Remarks by
David A. Kessler, M.D.
Commissioner of Food and Drugs
Hastings Lecture
Washington, D.C.
December 10, 1993

I'm honored to deliver this year's Hastings Lecture. I never knew Frank Hastings, though I certainly know of him and of his pioneering work at NIH during the 1960s and 1970s developing an artificial heart. I've also been impressed that Dr Hastings was obviously a man of character and conscience who was committed not only to advancing the public health but to advancing the cause of world peace. He was the kind of person who does public service proud.

Dr. Hastings was the first director of the Devices and Technology Branch of the NIH's National Heart, Lung and Blood Institute. So it seems appropriate to speak today about medical devices. I've chosen not to limit my remarks to cardiovascular devices, however.

Instead, I want to talk to you more generally about the introduction of medical devices in this country and some of the challenges FDA is now facing in piloting their path from the bench to the bedside.

I know that many of you are involved in one way or another with cardiovascular research, and so I do want to review some of the significant changes FDA has begun to make in how cardiovascular devices are regulated.

But that story is really one chapter of a larger book that might be titled "FDA's revitalization of medical device review and regulation".

As director of the NIH's artificial heart program, Dr. Hastings said that his goal was "to speed the day when safe and effective devices could reach the bedside and result in major reductions in death and disability due to heart disease."

 That goal stands today as a statement of what we at FDA are committed to doing as well--though our jurisdiction goes beyond cardiovascular devices. However, when Dr. Hastings set that goal in 1964, there was no government system to guide that process.

Some people don't realize that the regulation of medical devices in this country is relatively new. Until 1976, when Congress passed the Medical Device Amendments to the Food Drug and Cosmetic Act, devices could be marketed without any showing that they were safe and effective. Between 1990 and 1992 three additional device laws were passed extending FDA's authority: The Safe Medical Devices Act of 1990, the Medical Device Amendments of 1992, and the Mammography Quality Assurance Act of 1992.

There probably are not many terms in the English language that cover as much ground as "medical devices." Those words encompass a great diversity of products from bandages to heart valves, from thermometers to the most advanced therapeutic and diagnostic machinery. All of them, in one way or another, are now under FDA's purview.

Today, I want to begin by giving you a sense of the general framework that Congress created for overseeing all of these medical devices and a snapshot of how FDA's system has evolved. Then I want to go on to talk about why and how we are now taking significant steps to strengthen that program.

FDA oversight of devices involves a combination of activities: premarket review of devices, postmarket surveillance, enforcement action against firms that violate the law, and educational programs and research.

First, premarket review.

Reflecting the fact that medical devices vary enormously in complexity and risk potential, the 1976 law created a hierarchical approach to regulating devices. The FDA was required to categorize them into one of three classes, depending on the level of regulatory control required.

The underlying assumption is a commonsense one: the most risky devices need considerable control and oversight; less risky devices need less.

There are two basic routes to market for medical devices. The simplest route, a premarket notification--known as a 510(k)-- is for devices whose safety and effectiveness are well established, or for those devices whose safety and effectiveness can be assured by special controls.

 The manufacturer must demonstrate that the new device is substantially equivalent to a device that is already legally on the market. This is not an absolute finding of safety and effectiveness. Rather, it says that the new device is as good as what is currently out there.

Sometimes we conclude that a medical device is not substantially equivalent to a product already on the market. Some new feature or material may raise new questions about safety and effectiveness, or perhaps it's a brand new device for which safety and effectiveness may be unknown.

In these cases, we require the manufacturer to use the second route to market, a premarket approval application (PMA). In a PMA, the manufacturer must demonstrate with valid scientific evidence that the device is safe and effective for its intended uses. Both clinical and preclinical data are necessary.

The mechanism that facilitates clinical trials of significant risk devices is called an investigational device exemption (IDE). An IDE gives FDA reviewers an opportunity to review the proposed study protocol and also provides for protection of the rights and welfare of study participants.

When the PMA is submitted and we conclude that the data provided are sufficient to make an approval decision, we consult publicly with one of our medical device advisory committees. Our advisory panels are specially constituted groups of impartial physicians, scientists, and engineers -- plus a consumer and industry representative -- who review the data and make a recommendation as to whether the device should be approved, and if so, under what conditions.

Before concluding my remarks on premarket approval, let me emphasize a very important point. Many consumers--and probably many health professionals as well--assume that if a product is on the market, FDA has made a definitive finding that it is safe and effective.

That's not necessarily true--especially in the case of devices that were on the market when the 1976 medical device law was passed.

In order to prevent the use of medical devices in this country from grinding to a sudden halt, that law "grandfathered" in all devices already on the market -- that is, those devices were allowed to remain in general use until FDA called for PMAs.

 You need to go no further than a newspaper or the TV news shows in the last couple of years to grasp the significance of this point. Consider, for example, the highly-publicized controversy over the safety of silicone gel breast implants.

For some 30 years physicians have been implanting these grandfathered devices into women without knowing whether they were safe. When we called for PMAs on these devices, the companies were unable to provide data establishing their safety and effectiveness. Consequently, we have restricted their use while those data are collected.

We are in the process of calling for PMAs on a number of other grandfathered devices, including saline-filled breast implants, penile inflatable implants, testicular implants and cranial electrotherapy stimulators.

Let me go on to postmarket surveillance because no premarket review program, no matter how well executed, can assure device safety and effectiveness without an equally strong program of postmarket surveillance.

Once a device is approved and leaves the controlled environment of a clinical study -- that is, once it attains widespread, day-to-day use by practitioners across the country on thousands of patients -- unforeseen problems can arise.

Sometimes this is due simply to numbers: clinical studies on devices typically involve a limited number of subjects and therefore are unlikely to detect adverse effects that occur relatively rarely. Such effects may not be detected until years after the device is marketed.

Sometimes unforeseen problems are due to differences between the subjects in the clinical trials and patients who receive the device after it has been approved. And sometimes they're due to variations in physician skill and technique.

When an implant is involved, it may be a question of the long-term effect of the device in the body. No matter how much we know about the materials used to fabricate implants, some questions of durability, biocompatibility and toxicology may not be answered with certainty until the device has been in place for an extended time.

Let me add, however, that the effect of implants on the host and the host on the implant is an increasingly urgent area of research. More than 11 million Americans now have an implant of some type, and the number continues to increase. They are also being implanted in younger patients with the intent of leaving them in for longer periods of time.

In the past, we relied heavily on our two long-standing adverse event reporting programs to monitor devices in use: the Problem Reporting Program--PRP, a voluntary system through which health professionals and consumers could notify us about problems, and the Mandatory Device Reporting Program--MDR, which requires that manufacturers promptly report to the FDA when they learn that their devices may have caused a death or serious injury.

However, problems with Shiley heart valves, silicone gel- filled breast implants, teflon-coated jaw implants, and some other devices, demonstrated to us that we needed stronger, more comprehensive tools for identifying problems with devices in general use.

Congress recognized this too and included provisions in the Safe Medical Devices Act of 1990 that gave us new authority to monitor devices already on the market. I'll discuss those a little later.

A third critical element in our regulation of devices is, of course, enforcement.

When I assumed the position of Commissioner of Food and Drugs three years ago, one of my top priorities was more vigorous enforcement of the law.

We sent a message out to industry, not just medical device companies, but food, drugs, blood banking--all the industries we regulate--that we expect them to comply with the law and we will not hesitate to take appropriate action if they fail to do what is required of them.

There is no question that in the past couple of years, the FDA has taken a stronger regulatory posture against violative firms and products. We are less patient with firms that are not in compliance and we are using the several tools at our disposal- -product recalls, seizures, and injunctions.

The fourth element in our medical device regulatory program may be less familiar to you than the previous three I've discussed: premarket approval; postmarketing surveillance; and enforcement.

It is in-house laboratory research and it has proved critical to our ability to ensure the safety and effectiveness of devices.

To digress only a little, let me emphasize that FDA is a scientific regulatory agency, and establishing and maintaining a strong scientific capability is an integral part of doing our job. Many people outside the FDA would probably be surprised to know just how much cutting edge science is undertaken throughout the Agency.

Our devices center maintains small but highly focused physics, biology and engineering laboratory programs which we can quickly bring to bear in solving device problems.

You may wonder why that is necessary, when the manufacturer conducts the laboratory work necessary to demonstrate a product's safety and effectiveness.

The answer is that FDA's research program provides a complementary function.

Some of our laboratory work is aimed at assessing the adequacy of the manufacturers' tests -- "testing the tests," one might say.

For example, when we analyzed the test manufacturers have traditionally performed to establish the leakage rate for rubber gloves we found it to be unsatisfactory. We developed an alternative that manufacturers are now using.

Our laboratories also help us quickly find the cause when a device fails. For example, several years ago we were able to pinpoint the problem when a particular model of anesthesia machine malfunctioned, causing several deaths. This led to needed modifications in design.

More recently, our scientists have been working with a manufacturer to determine the cause of overheating and fires that have occurred with certain humidifiers and ventilators.

Equally important, our laboratories analyze safety problems affecting whole classes of devices.

For example, we have conducted studies of the effectiveness of latex and natural membrane condoms in preventing the penetration of HIV-size particles. We were able to confirm the effectiveness of latex, but we discovered that natural membrane products had pores large enough to permit significant passage of HIV. This led us to require warning labels on natural membrane condoms cautioning purchasers not to use these products to prevent sexually transmitted diseases.

In another instance, after our device reporting systems showed a disturbing number of allergic reactions to latex- containing devices, our laboratories were able to identify the specific proteins that induced the allergies. Once this was established, we were able to work with latex manufacturers to reduce the levels of the allergen in their products.

Other reports led us to suspect that infant apnea monitors might be malfunctioning in the presence of electromagnetic interference.

We were particularly concerned because the interference was of the type that might be produced by such common sources as television sets or electrical appliances, and because malfunction of the monitor could be fatal.

Our laboratory scientists confirmed and characterized the interference, then worked with apnea monitor manufacturers and standard-setting organizations to help correct the problem.

Lately we're discovering that the performance of other devices may be compromised by electromagnetic interference.

We recently tested several models of electrically-powered wheelchairs in our laboratories, and found that they were susceptible to sudden random movements in the presence of low-level electromagnetic emissions of the type produced by TV and radio transmitters. We're now gathering more information on this.

The point I want to underscore is that all of these research activities help us more quickly and effectively enforce the law.

In some cases this means giving us the information we need to require a product recall, or to issue an alert to physicians, or to call for a change in standards. In other cases, it means pointing the way to further research that manufacturers need to conduct. And in still other cases it leads to more effective quality control procedures on the part of manufacturers.

That brings me to the fifth and final element of the current system that I want to describe today. And that is user education.

Discovering problems with devices through our reporting systems or our research is, of course, only the first half of the job.

Once we learn of a problem and have adequately characterized it, we must communicate with the users of the device -- either health professionals or consumers--and sometimes both. Although letting users know about problems is also important for drugs and biologics, it's particularly urgent with devices. That's because the opportunity for product failure, or for practitioner or patient error, is so much greater for devices.

 And so we've developed a rapid-turnaround system through which we can send Safety Alerts on medical devices to hospitals and practitioners across the country on short notice, and we find ourselves using these communications tools frequently.

This, then, is a short course on the regulation of devices.

Let me now go on to talk about the changes and revitalization I referred to earlier.

It's fair to ask, what's broke? What is it that you have to fix?

I would answer that question in a couple of ways. First, as the FDA and industry have gained experience in the regulation of devices, a number of problems and potential problems have surfaced.

It's worth keeping in mind that device companies tend to differ in important ways from drug companies. They tend to be newer, smaller and less experienced in dealing with a government regulator and in sponsoring clinical trials.

The FDA cannot simply lift our decades of experience dealing with the pharmaceutical industry and apply it to the device industry. Different working relationships are required.

I've mentioned problems that have surfaced with some specific devices--the Shiley heart valve, silicone gel-filled breast implants, temporo-mandibular joints.

These have certainly focussed attention on whether more can be done to ensure the safety of devices.

We also recognize our responsibility to make sure we are moving promising new devices through the review system as expeditiously as possible and this has also been an area of increased attention.

Let me begin by describing our efforts to improve and streamline the premarket evaluation process.

One priority has been to use our resources more wisely by focusing on products with the most serious public health implications. To do that, we have created a triage system for device applications.

This means that a low risk product will generally get little more than an administrative review, whereas a device that presents high risks or is technically complex is going to get a full multi-disciplinary review by a team of scientists to determine its safety and effectiveness.

We have also adopted a "refuse to file" or "refuse to accept" policy for applications that are obviously deficient. If an application lacks essential elements for review, we are identifying those deficiencies and returning it to the manufacturer after a quick screening.

There simply is no reason for our reviewers to spend their time evaluating applications that would never be cleared or approved because of severe deficiencies.

Returning the application gives the sponsors early feedback as well -- they know what we are expecting and can submit a revised and comprehensive application without waiting to learn about the deficiencies after a full-scale review.

In addition to these initiatives, we have begun a policy of expedited review for devices that are medically significant. The most promising new therapies will move to the head of the line.

Patients and medical practitioners should not have to wait for lifesaving products while devices that are little more than duplicates of existing technology are reviewed first.

No longer do breakthrough products have to compete with products that may offer commercial advantages, but no significant medical advantages.

We're also working hard to improve our timeliness in reviewing applications. After a long period in which review times climbed, I can report that we're beginning to turn things around.

In the past fiscal year, we approved 24 PMAs, double the number approved in the previous year. Many of these approvals were for first-of-a-kind products. And a number of them were cardiac devices: the first implantable device that combined cardiac pacing with defibrillation; the first coronary stent; and the first drill angioplasty system. We're also making significant progress reducing the backlog of 510(k)s.

Another very important priority is improving the quality of the clinical trials conducted to support medical device applications.

Earlier this year an internal FDA committee evaluated the clinical trials in a select sample of device applications. Their report confirmed a pattern of serious problems in study design-- problems such as the lack of a clearly stated hypothesis, no clearly stated endpoints, and poorly chosen controls.

 The scientists and clinicians in our devices center had recognized these deficiencies and as the committee report documented, were forced to spend inordinate amounts of time bringing an application to a point where it could be approved.

Nobody--not industry, not the public, not the FDA--benefits from such an arduous process.

At best, the application will be delayed until many questions can be resolved, or additional data can be generated. At worst, the application will be disapproved.

We are now moving on several fronts to upgrade the quality of data that the industry submits.

We have participated in and sponsored several workshops on clinical trials -- some specific to devices in one medical specialty, others applying to all medical devices. We've had a terrific response -- one workshop on general issues attracted more than 600 members of industry and the medical community.

One function of these workshops is to get input from academia and industry on the development of guidance documents for sponsors of device clinical trials.

FDA is preparing--or in some cases, updating--a number of guidance documents. Some of them address a specific type of device, some cover whole categories of devices.

Just last month, for example, we jointly sponsored a workshop with the North American Society for Pacing and Electrophysiology, the American College of Cardiology and the American Heart Association at which we held discussions geared toward development of a guidance document.

These guidance documents are an important part of our effort to improve the quality of data. And they are an important way for the FDA to draw on the expertise of our colleagues in industry and academia.

Prior to their official release, guidance documents are made available to industry and the medical community for comment, and I would encourage those of you in this audience to become a part of this process.

Guidance documents have also been discussed at public advisory committee meetings. In June of this year, for example, the cardiovascular advisory panel discussed a draft document.

 Another way we are improving our premarket review process is by inviting sponsors of IDE studies to meet with us before they complete their protocols. This gives us an opportunity to ensure that the proposed study will produce the kind of data that can support a premarket application.

To bolster our in-house review capability, we're attempting to increase the number of clinicians on our device review staff. I think it's important that the clinical implications of a proposed new device -- its indications, its proposed labeling, its effect on patient management -- be considered early in the review process.

It's not enough to rely on an advisory panel to make the major clinical decisions. We must lay the clinical groundwork sooner, and more thoroughly. Improving our communications with industry has been another focus of our efforts to improve the premarket review process. We needed to build a more effective working relationship and we've done that in a number of ways. Let me give you an example. Industry had complained that they needed to know the status of their applications, while reviewers complained that they were frequently interrupted and distracted by such industry requests.

Our solution was to establish a status report system in which manufacturers can request, by FAX or by mail, the status of their 510(k)s after 90 days of review. We will respond within three working days.

Manufacturers can also request and receive up to five guidance documents through an automated phone and FAX system we've dubbed "Flash FAX."

To further improve communication, we've established a public "hard copy" docket at FDA headquarters where anyone can come and review all current device documents, including guidance documents on clinical trials, regulatory requirements for the manufacture, promotion, sale and distribution of medical devices; proposed and final regulations not yet codified; major speeches by FDA managers; and periodic publications.

More important for the majority of people who can't come to Washington, these same documents are available on an "electronic" docket which can be accessed by anyone with a PC or computer terminal and a modem.

Let's move on to postmarket surveillance, an increasingly important part of the regulation of medical devices. Congress recognized the importance of postmarketing surveillance when it passed the Safe Medical Devices Act of 1990.

 This law gives us four new tools to strengthen our postmarket surveillance: postmarket studies, user facility reporting, distributor reporting and device tracking.

The law requires manufacturers to conduct studies on the performance of certain devices after they've been approved and distribution has begun.

Devices subject to postmarket surveillance include newly marketed permanent implants meeting certain criteria, as well as newly marketed life-sustaining and life-supporting devices.

But FDA has the discretion to require a manufacturer of any device to conduct a study of the device's performance. These kinds of studies will generate longer-term data -- from a larger population -- than data gathered during the premarket testing phase. Several of these postmarket surveillance studies are underway.

For instance, we've asked manufacturers of implanted pacemaker leads to study the long-term performance of their products because of concern that some models may wear out prematurely, exposing patients to the risk of early device replacement.

Manufacturers of the newly approved implantable cardiac pacer, cardioverter, and defibrillator devices are conducting postmarket studies on their products, as well.

The second new tool is user facility reporting. With this tool, hospitals, ambulatory surgical clinics, nursing homes, and outpatient treatment facilities are required to report serious device related adverse events--quickly--to both FDA and the manufacturer.

In writing this provision, Congress wanted to be sure we went "right to the source" to obtain timely reports.

The third tool -- distributor reporting -- requires device distributors to report all serious device-related adverse events and serious malfunctions as they become aware of them.

With distributor reporting, Congress made sure that reporting obligations extended through the entire chain of medical device distribution, with no gaps along the way. Device manufacturers have been required to report adverse events to us since 1984.

Lastly, the new law gave us the device tracking provisions.

 Our past experiences have shown that when a problem developed with an implanted device -- like the Shiley heart valve -- we were sometimes unable to locate all of the affected patients. The device tracking provision solves that problem. It requires manufacturers to be able to locate -- or track -- certain permanent implants and life-sustaining devices at any time, even down to the user level.

This permits prompt patient notification or product recall if a problem is identified with a device that could cause serious health problems.

Devices subject to tracking include: vascular grafts, implantable pacemakers, heart valves and silicone breast implants.

Last year we logged more than 100,000 adverse event and product problem reports for medical devices. Each year the number increases, and I expect the numbers will continue to rise as these new reporting programs take hold.

To facilitate reporting of serious problems, and expeditious analysis of the reports, last June FDA announced an important new agency-wide program: MEDWatch.

MEDWatch is a very important program. It consolidates all of the forms that were previously used to report adverse events and product problems involving drugs, devices, and biologics into a single, one-page form.

More important, however, MEDWatch represents a partnership between FDA, health professional organizations, consumer groups, and industry to identify adverse events and product problems as quickly as possible.

Adverse event reports have led FDA to take important actions to prevent suffering and death. They are a critical element of our postmarketing surveillance.

Finally, let me take a couple of minutes to talk about the role of enforcement in a streamlined medical device system.

As I mentioned earlier, we have strengthened enforcement, relying on additional authorities designated by the Safe Medical Devices Act of 1990. We've also taken steps to streamline our enforcement process so that we can remove unsafe products from the market swiftly or work with the manufacturer to act immediately to resolve problems.

Let me give you a couple of examples.

 When the agency uncovers a significant health risk, we can now order the firm to cease and desist from distributing the device, and immediately notify distributors and/or users of the problem.

As part of this new SMDA authority, FDA can also require manufacturers to recall the device as necessary.Prior to this, we could only ask that they do a recall. And we're currently drafting the regulations to implement a new authority to require manufacturers to report all recalls to FDA. You may be surprised to learn that until now, FDA hasn't always known when a product had been recalled.

We just published a notice in the Federal Register proposing to update the device Good Manufacturing Practices regulations with the addition of preproduction design controls. Currently, GMPs require device firms to have a quality assurance program in place to make sure that their products will be manufactured according to the specifications they have determined themselves. With the proposed new GMPS, preproduction design controls should help ensure that quality is designed in, right from the start.

Almost half of recalls are due to basic design problems.

The new GMP regulations will also be in harmony with international standards under development, making U.S. products meeting our GMPs more competitive in the international market.

Our GMP inspections have traditionally been an important way to ensure that medical devices already on the market are safe and effective. We now also inspect a firm before we grant approval of the PMA to market a new device. Any manufacturer who cannot meet GMPs to produce its device properly must resolve the GMP problems before marketing the new device.

And we've now extended GMPs to other products before they're marketed, including Class III devices that come to market via 510(k)s. We're also maintaining a database to ensure that a firm currently in violation of GMPS does not receive marketing approval until those problems are resolved.

FDA can now assess civil penalties against companies that violate the law.

Just recently, we moved against the maker of a cardiac catheter whose violations created a public health hazard.

The manufacturer had been illegally experimenting on people with unapproved catheters, changing the designs of catheters without seeking FDA approval, and concealing from FDA documentation of wrong doing and of malfunctions.

These acts were associated with at least one death, as well as emergency heart surgery for at least 20 patients. The firm has agreed to plead guilty and pay $30.5 million in civil penalties, in addition to $30.5 million more in criminal penalties.

FDA is also paying much closer attention to the advertising and promotion of medical devices.

You may have heard that we required hearing aid companies to stop making exaggerated claims about the extent to which their hearing aids could enhance hearing.

This typifies our effort to ensure that labeling and promotion practices of device firms are truthful and accurate so that patients and health care providers have the information they need to properly select and use devices.

In conclusion, let me say that I have no doubt that our revitalized medical device program will meet the challenge of regulating a dynamic and growing device industry.

That means making promising new technologies available to clinicians as soon as possible. At the same time, it means keeping unsafe or ineffective devices off the market, and taking decisive action when we discover a problem. But we can't do all this without the help of the industry and the clinical and academic communities.

Device firms must understand the requirements of the law and abide by them. They must submit quality applications for the marketing of a new product, supported by sound, scientific data. And they must report adverse effects to us promptly, as the law requires.

Health care practitioners, too, have a responsibility to let us know when they see problems with a device. I want to stress how important that information is to us.

In these days of multi-center trials and epidemiologic studies, it's easy to overlook the value of one-on-one clinical observation in determining whether a product works the way it's supposed to, and whether it's safe.

And clinicians must join with us in demanding good data from the firms that manufacture the devices they use.

In the end, a strong regulatory program for medical devices benefits both the industry and the public.

By strengthening all of our activities -- product approval, postmarket surveillance, enforcement, research and education -- we are ensuring that we meet our responsibility to the American people, and at the same time earn the trust that the world has placed in our medical devices.

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(Hypertext updated by jch 1998-MAY-27)