time in dry heat after steam sterilization.

Conclusion

While steam has rarely been used in the medical device industry, many plastic devices sterilized by EtO and radiation may be compatible with lower-temperature steam. Many factors are pointing to steam as a viable alternative to the more-traditional methods of EtO and E-beam. The continuing development of combination products and increasing microbial challenges (e.g., prions) are two of the biggest factors.


References
1. Wayne Rogers, Sterilization of Polymer Healthcare Products (Shrewsbury, UK: Rapra Technology Ltd., 2005), 97–134, 244, 259.
Bibliography
Hancock, Charles et al. “Steam Sterilization,” in Central Service Technical Manual, ed. C Fluke et al. Chicago: International Association of Healthcare Central Service Material Management, 1994.

Joslyn, Larry. “Sterilization by Heat,” in Disinfection, Sterilization, and Preservation, ed. Seymour Block, 5th ed., 669–728. Philadelphia: Lippincott Williams & Wilkins, 2001.

Perkins, John. Principles and Methods of Sterilization in Health Science. Springfield, IL: Charles Thomas, 1970.

Pflug, Irving et al. “Principles of Thermal Destruction of Microorganisms,” in Disinfection, Sterilization, and Preservation, ed. Seymour Block, 5th ed., 662–663. Philadelphia: Lippincott Williams & Wilkins, 2001.

Validation of Steam Sterilization Cycles, Technical Monograph #1. Philadelphia: Parenteral Drug Association, 1978.

Wayne Rogers is a sterilization consultant based in Temecula, CA, and can be e-mailed at roger-wayne1@msn.com.

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