GOVERNMENTAL & LEGAL AFFAIRS

This year, there is a lot of FDA-related legislation moving through the House and the Senate. In addition, Congress is in the midst of evaluating other areas of significant concern to medtech manufacturers, such as U.S. patent system reform and the adoption of health information technology. Also on the docket are a wide range of regulatory issues with far-reaching implications for the medical device industry, including FDA initiatives for clinical trials management, adverse event reporting and recalls, unique device identifiers, and the advertising and promotion of medical devices. The final shape of these and other policy areas promises to have significant implications for firms operating in the heavily regulated field of medical devices.

To find out more about medtech's outlook in regulatory affairs, MX recently spoke to two experts in the field (see sidebar). In this excerpted roundtable discussion, moderated by MX editor-in-chief Steve Halasey, participants discuss the progress and expected outcomes of FDA-related legislation now being considered by Congress, as well as other regulatory developments surrounding issues such as intellectual property, medical marketing, and healthcare information technologies.

MX: This year, there is a lot of FDA-related legislation moving through Congress, including reauthorization of the Medical Device User Fee and Modernization Act (MDUFMA II). However, many in industry have expressed disappointment that Congress left so much on its plate over the summer recess, to be addressed in September. What is your sense of the progress and expected outcomes of this legislation, starting with what remains to be ironed out between the House and Senate versions of MDUFMA?

Susan Alpert: I don't think there's a lot that's problematic between the House and the Senate on the user fee component itself. We know that we're going to have user fees, and both the agency and industry have already made commitments about the amounts of the fees and how this five-year period of authorization will work.

Some questions have come up regarding FDA's commitment. But, in fact, the changes in FDA's commitment are not extreme, and I expect them to be ironed out in a fairly straightforward way.

However, there are a number of issues related to other proposals that are being included in the same legislation. In those areas, there are differences in the House and Senate approaches that will need to be ironed out. For instance, the proposals related to clinical trials registries affect industry because they impose requirements related to the timing of registration, the kind of information to be recorded, and follow-up and reporting. The shape of these requirements is very murky and still needs to be clarified.

How would you judge the cooperation of industry organizations when working with FDA to create a revised version of MDUFMA that could be sent to Congress?

Bradley Merrill Thompson: From my own observations outside the conference room, it seemed as though folks were getting along much better than in the past.

Alpert: The industry associations—represented by AdvaMed, the Medical Device Manufacturers Association (MDMA), and the National Electrical Manufacturers Association (NEMA)—made a concerted effort to work together as an industry prior to holding conversations with FDA, and the process worked extremely well. There were areas that were more or less important to each of the associations, but everybody's issues got raised and spoken to. We met many times, for many hours, to go over lots of issues. And the result really was an industry position.

In terms of our work with the agency, those upfront conversations made the process extremely efficient. Industry was able to speak with basically a single voice, and I think it benefited the industry to work that way.

Some elements of the proposed legislation are intended to address concerns about the safety of drugs, but could eventually also have an effect on medical device regulations. What other elements of the legislation might prove problematic for the device industry?

Alpert: The device industry gets swept in no matter what's going on. On several of these issues, we obviously knew that the concerns were around. With regard to clinical trial registries, for instance, that issue had been a point of industry discussion for many months. So we knew a proposal was coming, and it was not a surprise.

The pediatric legislation was a slightly different story. We have been working with several groups, including the American Academy of Pediatrics and the Elizabeth Glaser Foundation, on some approaches that FDA might take to dealing with the increasing public emphasis and concern about pediatric devices. So it was not a great surprise that this issue appeared in the legislation.

Having spent a fair amount of time working with a number of organizations, however, we were a bit disappointed that what was proposed in the legislation was pretty much where those organizations started several years ago. It didn't at all take into account our efforts to define what a good pediatric program would look like. So we were a bit disappointed that we had to go back and work through a lot of those same issues yet again.

The legislation still has some issues that will need to be dealt with. But, so far, we haven't been shocked or surprised at any of the proposals. And even the remaining issues that have already taken a fair amount of work were not unexpected in some part.

With regard to the regulation of combination products, are there provisions in the proposed legislation that would make matters more difficult—or perhaps simply leave unresolved known issues that should be addressed?

Thompson: The current proposals are really more in the latter category than the former. There are proposals that may be problematic for devices, or for drugs, but I don't see any proposals that are any more problematic for combination products in particular.

One combination product issue that has been a bit neglected is how to develop an integrated approach to adverse-event reporting. In the unfortunate circumstance that someone is hurt through the use of a combination product—and the product involves multiple manufacturers, or one manufacturer with multiple components that variously qualify as a drug, device, or biologic—it can be very difficult to figure out which reporting obligations apply to the situation. FDA has been working on a proposed rule for quite some time, but in this area it's very difficult to develop a truly unified approach by using the existing statutes as a framework for rule making.

There are other areas that could probably benefit from statutory clarification, but it might be a bit premature for Congress to take them on. For example, FDA has been working for quite some time to come up with an approach to good manufacturing practices (GMP) requirements for combination products. In this area, the existing statute is probably not so much of a problem. The statute gives FDA a fair amount of latitude about how to implement its broad directives, so the agency can probably use rule making to clarify whatever it needs to. But that issue does need to be sorted out one way or another.

A third area that has been neglected, and where some attention would be helpful, is that of international harmonization. All around the world, regulators are now coming to grips with what combination products are and the best approach to regulating them. But there's very little dialogue going on internationally about what the best practices are from a regulatory standpoint.

I don't know whether harmonization is a particularly appropriate subject for legislation. But harmonization is much easier to accomplish when you're building the system than later, after it's already constructed. So I'm worried that the lack of dialogue as we're developing our combination product regulatory systems will come back to haunt us later, when we end up with the inevitable conflicts among the approaches taken by different jurisdictions.

Alpert: A number of conflicts exist already. There are inherent conflicts within the three areas of FDA legislation that need to be ironed out. Europe regulates combination products quite differently, with different triggers. Asian countries haven't figured out how to manage most combinations, but they are approaching them on a product-by-product basis. If we wait much longer, it is going to be an incredible challenge to achieve harmonization.

What about other legislation that seems destined to have an effect on the medical device industry? As we speak, for instance, with Congress in recess, the Patent Reform Act of 2007 has moved out of the House and Senate judiciary committees, but the versions still remain to be reconciled. The current form of that legislation is opposed by a large number of life sciences organizations, including medical device companies.

And the American Life Sciences Competitiveness Act, which includes a lot of provisions that could benefit medical device companies, has been introduced in the House and referred to committee, but no corresponding version has yet been introduced in the Senate.

What are your thoughts on the potential for near-term passage of these or other bills that might be particularly useful—or particularly dangerous—to medical device manufacturers?

Alpert: As you can tell from all of the patent work that goes on between and among medtech companies, patent issues are a major concern for this industry. So the proposed changes represent an issue that will have an impact on industry. But until there is greater clarity about the changes, it is still a little hard to tell exactly what that impact will be.

Another proposed piece of legislation that will affect industry is the pet safety amendment to the 2007 Farm Bill. That amendment deals with what uses medical device companies can make of animals—particularly with regard to training and demonstration in the postmarket area. In some respects the amendment is repetitive to a lot of other legislation that's already in place for animal protection. But some aspects of the proposal are new and could have a great impact on the ability of device companies to conduct appropriate education and training.

So this amendment would regulate the use of animals in surgical training and so on?

Alpert: Yes. The intent of the proposal is to eliminate gratuitous use of animals for marketing purposes—or at least that's part of the intent. But the proposal goes a lot further than that, and at the moment it's quite difficult to know where the line should be drawn.

This is an industry that puts people into the field—into operating rooms and procedure suites—to work with physicians. Some of those individuals are purely technical help. Some of them also have sales or marketing responsibilities.

Frequently, medtech sales representatives—people who deal with sales in the field—are more than just salespeople. They're often also highly trained technical people who are there to help when questions about the use of a product arise. Many of them serve as instructors, performing training for their customers. But if they can't be properly trained, they can't be of use to physicians in that way.

The pet safety proposal is not intended to prevent training of physicians, but it doesn't allow companies to train their own personnel. And that means it will be harder to train physicians, because companies won't be permitted to train their own trainers.

So one of the challenges for this particular amendment is to figure out where to draw the line when a person with both sales and training responsibilities is assisting a physician. How this challenge is addressed could have a significant impact on the way device companies function in an area that's very important—and very different from the way pharmaceutical companies work.

In this case, lack of understanding about how this industry works has led to a bill that has the potential to have a detrimental impact on device companies and clinical care. If the legislation passes as currently proposed, it would severely hamper companies' ability to appropriately train internal personnel so that they can, in turn, train physicians and support them during patient procedures.

Earlier this year, Congress was considering legislation that would require pharmaceutical companies to obtain FDA approval of their marketing and advertising materials. There was concern among device marketers that such requirements might also begin to be applied to medical devices. After all, even without explicit authority, the agency sometimes tends to apply the methods used in one product sector to other product sectors.

Thompson: That's often true. It's less true when it comes to regulating promotional materials, simply because the drug center has the very substantial Division of Drug Marketing, Advertising, and Communications (DDMAC), while the device center has a much smaller group with a very different statutory mandate. They do share some best practices, but they also recognize the differences in some ways.

Alpert: In the case of premarket approval (PMA) devices, FDA has jurisdiction over all labeling under the approval regulations. But most marketing and promotion for devices cleared through the premarket notification (510(k)) process are not controlled by specific official regulations, and jurisdiction is shared with the Federal Trade Commission. Consequently, there is not the same level of engagement or oversight as for PMA devices.

FDA Initiatives

FDA already has a number of active initiatives in a wide variety of areas. Will the agency be able to do anything more in these area as a result of forthcoming legislation?

Thompson: There are at least five or six other areas where you probably will see a fair amount of activity.

One issue that is still very open is the regulation of genetic testing. The proposed legislation speaks in terms of having the Institute of Medicine conduct a study to determine the best regulatory approach to the genetic testing category.

But this entire issue is more complex because of its relation to the broader issue of how to regulate lab-developed tests. And independent of the legislation, there's a whole lot of pressure from all sorts of quarters to reconcile the tremendous differences between the regulations that apply to tests that are developed by traditional IVD manufacturers and those applicable to tests developed by laboratories.

FDA recently released a revised draft of its guidance on in vitro diagnostic multivariate index assays (MIAs), which deals with a narrow subset of lab-developed tests. Although narrow in its scope, this guidance is still profound in its approach, because it is among FDA's earliest explicit forays into regulating tests developed by laboratories.

Alpert: The question of what to do about regulating lab-developed tests is a long-standing issue.

Thompson: I've watched it with great interest for seven or eight years, and it's been moving at a snail's pace. But over the past couple of months, the activity has ramped up to the point that it's much more likely there will be some activity in the coming year than I would have predicted six months ago.

You mentioned that there are a number of additional areas where agency activity is likely.

Thompson: Yes. A second area would involve further adjustments in the advisory committee process. This is an area covered in the proposed legislation, but there are differences between the House and Senate versions. So this will be a topic of discussion in conference.

FDA is also still grappling with this issue. But fundamentally, the agency is going to have to come to grips with wanting to have its cake and eat it, too. On the one hand, FDA wants advisory committees that, if optimally composed, will include people who get their hands dirty working with drugs and devices—practitioners who actually use products in clinical trials or have some familiarity with them. But on the other hand, the agency seems to expect that the people it recruits will have no ties to the various parties who have an interest in producing or selling the drug or device.

FDA has to reconcile these notions with the concept of an advisory committee that doesn't make decisions—because FDA's panels are not the last word on anything. The main value of those meetings is the discussion, not the vote. The panels make recommendations, and FDA makes the decisions.

FDA will need to consider how to resolve some of these problems without disqualifying people who they find uncomfortably connected to the product. So perhaps the agency will simply require greater disclosure, so that everyone—FDA and the public at large—understands the members' potential bias.

So as long as people identify what interests they have, what matters is how well they can reason and how informed they are when it comes to discussing a product's potential safety and effectiveness issues.

The agency is going to have to sort this issue out. It has already released new guidance about advisory panels, but Congress apparently wants it to do more. So FDA is going to have to resolve this issue.

Alpert: Congress focused on the dollar. But it did so without recognizing that there are physicians who are working or have worked with medical device companies in the past, who may have been inventors of products that are now owned by different companies, and they are still receiving royalties. According to the proposed legislation, those dollar amounts would now become a means for identifying potential conflicts of interest—and thereby disqualifying those panel members.

On the drug side, it's essential to look for expertise in clinical trials work and in evaluating the clinical outcomes of those studies.

On the device side, it's equally important that the panels include highly qualified physicians, engineers, and others who actually understand how products are developed. The panelists need to understand the issues involved in working with devices—including areas such as advanced materials, biocompatibility, and sterility—and the people who have that kind of understanding will have done work in the field.

As a result, I believe it's going to be much more difficult to find highly qualified and totally nonconflicted individuals on the device side than on the drug side.

Thompson: Difficult—and wrong-minded. I mean, there really isn't such a person. Instead, the agency should seek out the people who have experience, because they are the people who have been involved in developing the field.

And then you want to put those people in a room and have them engage in a robust and focused discussion. And at the end of the day, FDA should consider what it has heard, and make its decision. That's the way the system works.

Alpert: Exactly.

When I was at FDA, seeing someone on a panel who was multiply conflicted was actually comforting. Because that kind of person has inevitably had a lot of exposure to what is going on in the field at different companies, and can bring a lot of expertise to the table.

Thompson: And the credibility of the system doesn't suffer, so long as all of those potential conflicts are open and acknowledged.

The lay press and the general public tend to assume that the mere existence of a financial tie necessarily represents a conflict of interest that is harmful to the process.

Thompson: Okay, but that suggests we need to educate the lay press, not change the system.

Alpert: The proposed legislation has not fully determined how FDA should define conflicts of interest. Not only is it unclear how those conflicts are supposed to be defined, it also isn't clear whether an advisory committee would be prohibited from having any conflicted people, or would be permitted to have one or even more than one conflicted person.

These are things that will get worked out. And along the way, hopefully, they will get worked out in such a way that preserves FDA's freedom to use its best judgment about who it selects and how it constitutes panels, so that it gets the best possible advice. That advice is very important for the decision making that FDA has to do.

Brad, were there more issues on your list?

Thompson: Yes. Another one is the area of third-party inspections, which has been an area of great mutual frustration for both FDA and industry.

Everybody thought that mutual recognition of third-party inspections was an idea with important potential for today's resource-constrained world. There was a strong feeling that FDA's need to focus on the highest risk areas could be fully realized only if there were some other system that could at least help out with routine inspections.

But despite such high hopes, when the last Congress finished its legislative work and the authorized program was finally implemented, the program just wasn't what it had promised to be.

Since then, just about everyone has taken a look at the program with an eye toward making improvements. FDA has been working on it. The agency entered into an agreement with its counterparts in Canada last fall. FDA earnestly wants to make this program a go, but its hands are fairly tied based on the existing statute.

Based on the current draft of the proposed legislation, it seems likely that some changes will be made in the statutes relating to third-party inspections. In that case, FDA and industry would have new hope that the program could be developed in a way that makes it more useful to everyone.

Alpert: There was a lot of discussion around the topic of third-party inspections during the negotiations between industry and the agency. At the beginning there were some concerns on the part of the agency, but I think we wound up in a position that the agency was also comfortable with.

Because Congress is unfamiliar with how the process would work, some members are concerned that FDA is somehow giving up its rights, authority, and ability to ensure compliance with regulations. But during the negotiations, we were very clear that that's not the intent at all.

The intent is to have an ongoing audit program that's more manageable for companies but doesn't take away any of FDA's rights or authority.

Thompson: It's basically a way to better leverage FDA's resources.

Alpert: And it works for industry, as well, because it saves companies from having a different inspector at their doorstep every week.

Thompson: It adds certainty to the process. And certainty in any process is a benefit. Any process works more efficiently if the rules don't change all the time.

Alpert: There is a timely and interesting angle on this issue of third-party inspections. This fall, the Global Harmonization Task Force (GHTF) will hold its 11th annual meeting in Washington, DC. And the chair is Larry Kessler of FDA's Center for Devices and Radiological Health (CDRH).

One of the GHTF issues in which FDA is very interested is the sharing of audit findings across all jurisdictions. So there is at least a desire on the part of FDA to share its findings with others, and to see what other auditors are doing.

But this desire places FDA in an odd position. It suggests that the agency is willing to share all of its audit findings, even though it won't quite harmonize its regulations in order to accept the findings of others. In effect, this creates a process where every regulatory body sees everything—but isn't allowed to use it.

This is an odd construct. And for industry it imposes a lot of risk everywhere, without the obvious benefits of a program for real mutual acceptance under third-party auditing.

FDA's interest in this sort of program may come to nothing. But it is an interesting twist that GHTF is forwarding the notion that all audit results would be open and shared among governments.

Susan mentioned that pediatric issues could be an ongoing challenge. Do you agree, Brad?

Thompson: The whole pediatric area offers important issues for the future. In about 2004 or 2005, Susan and I sat in a conference room several times when some of these issues were being examined. The attendees were a diverse group that included a lot of pediatric patient advocates, manufacturer groups, government agencies, and so forth. And in those meetings, there was a good, robust discussion of the issues related to the development and testing of pediatric devices.

Alpert: Representatives of the National Institutes of Health were in attendance.

Thompson: Correct. Now, if the proposed legislation is enacted, I think a lot of those groups will have to start getting together again and figuring out what to do. It's likely that the resulting legislation will raise a myriad of implementation issues that will have to be examined. There will be quite a bit of activity in the area, and it will require that diverse group of participants.

Congress has also become interested in the issue of unique device identifiers. How do you see this issue playing out?

Thompson: The unique device identifier issue has been very contentious, in part because the technology is being proposed as a solution for a relatively unspecified or undefined risk, but with a fairly high defined cost. So the first step, it would seem, is to figure out whether unique device identifiers solve a real problem.

FDA has been trying to proceed in a deliberative way, holding a public meeting and getting its ideas out to all of the industry stakeholders in anticipation of possible rule making. So the agency has been trying to look at these issues closely.

Congress may step in and take away the threshold question of whether unique device identifiers need to be implemented. In that case, the question will evolve into how to do it in a way that adds real value and doesn't waste precious healthcare resources.

When you are standing on the outside of this issue, it seems really simple: you either put a bar code on a product or you don't—end of story. But when you really look at the issues carefully, this is logistically a very complicated area.

Alpert: That's right, and there are a lot of unaddressed issues. The proponents haven't even decided whether the identifiers would have to be placed on the packaging or on the device itself. When you ask people in Congress and at FDA about this, the answer you get depends on who you're talking to. But the difference between these two requirements is like night and day.

Thompson: I'm afraid some people are being cavalier about the significance of that difference. But when the debate is so squarely focused on healthcare resources, it just doesn't make sense to waste them.

Alpert: It certainly isn't clear what real use unique device identifiers will be in solving actual safety issues. And it isn't a good idea to treat all devices equally, as though there is no risk-based issue.

On the issue of device safety, over the past year FDA has been especially concerned with questions about how best to conduct postmarket monitoring of approved devices. How do you see this area evolving over the coming year?

Alpert: This issue came up in proposed legislation in the form of a question of whether there ought to be money and resources earmarked for postmarket activities.

CDRH has already changed the way it looks at products in the postmarket environment, both in terms of the visibility of its program and what staff are assigned to it. Clearly, a lot of these changes have been made in reaction to public and Congressional concern over product safety and the objectivity of FDA's assessments of postmarket data.

CDRH took a good step by focusing its work and internal resources to improve communications among various groups within the device center. These changes have brought compliance folks and scientists—staff from the Office of Device Evaluation (ODE), the Office of Compliance, the Office of Science and Engineering Laboratories, and the Office of Surveillance and Biometrics (OSB)—into much closer contact over many more issues. And the center is also creating working groups that are developing expertise in specific product areas. And once this expertise has been developed, it will be a great benefit to both the agency and to industry.

But in the meantime, there is a concern that legislation could have a harmful effect on both the intent and the process.

Are FDA's rules flexible enough to implement a closed-loop system, in which postmarket data are cycled back into consideration by agency personnel at ODE who are evaluating the design of new devices?

Alpert: Well, companies in industry do this. FDA can also do this through its own practices and procedures.

What FDA doesn't have is infrastructure. The agency's infrastructure needs are real; it needs to develop an infrastructure that allows broader access to and coordination of information and data within the center.

There is no problem with determining who does what. It is within the agency's purview to make those kinds of changes. But the agency does have to develop its expertise in specific product areas. If the folks in OSB are going to be the key players in designing postmarket trials, for instance, then they need to have a thorough understanding of technologies used in the field because the type of technology being studied has a significant influence over the shape of postmarket trials and the questions that they address.

A true closed-loop system involves a lot of moving parts, including the clinical research organizations that conduct postmarket trials, the technologies used to record and communicate trial data, and the recipients of those data—both in the agency and in industry. Oftentimes the loop isn't quite as closed as it's supposed to be, because there are so many parts in motion.

Alpert: That's true. But the device center actually has adequate postmarket authority to do everything that it needs to do. On the device side, when FDA orders condition of approval studies under Section 522 of the FD&C Act, the agency has full visibility into the progress of those trials. CDRH is in a very good position to succeed in the postmarket work that it's doing because it has the kinds of controls and visibility that it needs.

That's very unlike the situation on the pharma side. By contrast, the drug center has had a harder time, because its authorizing legislation didn't provide all of the same authority that the device side has.

So the key challenge for CDRH is the absence of necessary infrastructure?

Alpert: The device center needs financial support for infrastructure, some of which is coming from the negotiated user fees. Some of that money is intended to help CDRH build that infrastructure.

Neither of you has mentioned the complex area of healthcare information technology (IT). What are your thoughts about the regulatory and other issues that need to be addressed in order to move this field forward?

Thompson: I am always skeptical of government leadership in that area. I expect the long-term solutions to come more from private industry, so I think the best role for government is to stand back and allow that to happen.

Having said that, I am disappointed that it's 2007 and we're not any further along than we are. I'm generally disappointed in the private sector for not being able to come together better than it has. But I guess I'm equally skeptical that a public initiative is likely to be the solution.

Alpert: A lot of the healthcare IT discussions that have already been held relate to the lack of a ‘healthcare system' in the United States. Because if there were such a system, it would make sense to work toward making the system functional in an electronic environment.

But the United States doesn't have the kind of coordinated systems that lend themselves to being moved easily into an electronic environment. And the challenge of creating those kinds of systems first, I think, has impeded a lot of the work in this area.

There are individual hospitals that have dealt very well with the electronic environment for recordkeeping and operational information, but they're few in number. This is not a common approach, so the distance between where we are and where we need to go is very large.

I was at FDA, on the drug side, when we began to use electronic review processes. And one of the things that we learned early on is that you shouldn't adopt a standardized system until you have had a little experience—because inevitably you would pick the wrong system, at the wrong time, and would commit people to something that wasn't the right outcome.

So we clearly need to move in the direction of greater adoption of IT systems. But there is still a fair amount of advance work that needs to be done.

Healthcare IT is not about just electronic health records. It's really about all kinds of healthcare information and communication. In the cardiovascular sector, for example, devices now generate a lot of information that is, in fact, sent electronically from the devices in patients' homes to physicians and managing hospitals. All this information is becoming available, but the ways in which it can be most useful are not yet clearly developed.

There's a lot more to creating and working in an electronic healthcare environment than simply having an electronic record that a person can carry from place to place.

Kaiser Permanente has implemented contract language that effectively requires medical device manufacturers to be responsible for the compatibility of their equipment with any standard IT system that Kaiser adopts. Is this a way that institutions in the private sector can influence and stimulate the development of healthcare IT systems?

Thompson: Yes. I've seen that occur in other places, such as the Clarian Health System, and I think that's the way the system is supposed to work. Ultimately, I think that's where the impetus will come from.

Alpert: We haven't really seen all of the work that's being done by communication companies that are developing handheld technologies—the firms that we think of as our phone companies. Those companies are working in the healthcare arena, and they're beginning to look at their products as both monitoring and communicating devices.

Thompson: Isn't Medtronic a participant in the Continua Alliance, the healthcare IT consortium that includes device companies as well as communications companies and firms such as Cisco and Intel?

Alpert: Yes. I attended a couple of meetings with communications firms outside Medtronic, and it was clear they are very engaged in figuring out what their role can and should be in this changing healthcare environment. They recognize that they actually have a lot of technologies that can be adapted for this environment.

But I share the concern that those companies haven't stepped forward to take on more of a leadership role in determining what the system should look like. All of the products used in healthcare environments need to be interoperative on the first attempt. If we're going to achieve any acceptable level of safety and coordination, the healthcare system just can't afford to go through a period of discovering and lamenting that fact that such-and-such a device and system aren't compatible with one another.

So I think this is an area that still has a lot of room to grow.

Unaddressed Challenges

Aside from the issues now being addressed in new legislation or current FDA initiatives, are there other important issues that are not getting the attention they should?

Thompson: One topic that is rapidly becoming the unmentioned elephant in the room is promotional issues. I had an opportunity to moderate the device state-of-the-center session at this year's FDLI meeting, which featured a presentation by CDRH director Daniel Schultz, MD. During the question-and-answer session that followed his speech, the only thing the audience really wanted to talk about was promotional issues.

Questions that the audience raised included what uses of peer-reviewed literature are permissible, and what uses are impermissible; off-label promotions; and so forth.

Alpert: Yes, this is an issue of increasing interest since FDA's rule on the dissemination of information on unapproved and new uses for marketed drugs, biologics, and devices (21 CFR 99) died. The legislation had a sunset provision that was allowed to end the use of this provision.

Thompson: Part 99 really wasn't worth the paper it was written on. But there is currently nothing to replace it, nor is there any earnest discussion about developing guidance in this area. It's really almost unconscionable that FDA has abdicated its regulatory responsibilities to give guidance in this area.

Companies in this business are looking to do the right thing. They're in business now, they plan to be in the business 50 years from now, and their reputation is everything to them.

Companies want to play by the rules, so they go to some poor lawyer and ask what those rules are. But all that the lawyer can do is tell the company to rely on first principles: don't lie, don't cheat, and a few other general platitudes. And when the company asks questions that require more-specific answers, the lawyer can give an educated opinion—but there's no FDA guidance to back it up.

Such an absence of regulatory guidance creates two problems. First, it puts companies in jeopardy, because they can easily and innocently stumble into practices that FDA considers violative. Second, it encourages disreputable companies to push the envelope and do things that wouldn't be considered by companies that want to take the high road.

In the area of device advertising and promotion, everyone in FDA has an opinion. The problem is you can't find two opinions that are the same.

Alpert: And no one is willing to go on the record and make their opinion official.

Thompson: Right. So this is a constant source of frustration.

It also really impedes the whole medical device delivery process. Companies don't know what they are permitted to say about their products. And they don't know when it's appropriate to share information and when it's not appropriate to share information.

Alpert: And it's not good enough for a company to hear for the first time that it has created false claims when the U.S. attorney walks in and says so.

Thompson: The stakes are huge.

The absence of guidance invites the frequent involvement of the Department of Justice. What's the solution? Lots of guidance? A device-center equivalent of DDMAC? Or what?

Thompson: I think there are two distinct issues. The first is whether industry needs substantive direction. The second is whether industry needs a process that can be used to get input from the agency. And I imagine that the correct answer is that industry needs a little bit of both.

First and foremost, I would urge FDA to develop guidance that reflects what the FD&C Act requires in the way of using peer-reviewed literature, textbooks, and so forth. I have a long list of questions that come up every day from companies in this industry, so developing guidance to address those questions is at the top of my list.

Second, to handle the inevitable additional questions that aren't answered in the guidance—and have yet to be identified—FDA should create some process or mechanism for obtaining agency input. It doesn't need to be a big apparatus like DDMAC, it just needs to be a point person in the agency who will be able to respond with some authority over permissible promotional practices.

FDA has often invited industry to draft guidance. Is there an opportunity here for some of the industry's marketing associations to pull together that kind of effort?

Thompson: I suppose so. Normally I'm very bullish on that idea because it offers an opportunity for industry to add value by developing thoughtful approaches. The problem here is that if industry attempts to create guidance in isolation from FDA, the chances of coming up with something that FDA will find useful are very low.

I really think such an effort needs to be preceded by more of an in-depth dialogue between industry and the agency. After that, perhaps, industry could come up with a proposal. But there's got to be some dialogue first, because otherwise industry is just shooting in the dark.

So the effort might start with holding a public meeting, or something like that?

Thompson: Yes. It should start with some more-specific concrete dialogue. Then maybe industry can take a stab at it.

Alpert: But having a meeting at which FDA just gets up and talks about the topic doesn't work. There needs to be a lot of back and forth, so that whatever guidance is developed is in fact comprehensive enough. And there needs to be a structure that encourages industry to bring to the table all of the issues that arise with these types of communications, without having any concern about raising those issues.

Otherwise, it's totally impossible to get guidance out of the agency. Instead, the agency will just suggest that you send them your draft, and it will review the draft and tell you if it's relevant. Well, that's not what industry wants or needs.

Thompson: The considerations should be comprehensive. The issues in this area go way beyond FDA's usual concern over off-label promotions. They also involve basic but important things like rules for appropriate conduct at a trade show, handling promotion of 510(k)-pending devices, and a wide variety of other things. The agency has been talking about these topics for years.

Alpert: Right. And we're in a globalized industry, so the issues to be addressed also include international concerns.

When a company attends a multinational convention held in the United States, for instance, can it talk only about its offerings for the U.S. market? And then, when the company goes to a multinational conference held in some other country, is it then permitted to talk about its offerings for all markets? Matters such as this can be extremely difficult to manage.

Closing Thoughts

In closing, what notions do you consider most important for Congress, FDA, and industry to consider when handling current and future regulatory issues?

Alpert: This is going to be a very challenging time for FDA. Implementation of new legislation is always challenging, but in this case the new legislation will require changes because of modifications that have been made in the user fee program.

Beyond the legislative agenda, FDA must address all the matters that we've been discussing. Many of these areas are becoming more and more important to the regulated industries, and they should not be neglected.

It behooves FDA to take advantage of opportunities to work broadly across all of the participants in the healthcare environment. It is a huge challenge, but the agency should try to find ways to address all of these stakeholders in appropriate ways, and to put in place communications channels that will have a lasting effect.

Thompson: As the agency implements all of the new policies and rules that will follow this legislative cycle, it should remember to follow good guidance practices. More transparency and public participation is greatly preferable to unilaterally releasing guidance from the podium or some of the other practices the agency has followed in the past. The agency should make an effort to work in an open and participatory way that gains input from industry and results in better guidance.

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