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Finding the Right Off-the-Shelf Requirements Management Tool

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Six programs help design engineers with requirements tracking, modeling, analysis, and other tasks necessary for design control.

Using a requirements management system (RMS) can help companies address the design input requirements of ISO 9000 and FDA's quality system regulation. If the system is well designed and executed, it can reduce development time and costs by reducing the number of design iterations. Such success depends on the tools you choose.

A number of off-the-shelf requirements management products are available to satisfy the needs of an RMS. Because of space limitations, this discussion is limited to only six (Table I). While not comprising an exhaustive list, the products represent the range of approaches to requirements management. A summary of the features and functions of these products is shown in Table II.

Company Product Web Site
Integrated Chipware RTM
Quality Systems & Software Doors
TD Technologies Slate
Ascent Logic RDD-100
Vitech Core
i-Logix, Inc. Statemate

Table I. The manufacturers of RMS tools and their Web site addresses. None of the products surveyed had any interface to project management software.

Function RTM Doors Slate RDD-100 Core Statemate
Sources Y Y Y Y Y N
Requirements Y Y Y Y Y Y
Analysis and modeling N E Y Y Y Y
Safety analysis Y N N N N N
Interface control documents Y Y Y Y Y Y
Specifications generator Y Y Y Y Y Y
Compliance matrix generator Y Y Y Y Y E
Management report generator Y Y Y Y Y N
External interfaces Y Y Y Limited Y Limited
Learning curve (weeks) 1 1 1 3­8 1 2­4
Cost per seat ($0,000) 7 5­14 15 21 8 25
Platform (PC/Mac/Unix) PC/U PC/U PC/U PC/M/U PC PC/U

Table II. The features and functions of requirements management tools. Y = Yes, N = No, and E = External interface.

Requirements-Tracking Products. If your RMS involves large numbers of requirements sources, multiple levels of specifications, and requirements traceability, Doors or RTM may fit your needs. These products are good general-purpose requirements databases and can serve as a front end to a complete RMS. Neither of these products includes an analysis and modeling engine, but each provides interfaces to modeling tools like Statemate.

Requirements and Modeling Products. If your RMS consists of a combination of complex requirements and rapid system modeling in order to validate requirements, Slate, Core, or RDD-100 may help you keep organized. All these tools include both requirements and modeling components. RDD-100 has a significant learning curve but is a very powerful management tool.

Modeling and Simulation Products. If your RMS focuses on detailed product simulations and virtual prototyping, Statemate is a product that can handle these needs as well as interface with other products. It is a powerful function- and behavior-modeling tool with interfaces to requirements-tracking tools like RTM and Doors.

For a detailed comparison of these and other RMS products, check the International Council on Systems Engineering (INCOSE) Web page. According to the site, INCOSE is "an international organization formed to develop, nurture, and enhance the interdisciplinary approach and means to enable the realization of successful systems." INCOSE works with industry, academia, and government.

Edward V. LaBudde is managing director of LaBudde Systems (Westlake Village, CA).

Copyright ©1997 Medical Device & Diagnostic Industry

Industry and FDA Spar Over Labeling

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


For the medical device industry, FDA's new labeling initiative is just another case of treating devices like drugs. For FDA, it's just a modest attempt to help device users.

James G. Dickinson

FDA Reform Bill Stalls
HIMA­FDA Workshop Successes

Medical devices are not like drugs; FDA agrees with industry on that. But on the question of whether devices should be treated a little bit more like drugs, FDA and industry begin to part company.

The gulf widened in July during a Health Industry Manufacturers Association (HIMA) device submissions workshop with FDA in Washington, after Susan Alpert, director of the Office of Device Evaluation at CDRH, and Dan Spyker, deputy director of cardiovascular, respiratory, and neurological devices, described the center's new initiative to establish an abbreviated "essential prescribing information" (EPI) section in device labeling.

Until they did that, everything at the three-day meeting (HIMA's seventh such annual event) had been moving along just fine. It went well enough, in fact, to be ranked among the best U.S. regulatory meetings yet, regardless of product or industry category, because of its excellent regulator-manufacturer interactivity.

But you can snuggle up to FDA just so far before you find there are barbs of different kinds under the soft fuzz. In this case, the barb was FDA's well-meaning intention to solve the universal problem of health-care practitioners simply being oblivious to medical product labeling.

Alpert pointed out that FDA has conducted focus groups that demonstrate this to be the case, and in the spirited discussion that followed, nobody from industry disagreed. Alpert assured the HIMA workshop audience that "we don't have all the answers." She wants to work out a solution cooperatively with industry and practitioners, putting forth the draft EPI document as the basis for discussion. For most devices, she suggested, this modest concept would result in a summary of the most important information consisting of less than one page, although perhaps a bit more space would be required for extremely sophisticated devices like MRIs.

Although the document "Medical Device Labeling­Suggested Format and Content: Draft Document" was first exposed in April on the Internet, it seems few in industry noticed it there. Thus, the HIMA workshop was most manufacturers' first direct encounter with the draft, which was stuffed into every attendee's registration kit.

Lou Mazzarese, vice president for quality and regulatory affairs at U.S. Surgical Corp. (Norwalk, CT), greeted the Alpert-Spyker show with a blast that would be just the first of many. "We're in Washington," he observed acidly, "and to borrow from Reagan, 'Here they go again!'"

Mazzarese agreed with Alpert that health-care professionals do not read the existing labeling for medical devices. "But beyond that," he said, "we start to sustain some significant differences of opinion. This is disguised under the old practice-of-medicine [issue]. The FDA is continuing to focus on putting the onus of getting physicians to do [their jobs] on the backs of device manufacturers under the guise of these wonderful terms, essential prescribing information, abstracts, important information.

"I would submit," he continued, "that words like essential and important exist in the eyes of the beholder. I can't begin to design a label for my product that's going to be essential or important to every physician or every user of my product." In a dash of dark humor, Mazzarese suggested that "future sessions of Congress will accuse FDA of singular responsibility for eliminating what's left of the rain forest! We need to step back and focus on the need. I would submit that the need espoused by FDA is seriously flawed, so much so as to preclude any further discussion of when we do the EPI, or where or how. Let's get back to the need. Ever since the Temple Report [critiquing CDRH's device review processes], things like this at CDRH are part of trying to make devices more like drugs."

HIMA's Marlene Tandy thought the center's efforts would be better spent in medical schools encouraging or training doctors to do a better job of reading existing labeling, rather than creating another piece of labeling. Eve Ross of W.L. Gore & Associates (Newark, DE) took a less direct tack, professing confusion over the mixed messages FDA was sending about cooperation with industry. She agreed that device labeling simply isn't read and noted that physicians had stayed away in droves from FDA's focus groups about labeling, "which shows how important they think this topic is." Nurses, who account for 80% of those who do read medical product labeling, mainly for drugs, also told FDA they don't read device labeling, Ross said, and that if they were to read the labels, they would want them to be shorter.

"I am very concerned about Dr. Spyker's labeling guidance," Ross said. "Except for dental floss, I can't imagine putting the labeling into less than 12 pages. We do clinical studies for this labeling to produce information that, frankly, will never be read. I wonder how all this fits together."

And so it went. Nobody had a kind word to say about the CDRH device labeling initiative. Again and again, the theme came out of the audience: Devices are not like drugs.

The outnumbered Alpert and Spyker earnestly strove to turn the tide. Need had already been shown, Alpert protested, in FDA focus groups. The evidence showed, she said, that device users "simply don't know what's on the label. And we are not trying to make this education job the responsibility of manufacturers. What we're trying to do is make this information accessible."

Most important, she asked, when will the device industry admit that "labeling isn't a drugs issue, labeling is a products issue"? CDRH is "not trying to make drugs out of medical devices," she asserted. "What we are trying to do here is provide some consistent access to certain kinds of information that are useful to practitioners, like adverse events, contraindications, important things about precautions in handling patients. It's not to make them drugs­we know they're not. There are lots of devices where the practitioner knows you don't need much on the label except the name of what it is, and we're not trying to change that. We're trying to say where and when you need this information, how you organize it. Nothing more than that."

A skeptical questioner continued to see this as a burden being unreasonably put on the backs of device companies. "Why not put it on your Web site," he asked Alpert, "and publish it, and give people one place to go for the contraindications?"

Alpert replied that FDA might just do that. "Maybe not on our Web site, but someplace. I think that's a great idea. Maybe there's a way to globalize this information. I totally agree." Another questioner, however, rose to call this whole Web idea ridiculous. To avoid product liability lawsuits, no manufacturer would dare separate the product from its labeling in this way, he scoffed.

Exasperated by the rising wall of industry resistance to what FDA was trying to say, Spyker at one point countered Mazzarese's Reagan quip by invoking George Bush: "Read my lips: No new policies! One size does not fit all." After the lengthy presentations he and Alpert had made, Spyker seemed bewildered that their points had not come across. The draft guideline was not a new burden, he said, and there was no new labeling being proposed. "It's not our intention to make this an onerous task. It's not our intention to change what you're currently doing." Instead, the two maintained, FDA's intention is simply to have companies create a brief summary of their existing product labeling­an addition rather than a change.

Devices, of course, are not like drugs. But there is something very familiar about this device industry reaction to an FDA plan to make product labeling more useful to users. Industry can find nothing good to say about it­which is precisely what put the kibosh on FDA's 1979 plan to require patient package inserts in every dispensed pharmacy package of prescription drugs. The industry saw that as an unreasonable burden, and incoming president Ronald Reagan agreed immediately.

Maybe, then, devices are just a little bit like drugs?

The much-hoped-for FDA reform legislation was swept from the Senate's scheduled floor debate by the Democrats, led by Edward Kennedy (D­MA). The Democrats feared, among other things, that language aimed at keeping FDA out of off-label uses of medical devices would automatically prevent the agency from effectively regulating tobacco as a drug-delivery device.

Until this 11th-hour upset, senate passage of a bipartisan consensus bill before Congress adjourned for the summer had seemed assured. That would have left the House with little to do after the recess but join the parade. The president's signature seemed certain.

At the time of this writing, everyone was waiting to see what would happen, fearful that the loss of momentum would give outnumbered opponents all they needed to derail the bill by making a partisan squabble after the recess. The pharmaceutical industry, which had hitched its wagon to a broadly based bill that included device reforms, was rumored to be unhitching it in order to push through uncontentious renewal of prescription drug user fees, until now part of the overall bill, as a separate bill, unencumbered by medical device or other issues.

In its total spread of business, HIMA's July device submission meeting did far more in its three days than air dissension over FDA's labeling ideas. A great deal of constructive discussion, for example, occurred in six break-out sessions focusing on the reengineering efforts of the main reviewing divisions in the Office of Device Evaluation, with each of the division directors present. HIMA special counsel Nancy Singer, who is mainly responsible for the success of this annual event, asked participants to recognize that it's a hard thing for FDA managers to sit in these break-out sessions and hear all the suggestions­ "It's like listening to your customers!"

U.S. Surgical Corp.'s Lou Mazzarese reported on the final day on his group's lively discussions with Lillian Yin about her division of reproductive, abdominal, ENT, and radiological devices. Mazzarese said Yin has set review-time targets for 510(k)s and premarket approval (PMA) applications and exceeded many of them. Confidentiality is a big concern with Yin's new product development protocol (PDP) initiative, since manufacturers must go to panel early, in open public hearings. FDA is looking into that problem. Reviewers' questions to companies appear to be reasonable and pertinent to an application, but they aren't always consistent with public health. "There is still a tendency," Mazzarese said, "to address individual reviewer issues and preferences. Sometimes those particular types of questions may not necessarily [relate] directly to public health." Among the group's suggestions were improving reviewer-to-reviewer consistency, empowering reviewers to make scientific judgments, ensuring early dialog between sponsors and reviewers regarding review expectations, and urging manufacturers to make their initial submissions more complete.

Andrew Balo of St. Jude Medical (St. Paul, MN) reported on his group, which dealt with cardiovascular, respiratory, and neurological devices. Division director Tom Callahan told the group of a tenfold increase in investigational device exemption supplements in the last two years. He also reported that with more pre­PMA submission meetings to improve submission quality, CDRH could triple its output. Already this year 11 PMA applications have been approved compared with 6 for all of 1996, and Callahan expects the center will approve another 6 by year's end.

Requirements and expectations for submissions have not been clearly explained to companies by FDA, and reviewers' questions differ from person to person and division to division, Balo reported. The group was nearly unanimous that much of the information companies are required to provide doesn't bear directly on public health. Callahan feels that if companies were more cooperative with FDA reviewers and less antagonistic, that would eliminate many problems, because a lot of the questions arise from distrust.

Balo said his group also feels that the 510(k) process for these types of devices has slowed down since last year. According to the group, the reviewers need a better understanding of product technology, to make their questions to companies more pertinent. "A lot of the questions companies are getting back from FDA seem to be rote questions used before. FDA is just not looking into the specific device and the specific technology."

Representatives of the other four sessions reported similar assessments of the review process in their respective divisions. Virtually all agreed that the review process within FDA has become more reasonable, but that too many questions to companies bear little on public health.

Office of Device Evaluation director Susan Alpert said later that device reviewers' questions to sponsors are not supposed to be limited to matters bearing on the public health. She conceded, however, that reviewers should explain the reasons for their questions­"We don't do a good job of that," she said.

Copyright ©1997 Medical Device & Diagnostic Industry

Lasers Illuminate New Frontiers in Medicine

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Working on a microscopic level, new laser applications perforate, move, cut, and map human cells.

Long a mainstay of surgical applications, medical lasers are finding their way into ever more diverse niches. Some of these applications are within the medical mainstream; others are found outside, in the distant regions of bioscience, where their uses are guided by quantum theory.

This span of applications is bridged by the nature of laser light itself­a beam composed of nearly massless particles imparting energy that in one instance explodes cells and in another harmlessly holds them in place like a pair of subatomic tweezers. Laser light can map the topographical surfaces of wounds or­potentially­distinguish between cancerous and healthy tissue.

The Lasette (Cell Robotics, Albuquerque) uses MCR technology to decrease its size.


A new product that is near at hand is the laser-based lancet, a battery-powered laser designed to replace the stainless-steel products jabbed daily into countless fingers around the globe. Two companies are jockeying for the lead in this new marketplace. Both received FDA clearance this year.

TransMedica International, Inc. (Little Rock, AR), offers the Laser Lancet; Cell Robotics, Inc. (Albuquerque), the Lasette. Both are extensions of the laser scalpels first used by surgeons years ago. But this new breed of laser is distinguished by its limited cutting power and greater portability. These battery-powered lasers penetrate only to the capillary level, freeing a drop or two of blood in the process­enough to allow simple blood tests.

Using these lasers, health-care workers can reduce the risk of infection by bloodborne diseases, including HIV and hepatitis. But it is the patient who will reap the everyday reward­avoiding pain. "The sensation is gone before you see the blood," says Charles Vestal, president of TransMedica.

The Laser Lancet (TransMedica International, Little Rock, AR) penetrates human skin almost painlessly.A laser-assisted egg-hatching technique may improve the success of in vitro fertilization (Cell Robotics).Lasers weaken the ovum's shell without injuring its contents.

Laser-based lancets are virtually painless because the light beam vaporizes tissue rather than tearing it. Energy carried by photons excited with an erbium: YAG laser is absorbed by the water inside cells. The water turns instantly to steam, causing the cells to explode along the narrow path of the beam.

The device is expected to be especially appealing to diabetics, particularly the 800,000 Americans who have Type I diabetes. These patients require daily insulin injections and are advised to check blood glucose levels at least four times a day to help control the disease.

The device that promises to make this daily regimen less onerous was started not in the United States but in Russia, where Vestal, a hard-core entrepreneur, was exploring opportunities to distribute chicken from Little Rock's Tyson Foods. "I wasn't there more than a couple of days when this top expert in lasers walked in the door and asked if I would like to look at lasers that had never been seen before in the West," Vestal recalls. "I said, 'Yeah, cool.' "

The basic laser device was available, but Vestal still needed to add the electronics and other components that would make it a medical product. Those were designed by engineers in Little Rock, with the assistance of experts at Massachusetts General Hospital in Boston. As currently constructed, the Laser Lancet sends a laser pulse through a disposable plastic tube, creating a small slit, usually in the fingertip of the patient.

Size, however, is a problem. "Right now it is about as big as a loaf of bread­but we're working to get products that are much, much smaller," Vestal says.

Cell Robotics has an edge in the race to miniaturize. Its Lasette is just 7 in. long and fits in a zipper notebook similar to those used to carry daily planners.

The Lasette is also very light, less than 2 lb. It has an adjustable power setting to penetrate different skin types, as well as the necessary safety features. But the feature that really stands out about this new product is its use of rugged, solid-state technology.

The Albuquerque company achieved the laser's size and durability by using the multifaceted crystal resonator (MCR), a technology that permits the design and cost-effective manufacture of compact but powerful solid-state or crystal lasers. MCR, which Cell Robotics acquired in early 1996 from Tecnal Products, Inc. (Albuquerque), is a way of making laser crystals that act as their own resonators. Without mirrors, the laser can be made smaller and is less likely to malfunction from being jostled. "You can just put the crystals in and not spend a lot of time tuning up the laser," says David Costello, Lasette product manager. "Basically it's a way to make one laser after another very quickly and have them all work pretty much the same."


Just as lasers can create wounds, they can also map them. In much the same way lasers probe the earth's surface from orbit, laser light is being harnessed to scan the topography of torn human tissue. Using an off-the-shelf diode laser and legacy PC, Daniel Smith, PhD, and his colleagues at the University of Akron (Akron, OH) have constructed a device that profiles superficial injuries in three dimensions. These profiles might be used to evaluate wound repair or burn depth, to assess surgical reconstructions, to treat scarring, or to perform cosmetic surgery.

"Right now, determining whether a wound is healing on a day-to-day or week-to-week basis is reasonably subjective," says Smith, a professor of chemistry and biomedical engineering. His laser system would remedy that.

Red laser light emitted by a diode scans the surface of the wound, reflecting light to a sensor that generates a signal corresponding to the wound's topography. A sound generator, mounted beside the diode laser, emits high-pitch waves that complement the laser light, reflecting off the tissue and demonstrating surface texture. This texture indicates rate of healing, as the wound goes from a jelly to a progressively more ordered state. The data are represented in a kind of three-dimensional map constructed and displayed on a PC screen.

This three-dimensional measurement system could help people evaluate the wound-healing products now being developed, Smith says. "There's going to be a cost/benefit question," he explains. "Is it worth putting a lot of money into this product? Probably, if it makes the person heal 50% faster."

Modeling surfaces in three dimensions, says Smith, is already widely used outside of health care. For example, makers of extruded pipe and tubing use such systems to monitor product quality. But in that application, the products whiz by on an assembly line and the laser shoots them as they pass. In a medical application, the patient is stationary, which makes conducting a scan problematic.

Smith solved the problem by setting the laser and its accompanying sound generator in motion along the x and y planes of a table positioned above the wound. "It just goes back and forth­bam, bam, bam," explains Smith. A 30-second scan can cover a wound about two inches square, he says. Processing the image takes about 4 minutes.

The next engineering challenge is to eliminate the positioning table by electronically or mechanically steering the laser and sound generator. Ideally, the two energy sources would be mounted on a robotic arm, relaying spatial coordinates to the computer.


Somewhere between the effect of a laser-based lancet that penetrates tissue and light beams that bounce inconsequentially off wound surfaces are the LaserTweezers and LaserScissors, both developed by Cell Robotics.

The tweezers use a technique called optical trapping to catch and hold living cells and particles. Optical trapping is accomplished by photons that go through, rather than bounce off, a target. The photons are refracted slightly, imparting momentum to the surface that has bent their trajectory. The surface moves opposite the photons, like a backlash, pulling the cell toward the source of the laser light and effectively trapping it in the beam. The LaserScissors, essentially a highly focused and targeted laser beam, is then used to remove selected parts of the target.

These technologies have been used in the pursuit of basic science­to tease apart cells or document the functions of different organelles. But recently, engineers at Cell Robotics have applied these advanced techniques to medicine.


Using the company's in vitro fertilization (IVF) workstation, a fertilized human egg can be held in place by the LaserTweezers while a computer aims and then focuses a laser to weaken the shell of the ovum. Weakening the egg improves the chance that a viable embryo will hatch.

"Much of the problem that women in their late 30s and early 40s have becoming pregnant is not so much getting an embryo started but getting the embryo to break out," says Ronald Lohrding, PhD, chairman, CEO, and president of Cell Robotics. "When women approach 40, the shells become tougher."

Preliminary clinical results indicate that the laser-assisted hatching technique developed by Cell Robotics may triple the IVF success rate of these women. "We're able to cut little trenches in the shell so the embryo can crack the egg," Lohrding says.

The chief technical challenge facing engineers developing this workstation was to accomplish the critical weakening of the shell without injuring the fragile contents. "There had to be no possibility of damaging the DNA or the proteins associated with the embryo," Lohrding says. That meant choosing wavelengths shorter than visible light but capable of passing through the objective of a microscope.

Ultimately, the design task was simplified by having already developed technologies capable of optical trapping and optical cutting­the LaserTweezers and LaserScissors. "We already had the precision with which we could move and position the egg and accurately score the shell," he says.

The IVF workstation has everything needed to perform in vitro fertilization, from injecting sperm into the egg to improving the chance of hatching the egg. The product is already approved for use in Europe and has entered FDA-sanctioned clinical trials in Europe, Israel, and the United States.


Laser light unleashed inside the human body may provide information about the health of tissue, indicated by its fluorescence. Xillix Technologies Corp. (Richmond, BC, Canada) has developed a laser-induced fluorescence endoscopy (LIFE) system for detecting lung and gastrointestinal cancers. Bruno Jaggi, Xillix cofounder and chief engineer, believes that diseased tissue as small as 1 mm can be accurately identified with this technology.

The process begins with ultraviolet light emitted by an HeCd laser and fired through an endoscope or bronchoscope. The light is absorbed by tissue and causes a fluorescence that is picked up by a bundle of optical fibers feeding into mirrors and spectral filters. The light is split into red and green bands, each recorded by a charge-coupled device, processed by computer, and output in real time on a video monitor.

Healthy tissue returns a signal in the green band about eight times stronger than that of diseased tissue, says Jaggi. But distance from the fluorescing tissue also affects the strength of the green band, which could skew results. That, says Jaggi, is the reason for recording the red band, which shows very little difference between healthy or diseased tissue and thereby serves as a benchmark. "If you have a large change in the green due to an actual change in the spectrum, the ratio between green and red will change," he says. "If you have a change just because you go farther or closer to the tissue (with the endoscope), the ratio will not change."

Scientists working in this promising area must take a tentative approach, however. Whether cancerous and healthy tissues demonstrate such clear-cut differences in fluorescence is still debated by researchers.

The signals retrieved from fluorescence are very small. "You don't have that many photons to work with," Jaggi says. And human tissue is not the only source of fluorescence. Some bacteria fluoresce, as do the bits of feces and partially digested foods within the gastrointestinal tract.

It is not surprising, therefore, that a white-light endoscope has been tied into this system as a kind of medical fail-safe. "We think the way to introduce this new technology is in small steps," Jaggi says. "Physicians have used white light for the last 20 years. They are very good at looking at these images. What we're really saying is, 'Look, we're just providing you with new information in addition to what you already have.' "

So it is with the most far-reaching laser applications. Their true value relies as much on increased understanding of the human body as on technological development. Where these niche applications­and the technologies that drive them­will ultimately take medicine is one of the unknowns that drive pioneers in this industry.

Copyright ©1997 Medical Device & Diagnostic Industry

California Home to Almost One-Fifth of U.S. Device Industry

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


The Golden State has nearly 2000 medical device manufacturers and contract manufacturers, making the Pacific the largest region for device makers in the United States.

With almost one out of every five medical device manufacturers, California tops every other state in the union. This year the Golden State boasts nearly 20% of the total number of U.S. device manufacturers with just under 2000 companies, according to figures compiled by the FDA Center for Devices and Radiological Health's Division of Small Manufacturers Assistance (DSMA).

Figure 1. A breakdown of U.S. medical device manufacturers (including contract manufacturers) showing their geographic distribution among the top six states and the remaining states.

DSMA's deputy director, Lynne Rice, has noticed little rotation among the states. "Over the years, five states—California, New York, Illinois, Massachusetts, and Texas—have consistently led the list," she explains. "Unfortunately, because DSMA doesn't factor into the statistics the types of devices the firms manufacture, we can't pinpoint whether there is a relation between products and location."

The main reasons DSMA compiles these numbers, says Rice, are for planning workshops and watching for any shifts in the industry. "We want to know where the regulated industry is so we know where to put our resources," Rice explains.

Overall, the total number of registered medical device establishments, a group that includes initial distributors of imported devices, domestic distributors, manufacturers and contract manufacturers, specification developers, rebuilders and refurbishers, contract sterilizers, and repackagers and relabelers, has also grown (Table I). Every establishment category save for one—repackagers and relabelers—has expanded. Since 1994, the number of repackagers and relabelers has been declining. But 1997's drop of 313 was the most significant, as compared to 1995's decline of 143 and 1996's decline of 132.

Establishment Types 1994 1995 1996 1997
Initial distributors of imported devices 12,162 11,446 11,378 11,502
Domestic distributors 844 830 783 862
Contract manufacturers 2,297 2,423 2,106 2,196
Manufacturers 8,993 9,043 9,132 9,252
Specification developers 2,037 2,252 2,129 2,328
Rebuilders and refurbishers 670 778 805 826
Contract sterilizers 173 179 152 158
Repackagers and relabelers 4,116 3,973 3,841 3,528
Total 31,292 30,924 30,326 30,652

Table I. A breakdown of the number of FDA-registered establishments by type in August 1994, August 1995, July 1996, and July 1997.

The number of U.S. registered medical device manufacturers, including contract manufacturers, increased only slightly (2%), from 10,230 in 1996 to 10,420 this year. Such small growth doesn't necessarily mean the industry is stagnating, however. "It is just the natural growth of the industry," says Rice. "It represents the number of firms both entering and leaving the industry. When there is even a slight growth, it means we have more firms entering than leaving."

A few states did record notable growth, such as California, Texas, and Florida, which acquired 24, 24, and 20 new firms, respectively. (See Table II for the number of manufacturers registered in each state.)

State Manufacturersa Percentage
of Total
California 1971 18.92 4667
New York 791 7.59 2595
Illinois 633 6.07 1534
Massachusetts 587 5.63 1039
Texas 531 5.10 1162
Florida 497 4.77 1329
Pennsylvania 389 3.73 757
New Jersey 379 3.64 1026
Minnesota 334 3.21 565
Ohio 314 3.01 546
Connecticut 254 2.44 522
Michigan 253 2.43 507
Colorado 226 2.17 374
Maryland 214 2.05 470
Wisconsin 213 2.04 340
Indiana 204 1.96 335
Missouri 203 1.95 371
North Carolina 191 1.83 327
Virginia 178 1.71 432
Washington 163 1.56 389
Georgia 161 1.55 430
Arizona 157 1.51 310
Tennessee 156 1.50 291
Utah 137 1.31 212
Oregon 129 1.24 222
Puerto Rico 127 1.22 291
New Hampshire 96 0.92 148
Kansas 81 0.78 146
Oklahoma 72 0.69 138
Alabama 68 0.65 130
South Carolina 67 0.64 126
Rhode Island 66 0.63 130
Nevada 65 0.62 147
Iowa 52 0.50 90
Maine 45 0.43 76
Nebraska 45 0.43 73
Louisiana 44 0.42 93
Kentucky 42 0.40 81
Arkansas 39 0.37 77
Mississippi 37 0.36 58
New Mexico 34 0.33 58
Idaho 30 0.29 45
Vermont 26 0.25 50
West Virginia 24 0.23 42
Montana 21 0.20 35
South Dakota 21 0.20 35
Delaware 18 0.17 43
Hawaii 16 0.15 220
North Dakota 9 0.09 22
Washington, DC 7 0.07 55
Wyoming 3 0.03 7
Alaska 0 0.00 5
Guam 0 0.00 2
Virgin Islands 0 0.00 3
Totals 10,420 100.00 23,178
a Includes contract manufacturers.
b Includes initial distributors of imported devices, domestic distributors, contract manufacturers, manufacturers, specification developers, rebuilders and refurbishers, contract sterilizers, and repackagers and relabelers.
Source: FDA Division of Small Manufacturers Assistance.

Table II. State-by-state breakdown of the number of FDA-registered manufacturers and establishments as of July 30, 1997.

Home to such large FDA districts as Los Angeles and San Francisco, the Pacific region continues to contain the most manufacturers, nearly 25% of the entire industry. The Northeast region follows with just under 18% (Figure 2).

Figure 2. The number (and percent of U.S. total) of device manufacturers and contract manufacturers registered with FDA as of July 30, 1997, by region.

Copyright ©1997 Medical Device & Diagnostic Industry

Documenting a Failure Investigation

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Anita Thibeault, president of Anita Thibeault & Associates (Rogers, AR) and an MD&DI editorial advisory board member, explains how to properly document an investigation of a product, process, or quality system failure.

What is the proper way to document a failure investigation and the proper method of linking all failure investigations to a company's quality system?

FDA's quality system regulation includes requirements for failure investigations in several subsections of 21 CFR 820. The most commonly referenced section for failure investigations is the one dealing with complaints, section 820.198. However, there are others that include requirements for failure investigations, namely 820.90 on nonconforming product and 820.100 on corrective and preventive actions. Complaints, described in section 820.198, usually involve failure of a product. Section 820.90 deals with disposition of nonconforming product, requiring manufacturers to evaluate the need for an investigation of the problem. Section 820.100 deals with failure investigations for products, processes, and quality system element failures.

Despite all these mentions, there is no specific language in the regulation on what information is required for the documentation of the performance of a failure investigation. The regulation does state that causes of nonconformances relating to product, processes, and the quality system must be investigated and corrected in a manner that prevents the problem's recurrence. The corrective action chosen must be verified or validated to ensure that it is effective and does not adversely affect finished devices. Information on the cause of the problem must be disseminated to those directly responsible for ensuring product quality or problem prevention. The regulation, under section 820.100, requires that the activities and their results be documented.

The intent of the regulation is that manufacturers conduct investigations to a degree commensurate with the significance and risk of the nonconformance. Some times a very in-depth investigation is necessary and at other times a simple investigation can be performed and tools applied to monitor the problem in the future.

Proper documentation of a failure investigation should include the following information, at a minimum:

Unique Identification of the Failure Investigation. Investigators should use some element such as title, date, report number, or control number. This is necessary to trace the information and to monitor the status of the investigation. They should also identify the product, item, process, or quality system being investigated.

Description of the Problem. Investigators should either directly state or reference a complaint or nonconformance report. This information is used to trace the investigation to a reported problem and to provide historical data for future trend analysis.

Level of Necessary Investigation. Investigators need to decide whether an investigation will be simple, in-depth, or something in between, and explain their choice of approach. Not all problems require the same depth of investigation, so it is important that investigators state the reason for the level of investigation performed. This will help reviewers understand the investigation's results and conclusions. This information also provides historical data for future analysis.

Investigation Method, Procedures, Tests, and Inspections. During later analyses, reviewers will need to understand how the data were obtained. Without such information they will not be able to understand the foundation of the investigation or what the data mean. Omission of such information is analogous to omission of calibration on a tool used to measure a characteristic necessary for product acceptance.

Tools Used in the Investigation and Their Unique Identification. This information is used to trace each tool's calibration to ensure that the data are valid and can support the objective evidence.

Description of Examined Documentation, Components, Parts, Labeling, Packaging, and Processes. To analyze future problems, reviewers need to understand exactly what information was used to investigate a problem. Understanding such information helps reviewers make sense out of the collected data and conclusions. This information also provides the objective evidence necessary to support compliance with standards and regulations.

The Results of All Testing, Inspections, and Examinations. Such records substantiate the conclusions and the recommended corrective actions. This information can be attached to the failure investigation or referenced to a location where the records are maintained.

Analysis of the Results and the Analysis Methods. This information supports the conclusions and the recommended corrective actions. To use the information in the future, whether for analysis of other problems or for support of compliance to standards or regulations, reviewers need to know the method of analysis.

Cross-References to Other Failure Investigations, Complaints, Nonconformance Reports, and Other Sources Applicable to the Analysis. This information is necessary to establish links to the quality system and also to provide complete information for system analysis. For analysis of the quality system, it is necessary to evaluate system elements, such as problem identification and correction, for effectiveness. By combining related information concerning all kinds of failures, reviewers can determine the effectiveness of the higher-level system element. This information is then used to improve the quality system.

Signature of All Persons Who Investigated the Problem and Dates They Performed Tests and Examinations. Signatures and dates can be used in future analysis, either to support compliance to a standard or regulation or to identify investigators who can clarify data.

Actual Results of the Testing and Examinations. To provide a complete documentation package of an activity, investigators should include the actual data collected. Such data provide additional information on data collection and recording. This information can be used in later evaluations and to support compliance to standards and regulations.

Report of the Conclusions to Demonstrate Adequate Closure. Such documentation allows reviewers as well as technical personnel to understand the results of the investigation and the relationship to proposed corrective actions.

Recommendations for Corrective Actions to Prevent Recurrence of the Problem. When investigators have completed their work and analyzed the results, they should recommend a solution to the problem. This supports the corrective and preventive action quality system element and ensures quality system effectiveness.

Formal Acceptance and Closure of the Failure Investigation. This activity and subsequent documentation of its performance ensure that the activity was performed, reviewed, accepted, and completed. For a quality system to be effective, each activity must be performed correctly and meet system requirements. By formally reviewing all investigation files for completeness, soundness of data, and conclusions, reviewers can prove compliance with the quality system elements and standards and regulations.

Additional information, determined by whether the investigation requires root cause analysis and by the extent of the risk of problem recurrence, may be added.

The steps listed above are needed to provide complete information about the problem and to serve as a repository of information that can be used by other personnel and external auditors and assessors. Reviewers need such information to understand the cause of the problem and the choice of the corrective action as well as to prove that the company's own procedures were followed and that voluntary standards and regulations are being met.

A company's quality system should have cross-links between all its elements in the appropriate places. Failure investigations can be linked to various elements of the quality system by using procedures that state requirements for failure investigations and formal closure of activities. For example, if a complaint is received and the evaluation determines that a failure investigation is required, the quality system should include a procedure to govern failure investigations, their performance, the documentation required, and the management of the investigations. Typical management techniques include the creation of an official record for each investigation through the use of a log that records a unique number to identify the open investigation. This log is then used to manage the failure investigation by monitoring its status until it is formally closed. There should be rules for failure investigations that state acceptable time frames for performance and closure. Because real life is not perfect, the procedure should also include methods that can be used to extend time frames.

If this type of failure investigation procedure is used, then other quality system procedures, such as nonconformance handling, corrective and preventive actions, quality recordkeeping, document control, calibration handling, facility maintenance, and equipment maintenance, should include requirements for using the failure investigation procedure. Once these requirements are stated, the next step is to explain how to implement the failure investigation. The failure investigation procedure should also cross-reference all other procedures that refer to it to provide complete quality system linkage. The other quality system procedures should also state that formal closure of the investigation is required to complete the activity covered by the specific quality system procedure being used.

If a central database is used for all quality-related data, the failure investigation control number and its information can be related to all other data collected. If the database contains the cross-references listed in the failure investigation record, these data can be used to sort the database to find all links to a particular investigation or vice versa.

"Help Desk" solicits questions about the design, manufacture, regulation, and sale of medical products and refers them to appropriate experts in the field. A list of topics previously covered can be found in our Help Desk Archives. Send questions to Help Desk, MD&DI, 11444 W. Olympic Blvd., Ste. 900, Los Angeles, CA 90064, fax 310/445-4299, e-mail You can also use our on-line query form.

Although every effort is made to ensure the accuracy of this column, neither the experts nor the editors can guarantee the accuracy of the solutions offered. They also cannot ensure that the proposed answers will work in every situation.

Readers are also encouraged to send comments on the published questions and answers.

Copyright ©1997 Medical Device & Diagnostic Industry

Processes, Techniques, and Tools: The 'How' of a Successful Design Control System

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


The new FDA emphasis on design controls has caused manufacturers to refine and formalize procedures that were, in many cases, simply unstructured.

Medical device manufacturers undoubtedly are now familiar with the requirements for design control set forth in the new FDA quality systems regulation. What is less clear, however, is how to best achieve design control, because the requirements give individual manufacturers lots of flexibility for implementation options. Three questions that need to be studied are: How does a company analyze what additional processes are needed to satisfy the design control requirements? How can a design control system be effectively implemented and integrated? and Which tools and techniques should be used to implement the design control system? Manufacturers need to decide on a method, a general approach to solving or modeling a problem; a technique, which is the way that problem will be solved; and a specific tool or step taken to implement a technique.

Manufacturers can use optical comparators like the one shown here to aid in their quality design control process (Johnson Matthey, West Chester, PA).


Scheduled to take effect June 1, 1998, the new quality system regulation governing medical device production is the first revision to good manufacturing practices in the past 19 years. This revision's primary goal is to harmonize the GMPs with the ISO 9001 quality certification standard, which will enable medical device companies to satisfy both sets of requirements with a single quality system. Design control is the second goal of the GMP.

The design control process in the medical device manufacturing industry has evolved backwards. Early quality control involved testing the finished product for defects, which was inefficient, potentially destructive, and expensive. The quality movement recognized this inefficiency and implemented manufacturing for quality through process validation. Controlling the manufacturing process prevents many defects that previously would have been caught only through inspection of the finished product. However, complaint files indicated that too many devices didn't produce the desired results, operate the way they were intended to, or meet safety standards.

Design controls address user needs and desires, including safety and efficacy, early in the design process. A study of device recalls indicated that a significant number of device failures (about 44%) were caused by design defects. Experience in various manufacturing and software development industries led to the formulation of the "1-10-100" law, which states that every product flaw identified in the design process can be corrected at 10% of the cost of a flaw that is not identified until the product is being manufactured; every flaw identified during the manufacturing process can be corrected at 10% of the cost of a flaw that is not identified until after the product has reached the market. The ratios may not be exact, but the point is valid.

As stated in section 820.30 of the regulation, the design control requirements are broad. The section is less than 1000 words long and is intended to be flexible enough to apply to every manufacturer of Class III and II­and some Class I­devices. Much has been written and spoken about what design controls require. Good sources include HHS Publication FDA 97-4179, Medical Device Quality Systems Manual: A Small Entity Compliance Guide, which has a section on design controls. The Quality System Compendium, published by the Association for the Advancement of Medical Instrumentation, addresses some of the practical aspects of design control, including subsections on industry practice. Design Control Guidance for Medical Device Manufacturers from CDRH is essential to interpreting the regulation and implementing a satisfactory design control system. In addition, FDA, in coordination with industry, has offered a number of design control training seminars nationwide.


Before a design control system can work, the project must have management's support. Because a formal design control system is a different way of thinking about the design process, it often initially meets some resistance. Therefore, the first step in implementing a design control process should be education and training for the key people from management, marketing, sales, engineering, manufacturing, quality assurance, and configuration management, beginning with a common understanding of what design control involves, its benefits and problems, and the FDA requirements.

The design control process will be part of the larger design system already in place. Various designations of this larger system include the new product introduction process and product development planning process. In her book, Product Development Planning for Health Care Products Regulated by the FDA, Elaine Whitmore describes both strategic and tactical aspects of developing a new product, ranging from future-oriented activities such as technology forecasting and technology assessment to current activities of portfolio management of potential new products to actual product development. The book presents a rational approach to selecting new products for development and prioritizing product development projects.

Medical device manufacturers range from those that have already implemented a product development model that incorporates many, if not all, of the elements of design control to those that have no formally defined process. The challenge is developing a tailored design control process that makes sense for the company. Current processes should be reviewed to determine what design control elements are already in place. In some cases, a mapping of vocabulary may be sufficient. For example, one company conducted frequent reviews of the product development process and called them peer reviews. These peer reviews substantially satisfied the intent of design controls' design reviews.

A gap analysis can be used to review the existing system, and the Final Design Control Inspectional Strategy can be used as a checklist. If possible, an independent person or group should conduct this gap analysis. If an established model of a design control process isn't already in place, the initial goal should be to establish a repeatable process­a process that will allow the company to use the same procedure for both existing and future products, adding tasks and deliverables as necessary.

Making the process efficient or capable is the next­or possibly concurrent­step. The simplest way to describe the process is to break it up into a number of subordinate processes and relate them through process inputs and outputs. Some prefer to break up the process using the terms from the regulation: design and development planning, input, output, review, verification, validation, transfer, changes, and design history file. Others are more comfortable with the terms rapid prototyping, rapid development, rapid application development, spiral development, or concurrent engineering. Either way, every process described should have inputs and outputs, and the major functions or key processes identified through the process modeling exercise should be supported by standard operating procedures (SOPs). These can be individually designed, though there are commercially available SOPs that can serve as a starting point.

The easiest method for describing the design control process may be with a pencil and paper, creating a flowchart of tasks and activities with their inputs and outputs. Inputs may include feedback loops from other parts of the process to add functionality or correct problems in the system. For a simple process, this informal approach may be the best.

A technique of process modeling applicable to developing a design control model is Integration Definition for Function Modeling (IDEF0). This standard was developed by the U.S. Department of Commerce for displaying graphic representations of a process, system, or enterprise. The primary objectives of IDEF0 are as follows:

  • To provide a means for consistently and completely modeling the functions (activities, actions, processes, and operations) required by a system or enterprise and the functional relationships and data (information or objects) that support the integration of those functions.
  • To provide a modeling technique that is independent of computer-aided software engineering (CASE) methods or tools but that can be used in conjunction with those methods or tools.
  • To provide a modeling technique that has the characteristics of being generic (for analysis of systems of varying purpose, scope, and complexity), rigorous and precise (for production of correct, usable models), and concise (to facilitate understanding, communication, consensus, and validation). The modeling technique must also allow activities to be decomposed (further detailed) as necessary to describe the process so that all users of the model will understand it.

IDEF0 forces a measure of standardization and discipline into the modeling process. Many manufacturing industries use this as a standard because of its success record.

Software tools that run on all common platforms are available for automating the process description process. Several incorporate IDEF0, IDEF3 (process flows), and activity-based costing (ABC). These tools can be used for modeling the design control process. Some tools can launch applications and associated templates from the process model. By clicking on the appropriate activity rectangle or input/output arrows, templates can be brought up for the indicated process. For example, by clicking on a project plan document output, a template for the project plan will be displayed.

There are many other good process description techniques. A workbook, Mapping Work Processes, outlines the steps for teams and self-directed work groups to use in creating detailed flowcharts of existing processes. Also included are instructions on how to document work processes, which is a requirement for ISO registration.

Whatever technique is used to describe the design control process, the process will need to be reviewed and modified periodically to keep it effective and efficient. An established process should include all of the specified elements in subpart C of the quality systems regulation, beginning with design and development planning.


Three techniques are mentioned as project management tools in FDA's Design Control Guidance for Medical Device Manufacturers: program evaluation and review technique (PERT), the critical path method (CPM), and the Gantt chart. While these techniques can assist in project management, they do not completely satisfy the design control requirement for plans. For example, the design control inspectional strategy looks for descriptions or references and responsibilities for each of the elements of design control, as well as risk analysis and interfaces, but PERT, CPM, and Gantt are primarily scheduling and resource tools and would be unlikely to contain explicit information on organizational structure and responsibilities. Nevertheless, using these techniques encourage managers to think about all aspects of planning. Project management is essentially the planning, organizing, and managing of tasks and resources toward a defined objective. Three phases of project management are: (1) planning the project and creating a schedule; (2) managing changes; and (3) communicating project information.

A simple project probably doesn't require any tools other than paper and a pencil to implement the project plan. Simply list events, activities, milestones, estimated time to complete each activity or event, and the people or other resources that will be involved in the project. For more complex projects involving interactions that are hard to calculate or visualize, consider using commercially available software tools.

Look for tools that produce PERT and Gantt charts and generate the critical path. Some intuitive tools make identifying, scheduling, staffing, and monitoring design activities easy. Other desirable capabilities include allowing definition of tasks, supporting multiple task relationships, adding people and equipment resources to tasks, assigning costs to tasks and resources, allowing evaluation and adjustment of schedules, and providing a wide variety of progress reporting options for management. Project management tools range from the simple to the comprehensive, and thus complex. Experience has shown that simpler is usually better.


According to Design Control Guidance for Medical Device Manufacturers, "development of a solid foundation of requirements is the single most important design control activity." The design input section of the design control requirements is about establishing procedures to "ensure that design requirements are appropriate and address the intended use of the device, including the needs of the user and patient." But how can these needs be determined?

Sample process-flow diagram used for design planning.

Important sources include personnel from marketing, sales, customer training, and service and repair. They can provide customer input and complaints, warranty repair statistics, and service repair records, as well as information on any potential or pending lawsuits. Other sources include conventions, trade journals, trade shows, vendors, suppliers, academic institutions, government regulations, and standards organizations. More formal methods of obtaining requirements include focus groups, customer surveys, market surveys, and preferred customer surveys. Surveys can be conducted electronically, by telephone, in person, or by mail. Focus groups­discussions with small groups of participants­are a rich source of information, but their results may not be applicable to all customers.

It is important to identify the intended use of a medical device and examine the needs of the user and patient. An iterative process may be needed to clarify requirements and to provide the detail necessary for actual design. The biggest error in the design input process is not putting enough time and effort into obtaining a complete and unambiguous list of requirements. A recent study by the Standish Group, a well-respected market research firm, showed that the top three reasons why software projects were impaired were lack of user input, incomplete requirements and specifications, and changing requirements and specifications. These three answers accounted for 36% of the responses. The numbers may vary somewhat regarding medical devices, but the procedural problems are the same.

Requirements: (double-click to view in context) Status Priority Estimate
SR1: The modem port shall be initialed on system... Approved Low 5
SR2: Upon initialization, the modem port is prepared for.. Approved Medium 4
SR3: Protocol shall be no parity, 8 data bits, 1 stop bit. Proposed Medium 2
SR4: The modem shall also be initialized to auto... Approved High 6
SR5: Upon command from the front end, the system... Proposed High 9
SR6: The format for the data frame is as described in... Approved Medium -
SR7: Display output will be controlled via a dedicated... Approved High -
SR8: Textual data will be formatted as per figure 7. Approved Medium 3
SR9: Waveform data will be displayed in oscillographic... Incorp. Low 3
SR10: The system shall display a minimum of 5... Approved Medium -
SR11: The refresh rate for the waveform data display... Approved Medium -
SR15: The system shall also display the remaining life... Proposed Medium -
SR16: Display units shall be hours remaining, with an... Approved Medium -
SR17: ECG input shall be acquired by the software from... Approved Medium -
SR33: After the sample ECG is acquired, it is displayed... Approved Medium -

Capturing design input in a requirements database and assigning attributes can be done using computerized statistics programs (Incorp.=incorporated).

One difficulty is identifying design input; managing and tracing the steps from design input through design output, verification, validation, and design transfer is another challenge. There are techniques and tools to help solve both of these problems. A good database or spreadsheet program is an excellent tool for managing and tracing design input. For projects of intermediate to high complexity, the technique Quality Function Deployment (QFD) and a generic set of tools known as requirements management tools can be the answer.

QFD was developed in Japan in the late 1960s in an effort to get engineers to consider quality early in the design process. It expanded and implemented the view of quality as advocated by quality guru Deming, and it was embraced by the Japanese automotive industry. Toyota partially attributes its success to QFD, which reduced both its development time and the number of required change orders after production was started. Because of QFD's success in Japan, automotive-related training organizations started teaching it in the United States. It has since spread into many nonautomotive industries, including the medical device industry.

Draft Revision of FDA's Medical Device Software Policy Raises Warning Flags

Medical Device & Diagnostic Industry Magazine
MDDI Article Index


Unless industry gets involved now, complex and prohibitive regulation looms on the horizon.

A pacemaker and the software that operates it are clearly medical devices that fall under FDA's regulatory authority. But what about a software program that helps a health-care practitioner diagnose osteoporosis? If you don't know, you aren't alone. FDA isn't certain either.

In 1986, former FDA commissioner Frank Young declared that FDA's policy toward software would require the "least regulation consistent with the requirements of public health and safety." However, in the 11 years since he made that statement, the agency's demands on companies developing software that can be used with medical devices have been growing. The resulting policy is a confusing patchwork of exemptions and case-by-case assessments.

Recognizing this situation, FDA is reexamining and reformulating its medical software policy and asking industry to participate in the process. If industry wants to ensure that any new policy or guidance document for medical software conforms with the spirit of Commissioner Young's approach and does not unduly inhibit technological advances in the United States, it must get involved at the outset. To do this, however, manufacturers must understand FDA's current policy on software and how it developed.


FDA first formally stated its software policy in the 1987 "Draft Policy on the Regulation of Computer Products."1 This document provided guidelines about which software products were regulated as medical devices and which were exempt from particular regulatory controls, such as premarket notifications. A 1989 draft policy statement, "FDA Policy for the Regulation of Computer Products," reiterated the 1987 draft and has been the agency's operational policy ever since.

Supplementing this policy is the Reviewer Guidance for Computer Controlled Medical Devices Undergoing 510(k) Review, issued in 1991 by FDA's Office of Device Evaluation (ODE) in the Center for Devices and Radiological Health. This document focused on the software development process and described what information FDA reviewers expect to be included in 510(k) notifications and the approach reviewers should take when reviewing computer-controlled devices.

However, FDA's software policy began to slip behind technological advances. Thus, in September 1996, the agency began a major effort to reexamine its computer policy by sponsoring, with the National Library of Medicine (NLM), a public workshop to discuss the definition of medical software device, the criteria for defining risk categories, software quality audits, premarket notification, and other issues.2 The workshop's avowed purpose was to work with industry to better assess the risks to public health associated with different types of medical device software and to reduce the regulatory burden on industry. However, on the same day that FDA held this first medical software device workshop, ODE quietly released for comment to a limited number of trade associations and individuals the 82-page ODE Guidance for the Content of Premarket Submission for Medical Devices Containing Software (draft, September 3, 1996). This document, if finalized, would replace the 1991 reviewer guidance and, rather than reduce the regulatory burden on industry, would substantially increase the documentation requirements for U.S. medical software products subject to premarket submission requirements.

Because the 1996 draft ODE guidance represents a substantial investment of agency resources, one must question how amenable the agency will be to modifying it in response to industry comments. In addition, it is important to realize that the document will set the parameters for FDA's future software policy. With so much at stake, it is clear that the draft deserves more than a passing glance.


Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), a medical device is any "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is . . . intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease . . . or intended to affect the structure or any function of the body."3 Software that meets this definition is considered a device subject to all applicable FDA medical device statutory and regulatory provisions. Software can be a device by itself (i.e., stand-alone) or it can be incorporated into another device as a component, part, or accessory. Under the current policy, FDA distinguishes between stand-alone software and software that is a component, part, or accessory to a device.


Stand-alone medical software is neither a component nor an accessory to another device, but a separate product intended to receive medically related data as input and to relay the results through a general-purpose computer to a health-care practitioner or other user.4 Software that helps diagnose osteoporosis could meet this definition. Other examples include blood bank software systems that control donor deferrals and the release of blood products, software that analyzes potential therapeutic interventions for a particular patient, and hospital information systems. Any such software intended to aid in the diagnosis, cure, mitigation, or treatment of disease meets the definition of a medical device. However, it may be subject to different degrees of regulation depending on whether it falls into any one of three categories of exemptions: it may not be formally treated as a medical device, it may be exempted by a specific FDA regulation, or it may involve competent human intervention.

Not Formally Treated as a Medical Device. The first category exempts certain classes of software from the device definition. According to the 1989 draft policy, the following systems are exempt from FDA regulations and authorities, even though they technically meet the definition of a medical device:

  • Software intended only for use as traditional "library" functions, such as storage, retrieval, and dissemination of medical information.
  • Software intended only for use in general accounting or communication functions.
  • Software intended only for educational purposes rather than for diagnosis or treatment.5

Exemption by FDA Regulation. The second category applies to those stand-alone software products that are subject to exemption by a specific FDA regulation. These exempted software products include the following:

  • General-purpose software (e.g., spreadsheet, database, and word processing software) intended for broad general use, as long as it is not labeled or promoted for medical use.6
  • Software manufactured or altered by medical practitioners solely for use in their own practices.7
  • Software intended solely for use in nonclinical research, teaching, and analysis.8 This exemption applies to research and development efforts that have not progressed to the stage of human experimentation.

These products are currently exempt from most of the general controls under the FD&C Act, medical device reporting (MDR) requirements, and good manufacturing practice (GMP) requirements. However, they remain subject to the adulteration and misbranding provisions of the act.

The reference to products used in nonclinical research implies that diagnostic software (i.e., a medical expert system) would not fall within this exemption and could be subject to premarket submission requirements for a Class III device. For companies trying to find newer, more cost-effective approaches to the costly data collection currently entailed by clinical trials, this category is worth careful review. There could be circumstances involving minimal risk and reasonably prompt clinician intervention where the diagnostic system should be exempted and, under the current guidelines, is not.

Competent Human Intervention. This third category has been the most controversial. FDA stated in its 1989 draft policy that unclassified, stand-alone software products that are "intended to involve competent human intervention before any impact on human health occurs" would not be subject to active regulatory oversight. It is important to note that the term competent human intervention is only relevant to those stand-alone software products that meet the definition of a medical device, are not components or accessories, are unclassified, and do not fall into one of the above exempted groups of products.

If these criteria are met, the software product is exempt from registration, listing, premarket notification, MDR, and GMP regulations. Therefore, a stand-alone software program intended to be used by a physician to diagnose osteoporosis and calculate a drug-dosing regimen after he or she has manually input the variables would be exempt from FDA regulation.

However, because of confusion over the "competent human intervention" standard and the increasingly complex and sophisticated nature of software, FDA intends to eliminate this language from future policy statements. This elimination would represent a substantial change for many companies relying on stand-alone software and could subject them to the most stringent premarket regulatory requirements.


According to FDA's current policy, medical software that meets the definition of a component, part, or accessory is regulated according to the requirements of the parent device, unless the software is separately classified.

Software as a Component or Part. A software component is "any . . . software . . . which is intended to be included as part of the finished, packaged and labeled device."9 Most of the medical device software used by health-care practitioners is incorporated into medical devices as software components. For example, software is frequently used in infusion pumps, pacemakers, ventilators, magnetic resonance imaging (MRI) devices, diagnostic x-ray systems, and clinical laboratory instruments. If an osteoporosis software program were integrated into an MRI device, for example, it would be considered a software component and regulated as a Class II device, like the MRI device itself. Software components are actively regulated by FDA in the course of evaluating the parent device.

Software as an Accessory. A software accessory is a software "unit which is intended to be attached to or used in conjunction with another finished device, although the accessory may be sold or promoted as an independent unit."10 Accessories are typically marketed as finished devices, often not by the same manufacturer who produces the device with which the accessory is used. Some examples that FDA has given are software for the conversion of pacemaker telemetry data, off-line analysis of EEG data, calculation of rate response for a cardiac pacemaker, calculation of bone fracture risk from bone densitometry data, statistical analysis of pulse oximetry data, and calculation of the refractive power of intraocular lenses.

To determine whether a software product is an accessory, FDA asks, "Is the software specified or otherwise intended for use with a classified device?" and "Is the software directly interfaced with another device for transfer of data to and from the other device?" If the answer to either of these questions is yes, FDA has generally concluded that the software is an accessory subject to the same level of regulation as the parent device. Thus, if an osteoporosis software program were used in conjunction with an MRI system, it would be subject to regulation as a Class II device.

In some cases, the software accessory has a significantly lower inherent risk than the parent device. For example, a calculator programmed to automate simple calculations used with a Class III device might not pose a risk that would warrant a premarket approval application. In other cases, the software might introduce new capabilities for a device for which there is no predicate device. While premarket approval or clinical data could be needed to ensure the safety and efficacy of the new device application, FDA has not developed alternative, less restrictive procedures for evaluating software that imposes less risk than the parent device or that makes it safer to operate. This omission will pose a potential barrier for certain medical software applications if the 1996 ODE draft guidance is not modified.


Off-the-shelf (OTS) software is usually considered "general purpose" and exempted from active FDA regulation except for prohibitions against adulteration and misbranding. Thus, if an osteoporosis program were developed from a Microsoft Windows program and limited to listing symptoms like those found in a medical text, it would fall under this exemption. If, however, the OTS software were used to create a hospital information system or a medical treatment planning program involving radiation therapy, or to program a life-supporting device such as a pacemaker, the degree of regulatory oversight would increase, sometimes substantially.11

On June 4, 1997, ODE informally released a draft guidance specifically for OTS software, "Guidance for Off-the-Shelf Software Use in Medical Devices." At press time, it has not yet been announced in the Federal Register. Although the document was intended to expand upon the 1996 ODE draft guidance, its effect, if finalized, will be to substantially increase the documentation requirements for companies using OTS software.

According to this draft, all medical device manufacturers using OTS software in their products must perform a hazard analysis of the software as part of their overall system hazard analysis. The detail of documentation required by FDA and the level of life-cycle control needed by the device manufacturer would increase as the hazard to the patient from software failure increased.

If the hazard analysis shows that the software represents a minimal hazard (i.e., no possibility of serious injury), companies must fulfill certain basic requirements that include identifying the software and its developer; testing, verifying, and validating the software to ensure its proper use in the device; and developing a plan to maintain and control the software.

If the hazard analysis shows that the software represents a significant hazard (i.e., failure, malfunction, or misuse is likely to result in death or serious injury to the patient), the device manufacturer must meet a series of special requirements in addition to the basic ones. These special requirements include auditing the software developer's methods of designing the software and demonstrating that it was verified and validated using "appropriate and sufficient" procedures for the intended use of the OTS software. The phrase appropriate and sufficient is not defined in the draft guidance.

If the OTS software represents more than a minimal hazard upon failure but, after hazard mitigation, the residual hazard does not represent a significant hazard, the device manufacturer will be required to prepare a detailed discussion of that residual hazard and the concomitant benefits and risks the OTS software presents. According to the draft guidance, acceptable levels of hazard mitigation will depend on the specific medical device application.


The content of premarket submissions for medical devices containing software (i.e., 510(k) notifications and premarket approval applications) is discussed in ODE's 1996 draft guidance. If finalized, the guidance would apply to all software, including embedded software, operator-assisted software, and software accessories to medical devices. It would also revise the current three-tier process for determining the level of concern or severity of risk for medical device software.

The Federal Register notice of the 1996 draft guidance specifically sought comment on the proposal to replace the current three-tier process with a two-tier process where a lower level of concern exists "if latent failures or design flaws (direct or indirect) would not be expected to result in death or serious injury." A higher level of concern exists "if latent failures or design flaws (direct or indirect) could result in death or serious injury."12 A major problem with this proposed two-tier approach is the probability that most devices will be placed into the higher-level category. This would result in more extensive documentation demands and, ultimately, costly delays in the entry in these devices into the marketplace.

With regard to submissions for modifications to currently manufactured devices containing software, the FDA guidance "Deciding When to Submit a 510(k) for a Change to an Existing Device" (January 10, 1997) continues to be relevant. For OTS software, FDA has stated in its 1997 ODE OTS software draft guidance that changes representing a minimal hazard would not typically require a new 510(k) notification. For other devices, the intended use, function of the software, and degree of hazard mitigation would affect whether a new 510(k) notification was required.13 However, regardless of the significance of the change, FDA has recently stated in a draft guidance on software validation that the validation status of the entire software system should be addressed, not just the validation of the individual change.14


To a certain degree, FDA's review of its computer policy is an extension of its revision of the GMP regulations. Because of the new design control requirements, it is timely to ask whether these requirements lessen the need for 510(k) submissions for stand-alone and accessory software devices. FDA is currently considering this question as well as replacing the existing policy with one that classifies software on the basis of its own level of risk rather than on that of its parent device.

FDA is also considering software quality audits (SQA) and certification as a replacement for premarket notification of stand-alone software products. Such certification would be, in effect, a special control established for medical software devices. The SQA would be a critical review of the software quality assurance system, performed by a qualified and independent third-party auditor, to provide documentary evidence that a particular medical software device had been developed in accordance with appropriate industry standards or according to a recognized quality process, specification, or procedure established by the developer. The intent of the SQA would be to reduce or eliminate unnecessary paperwork for both industry and the agency without compromising the safety and effectiveness of medical software devices.

As FDA examines and prepares to revise its medical software policy, two new documents, ODE's 1996 draft guidance and 1997 OTS software draft guidance, threaten to impose new and more substantial documentation burdens on manufacturers who use software in their products. Industry must examine those documents and ask, among other questions:

  • Should diagnostic software systems that pose minimal risk to patients and involve reasonably prompt clinical intervention qualify for special FDA regulation exemptions?
  • How will the proposed elimination of the "competent human intervention" language from FDA software policy affect software products currently exempt under this provision?
  • Should accessory software that poses less risk than its parent device, or that minimizes the risk posed by the parent device, be evaluated differently from the parent device?
  • How will FDA ensure consistent application of the hazard analysis for OTS software across device categories, and how will "appropriate and sufficient" validation procedures be defined?
  • Will the suggested replacement of the current three-tier level of concern approach by a two-tier approach push more software products into the higher-level category?

FDA's position on many of the issues surrounding medical software is still being developed, and the agency is actively soliciting input. If industry wants to avoid restrictive medical software policies and increased regulatory burdens, it must fully understand the issues and implications of FDA's efforts and the new draft guidances and become an active participant in the policy making process.


1. Federal Register, 52 FR:36104.

2. 61 FR:36886.

3. Federal Food, Drug, and Cosmetic Act, as Amended, Sec. 201(h), Washington, DC, U.S. Government Printing Office, 1993.

4. FDA Regulation of Medical Device Software (Background), distributed at the FDA/NLM Software Policy Workshop, September 3­4, 1996, Rockville, MD, FDA, 1996.

5. "FDA Policy for the Regulation of Computer Products" (draft), November 13, 1989.

6. Code of Federal Regulations, 21 CFR 807.65(c).

7. 21 CFR 807.65(d).

8. 21 CFR 807.65(f).

9. 61 FR:52602, 52655.

10. "Everything You Always Wanted to Know about the Medical Device Amendments... And Weren't Afraid to Ask," FDA 92-4173, Rockville, MD, FDA, 1992.

11. "ODE Guidance for the Content of Premarket Submission for Medical Devices Containing Software" (draft), lines 2136­2147, 6379­6434, Rockville, MD, FDA, September 3, 1996. See also, "FDA Draft Guidance on Interventional Cardiology Devices (ICD)" (draft 4.1), Rockville, MD, FDA, March 3, 1996.

12. "ODE Guidance for the Content of Premarket Submission for Medical Devices Containing Software" (draft), lines 2136­2147, 6379­6434, Rockville, MD, FDA, September 3, 1996.

13. "Guidance for Off-the-Shelf Software Use in Medical Devices" (draft), Rockville, MD, FDA, Office of Device Evaluation, June 4, 1997.

14. "General Principles of Software Validation" (draft), Rockville, MD, FDA, Office of Compliance, June 9, 1997.

Suzan Onel is an attorney at the law office of McKenna & Cuneo llp (Washington, DC).

Illustration by Warren Gebert

Copyright ©1997 Medical Device & Diagnostic Industry

Displaying Investigational and Unapproved Medical Devices According to FDA Policy

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Manufacturers who follow FDA's policies when showing investigational or unapproved devices­whether at a trade show or on a Web site­can avoid arousing the agency's suspicions.

Displaying investigational and unapproved devices at trade shows, in directed mailings, and on the Internet is important to the vitality of the medical device industry. For instance, to attract investment capital, manufacturers need to educate potential investors about the kinds of technology under development. In addition, new devices often require substantial capital outlays by purchasers, who can use advance knowledge of upcoming devices to plan for this type of purchase. Finally, product development can benefit from early feedback from potential users and the scientific community. Even the display of a device with a pending 510(k) submission­that is, a device that may be a new brand of an existing technology­allows the manufacturer to hit the ground running with sales after receiving clearance and thus to compete better with existing brands.

Aware of the importance of such premarket exhibition, FDA permits the display of investigational and unapproved medical devices. But the agency has its concerns and therefore limits such display. One concern is that a sponsor of an investigational device may be a biased source of information with an interest in making claims for the device beyond what the clinical trial data support. Allowing sponsors to put their own spin on research results, the agency believes, could undermine the impartial scientific evaluation of investigational devices. It also could allow sponsors to create false or misleading impressions about a device among potential users, impressions that the agency fears could be difficult to dispel if the device is later approved for more limited use.

Another concern applies to the display of marketed devices that are under investigation for a new use or that have a 510(k) pending for such a use. Because FDA does not regulate the practice of medicine, users can engage in off-label uses without interference from the agency. FDA fears that displaying marketed devices for new uses may encourage such off-label uses before the agency has evaluated their safety and efficacy.

FDA's approach to the display of investigational and unapproved devices represents an attempt to balance these competing concerns. This article discusses FDA's current policies, possible revisions to them as part of a comprehensive trade show compliance policy guide (CPG) now under review at the agency, and the emerging question of how the policies apply to the Internet.


Since 1978, FDA has permitted the display and advertising prior to clearance of devices with pending 510(k) submissions. This policy is set forth in FDA's CPG 7124.19, which states:

Although a firm may advertise or display a device that is the subject of a pending 510(k)­in the hope that FDA will conclude that the device is substantially equivalent to a preamendment device­a firm may not take orders or be prepared to take orders that might result in contracts for sale for the device unless limited to research or investigational use.1

Thus, a device with a pending 510(k) may be displayed and advertised if the manufacturer does not solicit or accept any purchase orders. In addition, all claims made about the device must adhere to the intended use for which the 510(k) notification is pending.

FDA is considering revising the CPG to require that devices with pending 510(k)s be displayed with the label "Pending 510(k), not available for sale within the United States."2 This revised label would send a clear message to potential purchasers about the status of the device. Some manufacturers already use such a label to prove they are not soliciting sales.

FDA is also reviewing whether to liberalize its policy by allowing the display of uncleared devices before the submission of 510(k) notifications, so long as manufacturers are prepared to provide upon request "reasonable assurances" of intent to submit them.3 Such a relaxation makes sense because there is little reason to prohibit display while a manufacturer prepares a 510(k) notification, as opposed to requiring the manufacturer to wait until after it has been submitted. However, the revised policy will not be worth much to manufacturers if they must produce a mountain of evidence to prove their intention to submit 510(k) notifications. For instance, FDA has considered requiring manufacturers to produce their substantial equivalence data.4 But, as a practical matter, this approach would preclude manufacturers from displaying devices until their 510(k) notifications were almost complete and might even deter them from taking advantage of the policy at all for fear of opening themselves up to a potentially intrusive presubmission review of their data. A better solution would be to require manufacturers to provide upon request written certification of intent to submit 510(k)s for displayed devices. The certification would prove a manufacturer's intent while eliminating the need for an unwieldy evaluation of its substantial equivalence data.


Under the Code of Federal Regulations, 21 C.F.R. 812.7, a device studied under an approved investigational device exemption (IDE) application may not be represented as safe and effective for its investigational use or otherwise promoted until after FDA has approved it for commercial distribution. In 1985, FDA issued a guideline clarifying that a sponsor may publicize the availability of an investigational device to recruit clinical investigators for proposed or ongoing clinical trials.5 The recruiting process can include, among other activities, displaying the device. The guideline indicates that a sponsor should:

1. Announce the availability of the device only in medical and scientific publications or at medical or scientific conferences whose readership or audiences are composed primarily of experts qualified by scientific training and experience to investigate the safety and effectiveness of devices.

2. State in clear terms that the purpose is only to obtain investigators and not to make the device generally available. Enrolling more investigators or subjects than necessary to evaluate the safety and effectiveness of the device will be considered promotion or commercialization of the device. In addition, promoting availability of the device to obtain additional sponsors may be considered promotion or commercialization of the device.

3. Limit the information presented in any notice of availability to the following: the name and address of the sponsor, how to apply to be an investigator, and how to obtain the device for investigational use. The notice should further list the investigator's responsibilities during the course of the investigation: namely, to await Institutional Review Board (IRB) and FDA approval before allowing any subject to participate, to obtain informed consent from subjects, to permit the device to be used only with subjects under the investigator's supervision, to report adverse reactions, to keep accurate records, and, more generally, to conduct the investigation in accordance with the signed agreement with the sponsor, the investigational plan, FDA's regulations, and whatever conditions of approval are imposed by the reviewing IRB or FDA.

4. Use direct mailing for the sole purpose of soliciting qualified experts to conduct investigations. (Note: An undirected mass mailing will not be considered an appropriate means of soliciting clinical investigators. Such a mailing will be considered promotion.)

5. Include the following statement displayed prominently and in print at least as large as the print in the notice: "Caution­Investigational Device, Limited by Federal (or United States) Law to Investigational Use." (Note: a clear, unequivocal statement that the device is under investigation and is available only for investigational uses should be made in oral presentations.)

6. Make only objective statements concerning the physical nature of the device.

7. Ensure that no claims are made which state or imply, directly or indirectly, that the device is reliable, durable, dependable, safe, or effective for the purposes under investigation or that the device is in any way superior to any other device.

8. Not present comparative descriptions of the device with other devices but may include reasonably-sized drawings or photographs of the device.

9. Not include information regarding pricing data but may include information stating where such data may be obtained. A sponsor or investigator should not offer volume discounts for an investigational device. FDA would regard such discounts as the promotion of an investigational device.

It would be naive to assume that sponsors display devices pursuant to the guideline solely to recruit investigators. In fact, even FDA generally accepts that a device may be displayed while a PMA application is pending, even if the IDE study has closed and there is no longer any need to recruit investigators. FDA's chief concern is that sponsors should observe the key provisions of the guideline­for example, that the device should be labeled as investigational and that accompanying written and oral statements do not claim that the device is safe and effective for its investigational use. FDA is also likely to object if a sponsor conveys price information, solicits or accepts orders in anticipation of approval, or discusses the prospects for approval. These practices are likely to lead the agency to conclude that the sponsor is promoting the device.

FDA's revised trade show CPG may explicitly permit the display of investigational devices with an approved IDE if labeled "Work in progress." It also may allow the display of devices with a pending PMA application if labeled "Pending PMA, not available for sale within the United States." These revisions would help end the current pretense in FDA's written policy that investigational devices are displayed solely to recruit clinical investigators.

If FDA requests clinical data in support of a 510(k) submission, the prohibition in section 812.7 against promoting a device until after FDA has approved it for commercial distribution takes effect when the sponsor obtains an IDE, even if the IDE is for a nonsignificant-risk study that does not require advance approval from FDA. As a legal matter, section 812.7 probably overrides CPG 7124.19, which allows display and promotion of a device with a pending 510(k). The safest course for the sponsor, therefore, would be to follow the rules for displaying investigational devices rather than those for devices with a pending 510(k).


If a device has received 510(k) clearance or premarket approval, it may be displayed and promoted only for its cleared or approved uses. There can be no promotional display of investigational or unapproved new uses. The agency fears that because the device is already available for sale, the spread of information about a new use is likely to encourage it. This concern does not apply if the marketed device cannot be converted to the new use without modification by the manufacturer. The revised trade show CPG is almost certain to continue these policies.


One issue FDA has not addressed with published guidance is whether a foreign manufacturer that does not intend to seek clearance or approval in the United States can display its foreign-approved device at an international trade show held in the United States. However, the agency has stated in an unpublished writing that such a device may be brought into the country if certain conditions are met.6 First, the device must be accompanied by entry forms that disclose its unapproved status. Next, the manufacturer must indicate that the device is being imported solely for "testing or evaluation" and include a statement that remaining product will be destroyed or exported. Furthermore, when the device is actually on display in the United States, it must be labeled "Not available for sale in the United States," and no sales orders may be taken. FDA's current approach will probably be formalized in the revised trade show CPG.7 Presumably, the same policy will apply to a device manufactured here for export only. Otherwise, domestic manufacturers would be unable to show their devices while foreign manufacturers could. Such unequal treatment would only encourage domestic manufacturers to move offshore.

Regulatory Status Type of Acceptable Labeling and Promotion while on Display
510(k) submission pending (no IDE and device not available for sale in the United States) Promote only for intended uses covered by pending 510(k) submission.
Approved IDE Follow 1985 guideline and add label, “Caution - Investigational Device, Limited by Federal Law to Investigational Use.”
PMA application pending Follow 1985 guideline and add label, “Caution - Investigational Device, Limited by Federal Law to Investigational Use.”
510(k) pending (IDE) Follow 1985 guideline and add label, “Caution - Investigational Device, Limited by Federal Law to Investigational Use.”
Already available for sale in the United States but a new use is under investigation or FDA review Promote only for previously cleared or approved uses unless the device would require modification by the manufacturer to perform the new use.
Foreign approval only (no IDE, 510(k), or PMA application pending) Label device as “Not Available for Sale in the United States.” If the device is manufactured abroad, may import with certification that it is for testing and evaluation and will be reexported or destroyed afterward.
Foreign approval for a use different from use approved in United States Promote only for U.S. approved use.

Summary of current FDA requirements for the display of investigational or unapproved devices.

An important caveat is that this policy remains subject to the prohibition against off-label promotion. Thus, if a device is cleared or approved in this country for one use, it cannot be displayed at trade shows for another use that is only approved abroad. To be displayed, the device must be completely unavailable for sale in the United States for any intended use.


The Internet's interactive browsing capability and the multitude of Web pages that have sprouted for medical device manufacturers create an environment strikingly similar to a trade show. One could analogize Web pages to exhibit booths, with "handouts" now downloaded by modem and oral discussion at the booth replaced by E-mail. For the most part, FDA probably does not need special rules to address the display of investigational and unapproved devices on the Internet. For example, sponsors should be permitted to display investigational devices on Web pages intended to recruit clinical investigators as long as they follow the 1985 guideline.

There are some aspects of the Internet, however, that will complicate efforts to apply existing law. For one thing, information on the Internet cannot easily be restricted to specific audiences. For example, because laypersons have free access to sites that are intended for recruiting clinical investigators, sponsors cannot honor the 1985 guideline's requirement to "[a]nnounce the availability of the device only in medical and scientific publications or at medical or scientific conferences whose readership or audiences are composed primarily of experts qualified by scientific training and experience to investigate the safety and effectiveness of devices." It is possible to restrict access to a Web site, but only by prearrangement with those who are permitted access by being given a password. But this kind of arrangement undercuts one of the most useful features of the Internet­the ability to coordinate the activities of anonymous individuals who did not know about each other's existence.

The Internet also crosses international boundaries, thereby creating problems when approvals in the United States lag behind those in foreign markets. Vidamed, Inc. (Menlo Park, CA), received a warning letter issued in July 1996 because its Web page made safety and efficacy claims about its TUNA System for treatment of benign prostatic hyperplasia (BPH), which did not yet have 510(k) clearance from FDA. According to Vidamed, however, the device had received foreign approval for BPH and the company was using its Web page to communicate with foreign distributors. Nonetheless, Vidamed discontinued its Web page until it received 510(k) clearance for BPH from FDA in late 1996. Judging from the warning letter to Vidamed, FDA's position appears to be that a firm with a device cleared or approved for use in the United States may not display a new use for it on the Internet prior to clearance or approval, even if that new use has foreign approval. This position is in line with FDA's existing rule that a device already on the market in this country may be displayed at trade shows only for its cleared or approved uses. Unfortunately, as the Internet becomes ever more integral to commerce, this restriction could increasingly hamstring U.S. companies in foreign markets. Unable to display foreign-approved uses on their Web sites, U.S. manufacturers will have to compete against foreign manufacturers not subject to this restriction. Nonetheless, FDA is unlikely to back down, because it is most concerned about a manufacturer's dissemination of off-label information when a product is already on the market in the United States. There is no obvious solution to this dilemma.

Finally, the easy linkage among sites on the Internet tends to blur the distinction between the display of the device at the manufacturer's Web site and at other ones. If a manufacturer provides a link to a site that it controls, that linked site probably should be treated as part of the manufacturer's display, much like a second booth set up in a different part of a convention center. On the other hand, prohibiting manufacturers from establishing a link to an independent Web site arguably infringes upon the First Amendment rights of the manufacturer and of Web browsers.8 To a lesser degree, the same is true of sites that a manufacturer underwrites but does not purport to control.

This tension is not unique to the Internet. The same issue is at the heart of the intense controversy over FDA's policy toward industry support for continuing medical education and scientific conferences and distribution of journal articles and textbook reprints.9,10 Whatever the final shape of FDA's policy in this area, it should be feasible to extend it relatively unchanged to Internet links.


Although its trade show policy will be revised when the final CPG is issued, FDA's fundamental concerns are unlikely to change. They can be summarized as follows: First, if a device is on the market, it should be displayed and promoted only for cleared or approved uses. Second, investigational devices should not be promoted or otherwise represented as safe or effective. And finally, if a device has a 510(k) pending, it should be displayed only for the intended uses covered by the submission. Manufacturers who observe these three tenets almost certainly will avoid running afoul of the agency when showing an investigational or unapproved device­whether the display takes place in a downtown convention center or in cyberspace.


1. "Commercial Distribution with Regard to Premarket Notification (Section 510(k))," Compliance Policy Guide 7124.19, Rockville, MD, FDA, July 28, 1978.

2. MDDI Reports­"The Gray Sheet," April 17, 1995.

3. MDDI Reports­"The Gray Sheet," September 11, 1995.

4. MDDI Reports­"The Gray Sheet," April 17, 1995.

5. "Guideline for Preparing Notices of Availability of Investigational Medical Devices," Rockville, MD, FDA, November 1985.

6. Letter from Byron Tart, director, promotion and advertising staff, FDA Office of Compliance, Center for Devices and Radiological Health, to Jonathan Kahan, partner, Hogan & Hartson, Washington, DC, February 16, 1996.

7. MDDI Reports­"The Gray Sheet," January 17, 1994.

8. Reno v. ACLU, 65 U.S.L.W. 4715, June 26, 1997.

9. "Draft Policy Statement on Industry-Supported Scientific and Educational Activities," Federal Register, 57 FR:56412.

10. "Advertising and Promotion; Guidances," 61 FR:52800.

Jeffrey K. Shapiro is an attorney with the law offices of Hogan & Hartson (Washington, DC).

Copyright ©1997 Medical Device & Diagnostic Industry

Accessing the Hong Kong Medical Equipment Market

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Economic strength combined with lax guidelines for medical device imports make Hong Kong a ripe target.

Its commercial sector well versed in the ways of the East and the West, Hong Kong has long functioned as the bridge between the West and China. Hong Kong businessmen are accustomed to both Western and Chinese ways of doing business, and many medical device exporters have used Hong Kong agents and distributors to reach Chinese markets.

View taken above Hong Kong island across Victoria Harbor toward Kowloon Peninsula. Photo courtesy of Hong Kong Economic & Trade Office (San Francisco)

The handover of Hong Kong by Great Britain to China should not affect the quality of this service or Hong Kong's internal structure for importing U.S.-made medical devices. The region's role as middleman, however, is gradually changing as Chinese businessmen become more sophisticated in international commerce and start to venture into direct dealings with U.S. manufacturers.

Hong Kong enjoys the second-highest per capita income in East Asia and maintains an open market economy. For these reasons, U.S. medical device manufacturers should examine Hong Kong's market on its own merits. The market for medical equipment, which totaled $83 million in 1996, is served entirely by imports, according to the Hong Kong Government Supplies Department (GSD), and does not include medical equipment entering Hong Kong to be shipped to other countries (Table I).

1995 1996 1997
Total market size 79 83 96
Total local production n/a n/a n/a
Total exports 402 462 531
Total imports 481 553 608
Total imports from the U.S. 138 155 173

Table I. Summary of the Hong Kong medical equipment market. The numbers are based on U.S. dollars (in millions). The above statistics are unofficial estimates, as the majority of medical equipment imported by Hong Kong is shipped to other countries.

U.S. Department of Commerce figures show that Hong Kong's population of 6.2 million enjoy a per capita gross domestic product (GDP) of $27,577. GDP growth has averaged 4.8% annually for the past three years. This high standard of living is accompanied by expectations of a comprehensive range of medical and health services to be supplied by the public and private sectors.

According to the Hong Kong government, its market has been particularly advantageous for U.S. producers. In 1996, the Hospital Authority (HA), Hong Kong's largest independent care provider and medical device purchaser, bought $33 million worth of medical equipment, such as MRIs, ultrasound systems, patient monitoring systems, and ventilators from U.S. producers, who captured 49.9% of Hong Kong's total medical equipment market. In the same year, the HA purchased $5.6 million of U.S.-made medical supplies, such as sterile hypodermic syringes and needles, adhesive surgical tapes, and surgical and other consumables, representing 33.3% of Hong Kong's total medical supplies market. Because these trends are expected to continue, the U.S. Department of Commerce has identified medical equipment as the best prospect for U.S. exports to Hong Kong.1 Also, no tariffs or government-imposed obstacles hinder U.S.-manufactured medical devices from entering the market.


There are two effective means of penetrating the Hong Kong market--setting up a representative office or finding a reliable agent/distributor. Although it is possible for suppliers to sell directly from overseas to the private sector or the GSD, this occurs infrequently. Hong Kong has no special legislation regarding agents and distributors, which include a vast range of types, from personnel who stock retail stores to specialists who provide sales, engineering, and technical support for complex systems. Therefore, the following points should be included in written contracts to ensure mutual understanding: definitions of exclusivity and sales territories, proprietary information, specific targets and goals for sales activity, duration of the contract, payment terms, jurisdiction for contract enforcement, direct sales, cancellation notice period, and covenants restricting activity following cancellation of the contract.

As in the case of any foreign market, U.S. suppliers will gain the most by target marketing. Agents should be provided with technical catalogs in both English and Chinese. English-Chinese business cards are a must. Quotes should be given in metrics and on a delivered basis to Hong Kong, not F.O.B. (i.e., with shipping charges included). Abbreviations of cities and states should be avoided.

Personnel affiliated with the U.S. consulate general's office can provide assistance to manufacturers who are testing the Hong Kong import waters for the first time or who need an added boost to their present programs. For example, a manufacturer can choose from one of the following three Foreign Commercial Service programs. First, the agent/distributor service can conduct a customized search to identify foreign agents, distributors, and representatives for U.S. firms based on the examination of U.S. product literature by the foreign companies. The fee is $250.

Alternatively, a gold key service is custom tailored for U.S. firms planning to visit Hong Kong and includes orientation briefings; introductions to potential partners, agents, or distributors; and interpreters for meetings as necessary. The fee is $800 for two days of service with six to eight appointments.

Third, a customized market analysis provides firms with specific information on marketing and foreign representation for their products. Interviews or surveys are conducted to determine overall marketability of the products, key competitors, price of comparable products, customary distribution and promotion practices, trade barriers, possible business partners, and applicable trade events. The fee is $2300.


There are four basic categories of consumers of medical equipment in Hong Kong. The largest of these, public hospitals, account for 70% of the market. Private hospitals, private practitioners, and private laboratories account for 15, 9, and 6%, respectively.

Private-sector consumers have their own procedure for medical equipment purchases. Recommendations are generally made by department doctors or technicians and submitted to the department head for approval. Private hospitals may encourage open bidding (tender) from medical companies for necessary equipment, usually items costing more than $30,000. The hospitals may also structure the bids to be placed from a specific group of companies, or they sometimes may even deal with only one bidder (selective or single tender). Information about the open bidding is sent to local agents and distributors. Thus, although U.S. exporters should send product literature to the purchasing department of private hospitals to be kept for reference, the best way to promote and introduce equipment to private hospitals, practitioners, and labs is through a local agent.

The HA is responsible for the management and control of all public hospitals, correctional institution treatment centers, clinics, and maternity homes. The HA controls 43, or 90%, of Hong Kong's hospitals. Its 1997­1998 government grant is $2.85 billion. Additionally, the HA executive summary from 1996­1997 shows that $157.4 million has been earmarked for information technology development along with $251.6 million for the purchase of additional or replacement equipment.

The 10 priority areas identified by the HA as being in need of developing new or expanded programs to improve the outcome of patient care are: cancer; cerebrovascular disease; ischemic heart disease; end-stage renal disease; chronic lung disease; diabetes mellitus; prenatal, perinatal, and neonatal care; adolescent care; geriatric care; and services for the mentally ill.

Accessing the public health-care market is fairly straightforward. The Hong Kong GSD is responsible for the procurement of goods and services ordered by the government, including the HA. Individual HA-member hospitals decide what equipment is needed and report the functional specifications to the GSD in writing. The GSD usually makes its purchase by open tender, with decisions based on price, quality, and delivery. Selective tender and single tender are rare. The GSD gives no preference to any particular supply source from any country or organization.

Hong Kong is bracing for an influx of 2 to 4 million immigrants from China during the next 25 years, which will certainly increase the demand for medical devices. However, as medical technology becomes more expensive, the HA is increasingly careful to justify its high-technology purchases in terms of cost-effectiveness. As part of its annual plan for 1997­1998, the HA refers to a "seamless health-care environment that can be created by removing or reducing structural systems or process barriers." In effect, this means that private sector services are considered when the HA makes purchasing decisions. Such was the case with the gamma knife. The HA decided on the basis of efficacy, safety, and cost-effectiveness that just one gamma knife would suffice for Hong Kong's current population and that a private sector consortium would probably buy one. In exchange for the HA's promise not to acquire a gamma knife, the private consortium agreed to let public sector surgeons use the knife.

Potential suppliers must be prequalified with the GSD, which can be reached at 12 Oil St., North Point, Hong Kong; 852/2802-6102, fax 852/2807-2764. To become registered suppliers, companies must provide background information about the goods they offer. The GSD evaluates this information and selects qualified suppliers for inclusion on its register. The forecast of major Hong Kong government purchases, including the equipment, usage, and tender-issuing dates, is accessible on the Internet at the GSD home page: hk/gsd/tender.htm. Potential imports need not be registered, and only x-ray machines and other devices with a radioactive potential must be licensed by the radiation board.Inquiries regarding the import license of radiation medical equipment can be directed to the Radiation Health Unit, Department of Health, Third Floor, Sai Wan Ho Health Centre, 28 Tai Hong St., Sai Wan Ho, Hong Kong; 852/2977-1888, fax 852/2834-1224.

Maintenance is a strong purchasing consideration, and hospital administrators prefer to deal with companies that can guarantee immediate service. The ability to provide doctors with hands-on exposure to the product can also be vital in affecting purchasing decisions.


Because of Hong Kong's rising standard of living, improvements in health-care delivery and an influx of patients from China, the prognosis for Hong Kong's medical equipment market is excellent. The market, the procurement process, and the regulatory environment are not expected to be affected by the recent handover of Hong Kong to Chinese rule.


1. Hong Kong: Leading Sectors for U.S. Exports & Investments, Washington, DC, U.S. Department of Commerce, National Trade Data Bank, December 27, 1996.

Lauren Brosler is an international trade specialist for the U.S. Department of Commerce, Washington, DC.

For trade figures and reports on Hong Kong and China as well as information on upcoming trade missions and other trade promotion events in the region, contact:

Lauren Brosler
International Trade Specialist
U.S. Department of Commerce
Room 1015
Washington, DC 20230
phone: 202/482-4431
fax: 202/482-0975
E-mail: Lauren_Brosler@ITA.DOC.GOV

For information on the Foreign Commercial Service programs described in the article, contact:

Rose Mak
Commercial Specialist
U.S. Department of Commerce
Foreign Commercial Service
American Consulate General
26 Garden Rd.
Central, Hong Kong
phone: 852/2521-1467
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Copyright ©1997 Medical Device & Diagnostic Industry

How Design Controls Affect Sterilization Process Development and Validation

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI October 1997 Column


Design control demands that all factors affecting a product's performance be considered before production. For sterile medical devices, that means the sterilization process should be addressed during each phase of the design control process.

By this time, everyone within the medical device community knows that the new quality system regulation mandates design controls for many medical devices. Many in industry, however, may not fully understand how to incorporate manufacturing processes into the act of complying with design controls. This may well result from the fact that most manufacturers have long since subjected their manufacturing processes to process validation, as required by the now-superseded good manufacturing practices regulation. What's new is that under design controls, manufacturers are now required to undertake and document process development and validation early in the design phase for each and every applicable medical device.

The extent to which design control concepts are applicable to process development and validation depends on the nature of the process in question. The sterilization process, of course, is a critically important step in the manufacture of sterile medical devices. For that reason, it is subject to the design control requirements as outlined in section 820.30 of the quality system regulation.


The multifunctional design control process must involve many departments to be effective. This is especially true with sterilization. Sterilization cycles cannot be designed without input from the R&D and manufacturing functions, and conversely, designers cannot develop a safe and effective device without input from the sterilization function. Management with executive responsibility must play an active role in the design process by creating an environment where the concept of interdepartment communication and cooperation will flourish.

The effectiveness of a sterilization process for a specific medical device derives from the relationship between the robustness and the capability of the two proceses. Process robustness is the ability of the process to withstand product variations while maintaining its quality attributes­in this case a minimum, validated sterility assurance level. The process capability, by contrast, is a measure of the ability of the process to reproducibly manufacture product. In the case of sterilization, this means that the process for a specific device must be designed to be able to effectively sterilize a product or product family within the expected range of acceptable product variation.

The primary objective of design controls in the sterilization process is to ensure that an effective, reproducible cycle is routinely used to process a particular device or device family. Because of the importance of consumer safety in sterilized medical devices, risk management associated with sterilization cycle development is directed toward the ultimate safety of the processed device. Risk can be considered the probability of occurrence of a hazard causing harm; safety, the freedom from unacceptable risk. A 10­6 sterility assurance level (SAL; the probability of one nonsterile unit out of one million units processed) is generally considered an acceptable risk of nonsterility and is therefore used as a basis of sterilization cycle design.

The design control features of the new quality system regulation are outlined in section 820.30 and encompass the following elements:

  • Design and development planning.
  • Design input.
  • Design output.
  • Design review.
  • Design verification and validation.
  • Design transfer.
  • Design changes.
  • Design history file.

Many organizations have historically conducted sterilization validation studies under defined, preapproved protocols that used worst-case challenge conditions encompassing many of the concepts outlined in 820.30. Following the current domestic standards for sterilization validation­i.e., ANSI/AAMI/ISO 11135 for ethylene oxide, 11137 for radiation, and 11134 for steam­ensures that many of the elements of design control are addressed. However, the application of each section of the design control requirements may not be immediately obvious. The following discussion is intended to help clarify these requirements.

Design and Development Planning. This section of the regulation outlines the need for the design to be addressed in a plan prepared before starting the development process. For sterile devices, a sterilization master plan is often prepared that meets this objective. This plan usually addresses the equipment to be validated, defines in general terms the methodology and schedule to be used, outlines the responsible departments, and defines milestones where management reviews are required. The master plan is a dynamic document that should be updated throughout the product development life cycle. Copies of the plan and its updates must be placed in the design history file.

Design Input. FDA recognizes the design input stage, sometimes referred to as the requirements stage, as the basis of a successful sterilization validation program. The developers must match the product and packaging specifications to the sterilization process capabilities, taking into account such factors as gas access, material compatibility, safety, manufacturing process requirements, bioburden, and exposure. If requirements are not defined in this phase, the sterilization validation will be inadequate.

After being converted to specifications, the requirements of the design input stage should be testable. In the development of a sterilization process, these requirements are that the product have a defined SAL (10­6) and that both the product and packaging remain functional after sterilization. Since these requirements involve different aspects of product development, the input to a sterilization development program and its review are multidisciplinary, requiring the participation of R&D personnel, sterilization scientists, and packaging engineers.

Design Output. The design output stage supports specification development and results in establishing essentially all of the product specifications. Design output includes a description of the complete specifications and provides the basis for the development of the remainder of the device master record. In the case of sterilization, this should include a description of any restrictions on product or packaging temperature, moisture, or vacuum, as well as all the quality checks required for sterilization cycle control and monitoring. It should culminate in a description of the final sterilization cycle parameters.

Design Review. This stage occurs after each step in the design plan. The final cycle documentation must be reviewed and approved by the appropriate individuals, who should include as a minimum a sterilization engineer, a packaging engineer, an R&D engineer, and someone from quality control or regulatory affairs. A regulatory affairs specialist is especially pertinent if the intent or claim of the sterilization cycle validation program is to conform to a specific domestic or international standard.

Loaded cobalt 60 rods will provide gamma radiation sterilization.

Design Verification and Validation. It is common industry practice to validate all sterilization processes. This is commonly done under a comprehensive, preapproved protocol that clearly defines the acceptance criteria of the sterilization validation study and references a particular standard or guideline. The validation is performed under limit conditions or worst-case operating conditions and conducted with multiple lots or batches to demonstrate reproducibility.

The results of the sterilization validation must be detailed in a final report that is reviewed, approved, and signed. The final report and associated protocols should be permanently archived in the validation file, which should be a part of, or referenced, in the product's design history file.

Design Transfer and Changes. After the validation is completed, the specifications are transferred to a manufacturing function. This functional group is typically responsible for assuring that the validated sterilization cycle parameters are accurately incorporated into approved specifications.

Any subsequent design changes must be controlled through a formal change-control process. Any changes to the product-process specification must be subjected to the same level of controls and reviews as the initial development effort. That is, changes must be made under the design control requirements and reviewed and approved by individuals in the same functions and departments as those who approved the original design documentation. Changes to documents, such as correcting text or graphic errors or adding procedural text, must be made under the document controls section of the quality system regulation (820.40).


To effectively integrate sterilization process development and validation into a design controls program, medical device manufacturers may need to structure their procedures to integrate the additional review and approval steps at the appropriate intervals as defined in the regulation. While at first the necessity of these numerous review and approval steps may seem overly burdensome, redundant, and unnecessary, in the long run this comprehensive review process should lead to a reduction of errors and deviations. Adherence to these concepts will provide assurance that the sterilization cycle will be effective and will meet all quality requirements­which is, after all, the primary goal of all manufacturers.

Robert R. Reich is president of Pharmaceutical Systems, Inc. (Mundelein, IL).

Illustrations by Brad Hamann

Copyright ©1997 Medical Device & Diagnostic Industry