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Articles from 2003 In February

Medical Device Design: The State of the Art

Originally Published MDDI February 2003


The trends and technologies that are influencing the design of today's medical devices reflect an increased focus on 
the end-user and home healthcare.

PediSedate, an anesthesia delivery device developed by Design Continuum, relaxes children during medical procedures.

Stacey L. Bell

The way product developers approach medical device design is changing. “Five years ago, device manufacturers tended to focus on feasibility when thinking about product design,” says Tad Simons, director of healthcare and life sciences for IDEO (Palo Alto, CA). “Now, they're taking a more holistic view of product design—thinking about how the product looks, how it affects work flow, and how healthcare workers and patients use it.” Every product in every class is experiencing increased competition, so manufacturing is “a big issue for everybody,” Simons says. “Everybody wants to know: How do we create a product that stands out in the marketplace but is also cost-effective to produce?”

Making Products Faster, Cheaper

There's no denying that product development is expensive. It's estimated the concept and creation of a new device can reach upward of $500,000 before even one product is made and sold.

“The biggest challenge we see is that budgets are a lot tighter than they were two years ago,” says Doug Hiemstra, president of Hiemstra Product Development (San Francisco). “Across the board, medical device companies are looking for design firms to be more efficient and more cost-effective.” 

Take Respironics Corp., for example. Its CPAP nasal mask for sleep apnea sufferers had won a design award, but the high per-unit cost to manufacture the device's housing was prohibitive. When Respironics approached WhiteLight Design (Lawrenceville, GA) for help, the latter used miniaturization and parts consolidation techniques to reduce the manufacturing costs by more than 50%. 

“We created an injection-molded clamshell housing with many integrated internal mechanical features, including ribs, venting, noise management, and a convenient handle. The housing was redone into two pieces, rather than the previous four, and the size was reduced,” explains Willis Whiteside, president of WhiteLight Design. “We saved a lot on materials, and cut assembly time and cost. The new design significantly improved market adoption and thus, sales volume,” he adds.

Whiteside notes that CAD and rapid prototyping (RP) technologies were instrumental in the redesign. Together, these two technologies allow a company to see how a product fits together and works on-screen, and to create a working prototype in just a few days, before investing in high-cost tooling and manufacturing. Although both CAD and RP have been around for years, they have matured, helping to shorten development time and increase productivity and quality while improving a company's bottom line.

Medical devices are increasingly functional, stylish, and high-tech, like the CoolGard 3000 designed by Stuart Karten Design for Alsius Corp. (Irvine, CA).

For example, a few years ago, prototypes could be made from only a few resins. Today, additional resins and powdered metals are among the options, making possible more-durable component manufacturing. “Today's resins allow for much better controlled and defined features and have higher heat resistance, so manufacturers can do more functional testing and expose the parts to actual use conditions and harsher environments, such as sterilization cycles,” explains Len Czuba, president of Czuba Enterprises Inc. (Chicago). “The laser beams are also more sensitive. Therefore, the industry can make smaller and smaller parts with better-defined features and get better feedback on product functionality.”

Whiteside sees RP as a revolutionary technology that is here to stay. “Rapid prototyping technologies that create durable, usable parts could eventually render injection-molded parts obsolete,” he predicts, noting that for processing to be cost-effective, manufacturers typically need to produce at least 50,000 parts in an injection mold. Instead, he says, manufacturers are looking to lower-cost processes, including thermoforming or pressure forming, to consolidate parts and cut costs.

Czuba notes that a recent development in RP may speed the process and make it even less expensive. “One company is now taking a novel approach to RP,” Czuba says. “Rather than producing a part from a part file, Met-L-Flo makes a mold. So instead of creating an aluminum mold later, they are saving a step and creating a mold that can then produce parts by injection molding—often using the actual resin that will be used for the final product.” He points out that this capability also allows for better part definition and more-direct design evaluations.

CAD also may see a new, important iteration in the next year. Cesaroni Design Associates Inc. (Glenview, IL) is developing a three-dimensional digital man (think of the animated Shrek character) to test products in three dimensions. “We're creating digital images of anatomically different people that we can download on-screen. We then use them to locate potential problems with product concepts before we give a file to the model shop to produce a prototype,” says Bill Cesaroni, president of the design firm. One continual drawback of the design process, he says, is finding that a product concept doesn't work for some reason once a person is factored into the equation. “That's why we're trying to integrate digital users into the design stage. If we are designing a therapy or fitness product, we want to be able to watch how our ErgoMan's muscles are flexing as the product is working.”

Although 2-D users are already incorporated into current software offerings, Cesaroni says he wants “a Superman.” Two-dimensional adaptations move stiffly and are very limited, he explains, and designing and building a prototype is expensive. “Real people are the ultimate test. If we can test a new product on a digital person before we make even the first prototype, we will weed out 90% of problems and save a lot of time and money in the end.”

Work Flow Matters

Aspect Medical Systems's A-2000 BIS Monitor features a new enclosure that can be mounted on a pole with other equipment.

While device companies are taking a closer look at costs and speed in manufacturing, another of their concerns is making certain that users, primarily healthcare institutions and professionals, literally buy in to a device. It's well-known that the healthcare system is strained. Worker shortages are resulting in longer, busier workdays for those in the sector, and patient loads are increasing as the population ages—innovative medical device manufacturers are keeping these facts in mind as they design products.

A redesign project often meets several goals, improved work flow included. When IDEO redesigned the manufacturing process for the Dermagraft dermal skin product, manufactured by Advanced Tissue Sciences Inc., the result streamlined costs and made physicians' lives easier. 

“In the past, designers may have looked simply at how to get a product to work,” explains IDEO's Simons. “Today, we're looking at the process, at work flow, and asking, ‘How can I shape this product to make it easier or faster for the physician to use?'”

Dermagraft previously was grown in 4 ¥ 6-in. sheets that required manual seeding of the cells, rotation of the large growth containers, and injection of a growth culture. The redesigned growth environment, on the other hand, features a bioreactor system with stackable growth manifolds. Each manifold holds eight 2 ¥ 3-in. pouches containing matrices that can be automatically seeded, rotated, and fed. When the matrices have grown to a size that fits 80% of foot ulcers, each pouch is sealed and separated. The new Dermagraft is simpler to use, and the potential for product damage has been reduced. 

Similarly, more manufacturers are creating products that have easier-to-remove packaging and disposable elements to ease overstressed nurses' and other caregivers' workloads. (Disposables are facing a new design challenge of their own. See “Medical Devices Go Green,” this page.) 
Further, designers are looking at technologies being adapted to consumer markets, which, with their high product volumes, tend to lead the way in technological innovation. Many of these technologies could possibly improve medical product design. One example of a consumer-market crossover is the double-sided tape now being used to secure ECGs. Although ECGs have been used for decades, they historically had poor leads; the adhesive did not stick well to patients' chests, nor did the leads provide good measurements. When double-sided tape entered the consumer marketplace, it provided a solution to the ECG lead problem as well.

Similarly, while bar codes have been a part of consumer products for decades, it is only in recent years that they've become common in the medical arena. “Hospitals are using bar codes as a check-and-balance system,” Czuba says. “Scanned bar codes simplify recordkeeping, as in the case of implanted heart valves. The government requires tracking of such devices in case there's need for a recall, and scanning a bar code into a patient's on-line chart streamlines any potential notification process.”

“We're seeing a lot more bar code labels and radio-frequency identification chips in products now, so that the products can be scanned,” agrees Hiemstra. The practice helps track inventory and can reduce data-entry errors as well as mix-ups. “Nurses used to have to put a hand-written label on a vial to identify which patient provided a sample. Now hospitals or clinics may use a preprinted, adhesive-backed label from the patient record to make sure the sample is labeled properly, and so the diagnostics technician (or machine) can automatically read the label,” Hiemstra says.
Miniaturization is also a focus for manufacturers trying to please healthcare professionals. There is only so much real estate available at the bedside or in the emergency room, so devices are becoming smaller and more portable to allow professionals more room to work.

Aspect Medical Systems's A-2000 BIS Monitor, which measures the effects of anesthetics on the brain and consciousness, used to consist of a tabletop box and a cable that the patient wore, which occupied a lot of space in the operating room. To reduce the bulk, Design Continuum Inc. (West Newton, MA) designed a new enclosure that would mount on a pole with the anesthesiologist's other equipment and show data on a computer screen, also attached to the pole. The changes freed up space in the operating room and also increased market share. The monitor is now used at 60% of the nation's top hospitals, according to Aspect Medical Systems.

“Sometimes [a product redesign project involves] taking the user interface off a medical product and putting it someplace else, combining the medical product with wireless technology to free up space,” notes Stuart Perry, director of electrical engineering for Design Continuum.
Medical device designers also are adopting smaller but higher-powered, longer-lasting batteries and sensors from the cellular phone and electronics industries to fuel smaller, mightier designs.

“As products get smaller, an important challenge becomes keeping the displays crisp and clear,” Perry says. “A wide viewing angle is necessary, as are power management strategies.” There's a trade-off between how often a backlight can be used to light a display versus how long its battery can last, Perry explains. “In the next few years, we'll see more organic LEDs being used because that display technology has deeper color saturation, an extremely wide viewing angle, and remarkable clarity, and uses little power. The technology is being refined on cell phones, and once it becomes more pervasive in high-volume areas, we'll see it used more in medical device design.”

Dental View's DVA Perioscopy System,
designed by Stuart Karten Design, provides real-time visualization enhanced by intense
illumination and magnification.

Patients Have Their Say

In addition to considering how a product will be used, designers also think about how patients will respond to a device. “In the past, lots of manufacturers focused on the technology and idea for a device, and the user experience was secondary. Now, those factors are running neck and neck. It's a significant shift in the paradigm,” says Allan Cameron, industrial design principal and leader of Design Continuum's health and medical practice.

Sometimes a user's needs are interpreted incorrectly, and the resultant final design is counterintuitive. For example, one manufacturer, trying to develop a toothbrush that would appeal to children, made a smaller version of an adult brush. Sales were flat. IDEO observed children brushing and found that a large, thick-handled toothbrush—rather than a miniature adult version—that children could hold easily in a closed fist won the favor of youngsters.

Certainly, manufacturers have thought about human factors for years, but Cameron says there's a need to reframe the criterion. “We refer to ‘targeted' design,” Cameron explains. “There was a time when people wanted things to look pretty. Now we're concerned about the emotional response when people look at a product. Manufacturers now tell us what message they want consumers to get when they look at a product, and we create characteristics to reinforce those attributes.”

For example, Design Continuum and Geoffrey A. Hart, MD, were trying to create a “playful, nonthreatening” pediatric sedation device when they developed PediSedate. The colorful, toy-like headset lets children play with a Nintendo Game Boy system or listen to music on a portable CD player while a snorkel delivers nitrous oxide into their nose. The device relaxes children during medical procedures, easing the minds of their parents and the task at hand for healthcare professionals. 

Of course, adult patients' concerns tend to be more complex. Numerous devices are being designed to look like anything but a medical device to protect their users' privacy. For example, one blood glucose monitor for diabetics that checks the wearer's blood sugar level every 20 minutes is designed to look like a wristwatch. 

In many instances, manufacturers are developing different models of devices depending on whether they're intended for clinical or at-home use. Home-use medical products are a rapidly expanding market; in a 2001 FDA Consumer magazine article, William Herman, director of the division of physical sciences for CDRH, called home-care systems “the fastest-growing segment of the medical device industry.”

“IT [information technology] is making it all possible,” says Hiemstra. “Communication is key to device advancement. The IT sector is now merging with the medical sector, and that—coupled with advances in sensors, software, and other monitoring equipment—is allowing us to capture patient data outside of traditional settings.”

At-home devices record such patient information as blood pressure measurements, then transmit that information either over a computer line or wirelessly to the patient's healthcare provider, making device interface capability an increasing priority. While industry experts say that technologies like Bluetooth still haven't had much impact on medical device design, they believe such protocols will play an increasing role in coming years as the technology becomes more affordable and mainstream.

In the meantime, designers are focusing on how to make products easy for patients to use and understand. “Outpatient care is being driven by PCs, and I believe flat-screen technology will permeate all medical products in the future because it's the most explicit way to deliver instructions, and it's becoming cheaper,” Cesaroni says. “In the old days, you would give patients printed instructions, but who knows how thoroughly they read them. With a flat-screen display, they'll reference the screen to get feedback on how to use the product, or what the results of a blood analysis are. It's like the old saying, ‘a picture is worth a thousand words.'” 

Looks Count
We live in a society where people are obsessed with the looks and stylishness of their homes, their cars—nearly everything. That same perspective applies to medical devices, says Stuart Karten, principal and founder of Stuart Karten Design (Los Angeles). “Actually, it probably is even more important that a medical device look stylish and high-tech, because consumers want to have confidence in its ability to function the way it should. Often, a product's value is closely related to its appearance.”

Karten says his company sometimes will use metal finishes rather than plastic to give devices a higher perceived value, which often translates into higher sales. 

WhiteLight Design's Willis Whiteside agrees. He also uses metal sheeting occasionally, rather than plastics, to increase a product's appeal. “You're trying to create something that stands out in the market and creates a brand for a new product, giving it a competitive advantage,” Whiteside says. “Technology becomes a tool in achieving that goal, and our knowledge of design and engineering principles lets us use manufacturing processes in creative ways to design a device that looks expensive, but isn't.”


Today's definition of good design encompasses many components, including cost-efficiency, eased work flow, consideration of the end-user, a compelling look, and one more element that often separates good from great design: the so-called “wow” factor. 

“Great design all comes down to cleverness,” Karten concludes. “Technologies get you only so far. Engineering horsepower and creativity will find new ways to mix older and emerging technologies to create devices that are functional, user-friendly, and inspired.” 

Copyright ©2003 Medical Device & Diagnostic Industry

Hands-Free Medical Assistance Software Aids Emergency Treatment

Originally Published MDDI February 2003


NASA has awarded a grant to study the feasibility of a portable, hands-free device for emergency medical decision-making support to be used in space by nonphysicians. The Phase One contract award was granted to ibex Healthdata Systems Inc. (Rosemont, IL) and Johns Hopkins University. The device is intended to allow the space shuttle crew to treat a patient while receiving verbal instruction, guidance, and helpful graphic representations.

According to John Epler, chief technical officer of ibex Healthdata Systems, “Phase One will entail the development of a voice-activated device that will utilize an intelligent algorithm to provide guidance in establishing an emergent airway for a patient in space. The interactive hands-free software will process requests for assistance based on verbal prompts and algorithmic decision-making.” He adds that the first phase will focus “on validation of the proposed technology, as well as development of the necessary software and hardware into a beta-type device.” 

Successful Phase One results could support a Phase Two grant. In that phase, the focus would be on producing the first-generation software and hardware for hands-free, interactive medical decisions. Says Epler, “This has enormous implications beyond the space program and could provide laypersons with a simple way to get important medical information in order to treat injury and illness when access to trained medical personnel is not available.”

Copyright ©2003 Medical Device & Diagnostic Industry

Project Advisory Boards: Improving Product Development Quality and Consistency

Originally Published MDDI February 2003


Advisory boards enhance development efforts and help companies meet the ever-increasing challenges of developing 
and launching new products.

Richard Rosen, Battelle Memorial Institute

At a medical device development or R&D company, a part of the general manager's job is the successful execution of product development efforts. In organizations that conduct multiple R&D programs—often involving significant resources, multiple locations, and high technical complexity—it is a challenge for any manager or group of managers to provide the oversight required to ensure a program's success. What follows is a management tool that I have found highly successful in addressing this challenge. 

Consider your own firm's situation. During the conduct of your product development efforts, do any of the following situations sound familiar?

• Inadequate mechanisms exist to help identify and manage technical, schedule, market, and resource risks.
• The documented product development process is not applied consistently. 
• The company wants to provide growth opportunities for newer project managers and teams while managing the risk of using less-experienced staff. 
• Senior management cannot provide timely, consistent, cost-effective oversight product development programs.
• Ineffective mechanisms exist to keep a project on track as market and bus-iness conditions change. 

Advisory Board Composition

To address these issues, consider instituting an advisory board process to augment your in-place management review methods. Each advisory board (one per project) consists of a group of knowledgeable but uninvolved staff who are at a peer level with the project team members. The board's roles are to provide an objective overview of project progress, to provide technical and programmatic advice to the project manager and team, and to improve the quality and consistency of product development programs across the organization. More than just serving as technical reviewers, the advisory board must also have additional authorities that require their advice to be seriously considered and implemented. 

Because an advisory board typically includes a senior program manager and a senior technical staff member, it offers significant experience. This can be helpful in quickly identifying potential problems and risk issues so they can be addressed and resolved before they become larger problems. 

Advisory boards are also an effective mechanism to transfer best practices and lessons learned from one project to another.

On a personal level, the advisory board provides a mentoring function to the project manager. It offers support and guidance in key decision making, which can be effective in moving a project forward. It also minimizes the number of nonproductive activities that sometimes occur during large, complex development efforts. 

The advisory board also provides another point of contact to and from the customer, whether it is a contract product development client or a marketing or product line manager within the same company. In addition to direct contact with the project manager, the customer now has another avenue of communication with someone current on the specific project. This also provides another channel for the customer to provide constructive feedback regarding the performance of the project manager and team.

Advisory Board Authority

An important aspect of the advisory board is its authority to redirect the project if the team is not addressing technical, programmatic, or business issues. To be effective, however, it is important for both the project manager and advisory board to clearly understand that their roles are meant to be complementary. The advisory board is not intended to assume day-to-day programmatic responsibility. Complementary functions are achieved by holding both sides accountable for the project's success.


The advisory board chair, typically a senior program or technical staff member with prior experience in a relevant product development activity, should interact frequently with the project manager and team. This can be done through informal discussions designed to keep the chair abreast of current activities and any issues that may arise. Formal project advisory board meetings are conducted on a regular basis, with the frequency dependent on the scope and complexity of the project. With the use of appropriate tools and best practices, a short, one- to two-hour monthly meeting is usually sufficient to review the status of the project and provide redirection as necessary. 

A checklist that includes project objectives, a review of the key issues and decisions, and the status of action items assigned during the previous meeting drives the advisory board meeting agenda. See Table I for topics included in a typical advisory board meeting.

To minimize the effort required to prepare for a meeting, a standard set of project metrics, normally updated by the project manager on a regular basis in the course of managing a project, should also be reviewed during the advisory board meeting. In our experience, these metrics include seven items: schedule, milestones, costs, deliverable status, scope control, action items, and state-of-the-customer updates. 

To provide a good, high-level understanding of the project status, it is important that the project budget and costs be closely tied to performance of the team with respect to meeting the key milestones defined for the project. The state-of-the customer metric is simple documentation of periodic assessments made by the project manager and team, noting the perceived satisfaction of the customer or major stakeholders of the project. For this metric, as well as the others, standard formats and templates can be used to promote consistency from one project to another, simplifying the review process by the advisory board.

Benefits of an Advisory Board

Table I. Typical advisory board meeting agenda items. (Click to enlarge)

Implementing an advisory board process generates visible improvements and project outcomes. Some of the benefits include:

• More consistency in team performance, regardless of project size.
• Management of expectations among all stakeholders.
• Improved conflict resolution.
• A better support structure for project managers.
• Higher reported customer satisfaction with project results. 
• More consistency in project deliverables and documentation.
• Best practices effectively spread throughout the organization.
• More-accurate assessment of pro- ject managers and staff capabilities.
• Better understanding of key drivers in the organization and what it takes to effectively implement a project.
• Checks and balances to help redirect technical work, if necessary.

Advisory Board Pitfalls

Implementing an advisory board process can often meet with culture and organizational barriers. Commonly, an initial reluctance on the part of board members results from a perception of duplication of effort with the project manager's role. Additionally, when an advisory board is added, some project managers fear a loss of control with respect to day-to-day activities. For this reason, the advisory board process must receive strong and visible top-management support, and advisory board chairs must act in partnership with project managers—not as their adversaries or as whistle-blowers.

In order for an advisory board process to benefit your organization, it must be tailored to your culture and systems. What follows is a list of pitfalls that can hinder the successful implementation of the advisory board process.

• Advisory boards that are too busy to interact regularly with the project and do not review progress frequently enough to add value. 
• Advisory board chairs that assume programmatic responsibility instead of providing an overview role; this leads to confused and frustrated project managers. 
• Project managers that are not prepared for advisory board meetings with succinct summaries of standard metrics, potential issues, and program risks.
• Project managers that paint an overly optimistic picture by not disclosing information, issues, or potential problems. 


There are several lessons that I have learned during the course of developing and implementing these processes in an R&D organization. First, senior management in the organization needs to be prepared to clearly define and delegate authority and responsibility to the advisory board. Trust is a key factor. The implementation must promote and foster an environment that commends open, frank communication between the project manager and the advisory board, and that celebrates the successes that occur as a result of this partnership. 

In addition, advisory board meetings must also be conducted at a frequency sufficient to add timely value to the project, and key issues, decisions, and action items must be documented with assignments of responsibility.

Finally, companies should periodically review and assess the performance of the advisory boards for continuous improvement and increased efficiency. Firms should ensure time and again that the boards represent a value-added function in the product development process. 

Discuss this article on-line!  The author will be responding to questions and comments about this article in MD&DI's Author Forums through March 14, 2003. 
Visit and select the Author Forums link.

Copyright ©2003 Medical Device & Diagnostic Industry

In Pursuit of Failure

Originally Published MDDI February 2003


The medical device industry cannot deliver anything close to perfection unless it expects failure.

As NASA begins the massive task of finding and piecing together debris from the space shuttle Columbia, we are reminded of the many surprising similarities between the aerospace and medical device industries. Both involve life-or-death products, require the highest level of quality assurance, are subject to intense regulatory scrutiny, and rely on advanced technology for their most spectacular successes. 

Both, too, are subject to terrible failures. Granted, the scale of disaster in the aerospace industry dwarfs any failures the device industry can produce, at least in terms of immediacy and visibility. But for both industries, failures are viewed by the public as unacceptable. Accidents can happen in other industries, but not in these two. 

As the investigation into the Columbia disaster proceeds, the medical device industry can learn much by watching closely. This failure analysis will be conducted on a very public stage, and on a scale rarely seen. 

To gain from this example, though, the device industry must apply the lessons learned to the smallest scale. The mentality should be that no failure, however small or seemingly insignificant, should go unsolved. Too often are FDA inspectional observations and warning letters issued due to poor complaint-handling procedures. In this area, at least, the agency is right to hold companies to the strictest standards. Only by investigating and understanding all the small failures can the large ones be avoided. 

Moreover, the expectation and analysis of failure must be built into the product development process itself. Hazard analysis tools such as failure mode and effects analysis and fault tree analysis should be second nature to all engineers. So, too, should be an intimate understanding of how systems fail. 

Paradoxically, while the public expects perfection, the medical device industry cannot deliver anything close to it unless it expects failure. An imagination of disaster is a prerequisite for any engineer.

To help further this process, MD&DI will be publishing in upcoming issues a number of articles that bear on the processes and procedures of failure and hazard analysis. In this issue, for instance, beginning on page 64, author Mike Schmidt addresses risk management. Because Schmidt's article deals with one clause of an ISO standard, readers might consider this article to be for specialists only. Nothing could be further from the truth. We urge all readers involved in the development of medical devices to read the article, for the stakes are high indeed.

In addition, be on the lookout for a retrospective series on the subject on MD&DI's Web page, at This series will highlight the best articles on this topic from the past 10 years of MD&DI and its sister publications.

More on Author Forums
In last month's issue, we directed readers to our new Author Forums on the MD&DI Web site. Now you can communicate directly with the authors and share your thoughts with other readers as well. We're pleased to report that the forums are up and running, and already seeing activity. 
For this month's issues, the following authors will be prepared to respond to your comments and questions:

• Rich Rosen, “Project Advisory Boards,” p. 38.
• Jeffrey Shapiro, “FDA's Regulation of Analyte-Specific Reagents,”p. 44.
• Mike Schmidt, “Establishing Overall Risk for Medical Devices,”p. 64.

To go directly to the forums, simply type into the address box of your Web browser. Although we will eventually require registration with Medical Device Link to post, for the time being, no membership is required. And you may give your feedback on any article in the issue, regardless of whether the article's author has agreed to respond. Feel free to post your comments for the world, or simply to read what others have posted. We look forward to seeing you there.

The Editors

Copyright ©2003 Medical Device & Diagnostic Industry

Medical Devices Go Green

Originally Published MDDI February 2003


U.S. medical device manufacturers will soon need to ask another question as they design a product: How “green” is this device?
“An emerging design trend is to ensure that users can dispose of electronics products safely,” says Stuart Perry, director of electrical engineering for Design Continuum in West Newton, MA. Design Continuum has offices in Italy and Korea also, which puts the company on the front lines of new device requirements throughout the world. 

“In the United States, green design is often talked about, but it's not high on clients' priority lists,” Perry continues. “In Europe, creating an environmentally friendly product tops the list of concerns.”

European manufacturers' focus on reducing waste, product toxicity, and planned obsolescence, including single-use packaging, is the result of a new 
European Commission proposal, the Directive on Waste Electrical and Electronic Equipment (WEEE). The WEEE directive was created in response to increased concern about environmental toxins and the sheer volume of waste created by electrical and electronic equipment, which together have been identified as one of the fastest-growing waste streams in the European Union. Such waste already accounts for 4% of the municipal waste stream and is expected to increase in volume by 3% to 5% annually. 

To curtail the amount of pollutants released into the environment, WEEE requires that new materials be substituted for certain hazardous substances in the design of electrical and electronic products. It also directs manufacturers to recycle, and to label their products as recyclable. Ten categories of electrical and electronic equipment are covered, including medical devices and monitoring and control instruments. (Implanted and infected products will be exempt from the requirements.)

As of January 1, 2008, companies will no longer be permitted to sell products that contain heavy metals, lead, mercury, cadmium, or hexavalent chromium. Two types of flame retardants, polybrominated biphenyls and polybrominated diphenyl ether, also must be phased out of use; however, substitutions must not lead to lower fire safety.

“Most electronic packaging has lead in it,” Perry says, noting that designers will need to incorporate lead-free technologies into their designs as U.S. manufacturers become aware of the new EU mandate. “There is now a drive toward using lead-free integrated circuit packaging and soldering techniques. Another area of concern is battery disposal, since cadmium, which is used in the design of rechargeable batteries, is on the WEEE hit list.” Manufacturers are being required to consider a wide range of waste management aspects when designing new products or upgrading current offerings, and environmentally conscious design is gaining momentum, he says. 

To learn more about the WEEE directive, visit comm/environment/docum/00347_en.htm goods.htm

Copyright ©2003 Medical Device & Diagnostic Industry

FDA’s Regulation of Analyte-Specific Reagents

Originally Published MDDI February 2003


FDA's Regulation of Analyte-Specific Reagents

Confusing and at times counterintuitive, the ASR rule applies to materials used in in-house-developed tests, not the assays themselves.

Jeffrey K. Shapiro and Randy J. Prebula
Hogan & Hartson LLP

One of the most confusing areas of FDA regulation surrounds the requirements governing analyte-specific reagents (ASRs). ASRs are raw materials and components used to develop laboratory assays. This article will provide a brief background on FDA's regulation of ASRs, summarizing the key ASR requirements and addressing some common misconceptions and pitfalls in this area.

The story of FDA's ASR regulation begins with in-house-developed assays. On a daily basis, doctors send patient blood, urine, tissue, and oral specimens to laboratories for testing. The laboratories perform the requested assays and report the test results. Often, the labs use assays prepared by their staff members. These assays are typically referred to as in-house-developed assays, or, more colloquially, as home brews. 

Despite the informal name, home-brew assays are widely accepted as scientifically valid and are relied upon routinely throughout the healthcare system. They are extensively regulated by the Centers for Medicare & Medicaid Services (CMS) under the Clinical Laboratory Improvement of 1988 (CLIA). 

In August 1992, FDA issued a draft compliance policy guideline proposing to apply general medical device regulation to home-brew assays. The laboratory community objected, arguing that they were adequately regulated under CLIA, that FDA regulation would be duplicative, and that FDA lacked legal authority to regulate laboratory testing services. FDA withdrew its proposal, but insisted that it had authority to regulate home brews should it wish to do so.

In November 1997, however, CDRH published a final rule governing the use of ASRs in certain in vitro diagnostic products (IVDs) and in-house laboratory assays. The final rule was the culmination of a lengthy process in which FDA sought to determine how, if at all, it would regulate clinical laboratories that prepare in-house assays using ingredients purchased from third-party biological and chemical suppliers.1 In the ASR regulation, FDA invoked the restricted-device authority in section 520(e) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). It did so to impose certain restrictions on the sale, distribution, and use of ASRs when used as ingredients of home-brew assays and in certain IVDs.

As FDA made clear, the agency was not actively regulating the in-house tests and had determined that strong public health reasons existed for continuing this approach. In the final rule, FDA recognized that “the use of in-house-developed tests has contributed to enhanced standards of medical care in many circumstances, and that significant regulatory changes in this area could have negative effects on the public health.” The agency said that the laboratories would be responsible for both the quality and interpretation of results generated from those tests.2 Thus, the final rule focused not on the in-house tests, but on the ASRs that are used in preparing such tests.

Summary of the ASR Regulation
The regulation defines ASRs as “antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reaction with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens.”3 This definition includes many different types of chemicals and biological components, such as mouse monoclonal antibodies to cancer markers, oligonucleotides that bind with DNA or RNA from infectious organisms or viruses, and chemicals that react with cholesterol or digestive enzymes. The key characteristic of each component is its ability to bind to or react with a substance whose detection and measurement is clinically meaningful.

Under this definition, ASRs are not diagnostic tests, nor are they combinations of reagents, controls, disposable labware, or instrumentation provided for the performance of diagnostic tests. Rather, an ASR is a single (albeit key) component in any diagnostic test manufactured anywhere in the world, including in clinical laboratories, IVD device manufacturing facilities, and forensic or research laboratories. However, ASRs are only subject to regulation as medical devices when they are purchased by clinical laboratories for use in home brews or certain IVD tests.

Most such ASRs are classified as Class I and exempt from the agency's 510(k) premarket notification requirements. ASRs are classified in Class II or Class III when intended for use in blood banking, donor screening, and certain infectious disease testing. (FDA regulations for human blood and blood components require that tests used by establishments for these applications be approved by FDA. Accordingly, home-brew tests used in blood banking and donor screening require FDA clearance, approval, or licensure.4) Regardless of classification, all ASR manufacturers must comply with FDA's postmarket requirements, including establishment registration, device listing, and compliance with FDA's quality system regulation (QSR), medical device reporting (MDR) requirements, and ASR labeling and distribution requirements.5

To control the use of ASRs, FDA imposed a comprehensive set of restrictions. For example, ASRs may only be sold to: (1) diagnostic device manufacturers; (2) clinical laboratories that are CLIA qualified to perform high-complexity testing under 42 CFR Part 493, or clinical laboratories regulated under the Veteran's Health Administration Directive 1106; or (3) organizations that use the reagents to make tests for forensic, academic, research, and other nonclinical (nonmedical) uses.6 In addition, ASRs may be sold only for use in home-brew tests that are ordered on a prescription basis.

The ASR rule also comprehensively governs the information that manufacturers provide on the label or with the ASRs. For example, ASR manufacturers must provide specific information, including among several other items the proprietary name, common name, and quantity or concentration of the reagent; the source and a measure of its activity; and the name and place of business of the manufacturer.7

ASR manufacturers are not permitted to include in the ASR labeling or promotional materials any statement regarding analytical or clinical performance of the ASR.8 In our experience, FDA has interpreted this requirement to mean that ASR manufacturers are not permitted to pro- vide information on assay methods or techniques, nor are they permitted to assist the laboratories with the optimization of tests developed with the ASR beyond what we've already covered. It is also unlikely that FDA will permit ASR manufacturers to provide technical support for the ASR—beyond providing the identity and purity data. In fact, FDA has stated that provision of laboratory instructions on the use of an ASR would be viewed as “evidence that a kit or system is being marketed rather than used as an ASR or building block for an assay.”9

Similarly, providing ASR users with support, instrument setup, sample preparation, and data collection information exceeds FDA's expectations. The agency has stated that “the responsibility for developing this information is clearly assigned to the laboratory, not the ASR manufacturer. The only responsibility the ASR manufacturer has is to produce product according to the quality system regulation, to label it clearly as a building block for use in ‘home-brew' assays, and restrict sales to high-complexity laboratories.”10

The ASR requirements also extend to the clinical laboratories that purchase and use ASRs to develop home-brew tests. Specifically, laboratories that prepare in-house tests using an ASR purchased from a third-party supplier are required to append the following statement to the test report: “This test was developed and its performance characteristics determined by [Laboratory Name]. It has not been cleared or approved by the U.S. Food and Drug Administration.” This statement is not required when test results are generated using a test that was cleared or approved in conjunction with review of Class II or III ASRs, which require premarket clearance or approval.11 The statement is also not required if all of the ASRs in the home brew are created in-house rather than purchased.12

Common Misconceptions and Pitfalls
Because the ASR regulation is so complex, misconceptions common. Three requirements are critical.

ASRs Cannot Be Sold as Test Kits. By definition, ASRs are a single component of a diagnostic test. Many IVD manufacturers, however, market so-called ASR kits. These “kits” contain, in some instances, much more than a single component—such as an analyte- specific reagent coupled to a solid surface, positive and negative control solutions, instructions for conducting or validating specific test methods, and so on. Most likely, FDA would consider such kits to be finished IVD tests that require FDA clearance or approval. 

ASRs Cannot Be Sold with Validation Information. Some companies run afoul of the ASR regulation by providing technical assistance and assay validation information to clinical laboratories. These companies argue that, as the reagent's manufacturer, they are best suited to tell purchasers how the ASR should be used. FDA disagrees with this position, however. It believes that ASRs are merely ingredients of an assay, and that the test developer (i.e., the clinical laboratory) should fully control test development and validation. Any information provided by an ASR manufacturer to ensure that the final finished test performs appropriately likely will lead FDA to classify the company as a joint manufacturer of the diagnostic test.
Medical and Performance Claims Are Prohibited. Many ASR manufacturers make medical and assay performance claims. Under the ASR regulation, manufacturers may state that an ASR recognizes, binds to, or reacts with a specific analyte—Factor V Leiden RNA, Her-2/neu oncogenes, or cystic fibrosis genetic mutations, for example. They may not promote their reagents for applications such as the diagnosis of breast carcinoma, the determination of patients' eligibility for drug treatment, or the identification of differences in metabolic activity as an aid in selecting specific drug therapies. Rather than promoting an ASR with a known specificity, manufacturers making such claims are promoting the use of the ASR to achieve a specific result.

Finally, we have seen some ASR manufacturers tout the ability of laboratories to use their ASRs in tests that can “detect and quantitate” viruses, despite FDA's specific prohibition on providing analytical or clinical performance statements for ASRs. These types of claims are prohibited under the ASR regulation.

It is not surprising that the ASR regulation has proven to be one of the least understood and most abused FDA regulations. It is confusing and has counterintuitive features. For example, under the FD&C Act, medical devices and their components typically are subject to the same level of regulation. Under the ASR regulation, however, FDA regulates only the ASR components and not the home-brew assay itself (except in a few specific cases). To add to the confusion, ASRs are only treated as medical devices when sold to particular customers (clinical laboratories) for a particular use (home-brew assays). Therefore, a manufacturer of ASRs may find itself regulated for interaction with some customers and not others.
From the standpoint of clinical laboratories, it is problematic that the use of an ASR purchased from a third-party supplier is the trigger for the disclaimer of FDA clearance or approval on the test report. In contrast, if the ASR is developed in-house, the disclaimer is not required. Thus, the same home-brew assay may or may not require a disclaimer based upon whether any of dozens of ingredients were purchased or developed in-house.

It is also illogical (and perhaps even misleading) for FDA to require a statement that an assay has not been cleared or approved when the agency itself does not require the assay to be cleared or approved. By classifying them as Class I, FDA exempted most ASRs from 510(k) clearance requirements and, in turn, decided not to regulate in-house tests that are prepared from these ASRs. It makes little sense, then, to require clinical laboratories to warn physicians that the testing services were developed without FDA review. It would be more accurate to observe that the agency does not require such clearance or approval.

Ultimately, the ASR rule imperfections bear the hallmarks of a compromise. FDA felt a need to impose some level of regulation on home-brew assays, but settled for regulating some of their ingredients—at least for now. At best, the ASR rule may marginally improve the quality of some ingredients that clinical laboratories use in home-brew assays, albeit at the cost of significant administrative complexity. More importantly, the ASR rule may only be the first step toward significant FDA regulation of home-brew assays. For instance, FDA has recently made known its interest in regulating home-brew tests for genotypic analysis of certain retroviruses. Industry should be prepared in the coming years for a continued FDA involvement in regulating home-brew assays.

1. 61 Federal Register: 10484 (March 14, 1996).
2. 62 Federal Register: 62243, 26249 (November 21, 1997).
3. 21 CFR 864.4020(a).
4. 21 CFR 610.40(b).
5. 21 CFR 809.20.
6. 21 CFR 864.4020(a)(1) and (2).
7. 21 CFR 809.10(e)(1)(x) and (xi).
8. 21 CFR 809.30(d)(4).
9. Agency Information Collection Activities, 66 Federal Register: 1140 (2001).
10. Agency Information Collection Activities, 66 Federal Register: 1141 (2001).
11. 21 CFR 809.30(d)(3) & (e).
12. 62 Federal Register: 62249. n

Copyright ©2003 Medical Device & Diagnostic Industry

Preparing for a World of Change

Originally Published MDDI February 2003


How are device manufacturers getting ready for technological change and new market factors? Four industry executives share their views.

The course that the healthcare industry will follow in the next few years is being shaped by a number of influences. Among these are fundamental shifts in regulatory policies and payment mechanisms, the growth of new markets, and the promise of exciting new technologies. The complex, evolving relationship of these and other factors poses a great challenge to the device industry. It is a time of change, with rewards waiting for those who anticipate and adapt to the industry's new shape.

MD&DI asked four executives of medical device manufacturing companies to share their perspectives on the factors that are shaping the healthcare industry. The participants come from both large and small companies that serve diverse market segments, making devices for surgical and critical-care use, and for cosmetic applications. They also represent various regions of the United States. Participants are: David D. Hood, president, Integrated Medical Systems Inc. (Signal Hill, CA); Daniel A. Pelak, president and CEO, Closure Medical Corp. (Raleigh, NC); Thomas M. Prescott, president and CEO, Align Technology (Sunnyvale, CA); and Paul S. Weiner, CFO, Palomar Medical Technologies Inc. (Burlington, MA).

MD&DI: What are the key factors now driving the medical device marketplace? 
Hood: I believe the world is a changing place and we need to be more efficient at responding to the dynamics. The markets and the needs are global. The United States clearly has an aging population resulting from the baby boomer phenomenon. User-friendly rapid access to applicable information will be increasingly essential for our medical teams in the future. I believe the seamless integration of medical technologies with information and communication technologies will be even more vital in the future than it is today.

Pelak: Certainly favorable demographics are still playing a critical role in overall growth in spending for devices. It's a trend that has been going on for a while and it's going to continue for a while. However, I believe that the introduction of new technologies has really been key. The technologies that the industry has brought forward have been the key factors driving the medical device workplace.

There are a lot of things that I believe are about to change. Healthcare systems throughout the world are straining under the weight of these demographic trends and technological innovations. I think all of us within the healthcare industry have to be concerned because many of these systems are ready to break. It would be problematic for the patients who are served, but I think it's also going to be problematic for the suppliers to the system. So in terms of a potential issue in the future, as I see it, the strength of the healthcare systems worldwide is a concern to the industry.

Weiner: The industry we specialize in is cosmetic lasers used for permanent hair reduction, skin rejuvenation, photofacial treatments on vascular and pigmented lesions, tattoos, acne, etc. 

When we started selling our lasers seven years ago, we concentrated on the high-end market—that is, the dermatologists and plastic surgeons. We've captured a lot of that market. But our industry is similar to the way computers work: every few years you need to buy a new one if you want the latest and greatest technology. So every two or three years, the laser or light source technology that's out there becomes outdated, and the markets that we've been penetrating will usually step it up and buy the next generation of products. 

Over the last few years, we've also been penetrating down into the lower-end markets: the general practitioners, OB/GYNs, and even the spa and salon market. This market is worldwide and regulatory approvals for the devices are on a country-by-country basis and state by state within the United States.

The cost of the devices is also coming down, so they become a more affordable investment for smaller operations, such as spas and salons. The return on investment for these devices is about six months, so the financial benefits are obvious to potential customers. The whole industry has been driving in the direction of bigger markets, with lower prices, and better technology. 

Prescott: There are several broad drivers. Of course the whole demographic wave of the baby boomers has been well defined and documented. We're living it. From my perspective, the greater issue is the consumerist mentality and empowerment that has been seen relative to healthcare. Most healthcare consumers now have an unprecedented level of access to information via the Internet on diagnosis and therapies of all kinds. And often they use that first, even before consulting their healthcare professional.

In our case as a developer of new technology for straightening teeth without braces, many millions of people whose only alternative was to go with conventional treatment were unwilling to do so. We have the ability to tap into that value proposition for them. The issue is broader than just healthcare. It's more of a consumer-driven, feel-better-about-yourself sort of thing. You see that in weight-loss programs, in aesthetic procedures, and in people choosing better, healthier, more active lifestyles. 

I think that, ultimately, this is an effect of the boomers. But if you come back to that issue around healthcare and information, I don't think it's just a U.S. trend. I believe it's a global phenomenon. 

Consumer access to information via the Internet is very important. We feature use of the Internet, both in terms of accessing customers and patients, through making our digital interface a key part of the operating engine and the value creation for the doctors. A big part of what we do—all the data and the 3-D models that become the aligners that move teeth—is all enabled through the Internet. So the very technology that we're using to make this a cost-effective proposition is also a key part of what touches our doctors and is part of their on-line experience.

MD&DI: How much influence are group purchasing organizations (GPOs) in healthcare today? 
GPOs are a significant influence and an important enabler for the medical industry. Bottom line, the medical teams and caregivers must be able to get medical supplies rapidly and cost-effectively to have the best possible outcomes for their patients. GPOs should provide the medical teams access to both new and old tools that may decidedly influence patient outcomes. We need to be focused on the patient. Efficient and user-friendly access to information should allow buyers to rapidly gain access to the products and services they require.

Prescott: We operate in the overall dental industry, which is not largely affected by GPOs. But it appears that some of the dominant GPO influence is being questioned through adverse media and legislative pressure. There are good reasons for GPOs to exist, in that they can provide substantial value to members and shareholders. However, I don't think they should be a lockout for competing firms, large or small. Companies can win or lose share, but I think all of our best interests are best served in a competitive setting. My guess is that a lot of firms that are rethinking their GPO strategy.

Pelak: I think that the GPOs will continue to maintain some influence into the future. However, I believe it will wane in the ensuing months and years. I think the recent scrutiny of GPOs within the national media will serve to lessen the influence over time. I think local hospital boards are going to be asking more questions about the value derived from their association with these groups. I believe that those concerns and scrutiny will cause the GPO's influence to wane as time goes on.

MD&DI: How have your company's working relationships with various government and regulatory agencies changed in recent years? 
Actually, our primary interface with government perspectives at Closure is with FDA. And we've seen little change in the agency. With that being said, however, with the proposed changes in user fees, we're actually quite enthusiastic about possibly faster action and greater service from this regulatory body.

Hood: I believe working relationships with the government have changed dramatically, allowing companies to work closely and collaboratively toward innovations that meet the needs of our medical teams and their patients. We have worked closely with the government team at the Walter Reed Army Institute of Research and at FDA to rapidly develop our cornerstone product. FDA can provide insight and input related to ensuring the safety and efficacy of the product.

Like FDA rules, the Centers for Medicare and Medicaid Services (CMS) coverage and reimbursement decisions must be considered early and incorporated into the design approach. 

Prescott: Because of the nature of our specific market with a Class I device, we don't feel the same challenges as other firms. That said, I believe FDA and CMS are working to speed the processes in their approach to decision making. Certainly, from our perspective, we have very efficient working relationships. 

For reimbursement, many small, single-product firms face very critical decisions on coverage for a product or procedure reimbursement. And with looming federal deficits, CMS decisions are going to continue to be sum zero, with winners and losers. I think it's going to be very difficult for new technologies to demonstrate that they are not just equivalent in cost, but that they are actually reducing costs. 

There are some compelling technologies out there. Developing a coherent reimbursement strategy and achieving a reasonable reimbursement level on the devices might actually take longer than FDA approval. You not only have to have the same kinds of data, you also have to have cost-benefit analyses and marshall popular and political support—both in the industry and among consumers. It is clearly a more complex and critical area than it was five years ago.

Weiner: All of our devices are FDA cleared through the 510(k) process rather than a PMA process. These are noninvasive procedures; instead of taking maybe five to seven years for a PMA application, we do a 510(k), which generally takes about 90 days for FDA to review. 

Certainly over the last few years, there have been a number of changes with FDA. That's because as more and more devices are being developed and going through the agency, FDA is becoming more familiar with these devices and their overall safety. This allows us to get the devices through FDA a lot faster. And there are more predicate devices out there, which means you don't have to do as many clinical trials to prove the safety and efficacy you need to get the 510(k) clearance. 

With our first device, which was approved in 1996, it took us about a year to get clearance from FDA. Clearances now take about 90 days. 
Once you get past FDA, you're in good shape for obtaining regulatory approval from other countries. Europe requires the CE mark, which is not too difficult to obtain, especially once you've received FDA clearance. There are other areas of the world, such as Japan and China, where you need different approvals. Palomar has its international distributors work with their local governments to get the regulatory approval for the devices.

MD&DI: Considering the dramatic technological changes that have taken place in healthcare in the past decade, what do you foresee as the “next big thing” in medical technology? 
I believe the next big thing in medical technology relates to the integration of technologies to more efficiently support the medical teams and patient outcomes. There will be a seamless integration of essential medical equipment with smart power sources, very user-friendly information and data-related technologies, and versatile communications capabilities. 

Prescott: It's pretty clear that over the coming decade the fusion of drugs and devices is going to be very important. You see that already in drug-eluting stents. And there are going to be a multitude of ways that this is going to play out, impacting a variety of products and procedures. I think it's extremely interesting and exciting.

There are companies, both large and small, that are working on integrating bioreactive materials with existing products to either improve efficacy or to open up a whole new therapeutic or diagnostic range. And I believe we're just scratching the surface.

That said, I'm not sure our regulatory agencies and those that have oversight are moving as fast as the industry. So there is probably going to be some stress, and potentially some braking effects, as research partners, regulatory agencies, and the like around the world have to understand the technology that just got complicated by the interaction of a drug. Are these things drugs or devices? Do you need an NDA? What's going to be the process to get through these? I believe they're just going to multiply.

Longer term, decades out, I can imagine a whole new class of what we'll call devices but may be molecular-size, nanotechnology-based systems designed for a certain purpose—diagnostic, therapeutic, or what have you. 
More prosaically, I'd say it would be great if the information systems scattered throughout the healthcare system—manufacturers, providers, and payors—could talk and we could do a better job of identifying costs associated with new technology. It would be ideal if we could see the impact that technology had across the continuum of care, and across the entire disease state as a whole, instead of this episodic view we have today. I don't think we're going to be able to show the value of some of these new technologies unless we're able to show how it impacts an entire disease state.
Weiner: As far as the cosmetic laser industry is concerned, more and more conditions that have been treated in the past with surgery, pills, or lotions or creams, can now be taken care of with one to five light-based treatments. This includes conditions mentioned earlier, like unwanted hair and vascular and pigmented lesions. 

But outside of the medical market is where we really expect to see the biggest change. Palomar is in the process of moving light-based cosmetic treatments and devices into the home. Now, that would not mean that there would not be a place for these devices in the medical community. There will always be a place in the medical community for the higher-end permanent types of treatments. But there's no reason that simple weekly or monthly maintenance treatments can't be done in the home. Therefore, we envision light-based cosmetic devices continuing to become smaller in size, more portable, safer, less expensive, and designed for consumer use.

Pelak: Many of the big things that have arrived in the past in this industry have come through venture funding. Unfortunately, what we see today is the drying up of venture funding in the medical device area in particular. I see this as a very negative trend for healthcare as a whole because many larger companies depend on venture funded smaller companies for their product development. I believe that this will have a negative impact on your question, which is: what is the next big technology? New technologies are not getting the same type of funding that they were just a few years ago. So I believe the change in the financial markets will cause drastic change in terms of technology trends in the future.

If I were to look at it believing that somehow our system has always been able to provide adequate funding for innovation, then I think the next big innovation is likely to come in the area of materials. I think that is the next big wave. The device industry at first had a mechanical orientation, then moved to an electromechanical orientation. I think the next big wave is in the area of biomaterials, unique polymers that are implantable or usable inside the body. There have been some breakthroughs in that area, but I think we're just scratching the surface. We certainly have seen the introduction of drug-coated stents. That's a first step, but I do believe that we're going to see that trend expand significantly. It fits particularly well with Closure Medical because our core competency is polymer chemistry and we've pioneered bioadhesives that replace sutures, which are a mechanical device. Consequently, we're continuing to accumulate knowledge and are looking at novel compounds that could solve an unmet need inside the human body. 

As a consumer of healthcare, as we all are, I'm hopeful we will continue to see the innovation that we have seen over the past few decades. We will get through the financial issues surrounding healthcare delivery on a worldwide basis, but it will probably take different forms and potentially go at a slower pace than many of us would like to see. 

Copyright ©2003 Medical Device & Diagnostic Industry


Originally Published MDDI February 2003


David D. Hood, president, Integrated Medical Systems Inc., has been affiliated with the firm since its “spinning-out” from Northrop Grumman Corp. Hood previously worked with Rockwell International and Northrop Grumman, and has more than 20 years of product development and business experience. He has a bachelor's degree in electronic engineering from the Ohio Institute of Technology, a master's in engineering and scientific management from West Coast University, and a master's in business administration from the University of Southern California.

Daniel A. Pelak was appointed president and CEO of Closure Medical Corp. in September 2002. Prior to joining the firm, he spent 26 years with Medtronic Inc. Pelak has held positions in sales, sales management, marketing, and general management. He holds a BS degree from Pennsylvania Sate University.

Thomas M. Prescott has served as president and CEO of Align Technology since March 2002. Previously, he was president and CEO of Cardiac Pathways Inc., and held various sales, marketing, general management, and executive roles at Nellcor Puritan Bennett Inc., GE Medical Systems, and Siemens. He has a master's degree from Kellogg Graduate School of Management, Northwestern University, and a bachelor's degree, with emphasis in civil engineering, from Arizona State University.

Paul S. Weiner, CFO of Palomar Medical Technologies Inc., has been strategically involved in restructuring the company over the past few years. Prior to joining Palomar, Weiner was the CFO for an environmental consulting company and previously worked in public accounting. He currently serves as a member of the Financial Executive Institute, the National Investor Relations Institute, the American Institute of Certified Public Accountants, and the Massachusetts Society of Certified Public Accountants. Weiner is a graduate of Bryant College.

Copyright ©2003 Medical Device & Diagnostic Industry

Establishing Overall Risk for Medical Devices

Originally Published MDDI February 2003


In addition to reducing individual risks, device makers must develop an overall risk index in accordance with ISO/IEC 14971, Clause 7.

Mike W. Schmidt

For medical device makers, identifying and reducing their individual product risks is no longer enough. Clause 7 of ISO/IEC 14971 (published in December of 2000) states that after product developers have reduced all individual risks associated with a medical device as far as is reasonably possible, they must establish an overall risk level. This level of overall risk must reflect the cumulative effects of the individual risks. The clause reads as follows:

After all risk control measures have been implemented and verified, the manufacturer shall decide if the overall residual risk posed by the medical device is acceptable using the criteria defined in the risk management plan. If the overall residual risk is judged unacceptable using the criteria established in the risk management plan, the manufacturer shall gather and review data and literature on the medical benefits of the intended use/intended purpose to determine if they outweigh the overall residual risk. If this evidence does not support the conclusion that the medical benefits outweigh the overall residual risk, then the risk remains unacceptable. The results of the overall residual risk evaluation shall be recorded in the risk management file.

Compliance is checked by inspection of the risk management file.

Currently, the supplementary document ISO/IEC 14971 Amendment 1 is in its final stages of development; no further technical changes will be made. This supplement does not change the normative requirements, but does provide rationales for them. 

With regard to Clause 7, “Overall Residual Risk Evaluation,” the draft amendment explains it as a requirement for a manufacturer to look not only at the acceptability of individual risks, but to evaluate whether the combination of all individual risks associated with the device exceeds acceptable levels. Amendment 1 states that even when all individual risks are considered acceptable, the cumulative effect of those risks may be unacceptable. It goes on to declare that even in cases where this overall or aggregate risk exceeds acceptable levels, a risk-benefit analysis may still demonstrate that what might otherwise be considered an unacceptable level of risk is acceptable in light of the benefits provided.

Both the original requirement set forth in Clause 7 and the rationale given in Clause H.2.7 exist to ensure that individual (residual) risks associated with a device have been reduced as far as is practicable and that the cumulative effect of those residual risks cannot present an unacceptable risk to patients, users, other parties, or the environment. Although this goal is a worthy one, establishing a method for achieving it that is acceptable to third-party auditors and regulators (that is, establishing an acceptable level for cumulative risk and evaluating a specific device against that level) is not easy.

What follows is an examination of the issues associated with ISO/IEC 14971:2000 Clause 7 and alternative approaches to compliance.

Figure 1. Example of a graph used for determining a risk index.

Establishing Risk Indices for Individual Hazards 

Before looking at potential methods for combining individual risks to determine an overall risk level, it is first necessary to review the method defined in ISO/IEC 14971: 2000 for establishing individual risk levels. In essence, the standard requires that all hazards (i.e., potential sources of harm) associated with the device be identified. For each of these hazards, the likelihood that the hazard will occur (i.e., the likelihood that the initiating event will happen and, when it does, that there will be exposure to the hazard) must be estimated. Likelihood can be expressed as a numeric probability, or simply as remote, possible, likely, certain, etc. In addition, the potential severity of the harm, which ranges from minor injury through severe injury to permanent injury or death, must be estimated. Finally, likelihood and severity must be combined to establish a risk index. Acceptable methods for combining likelihood and severity include graphically, as in Figure 1, or mathematically, by the following equation: 

Risk Index = Severity Index ¥ Likelihood Index 

(Establishing the likelihood and severity indices typically involves assigning an arbitrary numeric scale—such as 1 through 10—to achieve normalized values.)

Both the graphical and mathematical techniques yield essentially identical results, but when one is evaluating individual hazards, the mathematical approach makes the combination of all individual risk indices into an overall risk index for the device appear more straightforward. However, some who perform risk assessment criticize the use of conventional probabilities in these calculations, asserting that the format of these calculations implies an accuracy that is rarely achieved owing to the extensive effort required to maintain adequately high confidence intervals. These individuals also assert that even if such accuracy were achieved, the meaningfulness of that accuracy becomes moot when the probabilities are combined with the severity values. (The severity values are coarse estimations if they are “less than death” or “greater than none.”) 

Whether the mathematical or graphical method is used, the standard suggests risk levels be allocated into three basic categories: unacceptable, as low as reasonably practicable (ALARP), and broadly acceptable. Unacceptable risks are just as the name implies—unacceptable under any terms. ALARP risks may be acceptable if an evaluation shows that the resulting residual risk is justified because there are product benefits that offset it. Broadly acceptable risks are those that are low enough in severity, likelihood, or both to be roughly equivalent to the day-to-day risks encountered in ordinary life. Implicit in all three levels, especially in the latter two, is the recognition that “zero risk” does not exist.

Finally, it should be kept in mind that earlier approaches to assessing the risk of medical devices, which used only risk analysis, have been replaced by the life-cycle model inherent in risk management. Risk management recognizes that risk estimations made during product development are only highly educated guesses. It is imperative that the initial risk analysis be continuously updated based on real-world experience, and that appropriate action be taken to achieve acceptable risk levels based on those updates.

While the recent revision of H.2.7 deleted the directive “add up ” to avoid specifying a methodology, circumstances exist in which simply summing the individual risk indices has merit. Similarly, qualitative methods can be valid if they are applied consistently. What follows is an evaluation of some alternative methods for combining individual risks to determine whether the overall risk level is acceptable.

Summing the Severity of Hazards

Summing the severities of all individual hazards to determine their cumulative effect is reasonably valid assuming all hazards occur simultaneously or within a short enough period that their negative effects (i.e., injuries) would, in fact, be cumulative. This principle can be illustrated with the example of a bee sting. Although a single sting may be annoying, it is generally not considered a major injury. However, if an individual receives many stings over a short enough period that the venom from any one sting is not metabolized before subsequent stings occur, the resultant injury could be significant, even fatal. 

The bee-sting example demonstrates that for the additive method to reflect accurately the actual result, the effects of the individual hazards must be cumulative; i.e., each injury's severity is magnified by the occurrence of preceding injuries, in addition to the hazards' occurring during a compressed time frame. 

Summing the Likelihood That Hazards Will Occur

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Similarly, the accuracy of summing the likelihood that individual hazards will occur is affected by the independence of the events. This means that if the likelihood of the occurrence of one event is unaffected by the occurrence of a second, the likelihood or probability that one of the two will occur at any single point in time is represented by adding the likelihood of each occurring. The probability that the two independent events will occur simultaneously, however, is derived by multiplying the probability of each occurring, which results in a reduced probability of occurrence. (For purposes of this discussion, combining the likelihood of individual events is discussed in terms of conventional probability where a value of 1 indicates certainty of occurrence and all other possibilities are expressed as decimal values less than 1.)

Because the ISO/IEC 14971 standard requires that hazards (events resulting in specific injuries) be identified before evaluating the likelihood that the initiating event will occur, a robust risk evaluation process will tend to incorporate all dependent events that contribute to the realization of a specific hazard. Therefore, for purposes of evaluation of risks associated with a medical device according to ISO/ IEC 14971, it is reasonable to assume that the risks are independent.

Summing probabilities ignores the issue of a compressed time frame when one evaluates the summing of severity levels, however. In effect, this approach assumes that all injuries resulting from the use of the device over its lifetime will compound. Obviously, this assumption ignores whether the device will be used on many patients over several years. 

Summing Individual Risk Levels

Based on the critical factors associated with summing the severity of individual hazards as well as summing the individual probabilities of their occurrence, it becomes clear that to achieve an accurate result, the level of interdependence of the hazards in terms of severity and likelihood is crucial. While the likelihood of the occurrence of individual injuries can reasonably be considered independent within the context of risk analysis according to ISO/IEC 14971, the dependence of those injuries in terms of cumulative severity will vary dramatically depending on the device, the number of patients on which it is intended to be used, and the specific hazards involved.

However, it is certain that the additive technique will always yield the absolute worst-case cumulative risk levels, since it effectively takes as given that all severities are cumulative (that is, that each injury increases the effective severity of the others). This technique also takes for granted that individual events will occur simultaneously or within a short enough period to compound each other's severity. (Any such case will be described as simultaneous.) From the perspective of probabilities, it must be kept in mind that the likelihood that any one event will occur addresses all cases, including those where the other events occur simultaneously.

Consider the example of events A and B, each of which can occur with or without the other. To understand better how the additive method can artificially inflate the aggregate probability, assume that either event will occur without the other 50% of the time, and therefore will occur simultaneously 50% of the time. If A and B were each to occur 10 times in 1000 opportunities, then five of those 10 occurrences would be simultaneous. This means that the actual probability that the two events would occur simultaneously is 5 times in 1000 opportunities. However, the additive method would indicate that the probability of simultaneous occurrence is 20 times in 1000 opportunities (i.e., 10 + 10), thereby artificially inflating the likelihood four-fold.

Furthermore, it is clear that performing an in-depth analysis of the severities and probabilities of individual risks to accurately indicate how these risks will combine is almost certainly impractical in light of the urgency to get beneficial products to market. The primary shortcoming of this approach is that if the same scale or threshold to determine acceptability is used for cumulative risk as is used for individual risks, the cumulative risk value will nearly always exceed acceptable limits, since hundreds of individual risks are associated with most medical devices.

This issue can of course be overcome by simply creating a separate scale for cumulative risk with higher thresholds for broadly acceptable, ALARP, and unacceptable risks. However, manufacturers who decide to take such an approach should invest significant resources into documenting how their alternate scale was developed and justifying the thresholds selected. Failing to do so could easily leave the impression that these cumulative levels were developed to ensure that all products will fall within acceptable levels. Leaving this impression on regulators or a civil court during liability litigation could be quite costly. 

An alternative to creating a separate cumulative scale for acceptability is to simply exclude all individual risks that are within the broadly acceptable limits, summing only those risks that fall within the ALARP category. 

This alternative method sums the risk indices for all individual risks that are greater than the broadly acceptable threshold, and so ensures that the result will tend to be conservative (i.e., erring on the side of safety because they are based on the assumptions that risks are dependent and compounding). But results will not be so conservative as to require a higher level of safety than is achieved in ordinary day-to-day life, because risks that are broadly acceptable were disregarded. This method permits maximum flexibility, by allowing multiple ALARP risks at the lower end of the range or only one that falls within the upper limits. 

The main drawbacks of this approach, however, are that by dealing with calculated values, the accuracy of the system can be perceived as far greater than it actually is, and that in an attempt to achieve such high accuracy, the system can become inherently cumbersome and unworkable.

Combining Individual Risks Qualitatively

Taking a qualitative approach typically involves bringing together a review panel of individuals who have an adequate level of distance from the specific device's development to review the risk analysis objectively and determine whether the overall, cumulative level of residual risk for the device is acceptable. The panel must consider the benefits provided by the device compared to those of the available clinical alternatives, such as pharmaceuticals, and the level of residual risk provided by those alternatives, as well as by similar devices. 

Clause 3.3 of ISO/IEC 14971 also requires the manufacturer to define a policy or procedure for determining the acceptability of all risks, including the overall residual risk. Such policies, like all other aspects of risk management, are, of course, subject to ongoing review and revision based on field experience. In essence, this requirement is intended to ensure consistency from device to device.

Thus, when developing a qualitative system for assessing risk, it is critical that a company take the following 

        1.  Establish a set of rules that will be applied when evaluating individual and cumulative risks for all products. 
        2.  Document the specific qualifications (training, education, etc.) of those who will apply the rules. 
        3.  Confirm that personnel assigned to apply the rules are not directly involved in the design or development of the product being evaluated. 

Because the second and third items are typical for documented quality systems in general, the following discussion is limited to the principles used to generate the rules of acceptability.

Probably the simplest approach to setting such rules is to place a limit on the number of risks falling in the broadly acceptable and ALARP regions of the graphical analysis. Although this technique is simple in theory, it can cause difficulties when all risks are categorized as broadly acceptable and none fall within the ALARP range, yet the limit for broadly acceptable risks is exceeded. 

Of course, this same principle can be applied to actually overcome this difficulty. Since broadly acceptable risks are just that, a reasonable argument can be made that such risks should not be considered in establishing the acceptability of cumulative risks. Applying this argument eliminates the problem of deeming a product with only broadly acceptable risks unacceptable.

With this issue resolved, one final potential problem remains: If the quantity of ALARP risks serves as the final determinant of the acceptability of cumulative risk, how should the acceptable number of ALARPs for the device be determined? If the number is set assuming risks are at the high end of ALARP range (so that the maximum acceptable number of such risks is low), a device could have a quantity of individual risks that are barely within that range—realistically presenting a reasonably low overall risk level—but be rejected as unacceptable. If the acceptance level for the quantity of ALARP risks is set based on the assumption that they are all at the low end of the range (which then allows a larger number), a device that should be rejected for overall risk level could be considered acceptable. 

While these extreme examples can be addressed by assuming that the individual risks are at the median value of the ALARP range, the resulting limits will still be somewhat coarse and will carry the potential for inappropriate decisions. Furthermore, this method could be viewed as driving determinations of individual risk levels. For example, if a group making evaluations is readily aware that one more ALARP will put them over the acceptable-risk limit, the risk level selected for the next hazard identified might be perceived as suspect.

An alternative qualitative approach is to establish a group of experts with backgrounds in device regulation, liability, engineering (both electrical and mechanical, as appropriate), medical practice, and other areas. After this group reviews the risk assessments and all relevant safety-related information, each member of the group makes an acceptability determination from his or her own perspective. The group then attempts to reach consensus on the acceptability of the overall residual risk. Although this technique is subjective, it ensures that an appropriate evaluation is performed using predetermined limits for overall risk, and that various perspectives are considered.


As the ISO/IEC 14971 standard recognizes, the risk evaluation and estimation process will always be, at best, only partially scientific. What constitutes a broadly acceptable level of risk is driven by societal values, and perceptions are rarely based on quantifiable and predictable values.

Mike W. Schmidt is a senior standards compliance associate at Ethicon Endo-Surgery Inc. in Cincin-nati, OH. 

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Copyright ©2003 Medical Device & Diagnostic Industry

McClellan Hits the Ground Running

Originally Published MDDI February 2003


The new FDA commissioner is demonstrating an impressive decisiveness and understanding of agency bureaucracy. A top priority is reduction of medical errors.

James G. Dickinson

Who Reviews Combination Products? | Bard Avoids Liability for Labeling | Uterine Fibroids Device Cleared | Stair-Climbing Wheelchair | Carbon Dioxide Monitor Guidance | More Answers on Reprocessed Devices

By mid-December, after one month in office, FDA Commissioner Mark B. McClellan was making a mark as a leader who had hit the ground running. He impressed employees and outside observers alike as an extraordinarily quick study of the arcane labyrinth that is FDA.

In his first broadcast to all employees on December 3, McClellan hailed third-party inspections of medical device manufacturing facilities. Provided for in the new Medical Device User Fee and Modernization Act, the inspections are “a promising area for us,” he said, “to augment [our] limited regulatory resources.”

Responding to a question, he speculated that his background as an economist might bear fruit at FDA in a future initiative to apply cost-benefit analysis to the way the agency reviews product risks. He also identified reduction of medical errors as a top priority. 

Mark McClellan 
has proven to be a quick study of the agency.

Asked how FDA's postmarket surveillance responsibilities could be strengthened, he cited pilot programs in CDRH and sister centers that collect real-time information on the use of new products to identify problems more quickly. “By getting more information like that,” he said, “we can learn a lot more about why problems are occurring postmarket.” With such information, he added, FDA can, through updates to drug labels and to device guidances, “help people use the treatments in a way that will prevent errors.”

A few days later, McClellan's energy showed itself when a key FDA officer resigned. Kathryn Zoon, director of FDA's Center for Biologics Evaluation and Research (CBER), abruptly announced her resignation on December 13. Three days later, McClellan appointed Zoon's deputy director for medicine, virologist Jesse Goodman, MD, as her replacement. This unprecedented speed was made possible by McClellan's decision not to formally advertise the vacancy, as is usually done.

The last time a program center director of Zoon's rank left the agency was in January 1999, when CDRH director Bruce Burlington quit to join Wyeth-Ayerst. Then-commissioner Jane Henney took more than three months to name David Feigal as Burlington's successor.

Goodman joined FDA in 1998 as part of the Office of the Commissioner, where he led an interagency task force on antimicrobial resistance. “He later moved to CBER, where he has been active in a wide variety of clinical and public health issues including bioterrorism preparedness and response, product development, human subject protection, and blood and vaccine safety,” McClellan said in an e-mail to employees.

Who Reviews Combination Products?

When deciding which of its centers should be responsible for review of a combination product, should FDA change the way it decides that product's primary mode of action? Certainly not, Becton Dickinson regulatory affairs vice president Pat Shrader told an FDA hearing in November. 

The hearing was conducted to gather public input on the agency's formal establishment of an Office of Combination Products. Speaking on AdvaMed's behalf, Shrader said FDA's jurisdiction decisions over the past decade have produced a wealth of “interpretive instructions” on determining the primary mode of action. 

Pat Shrader spoke at a hearing on FDA's new Office 
of Combination Products.

More than 300 designation requests have been processed for potential combination products since FDA began looking at them in 1991, added David Fox, another speaker. Fox is a Hogan & Hartson attorney and former FDA Office of Chief Counsel senior drugs attorney. Many precedents were set in evaluating these requests, Fox said. They should be used to establish “limiting features,” he continued, to help decide combination product jurisdictional issues in the future. Without such limiting features, Fox warned, FDA could apply the principles that were unsuccessfully used when it attempted to regulate cigarettes as combination products.

Based on mode of action, many apparent combination products have successfully been classified as single-entity devices, Shrader pointed out. These types of decisions, such as those on drug-eluting stents and wound dressings containing antimicrobial agents, have served both industry and FDA well. She cautioned the agency not to alter the factors it now uses to interpret the mode of action. These factors include evaluation of the combined product instead of the relative contribution of each component, and the primary intended function of the combination product.

When instances arise where the primary mode of action is obscure, Shrader told FDA it should first look to see if a similar device has been approved or cleared but with a different intended use. If so, then the product should be reviewed by the same center. Doing so would help reduce instances in which multiple premarket review systems would be employed for a similar product, which could hinder future product development. 
Additionally, Shrader urged FDA to let individual companies decide whether to make dual submissions to different centers. And the fact that one center may have jurisdiction on the review side and another on the postmarket regulatory side should not influence any decision by the agency to require two separate application submissions, she added.

Bard Avoids Liability for Labeling

FDA's decision not to require patient-directed product labeling for an ambulatory, patient-controlled analgesia infusion pump (PCA pump) has allowed C. R. Bard to sidestep liability claims. Bard's pump was set up to deliver morphine when activated by a patient. The company was sued because one of its pumps delivered an overdose; a family member continued to activate the device while the patient was sleeping in the hospital following knee surgery. 

Bard's counsels successfully invoked Georgia's learned intermediary rule against a recent product liability claim in state court, affirmed by the Eleventh Circuit Court of Appeals. The learned intermediary defense has its roots in prescription drug liability cases. Many courts, including those in Georgia, recognize it in prescription medical device cases as well. 

The learned intermediary doctrine applies where drugs or medical devices are available to the public only by prescription from an authorized health professional. In such cases a manufacturer fulfills its duty to warn by advising the professional of the dangers of the product, and has no duty to warn the patient.

In this case, Ellis v. Bard, the plaintiff sought to assert an exception to the learned intermediary defense. As written by the Oklahoma Supreme Court (Edwards v. Basel Pharmaceuticals), it provided that “when the FDA requires warnings be given directly to the patient with a prescribed drug, an exception to the learned intermediary doctrine has occurred, and the manufacturer is not automatically shielded from liability by properly warning the prescribing physician.” 

However, in that case—unlike the Bard case in Georgia—FDA had required a patient package insert warning about risks associated with the product. Noting the difference, the Georgia appeals court ruled: “Without a specific FDA mandate in this case requiring a certain warning on a PCA pump, and in light of Georgia's well-established learned intermediary rule, we need not address whether an exception to Georgia's learned intermediary rule is warranted.” 

Uterine Fibroids Device Cleared 

Saying it could save many women from surgery, FDA in November gave BioSphere Medical 510(k) clearance to market its Embosphere Microspheres, which treat symptomatic uterine fibroids. Typically, women must have myomectomies (surgery that removes fibroids but leaves the uterus intact) or hysterectomies (surgery to remove the uterus) to treat the problem. The microspheres, however, shrink fibroids, and thus avoid the need for surgery.

According to the company, the miniature beads block the growth of fibroids by cutting off their blood supply. BioSphere Medical believes that Embosphere is “the first and only device to receive clearance from FDA for this indication.” 

In U.S. clinical trials involving 182 women, the company said, Embosphere Microspheres were shown to provide substantial improvement in major symptom categories, including pain, excessive bleeding, and bulk uterine. These improvements were similar to those experienced by hysterectomy-treated patients; however, significant adverse events were rare in the UFE group. Overall adverse events were fewer, in number and in severity, than in the hysterectomy group. Additionally, BioSphere said, at six months follow-up, the size of the fibroids and uteri decreased substantially among the UFE-treated group. 

In April 2000, FDA cleared Embosphere Microspheres for treating hypervascularized tumors and arteriovenous malformations.

Stair-Climbing Wheelchair 

An FDA panel has determined the iBOT 3000 investigative device to be safe and 

The mass media had a field day in November with the stair-climbing wheelchair. The new device was developed by Independence Technology. The iBOT 3000 Mobility System came before FDA's Orthopedic and Rehabilitation Devices Panel on November 20. Network television and wire services quickly issued stories describing the device's climbing capability and focusing on the news that the panel voted unanimously for its approval. FDA's concurrence would mark the first approval of such a device anywhere in the world, the company claimed.

The FDA panel, however, supported placing limitations on the device. First, it may be sold only with a doctor's prescription. Second, users must receive strict training to ensure proper device operation. Clinicians must undergo certification to train patients on the iBOT and, according to the panel, the company should update such certifications annually and as changes occur to the device.

Requiring the patient to have the use of at least one upper extremity for chair operation, the iBOT “operates on a system of electronic sensors, gyroscopes, and software,” the company said. Capable of providing mobility in confined spaces and at elevated heights, the device can also ascend and descend stairs, climb curbs, and traverse rough terrain.

A 20-subject pivotal trial proved the four-wheel-drive device to be relatively safe and effective. Adverse events in the trial included two bruises, five falls (two patients fell with their own mobility devices, and three fell with the iBOT), and four adverse events unrelated to use of the iBOT device.
Independence Technology (Warren, NJ) is a subsidiary of Johnson & Johnson. The iBOT was invented by Dean Kamen, better known in recent times for his nonmedical invention, the Segway Human Transporter.

Carbon Dioxide Monitor Guidance

CDRH has posted to its Web site a special controls guidance to describe a means by which cutaneous carbon dioxide (PcCO2) and oxygen (PcO2) monitor devices may comply with the requirement of special controls for Class II devices. Issued on December 13, the guidance is entitled Class II Special Controls Guidance Document: Cutaneous Carbon Dioxide (PcCO2) and Oxygen (PcO2) Monitors; Guidance for Industry and FDA. 

The new guidance supersedes a draft issued on February 12, 2002. The new guidance discusses the testing required to support either a traditional or abbreviated 510(k) for a cutaneous carbon dioxide or oxygen monitor. Such testing should be performed under the following conditions: 

• Ambient temperature between 15º and 35°C. 
• Barometric pressure between 68 and 106 kPa. 
• Ambient humidity between 30 and 90%. 
• Line voltage for line-powered devices between 110 and 125 V rms.

Each 510(k), the guidance says, should identify the risk analysis methods used to assess the risk profile in general, as well as the device's design and the analysis results. The submission should also explain how the device addresses the risks identified in the guidance, as well as any additional risks identified in the risk analysis. 

According to the document, health risks generally associated with these monitors are improper patient management, electrical shock or burns, and electromagnetic interference. Electromagnetic compatibility (EMC) is defined in the guidance as “the ability of a device to operate properly in its intended environment of use without introducing excessive electromagnetic disturbances into that environment.” A complete description of the monitor's EMC characteristics, it says, should be included in the 510(k), as well as information to verify those characteristics. 

“All devices should be tested,” the document says, “with the third wire ground connected at the plug end of the power cord.” An exception is devices intended for home use. Such devices should be tested “with the third wire ground disconnected at the plug end of the power cord.” 

The guidance can be accessed on FDA's Web site at ode/guidance/1335.html.

More Answers on Reprocessed Devices 

In its third addition to a July 2001 guidance, CDRH has released a revised final guidance on its single-use device reprocessing policy. The document is entitled Frequently-Asked-Questions about the Reprocessing and Reuse of Single-Use Devices by Third-Party and Hospital Reprocessors; Final Guidance for Industry and FDA Staff. The revision provides two new questions and answers, quoted below, concerning registration and device listing.

Q: My establishment is registered as a manufacturer of medical devices, some of which are labeled for single use. We also reprocess for reuse some of the single-use devices that we manufacture. Do we have to add the establishment operation type of “Reprocessor of Single-Use Devices” to our existing registration information?

A: Yes, your establishment needs to be registered for all of the operations that are being performed at the same location.

Q: My establishment is registered as a manufacturer of medical devices, some of which are labeled for single use. We also reprocess for reuse some of the single-use devices that we manufacture. Do we have to update our existing device listing information?

A: Yes, your establishment needs to have all of the operations that are being performed on a particular device listed with FDA.

The guidance may be accessed on FDA's Web site at ohip/guidance/1427.html.

Copyright ©2003 Medical Device & Diagnostic Industry