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Transcript: Town Hall Discussion With the Director of CDRH and Other Senior Center Management, October 7, 2010

CENTER FOR MEDICAL DEVICES AND RADIOLOGICAL HEALTH TOWN HALL MEETING

TRANSCRIPT OF PROCEEDINGS
Irvine, California
Thursday, October 7, 2010

Reported by:
SUSAN SHANSTROM
CSR No. 13526
Job No. 146709

Transcript of Proceedings, taken at 18800 McArthur Boulevard, Main Ballroom, First Floor, Irvine, California, beginning at 8:10 a.m. and ending at 12:05 p.m. on Thursday, October 10, 2010, before Susan Shanstrom, Certified Shorthand Reporter No. 13526.

APPEARANCES:

Dr. Jeff Shuren, Director, CDRH
Dr. Bill Maisel, Deputy Director for Science, CDRH
Dr. Alberto Gutierrez, Office of Invitro Diagnostics, CDRH Mr. Steven Silverman, Office of Compliance, CDRH

Irvine, California, Thursday, October 7, 2010 8:10 a.m. - 12:05 p.m.

PROCEEDINGS

DR. SHUREN: Well, good morning. Can everyone hear me? I'm Jeff Shuren, the director of FDA, Center for Medical Devices and Radiological Health, and I'm very pleased to be here today on the West Coast and eager to hear your thoughts, concerns, and ideas about medical device regulation.

This week my staff and I began to turn our attention to strategic planning for 2011. Many of you may remember that CDRH implemented an aggressive plan in 2010, which we posted our or website. We included deadlines for each of the 2010 strategic plan goals in an effort to be as transparent as possible as we move forward to implement the plan.

I'm pleased to say that so far we have accomplished over 90 of the 107 actions we committed to complete by September 30th of this year. One of those actions was to hold town hall meetings to engage in a dialogue with local communities that are constituents. Today is our third such gathering. And assuming we leave here without any physical harm, we will plan to hold more of these next year.

As you would expect, the main topic of interest at both of these earlier town hall meetings was the 510(k) and use of science reports, and in particular their impact on industry's ability to develop new innovative medical technologies, as well as to have predictable regulatory pathways to market, while assuring that devices are safe and effective.

While the public comment period for both reports ended on Monday, we will take the comments we hear today into consideration. After reviewing all of the comments, we'll determine and announce which recommendations, in their current or modified form, we will adopt, as well as our estimated timeframe for completion.

There will be many more opportunities for you to be heard. Many of the recommendations are regulatory actions that will have their own individual comment periods, such as draft guidances and proposed regulations, so that you can weigh in on our regulatory proposals before we finalize them. I recognize that there are questions or concerns about some of our recommendations, because the proverbial devil is in the details.

Our intent behind these two reports was to first give the public the opportunity to weigh in on the big vision, and then a second opportunity to weigh in on specific regulatory policies before finalizing them. Regardless of which recommendations we decide to implement, our plan is to proceed in a deliberative, orderly fashion and to continue the public dialogue.

Of those recommendations we adopt, we intend to focus first on those actions that will have the greatest public health impact, rather than try to implement everything at once. Recommendations we do not adopt we will refer to the Institution of Medicine for their consideration.

I'd like to take a moment to introduce my colleagues from CDRH who are joining me here today to help answer your questions. First, I'm happy to welcome Dr. Bill Maisel, CDRH's new deputy center director for science; Steve Silverman, director of CDRH's Office of Compliance; and Alberto Gutierrez, CDRH's director of the Office of Invitro Diagnostics. Unfortunately, Christy Foreman, our acting director of our Office of Device Evaluation, couldn't make it. Her plane had mechanical problems, and so her flight was cancelled.

I think this kind of center public interaction is, at least for us, unprecedented, and also, for us, invaluable. It provides us with insights on how we can do our jobs better and more creatively, and gives you a chance to hear directly from us on the matters that matter most to you.

One thing we've heard at both town halls is that providing clear predictable pathways to market will help foster innovation. It is our intent to support predictability and innovation through the implementation of some of the recommendations in the 510(k) and use of science reports. In addition, we've already held our first public meeting specifically to discuss what the federal government as a whole can do to encourage innovation in medical device development. The meeting was chaired by members of a new interagency council on medical device innovation, which is comprised of the FDA CDRH, the Centers for Medicare and Medicaid Services, the National Institute of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Department of Defense, the Defense Advanced Research Projects Agency, and more recently the Federal Communications Commission.

At this meeting we received input and ideas on ways the federal government can minimize or even remove barriers that may hinder the development of medical devices, to address unmet public health needs. We've already taken the first steps to implement one of the recommendations we heard from the venture capital community to allow CMS to begin their national coverage determination process while the medical product is still under premarket review at FDA, what we call parallel review, to reduce the time it takes for a product to receive adequate reimbursement, which means the time it takes for patients to have meaningful access to a new technology.

This balanced public health approach to both assure that devices on the market are safe and effective, while facilitating innovation, is new for CDRH, but one that falls squarely on our mission to protect and promote the public health, and one we believe is responsive to the concerns we have heard so far in our dialogue with the public.

Let me take a few minutes to walk through logistics. The morning is broken up into two parts. We opened it up for anyone who wanted to make formal comments to sign up, and we have 15 people who have done so. So the next part we're going to have each person come up. I will call their names. You have five minutes for providing comments. I ask that you please stick with those five comments.

Heather Howell, who I think you met, will be in the back and she will be signaling when you are running out of time, and also when she will cut you off, as well. She is tough, because she has done that to me on numerous occasions.

We'll then take a short break, maybe about 15 minutes, and we'll come back, and then it's an open Q and A session. Anyone can come up to the microphone. We have one on each side. You're welcome to make comments. If you want to make a comment, I ask that you keep it short. Whatever you do, please introduce who you are and who you are affiliated with. But you can also ask any question that you like. And to the extent that we can, we will answer it.

I'm going to apologize in advance. Sometimes if we are in the midst of developing regulatory policy or we have a document that's under development, we may not be able to discuss the underlying policy at the time, if it's not been put out in draft. We may not be able to discuss distinct and strict timeframes for when something will come out. I apologize for that in advance. So if we do so, we're not trying to be evasive. It's simply federal government policy. That's all.

Therefore, let's go ahead and get started. The very first speaker is David Gallaher.

MR. GALLAHER: Good morning. My name is David Gallaher. I'm the CEO of the California Healthcare Institute, and I'm honored to welcome CDRH's leadership and Dr. Shuren and his colleagues to our state for this town hall meeting.

California Healthcare Institute is a statewide public policy organization. Our 300 or so members include California's leading universities and private research institutes, biopharmaceutical companies, medical device and diagnostics firms, along with venture capitalists and other professionals who support the industry. Our mission is to improve the environment for biomedical R&D in California.

California has a special place in life sciences. Our state is the birthplace of biotech, and it's home to the greatest concentration in the world of medical device and diagnostics companies. All together the life sciences sector in California employes some 275,000 people, and about 112,000 of these jobs in devices and diagnostics. That's roughly one-third of the total U.S. medical technology workforce.

Back in January of this year, the CHI board identified FDA, its policies and activities, as the most important government related factor in their businesses. And going to the proposed changes in 510 -- 510(k) regulation that Jeff just mentioned, the ongoing institute of medicine study and the approaching medical device user fee negotiations, our device and diagnostics members have been acutely focused on FDA. There's a pervasive sense that the medical technology business has in recent years become much tougher, so this is partly a reflection of the global financial crisis and the reduced availability of venture capital, which is down almost 50 percent from two years ago.

But there's also evidence that the regulatory process itself has become more difficult and less predictable. To many it seems the demands for clinical data have risen sharply, the backlogs have grown, and the communications with reviewers has grown harder.

Dr. Shuren has recognized that FDA plays a pivotal role in influencing medical technology investment. To the degree that FDA's regulatory pathways are predictable, reliable, and efficient, investors are prepared to back promising inventions in the U.S., and this helps build our domestic industry, which creates high value jobs and innovations for patients.

But when companies view FDA regulation as unduly slow and uncertain, many decide to move clinical trials and product introductions offshore. This is a disadvantage for American competitiveness and in some cases it results in foreign patients receiving the benefits of American innovations first. We believe that our industry and FDA have a strong shared interest in improving regulation in ways that encourage innovation, maximize safety, and provide new technologies to patients as quickly as possible.

Toward this end we look forward to engaging with Dr. Shuren and his colleagues in a constructive dialogue. It's clear that FDA's new leadership is in a self-critical mode today, and in a period of tight budgets and growing workloads, the Agency is endeavoring to innovate in the way that it conducts business. In this vein, CHI and the industry we represent welcome the chance to partner with FDA to achieve our common goals. Dr. Shuren, colleagues, thank you.

DR. SHUREN: Thank you. Richard Eaton.

MR. EATON: Good morning. I'm Richard Eaton. I'm the industry manager at the Medical Imaging & Technology Alliance, MITA. We're based in Arlington, Virginia. We're the largest U.S. trade association and the leading trade association representing medical imaging devices and radiation therapy devices.

I want to thank Dr. Shuren and FDA colleagues for holding this town hall meeting today. My remarks are basically focused on predicate devices.

Predicate devices are key to the 510(k) process with respect to medical imaging devices. They're uniquely suited to medical imaging devices which evolved incrementally over time. For example, diagnostic imaging devices are continually evolving with new upgrades, features, and options. Through the 510(k) process and use of predicate devices, it helps foster product innovation and brings the benefits of new technology to patients, often used by the medical imaging devices, predicate devices in terms of split predicates and multiple predicates.

Split predicates, for example, can be one predicate used for SE for technology, and one use for SE for intended use. Multiple predicates can include the example of use of more than one predicate to demonstrate that each functional component of the new device is substantially equivalent to its corresponding predicate.

Now, one of the issues that FDA raised in its 510(k) report recommendation is when should a device no longer be a predicate. MITA firmly believes that all cleared, legally marketed devices which have not been rescinded should be available as predicate devices. We also firmly believe that you should not base the availability of a predicate on the age of the device. Many older devices are still in operation and are still clinically relevant. The withdrawal of older devices simply because of their age will only impede access to care.

Now, I'd like to make a few remarks about the de novo process. MITA agrees with FDA's proposal on the recommendations to revise the existing de novo process. The current process is time consuming. It's cumbersome, and the applicant must first get an FDA determination of NSE before initiating the de novo process. So we have a few recommendations.

First, eliminate the need to go through the 510(k) NSE process prior to commencing the de novo process. Second, ensure classification decisions are based on legitimate risk assessments and the need to ensure patient access to new products. Third, create a fast-track de novo process for obvious class 2 products; and fourth, eliminate the need to create new regulations or special controls unless needed on a case by case basis.

One option that we offer for consideration includes dividing devices into generic and non-generic devices. Generic devices could include those devices which are already regulated which have predicates, but are NSE because of minor differences when compared to the predicate for intended use, technological characteristics or performance without predicate. Eligibility criteria could include new or modified devices of a given generic device type, low or moderate risk devices for which general or special controls or consensus standards are sufficient to provide a reasonable assurance of safety and effectiveness and submission of this by the 510(k) process.

For non-generic devices, consider developing a guidance for devices which do not have predicate. Under a risk based approach, FDA may require data necessary to provide reasonable assurance of safety and effectiveness, the eligibility criteria here on low or moderate risk devices, where general and special controls are sufficient to provide a reasonable assurance of safety and effectiveness. It should be noted currently that these devices would have been determined to be NSE due to differences in intended use, technological characteristics, or performance.

In conclusion, our recommendations are as follows: For multiple or split predicates, retain the use of multiple and split predicates. They are a safe and effective means to demonstrate substantial equivalence to previously cleared devices. We believe that FDA should provide more training to reviewers on how to handle both multiple and split predicates.

On the de novo process, we believe that FDA and industry should jointly develop a least burdensome de novo process to eliminate the need to go through traditional 510(k) process only to be found not substantially equivalent. We believe that to allow these devices to be placed on the market prior to the traditional method of developing a special controls guidance, because that is a time consuming process.

Thank you again for holding this meeting. I appreciate it.

DR. SHUREN: Thank you. Mark Deem.

MR. DEEM: Good morning, Dr. Shuren, others from the FDA. Thank you for coming back out to the West Coast again so soon.

My name is Mark Deem. I'm a managing partner and chief technology officer for the Foundry. We're a medical device company incubator based in Silicon Valley. Over the past 12 years my partners and I have founded 15 or 16 different medical device companies that today are treating patients suffering from stroke, obesity, heart disease, vision loss, loss of mobility, and hypertension.

I'm here today because I believe that our ability to continue to pioneer life-saving new technologies for patients here in the United States is in real danger. While there are certainly a host of macroeconomic conditions that are influencing the ability of entrepreneurs like us to raise the money required to bring new therapies to patients, the single biggest contributor to the fear and uncertainty within the financial ecosystem that supports us is uncertainty in dealing with the FDA.

Across our portfolio of companies, we've seen the full gamut of experiences in dealing with the Agency, the good, the bad, and the ugly. In cases where we can establish a line of communication with the examiner, and where there is clear direction from their management, we're generally pretty good. When the reviewer is relatively uncommunicative, but where we can still establish a link to management, it can be bad but manageable. But when the reviewer is unreachable and the management is absent, it's just plain ugly.

It seems to me that many of the regulatory problems that are being discussed today are human problems that do not involve the structure of the regulatory system. I had the opportunity to hear you speak at the recent Stanford roundtable. You mentioned that within your financial constraints, you're forced to make hard decisions. One example was whether to hire a scientist or a manager. Please, hire the manager. I think we -- we need to get some training in management for some of the very bright, very dedicated, but inexperienced reviewers that you have in the ranks today, and we need to further open the lines of communication.

I'd also like to follow up on a point made by Dr. Mackower at the Stanford meeting. In the absence of clear direction of training and implementation, the best changes being enacted within the Agency can have unintended consequences that ripple out from the Agency, through our efforts, and then they crash on the shores of patient care.

An example of this relates to the direction given to review teams to ensure that IDEs can clearly end up with approvable study designs and data. And this is a head-slappingly obvious idea. It sounds like a great idea, but in its execution we've seen examples where reviewers are locking down, requiring so much data to get an IDE that it becomes impractical to supply it.

As a result, I embody some of the -- some of the trends that David mentioned. In many cases my peers and I are not even structuring or financing our companies to get trials done in the United States primarily. We develop groundbreaking therapies here in the U.S. We take them overseas to conduct our clinical trials, and then we stay there to commercialize them, while we make plans and negotiate with the Agency for U.S. approvals. Given the three to five year timelines required to negotiate the U.S. IDE and PMA process, this means that thousands and thousands of patients outside the U.S. are benefiting from healthcare innovations, that we've developed, before our own citizens can.

Patient harm is most often discussed in terms of how a device that has been cleared by the Agency has hurt a patient. What we are seeing today is a different kind of harm, one that needs to be recognized by the Agency, by congress, and by the public, the harm of withholding quality care from patients who desperately need it. We're already seeing this happen, and indeed my partners and I are orchestrating it, and it will only increase in the future unless we can come up with reasonable change.

At Stanford you also asked industry to work with the Agency in areas where we agree, and to state publicly where we see positive change. One area in which we are in violent agreement is the need to fix the dysfunctional de novo 510(k) system. There are many promising new therapies in which known technologies with well-understood characteristics are used in new ways to help patients. In many cases where risks don't justify putting these therapies through the PMA process, the de novo system should be a perfect option. But as you stated, the process is broken and needs fixing. We're looking forward to working with you to fix this -- this much needed option.

We've got several examples of great sounding technologies lately that we've not been able to finance because we proactively told our investors that we're probably looking at a de novo classification. They shut down the investment and those technologies are shelved today. The elimination of the need for an NSE determination and immediate entry into de novo classification is a key first step, and I think there are many other suggestions that I endorse, as well. Thank you for your time.

MR. SHUREN: Thank you. Jack Dhuwalia.

MR. DHUWALIA: Good morning, Dr. Shuren, the FDA panelists, and friends. Oh, God, I'm so -- so nervous, I could just sing. Thank you for giving me the opportunity.

Thoughts, concerns and ideas is what you wanted. That's what I heard. Each of those, that's what you'll get. You know, I'm on a sugar diet, so I cannot have sugar coat delivery either.

I'm Jack Dhuwalia, president of JD Consulting, an independent consulting firm specializing in medical products. My topic today is the current trends in 510(k) review process.

An idea: Today we have an opportunity to bridge a seemingly widening gap between FDA and the device industry. Most solution -- my solution is to apply -- I'm a technical guy -- apply risk management. What an idea.

Question: How much risk is FDA willing to take? No, not in the device risk to patient. I'm not talking about that, but risk of not having the data addressing every possible question FDA could think of. Risk versus benefit evaluation is the key to item defined high risk items so that high risk could be mitigated. That's what an engineer does. Accepting low risk items is a recognized concept per ISO 4971, an FDA recognized consensus standard.

If FDA weighs all the risks the same, there grows the chasm. I propose that objectively -- I've got to move the mic here. There you go. I propose a process that objectively evaluates how the public health will incrementally be protected. And it would cost. Somebody has got to do it. Cost versus benefit, that's what we're talking about. That's basically -- all do that in our daily life. Is it worth it? Do I get the right benefit? It is the white elephant which must be addressed. Otherwise, the dance will go on and on, and the chasm will keep widening.

These are some of my thoughts. I submitted three additional opinions as follows: Number one, FDA's effort to fix the 510(k) process is unnecessary. Number two, recent FDA reviewers are blocking the path to introduce new products in the U.S. I think you may have felt that or heard it.

Page 2. There we are. I only have 30 pages, folks. Number three, proposed changes to the 510(k) process will do irreparable harm to U.S. device industry health. I propose a balanced approach. Here's a thought. In essence, I was told if it ain't broke, don't fix it. The device industry has had a good safety record for over 30 years. A recent independent study reported that of all 510(k) devices cleared in the last five and a half years, 0.16 percent of those were class 1 recall, the most serious recalls. This rate is very small as compared to other products of other classifications. To date, substantial equivalence for 510(k) has worked well for over 50,000 devices. Why change? The system isn't broken? Why fix it? Something to think about.

A comment: Recently there has been noticeable change in the review process. I've noticed that. New questionably -- questions have been raised while objectively seems to be missing. Often the questions appear to be arbitrary and capricious. Oh, harsh words. Okay. It seems as if the reviewer is making his or her own rules, sometimes in conflict with conventional wisdom and with the FDA policy. What's going on?

Thank you. I don't think my time is up yet. In my observation, the collaboration that had distinguished the relationship between the device industry and FDA has been eroding. I want to believe that FDA wants to bridge the gap. I believe the industry does too. There's a thought. Slowing down the 510(k) reviews and insisting on clinical trials in the name of safety won't protect public health. It will likely hurt device industry health and keep innovative products out of use in the market. American public loses.

From a movie I got this line, show me the money. How many -- how many heard that line? Okay. Here's how it applies. Where is factual data, not opinions, supporting the massive proposals to change the FDA 510(k) process? Where's the data? And the data would be in the form of percent reported of all the devices used over the 510(k). We're talking about serious events or deaths.

Let's look at some numbers. It gives a perspective on what's going on. Let's go to the recent 510(k) workgroup. Wonderful job. Wonderful reading. It puts me to sleep every time. Just kidding. About a hundred page document, hundred and twenty page document. They're proposing a new class to be devised, a group. Okay?

I conservatively estimate an additional cost of one to two million dollars or more just to take care of the animal studies required and the clinical trials, clinical data required following the protocols, following the procedures. And it will extend the time from one to two years. Most innovations developed by smaller companies can ill afford this burden.

Folks, we're talking about losing American jobs for what real benefits. The most -- there are -- I just have a paragraph left. There are more effective techniques demonstrating safety and effectiveness other than by clinical trials, typically conducted with two patients, for devices, which is, at the best, pseudo science. Clinical trials in large number of patients are very important, recording side effects, interactions for drugs. Devices really don't have that need.

Dr. Shuren, I want to believe that you care about medical device industry health as much as public health. I suggest a balanced risk based approach. Life will be better with everybody working together. Thank you.

DR. SHUREN: Thank you. Rita Redberg.

MS. REDBERG: Thank you for the opportunity to speak this morning. I'm Rita Redberg. I'm a professor of medicine and a practicing cardiologist at UCSF Medical Center. I'm also the editor of the Archives of Internal Medicine.

As you know, cardiology is one of the most technology intensive specialties, and so I'm seeing another view of cardiology devices. And my main interest is in making sure that Americans have the best -- and by best, I mean safe and effective -- medical devices in the world.

I think it's important that we have innovation. I also think it's important that that is not done to sacrifice safe and effective. Right now we have the most medical devices used in the United States, but it's not necessarily giving us the best medical care.

I think it's important that we look at the quality of the data to approve devices. I hear a lot of people use the word groundbreaking, and I think that's great, but I don't think groundbreaking should be taken on face value. I think if you want to say it's groundbreaking, there should be clinical data to show that this is an improvement. And clinical data generally means a clinical trial. It means, you know, at best, but not always, a randomized trial and a blinded trial with active controls and clinical endpoints that are meaningful to patients.

Right now we have a proliferation of devices used in the United States, and we don't have the data to show that our patients are doing better or have better health because of the use of these devices.

I just want to give one example. We published a paper recently in the JAMA looking at the data for premarket approvals and found that there was a minority of trials that backed up premarket approval devices that were randomized and blinded, which I believe the FDA is currently working on to improve standards for premarket approval devices.

But what I -- we also find is that a lot of high risk devices don't even go through the premarket approval pathway. They go through -- the majority of high risk devices go through a class 2 or 510 clearance pathway. I believe the GAO report issued last year said that 60 percent of high risk devices were going through a 510(k) clearance.

I'll say, you know, industry perspective is important, but I got tons of e-mails from doctors all around the country saying that they felt we were using too many devices without adequate clearance, after we published that article in JAMA. So I know that there are a lot of concerns among doctors about getting good quality data for device approval.

To use just one example, the inferior vena cava filter, which there was recently an article published in the Archives of Internal Medicine last month, the IVC filter, so one that goes into your inferior vena cava to prevent blood clots, was approved through a 510(k) clearance. It was meant to be a retrievable filter, although only less than 7 percent are actually reviewed. So we're talking about basically a permanently implanted device.

The doctor that wrote to us and wrote up the article had one of his patients three years after an IVC filter was placed come back with perforation of the heart, because the filter had fractured and embolized. So they went back and looked at all of their patients and discovered that 25 percent, so one out of four patients with this filter, had a fracture and embolizations.

You know, that is something that we didn't -- we didn't know about and they obviously -- they reported, they reported to the -- you know, he sent it to us. The first thing he said was please make sure you report it to the FDA. He said he was already in discussions.

But when I looked into this device, it had gone through on a 510(k) clearance. There was no clinical data. To me, this is a high risk device with potential for death. And, indeed, a lot of their patients were dead at the time he tried to follow them up, not clear from the filter or other reasons.

The FDA did issue a warning the same day that we published the papers, but the warning stated to retrieve the filters, which, you know, clearly doctors are not retrieving these filters for whatever reasons. And now it's -- you know, the data for retrieval of filters only went out to six months.

But the other thing that was striking is that there were a thousand adverse events reports reported to the FDA since 2005 of that IVC filter. My understanding is the FDA issued the warning on that day, because there isn't a really -- a way to monitor, and so the FDA wasn't aware that there were a thousand adverse event reports for IVC filter fractures in the system.

And so I think we need better safety reporting, better post marketing surveillance, you know, better IT and structures to be able to look at safety signals, because it -- it -- you know, we can't rely on journals like mine publishing papers about problems to start looking for serious adverse events reports. But, you know, this is a device that's used in hundreds of thousands of Americans, and so, you know, the potential for damage and death due to this device is not trivial.

And so while I certainly -- I think it's important to move things out, I also think it's important to be sure there's clinical data, and that if there is a new classification of 2B, it's not used for high risk devices. I think high risk devices need clinical trial data.

You know, this was a class 2 device, which, you know, is the same as a mercury thermometer. I think for things that are not implanted and not permanent, you know, those could be appropriate, but not for permanently implanted devices that have a potential to cause serious adverse events, including death.

And the last thing I'll just say quickly, on the FDA and CMS collaboration, I think it's a good idea to get things moving quickly, but I think it makes it even more uncommon to make sure that there's adequate data before FDA approval if things are going to move that quickly. I served for four years on the Medicare Coverage Advisory Committee and had the opportunity to review many devices. One of our meetings was defibrillators, ICD's in 2003. At that time I noted that the data, that was mostly on the basis of the MADIT-II trial, did not show efficacy in women. There were very few women in the trial, only 10 percent. The PI told me it's because women don't get heart failure. That's why they weren't able to enroll them adequately in the trial. It's in the transcript. And -- and that got approved by Medicare. It's now used, you know, in millions.

We published a metaanalysis a month ago. All of the randomized trials of ICD's in women, there was absolutely no benefit. The hazard ratio was one. And so now we have, you know, a device that was FDA approved, Medicare approved, and we still don't have data. You know, maybe -- you know, if you talk about it, people say we can't deny women this lifesaving device, but we don't have the data it's lifesaving. I agree we shouldn't deny women lifesaving devices, but I don't think we can say that, unless we have data that actually shows it's lifesaving. That data should be in women, as well as in men.

Obviously, the other issue with Medicare is that most clinical trials tend to use a much younger population than Medicare, and there's a lot of concern you can't extrapolate from middle aged basically healthier people to an older Medicare population, which has multiple comorbidities. And so I think, you know, that we -- you know, it's great to -- I have a lot of colleagues who are doing very exciting, you know, high-tech work in the Silicon Valley area, and I support that, but I don't support it moving through at the expense of patient safety, and I don't think you can rush that part of the process. Thank you.

DR. SHUREN: Thank you. Roger Lewis.

MR. LEWIS: Good morning. It's a pleasure to be here. Thank you to the organizers. My name is Roger Lewis. I'm a professor in emergency medicine at Harbor-UCLA Medical Center, also affiliated with the Los Angeles Biomedical Research Institute, the David Geffen School of Medicine at UCLA, and Berry Consultants, which is a statistical consulting group that focuses on clinical trial design.

I'm going to limit my comments to two apparently disparate issues, but the common theme is that the ability to continually learn from and react to accumulating information is a key feature of effective device regulation.

First, I'd like to comment about a success at CDRH and give credit where credit is due. As we all know, the resources and time required to conduct high quality medical device trials pose a key challenge to device manufacturers, yet, as was just mentioned, new and valid clinical data are often required to appropriately inform medical device regulatory decision making. Clinical trials that are adaptive by design, in which key trial characteristics are modified in response to data arising within the trial itself, hold the promise of increasing statistical efficiency, improving the ethical balance within those trials for the patients, and better estimation of benefit and safety.

CDRH has been a leader in the development of rigorous adaptive clinical trial design. They have not just been open to innovation, but in many ways have helped to drive appropriate conservative innovation. They have encouraged thoughtful innovation, at least a better clinical trial design, and an increased chance of bringing a beneficial device to market. In fact, the leadership within CDRH has guide -- has guided the thought process within other centers and has contributed to the recently released guidance on adaptive clinical trial design from the other centers. So adaptive clinical trial designs, when rigorously designed, allows us to continually learn from and react to accumulating information.

The second point I'd like to make is related to a challenge. In the October 2010 issue of the peer reviewed journal, Annals of Emergency Medicine, there's an article on the accuracy of a 510(k) approved device for the noninvasive measurement of carboxyhemoglobin. As you probably know, carboxyhemoglobin level is an important determinant of the need for intensive therapy for patients who have suffered life threatening carbon monoxide poisoning.

The validation data that were originally submitted to the FDA by the manufacturer suggested an accuracy of plus or minus 3 percent in the absolute level of the carboxyhemoglobin level. But, of course, those data are not freely available, nor are the details of the circumstances under which those data were collected.

In the real world use of that same device recorded within the journal I just mentioned, the authors found that one-third of the measurements were off by more than 5 percent in the absolute difference. And much more concerning, the sensitivity of that device was 48 percent, 11 of 23 patients, in detecting clinically important, life-threatening, carbon monoxide poisoning. In other words, it was no better, just a little worse, than flipping a coin. This represents new information about the performance of this device in a potentially life- threatening circumstance.

So how can and should CDRH respond to this kind of new information? Well, if we refer to the preliminary report of CDRH from their working group on the 510(k) process, August 2010, it states, and I quote, FDA has not provided clarity regarding the circumstances under which it might exercise its authority to rescind or modify the scope of a device clearance, and to date FDA has largely limited its recision of 510(k)s to situations involving fraud.

Without a recision regulation, it is not clear to center staff or industry what other circumstances might warrant a recision, such as specific concerns about the safety and/or effectiveness of a marketed device. When we think about an approach to the total product lifecycle, we need to include the potential recension of the clearance for devices in which there are important valid and reliable data that suggest the device is either dangerous, ineffective, or has other limitations. This again, illustrates the fact that the ability to continually learn from and react to accumulating information is a key feature of effective device regulation, and I urge the center to find a way to clarify situations under which a device clearance ought to be rescinded because of information that illustrates that there is a threat to patient safety and well-being.

Thank you very much.

DR. SHUREN: Thank you. Thomas Chaly.

MR. CHALY: Thank you for giving me the opportunity. I'm Thomas Chaly from the Feinstein Institute of Medical Research, North Shore Long Island Health System, New York.

For the last 20 years North Shore and other non-profit medical institutions in this country have been manufacturing innovative radiopharmaceuticals for Positron Emission tomography, also known as PET. Since these radiopharmaceuticals are very short-lived, they have to be manufactured in medical institutions and not by pharmaceutical companies. Once manufactured, the radioactivity decays very fast and in a few hours the radioactivity disappears completely. Therefore, there is no shelf value for this drug. They are different from regular drug products.

In 1997, Congress realized the potential of these drugs and passed the FDAMA Act which required the FDA to help medical centers to develop NDAs for these drugs. Under the previous FDA division director, Dr. Mills, and also with the help of Mrs. Jane Axelrad, regulatory policy FDA, North Shore Health System received FDA approval for two of the three important PET drugs. It was a successful, coordinated effort by FDA, and we are very thankful to the FDA team for the friendly communications and -- with our center and the PET community.

Since then, the nuclear medicine community and PET centers have requested the FDA to approve the third drug, Fluorodopa 18 injection, for evaluating Parkinsonian syndromes. This is the only PET drug that remains to be approved by FDA which is used for regular diagnostic imaging. There was a public meeting conducted by the FDA on July 28, 2000, during which FDA promised further discussions to develop a NDA for this drug.

For many years, medical institutions in the US have been using Fluorodopa PET for routine clinical diagnosis even though there was no reimbursement for the scans. These medical centers have indicated to FDA -- indicated to us that they cannot afford to continue this service any further without reimbursement. If there is no FDA approval by December 2011, the day the new CGMP rule will be implemented, medical institutions may decide to stop scanning patients once again. Medical institutions have already stopped scanning patients since they cannot afford to finance for this free service. Those patients who can afford it travel to Canada for their scans, and those who cannot are left out.

Patients with Parkinsonian syndromes are asked to undergo Fluorodopa PET scans by their physicians to determine the right treatment, since the cause of the symptoms are unknown. It may be due to Parkinson's disease itself, or due to other medical conditions, such as psychogenic or drug induced, vascular, et cetera, that require completely different treatments. Fluorodopa PET scan is the only diagnostic tool used for discriminating between these two conditions. With the help of Fluorodopa PET scan, 20 to 25 percent of Parkinsonian syndrome patients could be misdiagnosed -- without the help of Fluorodopa PET scan, 20 to 25 percent of Parkinsonian syndrome patients could be misdiagnosed with the physical examination alone, and they may be subjected to incorrect treatments, causing several unpleasant side effects, and not to mention increased healthcare costs.

When we informed the FDA division director about the problem that we are going to face in December 2011 without FDA approved NDA for Fluorodopa PET, he indicated to us that we'll be able to continue Fluorodopa PET studies even after 2011, with payment under a special IND, with payment. We welcome this and we are very thankful, but we are puzzled why the FDA has to -- has not yet established an NDA which will provide added protection and oversight for this drug. After all, that was the intent of the FDAMA Act.

After 20 years of safe and effective use of this drug, an NDA seems more reasonable than a special IND. Thousands of patients have been exposed to Fluorodopa F 18 injection without any side effects or safety problems. There has not been a single adverse event of death for the last 20 years. Furthermore, the drug is already approved in Europe. Presently, based on physicians' requests, our center is providing this service for routine clinical diagnosis hoping that an NDA will be approved by FDA in the near future.

The medical centers have proved the safety, efficacy and specificity of this drug with several publications and clinical studies. Fluorodopa F 18 PET has a long history of safety and effectiveness. This drug is superior to the cocaine analog imaging agent proposed by pharmaceutical companies. Cocaine analogs are known to stick to the striatum like glue. So if you are labeled with Iodine 123, which has a half-life of 18 hours, it can remain in the striatum for a long period of time and can damage the brain damage.

On the other hand, Fluorodopa F 18 injection is an analog of LDOPA, which is used for treating Parkinsonian patients and the residence time is very short and the patients can go home without worrying about radiation.

There's a real medical need for Fluorodopa PET for differential diagnosis of Parkinsonian syndromes. The benefits are far greater than the risks. Fluorodopa helps patients and their physicians to decide on their treatment. Since there is no FDA approval, there is no reimbursement and the medical institutions are finding it financially difficult to fund the scans.

Once again, we need a coordinated effort from the FDA and a team that can help us to preserve and protect this innovative technology. We are requesting the FDA to approve this drug, with a priority review process so the drug will be available even after the CGMP deadline, for all, for all patients. We must not ignore the patients with less financial fortunes in getting this scan.

The medical institutions are not doing this for profit, unlike the pharmaceutical companies. We are doing this to help the patients. That's all I have to say. Thank you.

DR. SHUREN: Thank you. Janet Trunzo.

MS. TRUNZO: Good morning. I'm Janet Trunzo with the Advanced Medical Technology Association. Our association represents manufacturers of diagnostics and medical devices, and our members range from the smallest to the largest medical technology companies.

Advamed supports the efforts of FDA to seek feedback from stakeholders through these town hall meetings. Advamed also commends CDRH for the development its strategic plan. The plan is consistent with FDA's mission to protect and promote the public health by assuring the safety, effectiveness, and quality of medical devices by fostering innovation and providing the public with accurate science based information.

Today, however, I would like to focus my remarks on the 510(k) process in light of the fact that the comment period just closed a few days ago. First, Advamed believes that the 510(k) review process is well designed to assess the safety and effectiveness in low and moderate risk medical devices whose risks are well understood from experience with similar devices. We also believe that regulatory requirements should balance FDA's dual mission of protecting the public health, while facilitating innovations that benefit patients, but patient safety is the number one priority for medical technology companies.

We urge FDA to move forward with changes to the 510(k) program in a way that builds on the strengths of the program. While many of these recommendations have the potential to increase the efficiency and consistency of the review process, others could actually chill device innovation and the flow of improved products to patients. Advamed is concerned with the sheer number and scope of the over 60 proposed changes could negatively impact the Agency's mission to ensure American patients have timely access to safe and effective medical devices. Implementing so many changes could likely overwhelm the Agency and in the industry and have the effect of disrupting rather than improving an already effective program.

Rather, FDA should focus on changes that are targeted, have a corresponding public health benefit, and strengthen the current system and proposals that enjoy broad agreement, such as increases in reviewer training and management training, development of specific guidance documents, and improvements in the de novo review pathway.

In our comments, Advamed supports a number of FDA recommendations and highlights many other proposals that with modification could improve the predictability and efficiency of the 510(k) process. Changes that have the potential to disrupt the program are the following, just naming a few: The consolidation of the terms intended use and indications for use could significantly alter their current meanings, add confusion to the process, and increase delays and product clearances. Limiting the use of predicates; any recommendations to limit the number of multiple predicates or even disallowing the use of a split predicate in a 510(k) submission would unnecessarily limit the range of evidence that a company could use, and could unnecessarily complicate the review process. Greater authority to rescind 510(k)s; FDA currently has extensive post market authority to remove a device from the market that it deems a danger to the public health without expanded recision authority. Advamed is concerned that expanding FDA's recision authority could lead to more arbitrary removal of products from the market than under the current procedures, and have a domino effect on the medical devices that are currently on the market. Changing FDA's least burdensome guidance document; the current least burdensome guidance document is a carefully worked out document designed to achieve the objective that was defined in the FDA modernization act of 1997. Rather than rewriting it, FDA needs to train a new generation of reviewers on how to use it properly. Establishment of a class 2B; while Advamed supports identifying a small focused subset of class 2 device types that would be subject to special requirements, we do not support, however, the class 2B category as defined in FDA's recommendations. FDA's class 2B proposal appears to include a much broader category of device types, and the proposed additional requirements for this category are unnecessarily burdensome and not what we had envisioned.

Advamed looks forward to working with FDA and other stakeholders on ways to improve the 510(k) program that will increase the clarity and efficiency of a process, but will not unnecessarily burden a process that has served American patients well for over 30 years. Thank you very much for allowing me to speak today.

DR. SHUREN: Thank you. Sybil Goldrich.

MS. GOLDRICH: Good morning. My name is Sybil Niden Goldrich, and I have been an activist in the field of breast implants for 22 years. Thanks for coming to California. I appreciate it. I've gone to Washington many times.

Announcement of approval of silicone breast implants was made on the Friday of Thanksgiving weekend 2005, assuring FDA minimum press coverage. A substandard product not worthy of approval, a product that had been commercially available for close to 40 years and still did not have adequate long-term scientific studies, had been awarded a coveted prize, FDA approval. The product was approved despite objections from FDA's own scientists who recommended that implants not be approved.

As a political compromise, FDA tried did three things to try to reduce the risk to women when they improved silicone implants, even though it was very clear that FDA had no ability to enforce the compromises that they made. First, they required that each of the implant makers study more than 40,000 women for more than ten years to determine the long-term risks. It's nearly five years since that request. What have you received about those studies?

Secondly, the FDA issued a warning on their website that women with silicon gel breast implants undergo breast MRIs three years after getting silicon breast implants and every other year after that. Unfortunately, most women getting breast implants don't read the FDA website, so it isn't surprising that despite these warnings radiologists tell us that women with silicon breast implants are not undergoing screening with breast MRIs. Further, MRIs can cost an average of $2,000, well out of the reach of most people.

Third, FDA required that manufacturers provide patient booklets to warn women about the risks of implants. Unfortunately, these patient booklets are 40 pages long, very technical, written at a reading level for college graduates and perhaps graduate students, and probably written by lawyers. They are not understandable or useful in explaining the risks to the average person, because the average person does not read a 40-page booklet before getting any medical treatment.

Dr. Shuren, just as you are reexamining other questionable approvals that were made over the objections of FDA scientists during the eight years prior to your becoming director, I ask you to do the same for silicon breast implants. The FDA based its decision on very short-term data, even though the type of silicon breast implants approved by the FDA had been on the market for more than ten years and the agency could have required long-term data on thousands of women.

The problem with silicon breast implants is that they are increasingly likely to break every year that they are in the body. And in the meantime, a newer type of silicon breast implant made of a thicker gel, and nicknamed Gummy Bear implants, have been available through IDE's. My question to you is, has the FDA ensured that these IDEs are gathering useful data, or are they being used as an excuse to sell these experimental devices to women who are not aware that the Gummy Bear implants have never been approved by the FDA?

In summary, under your leadership it would be important to women considering implants and those who already have them if, number one, FDA reexamined the approval decision of silicon gel breast implants. They should not have been approved. And unless post market studies are adequate to prove that they are safe for the long term -- for long term use, FDA should rescind approval. They are a class 3 device, nothing more. FDA provides -- should provide more warning to women with silicon implants to get regular MRI's to check for leakage. FDA should improve and provide short understandable patient booklets on breast implants that truly warn women about the risk of silicon gel breast implants. And FDA should make sure that Gummy Bear implants are being sold appropriately, regulated through IDE, and not sold to patients.

Thank you for your attention. I have provided a folder with additional materials so that you'll have a comprehensive view of the history of the ill-advised approval of these products.

And because it's breast cancer awareness month, I'd like to show you something that we published a long time ago, but it's still true, silicon breast implants hide cancer from mammograms. And here you have a picture of a breast cancer -- a mammography with a breast cancer, a mammography with an implant. It hides the breast cancer.

Thank you for your attention. I appreciate it.

DR. SHUREN: Thank you. Anette Asher.

MS. ASHER: Follow the data. That's all really what our roles are in our life science industry. It's all about the data.

My name is Anette Asher. I am CEO of the Life Science Information Technology Global Institute. We are a nonprofit organization modeled after the ICH, the international conference for harmonization, and our mission is to develop a guidance document called the good informatics practices guidance. So it's all about anything IT in your healthcare or life science environment. Yes, we do include healthcare at this point. And life sciences, as we define it at LSIT, includes not only medical devices but drugs, biologics, diagnostics.

So what this GIP guidance document is, our goal is to basically help FDA and work with FDA to harmonize some of the processes when it comes to trusting the data. And data sits on IT. It sits on some sort of IT system -- or I've got an app for that. And our goal is to make sure that data can be trusted by anyone who is to review it, collect it, use it, share it, whatever, exchange it, et cetera. And we address things such as security and integrity of the data, data management, infrastructure and architecture of an IT system that the data sits on and gets worked within, as well as the verification and validation of the software or the IT product that's probably in your medical device.

So our goal is to accelerate this process of helping medical device companies adopt faster, better, cheaper technology. And by having a playbook such as GIP, we believe we can help do that by facilitating a common understanding of some best practices that we've aggregated throughout the world, best practices in IT systems and management, and bringing together and citing the references and CFR's and standards that are already out there. So we're not creating any new standards. There's enough. And so we just want to put them all in one place so that it becomes a useable tool from the CFO to the regulatory affairs professional, and certainly for the CIO and his team and the quality team. So that's what I'm hoping to do, Dr. Shuren and FDA panel, that perhaps we can have a further discussion to share what our goal is to help us all when it's following the data.

On a second thing for why I am here, I am a member of a very new organization called the Healthcare Security Alliance, and I'm very motivated to share with you, those of you who are in the medical device field, this alliance is comprised of CIOs and chief security officers of hospital systems, including teaching hospitals, from UCSF to Harvard, et cetera, and they are concerned about managing their compliance when it comes to HIPAA 1 and HIPAA 2.

Medical devices are -- there are some old systems out there -- Dr. Eaton, I'm sure, can relate to this, that -- that do have very old operating systems operating on Windows 98. There are no patches. There are no ways to work with these systems to assure continued security and compliance using these devices within a provider or hospital setting. So I just throw that out there in hopes that we can come to other common understanding and accelerate, as FDA is wanting to do, accelerate the pathway to market and help these medical device companies to update and upgrade their systems. Thank you.

DR. SHUREN: Thank you. Joe Panetta.

MR. PANETTA: Good morning, Dr. Shuren and members of the offices of -- the Centers for Devices and Radiological Health. My name is Joe Panetta and I'm president and CEO of BIOCOM.

BIOCOM leads the advocacy efforts of the medical device bio technology communities here in Southern California. And on behalf of all of our members, welcome to Southern California. Our membership includes universities and research institutes, and our membership in medical devices ranges from emerging growth companies to very small entrepreneurs just seeking their first investments and doing their first RND.

Many of the business plans of our medical device and diagnostic members rely heavily on the 510(k) process, and we appreciate the relationship that we've had over the many years with FDA. We'll soon be releasing our fifth biannual report on the working relationship between the industry and the FDA, in conjunction with Price Waterhouse Coopers, and we look forward to sharing the results of that report with you, as well.

We have a letter on file reflecting many of our concerns in detail, so I won't belabor every point in our letter. And many of these points have been made already by a number of our speakers, and done very eloquently.

We know that the FDA's primary mission is to protect and promote public health as it relates to approval of drugs, devices, diagnostics and, the food supply. And where it comes to medical devices, we believe that the FDA has done a very excellent job and set the gold standard for the world.

Dr. Shuren, in your cover letter attached to the report, you restated the Agency's goal in this review process as looking at ways to foster medical device innovation, to enhance regulatory predictability, and to improve patient safety. Our members share a common goal with the Agency and support the desire to improve public health by bringing innovative, high quality devices to market in a timely fashion. However, the number one challenge that BIOCOM members continue to hear -- or to face, and that we hear from our medical device industry membership is that a 30 day 510(k) review doesn't really seem to exist anymore. With each coming year, they state that the 510(k) review times become longer, more unpredictable, and more data seems to be required than in previous submissions. And they feel that this doesn't relate as much to the quality of the submissions that they make, but rather a lack of communication between reviewers in the industry, as well as the need for greater reviewer access to training and education on the newest technologies.

We want to work with you to get the program back on track. We understand how the wide array of new innovative technologies can challenge the Agency to create science led regulation that enables and accelerates and does not inhibit the development of a new generation of even more effective and safer products. One way the Agency can help to create regulation that enables innovation is by reducing that regulatory uncertainty. For example, some innovators are small companies with limited experience bringing medical technology to commercial development. One way FDA can start creating a science led system is by engaging in early, more regular, and interactive communication with the industry during the process.

We also believe that reviewer staff capabilities can be enhanced through collaborative training program and FDA sponsored educational programs to enhance their familiarity with newer medical technologies. The Agency can also work together with the industry to clarify the submission requirements for emerging technologies, to set clear standards, and to develop better guidance documents.

In our comments on the CDRH internal 510(k) working group report, we said that many recommendations from the working group appear to be aligned with the industry's concerns on how the 510(k) process could be improved. However, we have an open question as to whether all of the proposed changes would actually serve to foster the goals of medical device innovation, enhance regulatory predictability, and improve patient safety. In fact, the report contains some proposed changes that could force the industry to over report, risk legal breach, and may lead to a costly and unnecessary burden on FDA and industry resources.

We're troubled that we've received reports from many of our member companies that CDRH already appears to be instituting some of the recommended changes about which the industry has expressed concerns and objections. The FDA says that the report recommendations are preliminary and have not been implemented, but we are anecdotally aware of a letter from the FDA that states the use of split predicates may not be allowed. And we hope that you'll maintain the spirit of good will and cooperation, as you have in the past, between the Agency and the industry, of which this town hall meeting continues to represent.

No one benefits from bad actors, and as an industry, we have a vested interest in ensuring that all devices brought to market are safe and effective. Our members here in Southern California and BIOCOM in particular stand ready to act in good faith dialog with CDRH so that the interests of all of our members and all involved can be served, because ultimately it's about the patient and the consumer.

So in conclusion, the report does acknowledge the importance of enhancing innovation, and we commend the Agency for recommending the importance of that, for recognizing it. However, in our view, the majority of the recommendations will result, if implemented, in forcing the industry to over report, to risk legal breach, and may lead to costly and unnecessary burden. We know that the FDA is recognized as a world leader and regulatory review. Faster review times, quicker decisions to terminate unsafe devices and higher success rates will help to reduce cost and help innovators to achieve their goal of product development, and we'll get these products to patients more quickly. We appreciate the efforts of the FDA, the center, and the working group, and we know how much work has been expended in creating this report.

Again, we share a common desire to improve communication between the industry and the Agency, to improve patient care and safety by bringing innovative, high quality devices to market in a timely fashion, and we're confident that the Agency will continue to work with all stakeholders in an open manner, and we seek the opportunity to continue to do this. Thank you.

DR. SHUREN: Thank you. Paul Biggins.

MR. BIGGINS: Thank you, Dr. Shuren. My name is Paul Biggins. I'm with Toshiba Medical Systems. We're a manufacturer of diagnostic imaging equipment. And I'm also representing the medical and technology alliance as the x-ray section chair.

I'm going to talk about a couple subjects. I'm going to start with off-label use. Well, before I start that, my background is I've been in this industry, in the medical device industry, primarily diagnostic imaging, for over 30 years. During that 30 years there's been a number of changes that have improved the patient care, reduction of -- especially with diagnostic imaging there's been a -- from 19 -- from the 1980's, when I started, until now there's been a drastic reduction in exploratory surgery, unnecessary surgery, that type of thing, which, of course, correlates to -- to hospital infections, that type of thing.

So off-label use. MITA opposes any statutory changes involving off-label use. FDA currently has more than adequate enforcement powers related to off-label matters. More significantly, this concept could limit the ability of physicians to act in the best interest of the patients. As such, it is contrary to express statutory requirements that the Agency not regulate the practice of medicine. It could also require companies to submit unnecessary information to the FDA having nothing to do with the company's activities or objectives.

The next thing I wanted to -- to make a statement on is the -- is device modifications. The studies suggested that, perhaps, manufacturers should report changes, no matter how minor, in some manner every three years or so. First, there's a long-standing guidance that describes when the submission is needed for change. That guidance properly separates significant modifications requiring a new clearance from minor modifications which do not. We also note that the -- we also note the current regulatory system establishes modifications should be submitted in cases in which the change might significantly affect safety or effectiveness. That standard should be maintained.

Second, just because a company may not have applied the tests correctly in the past is not the reason to force industry and the Agency to deal with a flood of information. MITA is concerned that the FDA lacks the resources and sustainability to deal with this information. An analysis of 510(k) review times is indicative of this issue.

Third, FDA can learn about such changes during inspections and in subsequent submissions. The requirement that all modifications be submitted even as part of an annual or thus frequent report would burden the FDA with meaningless changes and increase the burden on industry for no benefit. It should also be noted that the change would already have been made without FDA oversight, and so this seems to be like closing a barn door after the horse has left. Furthermore, if the company did not make a submission, as required, the FDA can consider enforcement action.

Fourth, the Agency's express concern is that companies are implementing modifications without necessary clearances. But if a company is going to break the law, deliberately or inadvertently, requiring some filing two to three years later, wouldn't make a difference.

Finally, by the time the report goes to the Agency, the third change would have already been on the -- would have already been made and beyond the market for substantial time. Any such requirement along the line suggested simply doesn't address this issue raised by the Agency. MITA suggests that the answer lies elsewhere. QSR systems are in place to ensure that changes are assessed and validated. Likewise, including literally all modifications in the submission adds burden for no benefit. At the very least, any such new obligation must include at the (inaudible) level. Thank you.

DR. SHUREN: Thank you. Victoria Pearson.

MS. PEARSON: I'm Victoria Pearson, with Medtronic, Santa Rosa, California. I would like to thank the Agency for proposals for improving the consistency and effectiveness of the regulation of medical devices.

First, Medtronic commends the Agency for their courage and transparency in identifying the 60 plus opportunities for creating a more predictable regulatory environment. The Agency's plans to enhance reviewer manager expertise, training, and knowledge should help improve the uncertainty and inconsistency of decisions. Medtronic supports the proposal to create a limited but well-defined subset of devices, as recommended by Advamed.

The proposal in the FDA draft, however, seems to go further than Advamed originally suggested, and is looking for more data. Clearly there is more work to be done. Their clear and concise guidance is necessary to provide clarity on the scope of the proposed evidentiary requirements, and they should be -- it's necessary to help industry plan appropriately and budget appropriately. We would like to ask for more clarity around any new requirements for substantial equivalence, and we would like to have adequate time to incorporate these new requirements into our development programs.

What we hope to avoid is industry -- is industry trying to guess what the new requirements are. We make our submissions and then have significant deficiency questions, which set back our programs months and sometimes years. For example, the recent -- the current infusion pump initiative, although we welcome it, we feel that there is additional clarity required around FDA expectations with regards to clinical data requirements, as well as assurance case reports.

We agree with a lot of the comments today that there is ambiguity around the definitions of intended use and indications for use. Clarity of these terms is essential, and clear training around the definitions of these terms is essential to help industry move forward. We also suggest that there needs to be clarity around the off-label use determination. Thus, enhanced focus and education on these terms will help ensure a common interpretation across the Agency, as well as across industry, the medical device sector.

With regards to the 510(k) proposal to share all known data on class 2 devices, if you're submitting a 510(k), we believe this is overly burdensome and an unreasonable request for those class 2 devices that have been commercially available for 30 plus years. We ask FDA then to clarify what it is they want to know and why they need to know that.

With regards to the proposals around the use of predicate devices, we again believe there's need for clear guidance on when certain predicates may no longer be appropriate, as well as guidance on the use of split and multiple predicates. We believe that the elimination of split and multiple predicates could significantly impact the 510(k) program by limiting the scope and the number of devices that go through this program. Improvements to the de novo process may help mitigate this risk, but they need to be done carefully with an eye to the impact of -- to health.

So in conclusion, Medtronic has four major asks or suggestions for the -- for Agency consideration. First, we ask for careful consideration of the comments you have received thus far, and that you consider them across the full spectrum of the medical device industry, taking into account the opinions of IVD companies, as well as small companies and large companies like Medtronic. We advise that it is critical to put out for notice and comment more specific details on FDA proposals. This is essential for industry to fully understand and react to the impact of the proposed changes.

Third, it would be valuable to know the priorities of FDA's proposed initiatives. This would help ensure focused industry participation and hopefully provide more useful comments to the Agency. Medtronic welcomes a game plan that identifies which items FDA plans to take on and in what order.

In closing, Medtronic would like to request a seat at the table. We would like to work in partnership with the Agency and with other medical device companies on the proposed changes to the regulation of devices as we further vet these out. I would like to thank you, Dr. Shuren, and your staff for this opportunity. Thank you.

DR. SHUREN: Thank you. Steven Dolle.

MR. DOLLE: Good morning. This is a smorgasbord of topics. I have five minutes. I'll try to make the best use of my time. In 1992, I would have been happy to leave the medical field after 17 years in nuclear medicine imaging, ten years owning my company, working at over 50 hospitals. I did regulatory affairs, trained doctors. I was a medical intuitive, something you didn't say much about, did feasibility planning, some private marketing for facilities, and then I had a car accident. I had a brain injury.

I developed post traumatic hydrocephalous. I went down to maybe a 7th grade level. I was put on permanent disability. And I had worked with CNS shunts before all this happened, and I knew them to be problematic. I knew what some of the issues were. And then what happened to me was really pretty about standard in the industry. I've had eight surgeries so far today. Four of the eight have had problems that should have been reported and were preventable, including the one that I have now, which is the subject of that report I gave you.

I'm responsible for the 1999 STAMP conference that you guys had at Bethesda, Maryland. I petitioned FDA in 1996. I wrote this incredible petition on CNS shunts. The focus was anti-syphon shuts, but I elaborated on some of the issues, the broader issues, and then I invented a testing system, the first ever, called the DiaCeph test that used non-evasive parameters to look at disease, disease data. And that -- I had a start-up company. I could not get funding. I was shut down by UCI. Everywhere I went it was political. In 1999, one of the people on my advisory board relied on a study done, I think, in '98. It said that most patients would be unwilling to go on the internet to look up health information. That's what -- these were the experts. These were the people leading us, advising you. Boy, were they wrong.

My DiaCeph test could be an app for a mobile phone today, but there's HIPAA issues, there's -- the nice thing now is we don't have reimbursement, but these apps are almost free. So what the mobile phone stuff has done in recent years -- it's going to have to be clinically developed, probably big challenges in teaching patients. Normally physicians historically want to be reimbursed for looking at something like this. I think they can be pressured to examine these things and these apps and these outcomes without getting a reimbursement fee.

I spent time last night, because I want to focus on social networking, HIT and mHealth, and I spent time last night looking on Facebook. I don't know if you guys know, Facebook is about 25 percent of the traffic on the internet today, and so I was wanting to see the status of what the medical companies are. And I was on the FDA site, CDRH site. I was on Medtronic, Johnson & Johnson, Edwards Lifesciences, a number of -- and they all had the same thing, which is like somebody had taken something with from Wikipedia and pasted it up there and say they're here, but they're not, like nobody's -- it's like an empty building. And I thought, you know, the social networking, once this gets underway, will really help to address a lot of these issues. I'm very critical of the way 510(k) have been used. I think -- especially in CNS shuts. It's been a major problem.

I asked you guys in 2002, when you came up with some new post Parkinson surveillance, to add shunts. And one of the guys, one of your top people wrote me back and said it wasn't necessary. Again, four of my eight shunts have had preventable problems.

So I like -- the mHealth apps really haven't gotten underway, what we can do with disease management. But between HIT, between social networking sites, like Facebook, where companies can market -- I mean, companies want to reach out to patients. They know now that the patient is the customer, no longer the physician. That's the future.

The nice thing about the social networking and these sites, once you put it in a digital form, you have a digital paper trail. So if people are not honest, you're going to catch them. The other thing is they're going to get user experiences from patients so much sooner.

On these bulletin boards, internet forums with patients, the stuff that you read -- I've been on there over the last ten, fifteen years and have helped people, and I write things. But it's just over and over and over again. It's just -- it's tragic. This is just with these shunt devices. And if industry knew it was going on -- for instance, the biggest thing in recent years with shunts has been programable shunts. But the truth is, they have a lot of problems losing their settings. But it's not being reported. It's saying it's a small percentage, and it's not. Stuff like that would not happen if this stuff was available on social networking sites. I think it's a great opportunity. And again, I believe companies want to market to patients, and patients want to get better, and somehow CDRH needs to find a way to merge those two and use these mediums as -- for documentation, so -- also, I've got a very big website I've had up for about six years. I have a communications company. I put my Diaceph technology -- I've got a big section -- it's used around the world -- on hydrocephalus.

And what's happened the last six months, these internet scrapers, these are people over in East Block, have taken content that I've written, and they've posted it into hundreds of websites that sell on-line drugs. So what's happened is my ranking, if you know anything about Google and Yahoo, my page ranking has gone into the toilet. So when you search stuff on hydrocephalus, six months ago I would show up really high. I would get -- I do some patient consulting. I would have people contact me from around the world. But when this internet scraping happened, they took my company name, my URL, and they pasted it -- it's a hydrocephalus link -- into hundreds of these sites. So they did it for either of two reasons. Either they did it to direct traffic to their on-line drugs, which were probably counterfeit, which you guys -- the other divisions should be concerned with, or it was somebody affiliated with the shunt device industry who's not happy with some of the things that I've written about.

And so what it did, I mean it -- it took my traffic and destroyed my ranking. I would think you guys -- especially as we get into HIT and social networking, some of the things that can happen, in addition to HIPAA and privacy, are some of these things that some of these malicious groups -- you know, where there's no law of the land. You know, it's actually illegal here, because it's copyright protected, your content. So when they do that, it's copyright violation. But you can't enforce the law over there, so the search -- you know, Google and Yahoo, they have the wherewithal to address these things and you would need to work with them to address these issues when they come up.

And then -- I'm down to a few minutes here. Probably one of the things that's interesting when you look at medical studies, they always talk about the placebo effect, which is anywhere from 15 to 25 percent of a response. You get a positive response for something that you can't explain. I found out in 1981 that I'm a medical intuitive. And I didn't know what to do with it. I worked up 15,000 patients. So many of the times I worked people up, I would read them and I would find out that -- at the end I was 80 percent correct. And a good -- a good clinician has that skill to some level.

What's happened in the last six or seven years, because of my brain injury, I gravitated to these -- drumming. I'm a musician. So I've been very involved in drum circles, and it's heightened these intuitive senses. So I am including this in a book. I think it's interesting -- the lady talked about breast implant problems. I have actually used something called applied kinesiology, which is a little bit voodoo science. Chiropractors use it. I've been using it about ten years to evaluate my shunt, and it would seem with applied kinesiology -- and, again, it's a subconscious thing, that the body knows what's wrong. It's just you consciously don't. And I believe that's how applied kinesiology works, and I've been able to use this to evaluate my shunt performance. And I believe you could probably use it with leaking breast implants. It's just one test that a clinician can do in their office. It takes a matter of a couple of minutes. It's like a pass/fail. It's probably about 70 percent sensitive.

But it's something that's interesting, especially with some of the things I'm doing now with medical intuitive. I mean, I can't dismiss it. I cannot dismiss this. People have come to me in recent months and I am right on. And I use my medical background, so not only can I -- I can tell them what's wrong. I can give them the name of the disorder. And I'm -- as scientist, I'm trying to explain how that is. I suspect it's something with the subconscious and you're picking up body language. And all this stuff I do with these drum circles is very -- very primal. It goes back thousands and thousands of years.

So in closing, I would hope that you can adopt some of these mHealth and HIT technologies and act on some issues with these shunt devices. It's getting a little bit old. Thank you.

DR. SHUREN: Thank you. Matthew Jenusaitis.

MR. JENUSAITIS: You know, in rock concerts they always save the best for the last, but Stephen is a tough act to follow. The other thing is I notice we're like 45 minutes ahead of schedule. It would be great if we could do this in the 510(k) process every time. Sorry. I know it's a cheap shot. But thanks, Dr. Shuren, and thanks to the representatives of CDRH and the FDA that have come here to Southern California.

You know, I grew up in the medical business, and my dad is a small town physician that carried a bag and made house calls. And I've been in the medical device business for nearly 30 years, in all different kinds of specialties. I've worked in large and small companies and for investors and commercial businesses.

I'm the president and CEO of Octane. Octane is the Orange County Technology Action Network, and we are a regional innovation cluster comprised of medical device manufacturers, academicians, investors, entrepreneurs, and advisors. We connect people and ideas with resources and capital to fuel technology and industry growth. We generate over 3,000 patents a year in Orange County, and this intellectual property forms the basis of a medical technology ecosystem that fuels our economy and ultimately creates jobs. Our goal is to have a lasting impact on both our local and national economies. We have more than 3,000 members.

Orange County is home to more than 500 biomedical companies and one of the most robust areas of medical technology innovation development in the country. Our large member companies include Allergan, Edwards Lifesciences, Bosch & Lomb, and Abbott Medical Optics. The Southern California workforce associated with these and all of our member companies is roughly 20,000 people. Unfortunately, our unemployment rates are unacceptably high in our local economy as well as the rest of the nation, and we're all struggling with recovery.

The medical device business is one of the last industries where the United States truly has a global competitive strategic advantage, but we risk the loss of leadership, much like we've previously faced and lost with the automobile, steel, and computer industries.

I want to commend the spirit of open collaboration and the genuine desire to improve upon the systems and processes. While intended to be in the best interest of patients, clinicians, medical device manufacturers, and our economy probably have some opportunities for improvement. These opportunities need to include increasing the transparency and predictability of the FDA. I feel that this could be accomplished in a number of ways. It's always easier to articulate than to implement, but if the job was easy we wouldn't need you guys.

First, very much in alignment with your stated goals and objectives, I would like to see more transparency in the Agency and more effective utilization of the medical device modernization and user fee act. When MDUFMA was originally implemented in 2002, it was promised that the direct funding of review activities would ensure that the Agency had adequate resources to expediently review and work collaboratively with companies submitting new technologies for approval.

Unfortunately, the Act hasn't effectively delivered on the promise, while simultaneously taxing the companies looking to bring new innovative technologies to market. The Act did seem to have some impact on the number of PMA and 510(k) approvals and their associated timelines in the early years, but more recently, however, the approval process for new products has become more difficult, timely, and variable.

In addition, the Agency has become less consistent, where agency recommendations for meetings or change in midstream and panel reviews are disconnected from the approval process. This lack of predictability creates more uncertainty for manufacturers and more risk for investors.

Second, I feel like there's a lack of common alignment and incentives between the stated goals of the Department of Health and Human Services and the reviewers at FDA. I wholeheartedly applaud the goal to facilitate medical device innovation, and I'm really committed to working collaboratively between industry and the Agency to realize its success.

I fear, however, that unless there's a common incentive for both the developers and the reviewers of new technologies to identify and process applications swiftly, we'll lose our ability to safely bring new technologies to market, and more importantly jeopardize our economic recovery through the loss of innovative competitiveness. These shortcomings and the associated uncertainty in the minds of technology investors reduces companies' abilities to access funding. Innovative, promising technology medical device companies are reducing their workforce and laying off employees because they can't access the required funding to keep their doors open.

The FDA not only needs to balance the desire for new technologies with the need for patient safety, but also the importance of innovation and new technology in our national economy. I truly feel that we all have very, very common objectives. We want new innovative technologies to be made available to help patients. We want to ensure the safety of the American public. We want to retain our global competitive strategic advantage in the medical device business, and we want to see the unacceptably high unemployment rates fall and our economy grow. The objectives don't come without a cost, however. And clearly two of them are understanding where we need to be better and developing a collaborative path towards their achievement.

I appreciate your time. You'll always have our support, our constructive criticism, and assistance. Thanks very much.

DR. SHUREN: So as mentioned, we are ahead of schedule. Maybe we'll be able to replicate that in other further programs. Why don't we go ahead -- it is now -- at least on my watch it's ten of 10:00. Why don't we take a 15 minute break. We'll come back at five after 10:00, and we'll start the Q and A session at that point, and we'll continue on until 12:00 or we run out of questions.

(Recess.)

DR. SHUREN: So the way this session works, anyone is welcome to come up to the microphones to -- if they want to make a comment, they're welcome to make a comment, again, to keep it brief, and to ask a question. I'll ask folks, too, that if you do have a question or comment, just stick to the one question or comment. And what we'll do -- and if you have another one, then, you know, please go back, if you will get back in line so everyone has a chance. There are microphones on both sides here, and we'll just alternate between microphones if there are people lined up at both. Again, please state your name and your affiliation. Why don't we go ahead and get started.

MR. DHUWALIA: Is this on?

DR. SHUREN: Yes.

MR. DHUWALIA: My name is Jack Dhuwalia. I'm with JD Consulting, and I have a question. The question is about the intent behind FDA's wanting to make sure that nothing goes wrong with the product at the time of submission. So the question is: Are you worried -- is FDA worried about what the product might do down the road, a couple of years down the road, so if something goes wrong maybe somebody might get blamed?

DR. SHUREN: This isn't an issue about blame. It's about a risk/benefit determination, and the standard for a device to be marketed in the U.S. is the same for all devices, it's reasonable assurance of safety and effectiveness.

What you have to do to demonstrate that you meet that standard depends upon the risk of the device. And a class 1 device generally is going to provide us with any information in advance of coming on the market short of registration of listing. It has to comply with quality systems, et cetera. If you are a high risk class 3 device, you're generally going to have to submit premarket approval application and independently demonstrate that you are -- have reasonable assurance of safety and effectiveness. And the 510(k) program available to most of the devices we review under premarket review programs is simply showing substantial equivalence to a predicate device, and all of this to get to this issue about the reasonable assurance of safety and effectiveness.

So while we've learned about what may happen to a device down the line, if there are legitimate safety concerns about what will happen to a patient because there are long-term effects, that is something that we would be taking into consideration in making a risk/benefit determination.

MR. DHUWALIA: All of that is totally understood, and I'm agreeing with that. I'm looking at the time. So the concern is today, at the time of the submission, does the device meet those requirements and is it safe enough to put on the market, or are we looking at, gee, what's going to happen a year down the road to the device? Is that the concern?

Right now are you folks concerned about what might happen? Because a lot of times the device problems won't show up until a year or two years down the road in the field, because of whatever reason, some quality concerns with the company, maybe somebody didn't manufacture correctly, perhaps there is more human error in the field than was expected. So there's -- there's a host of problems that occur after the fact.

So my question was, and I would like to know, is there an intention of trying to time shift and trying to figure out what's going to happen, what could go wrong, and then trying to make sure that, oh, my God, we don't know enough about it, what's going to happen? So is that a fear that's driving a lot of the questions that are coming up? I hope I'm clear in my question.

DR. SHUREN: Yeah. So if it is a question about a device failure down the road, it depends on the reason. If this is because of the durability of that device and we have reasons for concern that over time that device may fail, and we need information about it, that, we believe, is a legitimate concern. We do that with hip implants, by the way. Traditionally we'll get data for two years, and then we'll have the manufacturers conduct follow-up studies that go on for seven years. That's, if you will, a split the baby, that we have adequate assurances this can go into someone, but we don't wait the full seven years before we let it come on the market.

That is different from if we have a concern a manufacturer may make a change in their processing down the road. We handle the that differently. That's not something that we're dealing with up front in the 510(k) review generally.

MR. DHUWALIA: Thank you.

MR. LAWFORD: Thank you. Dr. Shuren, my name is Ceo Lawford (ph.). I'm -- flew in yesterday from Europe, where I have one company in Switzerland, and I'm also the vice president for public and regulatory -- public and government affairs in af emergo (ph).

Now, you kind of partially preempted my question. We have been watching with astonishment, if not stronger, that the FDA is strongly amending, to put it very politely, a program which has very successfully just -- not only very successfully served this country for almost 30 years, but also has been recognized for -- by most of the non European, non U.S. worlds.

I would ask you -- most of the comments this morning refer to that -- whether the FDA is considering a staggered approach for data in a very structured and transparent way by which the pre-approval, premarket market access would be balanced by a stronger post-market surveillance program very much like -- this is currently the case in Europe. Please take into consideration that healthcare in Europe is not -- is probably equivalent, with the exception of the UK, or maybe even better, for one-third of the cost.

And so the question is: Is the FDA consideration a comprehensive, predictable, and transparent system where a company coming up with a new product could say, okay, this is an implant, this is going to not touch the brain, but only the leg, so consequently you should do a literature evaluation and come up with a good PMS plan?

DR. SHUREN: All right. So a lot of things in the question. And you're going to have to keep them straight if I miss anything. First off, radical changes on the 510(k) program. Our intent is to strengthen the program. But if you really look at the recommendations, our intent are not making these massive wholesale changes.

Now, I know for some folks we really talk about clarifying certain terms. And everybody is wondering about well, what are you going to do, is the intent to dramatically raise the bar for devices coming on the market, making significant changes in our interpretations. And the answer is no.

But when we went back and we actually started to collect data to look at what was going on, we saw that there was a lot of lack of clarity about the 510(k) standard. And that's internal interpretation at CDRH, and that was also interpretation by sponsors who were coming to us. So much of what you'll see in the report has to do with clarifying either what we do under 510(k) or when we might expect certain kinds of data, like clinical data or manufacturing data.

Now, the use of post-market tools to sort of help inform with the 510(k) process is something we think is -- can be very important. And so part of the report talks about our ability to make better use of information regarding a device once it's on the market, particularly better use of real world experience as it's being developed. And we think that that could actually better inform us. Particularly as we're seeing incremental innovations for devices that are on the market, we might even be able to use that information in lieu of other data requests or complementary to other data requests that we might otherwise have in a 510(k) submission.

But the real condition precedent to getting there is to have a unique device identifier, which currently doesn't exist. And it's an issue, also, with Europe. In fact, that's why we've been working on a harmonized standard for unique device identifiers, part of the global harmonization task force.

MR. LAWFORD: Why is that the issue?

DR. SHUREN: Why is that the issue? So the idea is you need to be able to link the device with the patient's experience with the device. So if you're a drug, we can do that here in the U.S., because we have a national drug code. We'll link it up. For devices there is no such coding systems. The coding systems used now are generally for billing purposes. They're not very granular. You can't really tell in many cases whose device you're talking about, or even which kind of that device in a class. And that's where we're ultimately heading with the UDI, and that is the linchpin for us making meaningful use -- maybe that's the wrong term, to say meaningful use, but, in fact, that's what it would allow us to do. That's on the post-market side.

One comment with Europe. So, European standards, there are differences with ours. And I think there are good things about the Europe system, and there are some downsides of the European system. And the same with ours. Neither is perfect. But I will say, because many people point to I get on -- I can get on the market, in many cases, earlier in Europe.

I will tell you we have had cases -- I just had this recently -- of a company who has a product out in Europe and they were able to get on. They had to show performance. They didn't have to show effectiveness. They came to us and we said we need clinical data show it. They went back to actually pull their data and came in and said you know what, it doesn't work for that indication. So it's available in Europe. It doesn't work. They're coming to us with a different indication.

MR. LAWFORD: Thank you.

DR. SHUREN: That's caught under our system.

MR. LAWFORD: Thank you. I'm sure the opposite examples would also be possible, but thank you so much.

DR. SHUREN: And that's, I think, part of it, yes. Hopefully -- hopefully I will not be hearing from the State Department.

MS. GOLDRICH: Yes. My name is Sybil Goldrich, and I'm kind of playing Jeopardy to make a statement into a question. Did you know that the Office of Women's Health worked with the federal health agencies to get the money needed for research on breast implant rupture, and scientists that are working at FDA and were reassigned because they were -- they had testified against the approval of breast implants, are still within the Agency? And I urge you to use them, because they have a great deal of information and knowledge about breast implants.

The other thing is that during the course of your predecessor, the Office of Women's Health was demoted so that it did not report directly to the commissioner. And I know that you report directly to the commissioner, but they were demoted and set aside. And I believe they could be very helpful to you, especially if they reported to the commissioner, as they did when Dr. Kessler established the Office of Women's Health.

And the other thing I just wanted to ask you is whether you realize that over a course of years, since 1976, when the food drug and cosmetic act defined what safety was, in 1982 breast implants were required to be proven safe and, therefore, were changed from class 2 to a class 3 device. And now we're talking in terms of reasonable assurance of safety. I think there's a substantial difference between what the act requires and what is now being colloquially required by FDA, and I was wondering whether you would look into that.

DR. SHUREN: Just to -- just to clarify, in terms of -- you're talking about under which standard?

MS. GOLDRICH: I don't understand your question.

DR. SHUREN: As I said, the standard is reasonable assurance of safety and effectiveness.

MS. GOLDRICH: Right.

DR. SHUREN: So we've got one way for trying to make that determination if you go the PMA pathway, and another way to go there if you're going the 510(k) pathway.

MS. GOLDRICH: Well, I -- I can only refer to the historical use of the word safe or reasonable assurance of safety. In 1982, 1988, 1991, up until the approval of breast implants, a year before they were using the word safe, you must prove the product safe. And then they went to a reasonable assurance of safety. And I do believe that there is a difference and it should be considered regardless of what process a device goes through.

DR. SHUREN: So reasonable assurance of safety and effectiveness is the statutory standard. And how that is interpreted over time has changed over time.

MS. GOLDRICH: Yes, it has changed.

DR. SHUREN: And particularly how that may apply for particular devices. And I agree with you. That's part of the debate that's going on right now. And in our recommendations what we are saying we should do is provide greater clarity regarding what the expectations are for that demonstration, and 510(k) for substantial equivalence, to kind of get to the reasonable assurance of safety and effectiveness question. Because we happen to be in agreement that our program needs to be more predictable, consistent, and transparent.

And the way for doing that is to try to be more up front about what criteria we use and what our expectations are, and, just as important, when our expectations should change for a particular kind of device. Because there's new science that would cause us to have a different expectation that we can communicate that in a timely manner to the public, which has been a great challenge for the Agency.

MS. GOLDRICH: I will tell you that the FDA did provide a draft guidance document for the manufacturers of breast implants. Unfortunately, they didn't follow it, but you did do the right thing and provide draft guidance to the agency.

The other thing is, I worked many, many years ago on rewriting the information booklet for women for the FDA, and I volunteer to help you with that again anytime you want.

DR. SHUREN: Well, thank you. I'll also say we do have a very close relationship with the Office of Women's Health. We have a number of projects underway with them. And right now, as you probably know, we're looking to find a new head for that office who, for better or for worse, moved over to our center for drugs.

MS. GOLDRICH: Thank you very much.

DR. SHUREN: My colleagues here seem to be very comfortable sitting in their chairs, but they'll be happy to tell me afterwards, well, why didn't you say this, why didn't you say that. I said the same thing as I was walking the plank, too.

Why don't we try to give other people a chance.

MR. BEN: All right. My name is Charles Ben (ph.), and I work for ACON Labs. I've got a question and a comment. My question, again, is in the line of the gentleman there about post-market surveillance. Currently the FDA seems to be skewed between post-market surveillance and trying to obtain data when you submit 510(k). Requiring extra clinical data in some 510(k)'s which are -- at this point in time we don't know which of those devices will require 510(k) -- will require clinical trial. The FDA has suggested that some devices will have a clinical trial.

But, again, our question is, is clinical trial the best way to really show a great level of safety. Because again, clinical trial we -- I don't -- ACON don't oppose clinical trial, but clinical trials most times are not the best way of obtaining clinical measurable data, because -- why do I say that? Again, yes, I mean -- again, I keep saying we are not against clinical trials, but clinical trials are so much stage managed that basically you have the protocol. You have very hand-picked investigators. You've got the monitors who basically assure that investigators do not deviate from the protocol. That is not real life data.

Again, basically you have data that at least shows some safety, but again, to have the level of safety that you want to get, clinical data is not going to do that. Because basically, for you to get real live data or data that's really meaningful, you have to really put more emphasis on post-market surveillance than clinical data.

DR. SHUREN: So in terms of data we would need for safety -- and you mentioned clinical data. And this is actually -- this is a very important point we should talk about, first mentioning clinical trial. And I'm going to throw a lot of issues in here you didn't raise, but I'll take the opportunity.

So much concern has been over FDA asking for clinical data. And let me say, the data that we ask for for 510(k) runs the gamut. Clinical data, in our view, doesn't necessarily mean a clinical trial. It's really anything involving a person. So if you think about in the invitro diagnostic context, we often have clinical data. It may be dealing with human specimens. And we may not be dealing with a full-blown trial on individuals. So it really runs the gamut. And when we deal with non-invitro diagnostic devices, it's only about 8 to 10 percent of them do we ask for clinical data. And for many of those it's not actually a controlled clinical trial.

We think the issue is about what's the data we need, what's the appropriate data we need to answer regulatory questions. And so in many cases we don't need clinical data to answer those questions, and we don't ask for it.

In other cases, we believe clinical data is important to address those questions, and we know there have been concerns raised about are we asking for it in the appropriate circumstances, or when we ask for it are we asking for the right data. And that is a journey we think we need to go down and we need to have that discussion and we need to provide that clarity.

We agree that there are cases where we were probably asking for things and were asking for more than we should have, or there were long delays in getting to an answer, and on a clinical trial for figuring out endpoints or design. Many of the recommendations or some of the recommendations in these reports try to get to that, try to get to can we have a clinical trial process or IDE process that is better informed, more consistent in how we apply it, more targeted in how we do it.

Backing up now to safety. Yeah, there are times to address a safety question. You want clinical data or you may need a clinical trial. I actually don't believe that we should for all devices say, yeah, there's a safety issue, but we'll address that once we put it on the market and see what happens to people. That's human experimentation. That's human experimentation, and we should not do that. But we have to be smart about when we need clinical data and apply it appropriately, and we take that very, very seriously.

MR. BEN: Yeah, point taken. I'm not suggesting that we do away with clinical trials. The concern of my industry, of my company is, again, if we start to go down that line, down that path of clinical trial, what level of clinical trial will the FDA be requiring for a 510(k)? Because this is basically what's going to be the big problem of stifling innovation. So the amount or the level of clinical trial, again, I don't expect you to answer that here, but that's the main concern, basically going down that path, that we will have.

DR. SHUREN: And so to give you the big broad answer, it's going to depend on the device that we're dealing with. Because in some cases it's appropriate to do, and other cases not. There's not going to be a one-size-fits-all answer.

Our intent is to provide more clarity about the circumstances under which we would seek clinical data. And then when we do, there are things on an administrative side that we think are important, our ability for tapping into experts outside the Agency so that we can address critical scientific questions and do so in a timely manner, better oversight inside the center through the creation of the center science council, kind of bringing together the best and the brightest of people to oversee these programs, and particularly tough scientific questions. And that includes when we're dealing with clinical trials. Beefing up on the expertise we also have in-house, one on clinical trial design, I think is very important. And that is an expertise that's not quite the same as just simply clinical expertise. And on the clinical expertise side, we can talk to experts outside the Agency, outside the center. But if we don't have people in the same discipline inside the center, they cannot have a well-informed discussion.

And many times I may have one expert in a discipline, and they are spread thin, or I may have no expert in a discipline. And then I have someone who doesn't understand the field having a conversation with someone who maybe does. And I can't do that. I at least need people who can talk the talk.

I'm a neurologist. Do you really want me as the person going out and speaking to -- maybe you do -- speaking to the orthopedic community on technology? I'll understand it to some degree, but not the same as an orthopedist who has been out there and who has practiced. We think that's important.

So those are the things that we all need to do. All of it ties into, I think, getting clinical data when appropriate, and targeting it as appropriate so we meet the least burdensome principle, which we agree with. And least burdensome is about the least justified burden, not the least that anyone can do, but justified.

MR. SILVERMAN: I just wanted to make a follow-up comment. I'm a lawyer, so I promise not to have any clinical conversations. I bring nothing to that table. The observation that I'll make, I think, is that post-market surveillance is a necessary, but by no means, sufficient means to assure product safety and efficacy.

Can we in some situations require post-market studies? Of course. When do we do that? Well, one of the situations in which we do it is when we see a signal, a potential problem with a product. And the source of that signal oftentimes, for example, is a medical device report or complaints from industry members or complaints from physicians.

All of those mechanisms are anecdotal. Medical device reports are demonstrably underreported. And the information that those medical device reports convey may reflect a stamp-shot view of a product, may reflect a skewed concern. I think that that is a substantial distinction and, perhaps, an inferior method in terms of talking about basic assurances of product, safety and efficacy, than identifying a subset of devices that may pose particular concerns, and as to those subset of devices having proactive discussions about what type of data we need as part of the device clearance or approval process.

MR. LAWFORD: Thank you. Don't worry. This will -- although I have 20 more questions, this will be the final one. At the OCRA meeting in June, which as usual, is very informative -- it's like testing the waters, I think, for FDA -- there was -- some speakers said, and I apologize for not remembering who it was, about a voluntary release about notified body audit reports to the FDA.

That is watched with major, major interest in Europe. And it will do something very, very good. It will weed out the bad breeders much, much more quickly than that positive list the FDA gave November -- I forgot when it was. A few years ago. Those notified bodies would be unable to perform third-party audits, or at least there were a person who would -- who would do that. That has led to major problems.

I think this will be -- if this happens, then I think a lot of companies will jump on that bandwagon. It's an excellent idea and it will greatly speed up the demise of notified bodies in Europe that don't deserve that name.

Now, question, what's the timing of all those nice changes that you mentioned, the 510(k) process, this audit thing? I remember the OCRA speaker said, oh, in 2018 the U.S. will have 13485, and I was glad I was sitting firmly.

DR. SHUREN: I guess, two parts on it. Implementation for 510(k), our intent is to come out to tell folks here are the recommendations we're going to adopt, and here is our estimated timeframe for implementation of those of each of those recommendations, understanding that we do not plan to move forward on all of them at the same time, regardless of what we adopt. We'll look for what has the biggest impact first.

And you should anticipate when we come out with that, it sort of probably will be more of a chart, here is what we're doing, here is the timeframe. We will also do a summary of the comments that we heard and kind of layout we heard, generally, support for the following. We're moving forward. We heard support -- there were some issues raised. We're doing this. And then there was disagreement over the following and we'll either say and we're pushing the A, B, and C, over to the Institute of Medicine, and maybe D, E, and F there was some disagreement over, but we feel we're going to move forward for the following reasons. We will explain it and put all of that out there for the public to see. That's our intent.

The single audit that we're talking about, and this is on quality systems for us, timeframe for it, well, it's going to take some time. The reason it's going to take some time is you've got several pieces to it.

First off is we're going to have to layout the criteria for the third party who's conducting the audit in order for the FDA to have confidence in them. As you've laid out, not every third party is the same. We right now have a third-party inspection program that's not used by many companies at all. But over that we have some oversight of those third parties, and -- to assure that they're doing a -- you know, a high quality audit. So that's element number one. And then we'd have to go do it -- or have another third party that's actually certifying them and we're overseeing that third party.

Second is you need a common reporting form. There's one under GHTF currently. It's too high a level to be of any real value for a regulator. So we're actually working with Health Canada right now on that, probably within the first to see if we can go to cycle audit.

And then the other piece is because you want to have that information in a way that's useful, go to each regulatory body. The best is to do it electronically with standards so that that information can be moved around as is best useful for different regulatory bodies that have different interest. And I'll -- a little bit more detail, some of the ISO inspections actually don't provide sufficient detail to be very meaningful for us. That's another problem, so that's got to be addressed. And then ultimately you've got to get other countries on board in order to do that. And that's why it's going to take time, but we've put this as a priority for us.

In the interim, what we're allowing to do is that we will accept reports, audits under the ISO 13485 standard, from certain bodies. And we laid out the criteria in a recent guidance, and we will use that in factoring in our own inspection priorities. So if it's high quality, we have confidence in it, and it looks pretty good, we will probably put that company towards -- lower on the list. We'll go out and take a look at that.

MR. LAWFORD: Can we know which of those notified bodies it will be?

DR. SHUREN: It's a draft -- it's a draft guidance right now. We will finalize.

MR. LAWFORD: Because that's very important for young companies. If a young company chooses the wrong body, wrong being not eligible under your program, they might have spent a lot of money and they have no resources to do it again.

DR. SHUREN: Right.

MR. LAWFORD: Thank you.

MR. McNERNY: Good morning, Dr. Shuren. My name is Kevin McNerny, and I'm not a lawyer. I'm what you call a medical device lifer. I have been in the business for 30 plus years, worked for little companies like Baxter, Johnson & Johnson, American Hospital Supply, Beckman Coulter, Allergan. And I worked my way up through the ranks. I'm a manufacturing operations guy. I'm part of that unknown, you know, group of people that help, you know, assure the quality of the millions and billions of products that have been made over the 30 years that I've been working.

More recently I have become president of an organization called Orange County Medical Device Network. We're a growing medical device professional organization that focuses on leadership development. And I can say that our membership is increasing. Unfortunately, a big part of that membership is unemployed, in-transition medical device professionals. They're coming in much faster than they are being -- you know, finding new opportunities. So it is good to have a fellowship, but it is not under the best situations.

I guess my question really evolves through my experience and career. As an engineering manager I get these new engineers who come on board and say, well, you know, something -- something -- we can make something better. We can make something better. Let's change it. And all these FDA regulations are just painful. Why do we have to go through all this.

And, you know, I asked that question when I was a young engineer, too. And I dove into the FDA regulations. I dove into the validation processes, good manufacturing processes, and it all made sense. It really did. And I was able to explain to those engineers that you've got to be careful, because when you make change there could be unintended consequences, and you have to make sure that you validated it. The FDA has outlined some excellent guidelines that you can interpret, you can follow. And it took time, but eventually most of them came around and all became good public -- you know, good community citizens like me.

Now, the problem I have is is that when I look now -- and that sort of equates to bringing world-class manufacturing processes, where you have run charts, you have SPC, you have -- you know where your scrap is, you know where your failure rates are, you have CAPA, all these great systems that the FDA has helped us put into the manufacturing organization. Now I see, well, the system is broken. We've got to make big changes. We have to change the 510(k) system.

And I think about it and I go back to my engineers who might ask, well, what's broken about it? Where is the SPC run charts? What about -- what about validating the change before you talk about it. Okay? What about the un -- you know, the change -- you know, the unintended consequences or problems that could come out of that change if you don't validate it?

Well, unfortunately, from a business side -- fortunately for me, I have grown up now and I'm now in management and I'm looking at hopefully being a CEO of another medical device start-up someday. There is a lot of opportunities out there. There is no money.

No money? There's plenty of money, actually. It's all out on the sidelines. It's all waiting to find a home, but it's a very emotional time right now. And it's -- you know, no one is going to make a move. No one is going to put any money on the table. Why? Because some unintended consequences that occur from we're going to make a change. And until that change is made or if that change is made in a negative or adversarial direction towards business, we're not going to see the money. And OCMD's membership, unfortunately, from that side is going to continue to grow in the number of unemployed medical device professionals.

So I guess my question is -- you know, that was my pulpit. Now my question is, you know, it's basic, you know, what is -- it gets back to the engineer in me. What is the, you know, failure rate? What is the problem we're trying to solve with the, you know, changes in the -- you know, the FDA approval or the 510(k) approval process? And if so, you know, what are those numbers? What are we trying to do to improve it? When are we going to know we're there? You know, give the engineer in us, or in me anyways, you know, something to shoot at so that we can -- you know, we can improve the system.

DR. SHUREN: So why are we even here doing the change, if you will, or, I would say, strengthening the program? And I really want to emphasize that, because we're trying to be clear about this is not some wholesale overhaul in the 510(k) program. But when I started at CDRH a year ago, when I was coming in the door I was hearing loud voices from industry complaining about the program, complaining about how it was being administered. And we started to say, you know what, before we start doing -- making any changes, go back, look into it. That's why we had our own assessment that we conducted. That's why we're also having an independent assessment by the Institute of Medicine.

Why? Because we wanted to have the two looks, get somebody outside the Agency to look at it, get, if you will, my outside auditor. But at the same token, good government is you've got to look -- take a look at yourself. And we felt we needed to do that. And we also have access to information that others don't, and that's why you see a complementary approach.

Those looks did uncover problems, and they run the gamut in terms of the program. There are some failures on the FDA's end. And if you looked at the reports, I think you see we're trying to be brutally honest about it. Those reports -- I'm not -- I would not view them as highly complimentary of CDRH. And I have been at FDA on and off since 1998, and I have never seen a report -- reports like that come out of the Agency. I mean, usually it's things are pretty good. Some stuff you can improve. We're already doing it. Thanks for coming.

That's not these reports. And we looked even at the understanding of our own people. We also started looking at particular cases, because I have been asking people, raise problems with me. That's inside the center and outside. And we've also come across plenty of times where either not only maybe we didn't handle it right, but also where industry didn't do it. This is a much more complicated problem. This isn't about a few reviewers deciding to make decisions on their own, and it's just about managers getting on top of them and everything is going to be better tomorrow. So the report tries to address a lot of these things.

Let me take a moment and maybe talk about the industry side, because there's stuff for all of us to do. I mention how our own people are not clear on the 510(k) standard. And there is lack of clarity on a number of these key terms. In fact, there are inconsistencies on the terms, like intended use and indications for use are inconsistent on the guidances. We went back to all of it, and we say different things in different places. Sometimes we actually call them the same thing, and that's not the case.

But we also found that we've got companies coming in and they don't understand the standard and they're wrong. They are wrong about it. So we need clarity for both us, and we need clarity for them. We need training for us and we need training for industry.

A second is we have issues with expertise, and that does become a funding issue, unfortunately, but it is. And some of it we can leverage for expertise outside the center, but it is not a complete substitute. We need help inside the center.

But the other is we deal with expertise from other companies where it can be deficient. You mention engineers. I love engineers. And I have got companies that have lots of engineers. They have no docs. And you know what? You can come up with really cool stuff and very novel ideas, but the human body doesn't recognize the term novel. And when biology hits machine, it can react in ways that aren't so predictable from the engineers.

And we've got companies who are terrific. We know they've got a consultant, a doc consultant and they're on payroll, and, you know, it turns out they're wrong. But I have never had a company come in and feel that they're wrong. Right? They always are, well, we're right about it. And we go through a process.

The third is on the clinical trials. We do have companies who are designing, when they do need a trial, very poor clinical trials. I think the center needs to take some ownership on it, because we are often you figure it out, come back to us. And it's got to be that to some extent. We can't be here designing for everyone. We do not have the people for doing it.

But at the same token, there are cases where it's unclear, even amongst experts, on endpoints, let's say. We need to solve that. We can't just sit there where we simply don't know, and the technology will just hang there until somebody figures it out. So we need to go back and think about mechanisms where we're proactively addressing those questions.

But it does go back to we do have companies who don't have the expertise to put together a good trial, and on top of it may come into us in a pre IDE meeting, and we tell them advice, here are the issues you need to address, or here is what you should do, and it gets ignored. And then they come back in the door with this study and we go you've got big problems here. Of course they felt we've spent all this money, and they push it on through. So that's another issue in terms of expertise.

And the last one is on the quality of the submissions we get. They run the gamut. We have some companies, they do a bang-up job on their 510(k). It's excellent work. It comes in the door. It really makes the review a lot easier. We have other companies, and they do a very poor job. And the center, for better or for worse, has taken the position that we try to help companies. We have been very much more focused on the small businesses than I think you'll see in other parts of the center, because we do recognize the differences with this industry and how many companies are small in size.

But that means that we expend a lot of resources to help some of these companies on their submissions. And that's even applications, where they don't even have the right predicates. I mean, we go predicate hunting for some companies. And that actually brings down the entire industry, because, I mean, it sucks away resources to help everyone else out.

And unlike with the drug side that sort of says, hears the minimum standards you've got to hit before we're actually going to take that submission of work, we don't really do that at CDRH. And it kind of begs the question, shouldn't we do that, because what we're really doing is we're taking the folks at the bottom of the barrel and dragging down everyone else. It that fair to the rest of industry?

So there are things we need to do, but I want this -- you know, if we're having this open discussion, there are things we need from industry to recognize that are industry's part. So it is much more complicated. That's why we're going down this path and that's why I think you're seeing so many different actions being taken.

But if you really sum them up, the big ones are clarify the standards and the expectations of the center, train people on it, fix the de novo process, and have better administrative oversight within the center. Those are probably the biggest ones in there, and many of the others try to deal with smaller problems on the margin.

MR. McNERNY: Thank you. You know, again, I really implore you to make sure that, you know, you embrace the idea that, you know, the charge has unintended consequences and manage that change to the best and understand that business is one of those unintended consequences. And if there is a way that you can manage that piece of it, publicly, you know, increasing the assurance that the changes aren't going to impact the community, I would appreciate it. Thanks.

MR. LEFFLER: Dr. Shuren, thank you for being here today. My name is Jeremy Leffler. I'm with BayBio. We're Northern California's life science and med device trade association. And, you know, we have kind of joked today a little bit about the timelines, the review times, you know, whether that's management resources or the -- what we're seeing as the risk adverse nature of the FDA. We could talk about that all day.

I'm curious about the new comparative effectiveness board and body that was recently formed. There are some med device companies represented on there. What is your prognostication of how that plays out in CDRH's review and approval process?

DR. SHUREN: Well, my own sense, and we're talking about PCORI, so the Patient Centered Outcomes Research Institute. This is something on the -- maybe in terms of our reviews, it's more something on the margin for what we do, at least at CDRH. I mean, we have got our standards. We have our programs, and that didn't get changed in healthcare reform legislation.

What the implications may be, however, on the reimbursement side is a whole other story. Now, there may be other implications as to what comes out of PCORI from an FDA standpoint, because they may be making pronouncements regarding that arguably could be inconsistent with the device label. That's an issue that's -- you know, from our perspective needs to be addressed. Or they may be making determinations that otherwise were determinations that normally would be made by FDA and now could be made out of this body. And it is, you know, to be seen what will happen.

Health and Human Services has representations on it. We specifically don't on the board. And then we will see what the ultimate makeup is of the methodologies. So the committee, I think, will have a big impact ultimately on what PCORI does.

MR. LEFFLER: So you talked a lot about clinical trials and data today. You don't see this body influencing the data that you're looking for?

DR. SHUREN: Oh, that we're going to wind up asking for data, because PCORI has something of interest?

MR. LEFFLER: Correct.

DR. SHUREN: No, that's certainly not the perspective for the center. I can never predict where the crystal ball -- what will happen in the future, but, no. And like I said, they didn't change our standard in what we look at. And I'll put it in this way, too. For many years people have raised concerns about cost that's been in the healthcare system. And everyone is worried about FDA is going to take into consideration cost, but we don't do that. In spite of people talking about it, in spite of expectations from other groups of what they're interested in, we have been -- as much as possible we protect the standards and we have the mandate and the mission, and that's what we follow.

MR. LEFFLER: Great. Thank you.

MR. KLEINHENZ: Dr. Shuren, thank you for coming. My name is Ken Kleinhenz, and I'm with Cytori Therapeutics in San Diego, California.

I have listened to all the presentations today and the comments, and there appears to be two camps. One camp is industry really feels as though the 510(k) process works, and that there are aspects in the proposal that industry definitely agrees with, for example, the de novo process being improved. And everybody agrees with that.

And then there's another camp that appears to feel as though industry and FDA have put products on the market inappropriately. And there seems to be a disconnect, and the disconnect in my mind goes like this. When there's an example of an blood filter product that was 510(k) cleared and yet it was intended to be used as a temporary, and it's being used as a permanent implant, where is the doctor's responsibility on that, and where is FDA's responsibility, and where is industry's responsibility? So that is one example.

The other example was an invitro diagnostic that was being used in the clinical laboratory. And it had a difference between 3 percent versus 5 percent. But my question is: Where is the clinical laboratory's responsibility to validate that their population is going to be appropriate for that assay under CLEA.

And then lastly, there's a discussion about breast implants and that the booklet is too big for the patient to read. So my question is: Where is the patient's responsibility?

My point is this: Is that FDA's responsibilities are to assure that the data is appropriate and, as you said, that the product is safe and efficacious. And my question to you is: Could you share with the audience and dispel some of these myths that FDA is ultimately responsible for everything that goes wrong with a product, and that industry has to take responsibility, the patient has to take responsibility, and the physicians have to take responsibility for their piece of the whole string of events. Thank you.

MR. GUTIERREZ: So I'll use an example. This is a complicated interaction between all of the sectors and their responsibilities. And how do you manage those responsibilities. So I'll use glucose meters, because I know that well. So, for example, we -- the Agency's since 1976 has been clearing glucose meters for management of diabetes. It's really for diabetics to manage their own diabetes. Yet, they are used in hospitals for all kinds of things. We don't look at the data for that, yet we cleared them.

Now, is there any responsibility for the FDA to actually understand how those meters are actually being used; for industry to actually, you know, make claims or not, and sell them; and for the hospitals to actually understand what are the limitations of what they use. So glucose meters actually are -- that are designed for over the counter are really not that accurate.

And if you begin to use those glucose meters to do tight glycemic control in an environment like a hospital, you are not necessarily under control. Okay? Is that the FDA's responsibility? The manufacturer is coming in with a claim that says we want this cleared for management of diabetes. We know they're ending up in hospitals and being used as that. Whose responsibility is it?

Well, it really turns out to be everybody's responsibility, and the FDA takes that seriously. We had actually a public meeting, too, so that we can actually let everybody know what are the issues that we're seeing when glucose meters are used really not in the way they were intended, because the practitioners don't necessarily know what the dangers are. They don't necessarily understand what accuracy does. They don't really understand what are the limitations of those meters.

So since we -- since we know that they're being used in -- under those conditions, there is a responsibility for the FDA to actually make sure that the meters are safe in the way they're being used.

Yes, you know, how do you that? Well, it's a combination of helping the industry make the appropriate claims, come in with the appropriate meters to be used in the appropriate situation, and so it's everybody's responsibility.

MR. KLEINHENZ: Thank you.

MR. SCHMIDT: Good morning. My name is David Schmidt. I'm a patient that was harmed by the FDA's 510(k) clearance process. Dr. Shuren, I have written a response to your August forward a message from the center director that I would like to give you this morning. In the spirit of transparency by the FDA, I'm also making this response available to any members of present attendance. Thank you.

DR. SHUREN: Thank you.

AUDIENCE MEMBER: We have at least two JD's up there, so this is kind of a JD maybe question. But we talked about the notified body audits. Okay. And the question is, can they become the basis for any sort of let's say evidentiary action associated with either like a 483 or a warning letter based on the notified body audit. Because we now kind of keep those two activities different when the FDA comes in, versus notified body.

Second, to pivot off of that would be what about my customer audits. When they come in and audit me, would that also become a pathway to evidence associated with either criminal prosecution, a warning letter, and that stuff? That's question number one.

Number two, historically companies, I'll say, fight vigorously internally not to show anything more than substantial equivalence. We don't try to show substantially better, because that will pull the PMA trigger, because it's now NSE, because it is not just substantially equivalent, but substantially better. Are you actually maybe opening up a door where companies can show substantially better, okay, and demonstrate that inside the 510(k), but not pull the PMA trigger, because, as a lot of us understand, there's huge dollar impacts to companies versus 510(k) versus PMA.

MR. SILVERMAN: So I'll take the first question. No.

AUDIENCE MEMBER: I'll assume that's no to the first one?

MR. SILVERMAN: That's the best I could do.

AUDIENCE MEMBER: My hope is it's a no question -- yes or no answer, too.

MR. SILVERMAN: I'm playing devil's advocate, because I'm typically very verbose.

The Agency, if it's going to take -- in particular, if it's going to take an enforcement action -- and I would distinguish enforcement actions from things like regulatory correspondence, like we know as untitled letters, which are not enforcement actions, it needs to develop its own evidence. And if the Agency is going to go to court, of course, we need to develop our own evidence. But even in the warning letter and untitled letter context, my expectation is that we would not be, at least at this point, relying on information provided by a third party to issue a warning letter.

However, as Dr. Shuren pointed out, we want to work over time towards a single audit model in certain situations, because from the Agency's perspective in terms of our available resources, in terms of the recognition of the globalization of medical device production, the realty is that we have to be able to leverage our relationships with foreign regulators and trusted third parties.

If we are ultimately able to get to an acceptable single audit inspection model, then I would think that we could and would want to rely on the outcome of that audit to make, in our case, compliance decisions. But the distinction there is that it's not information developed by a third party for a distinct purpose. It's information that's developed by design for the Agency's own internal decision making.

That said, I think that this is a process that will evolve over time. And while we are working on the single audit inspection objective, one of the questions we are simultaneously thinking about, and this then goes back to 13485, is again, how can we, short of having a single audit, leverage information that we can receive from others. And the 13485 model is a good example.

When companies are willing to provide to us the outcomes of those audits, then it may give us enough confidence not to make a warning letter determination, but to take that company out of our inspection inventory for a defined period of time. Ultimately we want and will need to rely on information that is developed by parties other than FDA investigators. But there's always going to be a subset of actions that will require events specifically developed for the Agency.

MR. GUTIERREZ: And I'll take the second part. And, you know, it's -- whenever we actually sit here and speak about how the Agency -- how CDRH runs the program, it's a little difficult, because the program actually deals with a huge number of devices that do very many different things.

So it is not necessarily -- it is not true that you have to prove substantial equivalence and don't actually need -- you don't -- it disallows you to show that you're better than what's out there. Part of the reason the 510(k) has been so effective is that it has allowed for devices to actually become better over the years. And they are not the same device they were originally.

So glucose meters, again, is a great example. The first glucose meter came into the market just before the 1976 law. It was -- everything has been a 510(k) since then. But if you look at a glucose meter now and you compare it to the glucose meter that was on the market in 1976, they don't look anything like it, and the device is much better now. It has all kinds of safety things that it didn't in 1976. So, you know, devices -- the 510(k) program does allow devices to actually become better and to improve, without pushing them into the PMA.

The only thing that is going to push it into a PMA is if you make a claim that is either risky or you make a claim that is very, very different from what is actually there. So you have to be careful there. I think that the 510(k) program actually does allow for improvement and for people to actually improve their devices.

DR. SHUREN: And actually, to add something on as a complementary thought, we've talked about risk/ benefit determination. We understand that in particular when we're dealing with a new kind of innovative kind of technology that that risk/benefit determination, you have to accept a relatively small amount of benefit.

You've still got to tip the scales about this product coming on the market, because we recognize that in those cases the first iteration of a technology is not going to be the best shot at it, that it does have to get out there and with experience -- when the companies understand improvements to make and get more and more benefit out of it, we get that. I'm trying to instantiate that in a decision making process it's obvious we believe more complicated, but I want you to know we understand that important difference.

MR. BILLIG: My name is Mike Billig. I'm the CEO of Experien Group and I want to applaud you, Dr. Shuren, on your willingness to bring your staff out throughout the country, venture into troubled waters and basically try to share with us what your thoughts are on improving the system, and work with us as industry to try to make a better program.

I would like to first just make a comment, because I have been in the industry for 37 years, so I go back to pre-amendment times. And I can say that it was much easier back then when we had very small 510(k)'s. But I can say also that we have progressed very well and I think appropriately so on a number of issues.

Certainly it's -- we have gotten into a point where some of the issues that have been addressed and articulated on with de novo and everything else have to do with things that need to be done and need to be done quickly. I think that there's such an opportunity there to improve the system. But I look back also at the times back in the '90s, when we couldn't communicate with FDA, and they were very difficult, and much more difficult than they are today.

So I'm encouraged by the dialogue that's taking place. I have been to several of these going back in February, the Minneapolis one. We had somebody out at that meeting. And then I was fortunate enough to be at the Stanford Biodesign program that Mark Deem had indicated, and that was very, very encouraging.

So I think we're going in the right direction, and I think working together we can accomplish it. I'm an optimist, but I do believe it's achievable. And I like the intentions on FDA's part to work with industry to make this happen, because it is not going to happen to have individual silos out and not have things that are not workable with industry. All of us want the same thing. We want to bring good products to market and we want to do it the right way, so...

DR. SHUREN: Thank you. And if I had another chair up here, I would also let you sit up here, too.

AUDIENCE MEMBER: Dr. Shuren, you were quite honest there when you talked about that the 510(k) working report was brutally honest. And I have to applaud that you somehow or another put together an environment that would allow that frank of presentation of what was going on in the Agency. There is not a lot of CEO's here that could foster that kind of atmosphere within their own companies.

The 510(k) working group report was fascinating particularly on the substantial equivalence issue and the definition of terms and the demonstration, while in a way that no one else had, that, you know, even after 34 years there wasn't a common or consistent definition or intended use, indications of use, technology or what a new type of safety and effectiveness question is. You know, and those are the four key areas for determining substantial equivalence.

So what I'm -- the question I've got for you is just let us all know, what is the process going to be to -- to address this one -- particular, this one issue, because this is just so key.

Right now we have this sense that all these comments and the FDA report gets dumped into a hopper, you know, someone is going to turn a crank and something is going to come out at the other end. And this one is particularly concerning. I mean, you guys have -- this has vexed you for 34 years. So if you could just describe, what is going to be your process, who are the kind of people that you're going to be bringing together to try to address this one, because this is a -- this is probably one of the tougher ones that you've had to face.

DR. SHUREN: So moving forward to clarify term, we would do through our guidance process. It will be a public process. Anything will go out for comment. On some of these there may be more of a public dialogue on them, as well, before we would go and ahead and finalize. We're not going to just kick out a policy and that's it. So there will be ample opportunity to weigh in. And we may -- initial thinking is we may break these off as opposed to putting them into one big guidance, and just deal with each of the issues moving forward.

MR. BILLIG: Each of those terms?

DR. SHUREN: Each of those terms individually potentially. Regardless of what we want to do, we want to make sure there is ample opportunity for input on these. That is the intent. So as I said, many more bites of the apple on this.

But I'm glad that you raised it. Interestingly enough -- and, folks, we're going through the comments now where there are issues or concerns. We keep hearing, you know, we always worry about what you may do and how you may try to clarify. But if things are clarified right, it's actually a boon for everybody.

MR. BILLIG: Huge.

DR. SHUREN: It's huge. And so as much as people say to the FDA, to us, don't be so risk adverse, what I can say back to the public is don't be so risk adverse. You know, we should go down this path, and hopefully we will see the where the comments end up.

MR. BILLIG: And you think you've identified the team internally that can at least put together the draft guidelines?

DR. SHUREN: That's what we're doing now. That's what we wind up doing so we've got our implementation plan in place.

MR. BILLIG: Thank you.

DR. SHUREN: Yes. And we'll give everyone their home phone number, make sure they have a page on Facebook.

MR. LINFANTE: Hi. John Linfante, Excelsior Medical. Just -- I work for a small company and so, you know, the thing that we worry about is the requirement for more data, especially clinical data, might not only slow us down in terms of product development, as several people have talked about today, but the cost of acquiring that data might keep a small company from implementing an innovative product, an innovative idea, which, again, ultimately can have impact on the whole innovation and the whole question of, you know, employment, the jobless rate, and all the other stuff that folks have talked about today.

So I just wondered if you might talk a little bit about the difference between the big guys who can bring an army of people into meetings with the Agency and can provide data that is required, and small companies that have good ideas and really want to get them to market and are scared to death of the -- you know, the new requirements that might be coming along.

MR. MAISEL: So I think the issue of clinical data is obviously an extremely important one and one that we hear a lot about. One thing we don't want to do is just ask for clinical data for the sake of asking for clinical data, and appearing like we're somehow approving safety that way.

So whatever clinical data would ever be required has to address very specific questions that we have about safety or effectiveness. And I think what you'll -- what we hope to do is to clarify what type of -- what type of data would be required for different products. The -- one of the concerns we often hear about the class 2B issue is that we're somehow going to be asking for a lot more clinical data. And that was the not the intention of the recommendation of the class 2B process. The class 2B process was designed to better clarify where we're already asking for clinical data. So our hope is that we can clarify what the evidentiary expectations would be in that regard.

The other point you bring up is the issue of expertise. And it's on both side of the table. We as an Agency need to have clinical trial expertise and be able to ask for the right types of clinical data. As has already been mentioned, not every piece of clinical data is a randomized blinded clinical trial. And, in fact, in many cases those are unnecessary, particularly for many of the products in the 510(k) program.

So our job is to provide better clarity as to what type of clinical data we would be expecting for which type of products. And we want to continue the process where we can work with companies, all types of companies, and not -- you know, not marginalize the important smaller companies that have innovative products.

DR. SHUREN: And to add, we're sympathetic on -- you know, with small companies and what resources may be available. On the flip side is there is a regulatory standard. We stand behind that standard. If you notice, we're not saying go back to congress and change the standard. But the standard needs to be met, and that should be independent about the resources available for the company.

But it puts even more of an onus, I think, on us for getting it right, that we're asking for clinical trial data when it's appropriate, and we're asking for the appropriate trial. We do so in a timely fashion, and we only changed expectations if there is adequate support for doing so. And that's why many of the steps we talk about in the report are trying to address each of those particular concerns, because we think it is so important and we recognize that if we fail on any of them it will, in particular, hurt a small company that could not be able to hang on, if you will, for a longer period of time.

MR. ZAMBO: I almost sat down a moment ago, because I thought I had to run back to my office and tell them -- add a statement to our instructions that says if you're risk adverse, please don't prescribe this device. Advice from the director.

My question -- actually, you provided me a lead-in just a couple moments ago when you said that the first innovation is not necessarily our best shot at it, at the device, which I think is probably true in general. But it puts device manufacturers in an odd position.

Now, I work for a company that has got a non-American parent. And if you think it's hard to explain to non-regulatory executives -- by the way, I'm Steven Zambo with Hoya Corporation. If you think it is hard to explain to American executives what the FDA is doing, try doing this with foreign nationals who have -- look at me like you guys must be absolutely insane in the United States, which I generally agree with.

The concern I have is when I'm negotiating a clinical study or I'm negotiating results from a clinical study with the FDA in attempting to get an approval, and something comes up where the FDA says well, that particular characteristic there of your device, whether it be a complication or a simple finding in the study, is blocking an approval or at least delaying an approval, and I find that my response is, well, I understand that, I see that we're not that foolish, we do understand the characteristics of it, but that is the same characteristics that several other devices that you approved display. And the common response we get is, well, it is a lot harder to take something off the market than it is to prevent something new from coming on the market.

And that's where I have a difficulty explaining to my foreign executives, why my device is essentially acting like an approved device, I can't get the approval and the FDA takes no action against that approved device.

So I guess my question is: Is there any attempt or any thought at FDA to address that sort of disparity?

DR. SHUREN: Oh, assuming on the case -- and if you are -- I don't want to go into, you know, for specific products, but if you are having an experience and there was a difference of opinion, I do want to make sure you take advantage of pathways available to try to address that further up the line, because I do think that's important to do.

And I do want to raise, I know sometimes companies feel concerned about raising things, because it may upset the staff. The bottom line is we can't address problems if we don't know about them, and that's why it's critical to do. It's really more about how a company does it rather than if they do it. So putting that on the side.

The next is if we do have products on the market that we have concerns about, I do think it's an onus on us for at least using the tools available to us if it's appropriate to do so. So if there is a safety concern for a device that's on the market, we do -- and it's under 510(k), we do have our 522 authority to ask for specific post-market data on it. If it is enough of a safety concern, we think the product is adulterated, then we have authorities that we can take against that company, against that product, whether it be, you know, pushing for a recall or an injunction, or any number of different things that we can do. And that's Steve's job over here.

MR. ZAMBO: Well, Steve, perhaps we will be talking. Thank you.

MR. SILVERMAN: When it comes to injunctions, that's not the right thing to say to me.

MR. ZAMBO: I'll let that one pass.

MR. CHALY: I am Thomas Chaly from the Feinstein Institute for Medical Research, North Shore Long Island Health System.

Thank you FDA for these kind of interactions, and this is very important to have some connection between the public and the FDA. I have these comments that a few years back -- actually in 2000, we had a very friendly conversation, communication with the FDA, and we had a -- based on that one, we got the approval for two important PET drugs, FDG and ammonia. They are widely used now without any problem.

And there was a lot of push from FDA at that time to go into NDA process, get the NDA. And we did that. FDA was pushing us to -- to submit the NDA's. They helped us and we got the NDA's for those two drugs. At the same time we asked about the Fluorodopa, in 2000, year 2000, and FDA told us that we will have further discussions and we'll set that aside.

Nothing happened after that. And this has been going -- this drug has been in use for the last 20 years. And we tried to get an NDA for this drug. All the medical institutions in this country are -- and major institutions are providing the service without reimbursement. They can't afford it. They have to cover the cost.

So we want an approval from FDA to continue this service. So we approached -- so we told the present director that by the elimination of the CGMP rule by December 2011 the medical institutions are not going to provide this service and they will withdraw this drug from the market. And if it won't be available people will have to go to Canada and other places to get it.

It happened three months back when FDA announced the CGMP rule if our institutions stop doing these scans for three months, we ought to ship the patients to Canada and the poor people who cannot afford, they get left out. And now when I told the FDA director, he told me that -- in a face-to-face meeting he told me that we can continue to use this Fluorodopa F 18 injection a year after 2011 without an approval NDA, but he will provide us a special IND with the payment. What the medical institutions do not understand is how he's going to provide the payment.

DR. SHUREN: So I'm very happy, if you want to e-mail me the information, to share it with the part of the Agency who would deal with this, because this will be in our center for drugs, which, by the way, is the evil empire. So I thank you for raising that here, so thank God you don't have to deal with them. And I do have Janet Woodcock's phone number, and I will get that to you. I'm willing to deal with the possible, not the impossible.

MR. CHALY: No, we had a great cooperation with the former director. We had excellent communication with them, even the acting regulatory director, Ms. Axlerad. I don't know. We are getting great help from some of your department.

DR. SHUREN: I understand. Because I don't head up the drug side, and we're just not -- the folks here are just not involved. But I am very serious, if you will e-mail me, I will -- I will share it with those folks.

MR. CHALY: I will be happy to give you a card.

DR. SHUREN: Thanks. And that is also up on the internet, so you can find me.

MR. NOBLITT: First, thank you for allowing us to all address you and ask questions and provide you our opinions.

One thing, first of all, you've talked about a plan. Do you have a timeline for this plan, when it's going to be coming out now that the comment period is over and so forth. If you could address that. And within that plan is one of the objectives going to be a timeline for 510(k)'s and, perhaps, de novo applications, as well, whether or not -- and in particular are you going to stay with a 90 day goal for 510(k)'s?

I think you've heard a lot of questions and comments about uncertainty. And if there's a timeframe associated with it, regardless of what it is, it will at least provide some type of an understanding in trying to predict the future.

And then the other side of that is whether or not you'll be publishing those results to those timelines, in other words, 510(k)'s, PMA's, and so forth, on a frequent basis. There used to be an annual report that was published by ODE, and I don't believe that's been published for some time.

And I guess the last question is I'm curious, and I don't know that I have seen it recently, what is the current time for 510(k), an average time? And I know there's a variety of different ways to look at that, as well. Thank you.

DR. SHUREN: So when we would like to get out our plans on implementation, I would like to, but I don't have full control on this, but it would be nice to have it out by the end of calendar year, quite frankly. Because the folks here all feel we need to move forward to make appropriate changes in the program. But understand that to do that we need that plan in place.

I have got -- you know, CDRH is around 1,300 people, a little bit over that, full and part time. To get changes in an organization, you don't go out and do things piecemeal, I'm just going to do this, I'm going to do that. You need to go to the people say here is the big plan, here is what we're doing, here is how we're doing it, here is why we're doing it, and get us all to move. And that's why we have been pushing to get this done so quickly, so that appropriate changes can be made to the program.

And I'll caveat by saying we think most of the cases of 510(k), things go well. You know, we don't talk about all the products that kind of move through the system and there isn't a hitch. It's where there are issues that we tend to focus. And our attempt to is when we make changes is not to upset the applecart where things are working right. Okay.

MR. NOBLITT: Timeframe?

DR. SHUREN: You asked timeframe on 510(k). We have goals under MDUFMA. Those goals aren't changing. Those won't change. We had in the past put out information on an annual basis. And we do it with a report. I will tell you when we do it in a report there is such a clearance process in the government that you tack on a long time to get out the door. In fact, we were recently issued our performance report from the year before just a few weeks ago.

We are now, however, putting up dates on our website moving to a quarterly basis. So we're providing this more frequently. And, in fact, we have even made a higher level commitment as part of the Agency's FDA track initiative, which is to develop matrixes for all the centers on key activities and put that out for the public and update that on a quarterly basis, as well. And 510(k) performance, some of the measures are actually part of that, as well.

De novo doesn't have quite the -- while there are numbers in there, those were sets. Those were more statutory.

MR. NOBLITT: Great. Thank you.

MR. WARREN: Hi. My name is Ron Warren. I'm a regulatory professional and consultant to the medical device industry. I wanted to comment on a couple things from this morning, and a question.

There was a comment earlier about perhaps some of the issues are not a regulatory structure issue, but perhaps a human issue. And a question, just from my perspective as a regulatory professional, not as my company representative, but as regulatory professionals we really think hard about how to ideally present the information and organize it in a way so that we can be a good agent between the company and the agency, and make the submissions as top quality as possible.

But on the other hand, you have a very important goal to protect and promote the public health. But often when we hear comments back from the review team at FDA, they're constantly complaining about being under resourced and behind in their review cycles. And you don't get a lot of confidence that maybe the best review is being done on the work that you spent, you know, months or years formulating and putting together in a PMA or 510(k). And sometimes you get the impression that maybe it's being looked at the very last minute to meet a timeline and are they really able to commit to all of these great plans you're trying to improve the system.

You know, what kinds of things are you looking to do at the review staff level that might give us a little more sense that you are able to uphold your obligations that you are talking about today?

DR. SHUREN: So further question, first off, my own view is when you have problems or you are an organization that has to be able to adapt to changes in the future -- and that is the case with FDA. Not only do we have new challenges, we have new science. And we have to be able to prepare -- be able to address those in the future.

In fact, one of the challenges with 510(k), people talk about the program from years ago, years ago we had a small number of devices that were coming through. They were simpler. In fact, the early instantiation was really just a notification process. It really wasn't a review process.

We changed it to accommodate more devices, and then it got instantiated in law in 1990, when the law got revised. And over time the number of devices under 510(k) continues to grow, and they're much more complex devices. And that's one of the challenges for us dealing with it on the science side and what we may need on a 510(k).

I raise it because in those circumstances of problems to address, or world that changes that you want to be prepared for -- like in hockey you don't want to go after the puck. You want to be where the puck is going to be. It means you also have to invest in that kind of operation. You have to invest in making changes. It can't be all investing in just the day-to-day work.

And I have my staff say it. Hey, I have got so much on my plate. Should we really focus and make these changes, because I've got this device. I say if we don't do this, your workload is going to grow. Things will be more inefficient. We're going to be less successful. So you have to take some of the time to do that. That should never be an excuse, not to make important changes just because we have too much.

But because there is a lot on these folks' plate, we need to make -- do what we can with what we have to do the best we can. And, quite frankly, if we had more we could really make changes with the program.

So what are we doing with the reviewers now and actually with our staff? One is when I came in the door, there was no reviewer training for a new reviewer. Nothing. So we have actually developed training module, and reviewers have to go through it, and there's going to be a certification process to be reviewers.

Medical officers do not have a training module. That's changing. We have a leadership readiness program so that we can start working on the next generation of leaders as they come through. We're re-looking at our organizational structure, because right now Alberto's office and Christy's office are organized differently, even though we're doing premarket reviews.

Are we actually organized on the right lines? Because now it's sort of along product lines. Is that really the right way to do it? We are short on managers. We recognize that. And that's one of our discussions, is should we actually hold off on the few hires we might do on the scientific expert, bring in managers instead? Is that kind of a better way to focus and to do it?

Other things for reviewers are this training we talked about on the standards. If we're going to make changes, we have training on that. We're talking about interactive review and how we instantiate that better into processes.

Another is our basic business processes. When I came in the door, many of the things that people were doing were not written down. I would have people come in the door and say we're doing the following. For example, maybe going back to a company, asking for more data and questions on a device that they plan on not clearing anyway. I said, well, why are you going back to them if you're not -- there is nothing that would change that. You need to go talk to the company about it. Why are you sending them a letter asking for more, and it's -- yeah, they'll send it in, but I'm still not going to clear it. Oh, we've got a policy in place. We do all these cycles. What -- two cycles. And I actually know the policy, because I was at the table when we talked about it in MDUFMA. It was like no, but where is it written down? Oh, it's not written down anywhere. And in another branch they had a different interpretation of what the policy is. Those need to be down. We need SOP's on it. That helps reviewers.

And then the other thing we're talking about for the year to come -- so we're already setting up -- is some of the issues on time management. If you look at the calendars for people, the way we have meetings can really put a drain on people's time and it's inefficient.

E-mail, some people love to e-mail. I don't know about you, but if I could get rid of this Blackberry -- and I will pay someone to take it. Heaven help the person who invented this. That's all I can say. But these things on management, we're actually looking at ways even with their time, better time management, because we need to assure that we're handling workloads right.

But then the last thing I want to mention in terms of what's on people's plate -- and we can talk about all the things for management and the center science counsel, but the other is the turnover rate for staff, and that I continued to hear from companies that, you know, if you come in the door early and you talk to the FDA and something -- you don't get quite the same opportunity. No bang against Europe, but remember, you do come in to talk to the FDA, because we're the ones look at the product, not a third party. And by the time I get through a process, it comes out the door, I may have a key person in that team -- the lead reviewer may be gone. That is an issue. And, quite frankly, if we don't have the depth in-house so that you can have people who are replaceable, then turnover is also going to continue to seriously impact what happens in the review, because you're going to have new people in who are going to have to take over, who weren't part of it, and that's going to lead to delays. So all those pieces, things we're doing already, I think are going to help address it. Things we're going to do will help address it, and some of it ultimately is a funding issue to have a truly big impact.

MR. DOLLE: I'm Stephen Dolle again. So back to the basic user side of the equation. Is -- you're director of CDRH. What would you like to see from the patient community, from patient users? What can they do to facilitate all this, with their experiences, good and bad and everything in between? What do you have to say to them?

DR. SHUREN: Well, terrific question, so thank you for asking it.

The following: One, we need greater patient participation in what we do to understand their side better. And we're actually already talking about some steps we may be taking to better engage the patient and consumer communities. Also, I will say the healthcare professionals communities and other forums for industry to connect with the FDA, because we think those dialogues are critical to best understand the needs and interests of the different groups.

Second is for the patient side with patient reps to be much more engaged in terms of not only the needs of devices but the problems in how they are used or ways that they could actually be more useful for patients. You've probably seen -- we have launched an initiative on home use. We're seeing more and more devices that were designed for the inpatient setting moving to the outpatient setting, and they're not designed. And as a result, and because not taking into account how a patient may use the device, when they're expected to, or their caregiver, leads to failures that are avoidable in addressing. So that is the second.

The third is on the communication side. We can put things up on our internet. We can go talk to the press to get a message out. We can blast an e-mail. But time and time again, the hardest community to reach are patients. And ultimately communications have to be locally and looking at patient groups who are organized within local communities, who can do a better job in terms of pushing information out to patients so they're well informed about the appropriate use of a device, but, also, when there are problems, you know, to filter them back, and not for the FDA to necessarily say we're taking a regulatory action. But we are, and I hope you've seen this in our innovation initiative. It's about how do we feed information back and also work with industry so that the next generation of devices is better, and I think patients can play a critical role.

MR. DOLLE: I have one recommendation. So around the country you have all these patient organizations, disease organizations. And by in large most of them get their funding from the industries that support the various drugs and medical products, and I think that presents a conflict.

If there is a way between NIH and Washington to give funding to these 501(c)3's so that they can operate more independently of industry, and so that they can do more accurate reporting, their feedback and they can -- because by in large they're still dominated by industry and, you know, you're not getting true data back.

DR. SHUREN: So we've had that raised to us. We are looking at maybe making -- putting out grants for a certain amount. We don't have a lot of -- FDA doesn't. NIH maybe. But I think the other thing is local communities in terms of connecting. You know, a local community can get together on crime watch. Right? Local communities can get together on healthcare. And given the IT tools available today, it's easy to communicate.

I mean, I'm part of list serves and web sites and things in my community. There are a variety of different issues, but I don't see them organized on some of these health issues that, in fact, they could do at a grassroots level.

MR. DOLLE: Where are you guys at with WebMD, with your partnership?

DR. SHUREN: So the partnership has been more on the drug side for pushing out information, and we've been looking at more involvement on the device side also for getting information out.

MR. DOLLE: Okay. Great. Thank you.

DR. SHUREN: You're welcome.

MS. MAZOLLA: Hi. I'd like to say I'm -- this is a fascinating conversation. I'm Laura Mazolla with the IVD company up in San Francisco called Wave 80 Biosciences, and we're still in development mode, but contacting the FDA, so we're learning about this process. And it's interesting to see all the changes that you're going through that we will eventually be experiencing.

But because our first product is an IVD for rapid HIV viral load, we're actually working with CBER. And I'm curious if you can comment on the changes going throughout your organization and how that will affect or integrate with the process that CBER is using.

DR. SHUREN: So while the report that we put out is a CDRH report, CBER was involved in what we were doing to make sure nothing we're going to do is going to be crosswise with them. And as we move forward, let's say there's a recommendation and we adopt it on some of the terms in the 510(k) standard, CBER would be a part of those discussions so that we don't do -- even if there is something that is a little bit more unique for the products we may be dealing with, we're also not doing anything that is untoward for the CBER programs. They're not the evil empire.

MS. LINDLEY: I'm Stephanie Lindley, and I work with Bioness. And my question actually goes back to a comment that you had made about picking the appropriate predicate, predicate research, and that kind of thing.

And I was wondering, as part of -- either as a measure to help strengthen the process, is potentially updating the 510(k) database and the kind of information available electronically to do better predicate research? And, for example, I know like for getting 510(k) information, a lot of times they're -- the information isn't there, even if there is say -- it says 510(k) summary. The summary is not there. 510(k) statement, it's requested, and then you don't get any of the information, or it's redacted to such a point that it's pretty much -- you just see the CDRH header and that's it. So the -- to get the kind of information we need to make proper comparisons and a good analysis, we don't get.

So is there a plan to either make more publicly available sooner maybe later 510(k)'s, because now you get a 510(k) which is 20 years old, and so that really doesn't help us if we're going to move away from saying -- using the older devices as predicates and using the newer ones. So if you could address that.

DR. SHUREN: Sure. In terms of the 510(k) summary, we started -- 0IBD has been putting out 510(k) summaries for a little while now. We made a commitment a few months ago to do that actually for all the devices that undergo 510(k). It's part of our transparency initiative. So that's -- that's now underway and we're kicking it off by certain review divisions in our office of device evaluation for starters. So that will happen.

In the reports what we talk about is on this point about providing better information for sponsors to make better informed decisions about what may be appropriate predicates. And we actually think that information would also help practitioners and patients, as well, for understanding on devices, a great example of how you can facilitate innovation, and safety, and safe use at the same time.

And that database would be a combination of 510(k) summaries that FDA has drafted. Or if a sponsor wrote it, we're going to edit it, so it truly reflects why we made a decision and what we based it on, without confidential commercial information. The second is some picture of the device. You know, a lot of times we get things on a device and someone says here's the predicate, but they haven't even seen the device. You know, they read about it, but don't necessarily understand the technology.

And I understand there were comments and concerns about putting that -- any such information out. First off, to clarify, we were never intending to put out detailed schematics with confidential commercial information. One, it would be unlawful for us to do. Secondly, there is absolutely no reason to do so. What -- all we're talking about, and even on a photo, and not photos that get into the mechanisms -- and again, that you can get confidential commercial information, but at least see the thing that you're talking about.

And the third was labeling. One of the challenges in the 510(k) program is we get draft labeling. We have some back and forth -- we don't see the final labeling when it goes out the door. And if changes are made, we don't see that at all.

So if you go now on the drug side, they're moving to one-stop shopping. You know, they will have the up-to-date labeling, things are accurate, and it's out there for everybody. You don't have that for doctors, patients, other healthcare professionals on the device side. It doesn't exist. So we were putting out -- can we get there not in the same as drugs. We're willing to sort of not do the same in terms of a review in advance, but at least getting to updated labeling that we can put one-stop shopping, and link it with the 510(k) summary and a simple photo so you can see what it is. That was the intent behind the recommendations, for the reason you laid out, help sponsors better identify appropriate predicates, but help healthcare professionals and patients make better informed decisions.

MS. LINDLEY: Thank you. And if I could make just one quick kind of kudo. One of the -- the edition of the TPLC reports, where if you're going for a coding you have all the related adverse events, that was really helpful in terms of our research for our latest submission. So I -- it's not fully implemented. For some devices it has this list. Others, it doesn't. But it is a very helpful tool. So if there's kind of a pick and choose of which kind of innovations to make and when, that was really helpful, so thank you.

MR. BILLIG: Yeah. Mike Billig. The question I didn't ask when I was up here earlier, the de novo process which you're spending a lot of time -- I know you and Christy Foreman and others have spent a significant amount of time trying to understand that better and see how it could be utilized. Do you have any gut feel as far as the timeline? I know you're going to come out with a report and everything, but the realty is, is that takes so long right now that it's in many cases beyond what a PMA takes. So is it going to be something that's going to fit in in the first half of the year or, you know, what's your prognosis on something like that? Because I do feel that there are so many different products, especially with the difficulty with split predicates and other -- other problems, that that, with that low risk product area, that it will be utilized and it's a perfect vehicle to provide a good amount of information to be able to bring a product to market.

DR. SHUREN: So first to say, we consider fixing the de novo process a top priority. So you can anticipate, just because we're hearing uniformly and we believe it is, that will be high on our list of things to do. I don't have a timeframe yet. I think there are some changes we can make more quickly than others.

We are in agreement that we need to get away from going through a full 510(k) process to go to NSE, to then get into de novo. And most of these things are more of an issue I should say for the non invitro diagnostic devices. It has been different. Where on the IVD side, a lot more things do go de novo. It's been, you know, less of an issue. And it's for a variety of different reasons.

Then there's a second about specific controls, because if we have special controls in place, then there's this whole idea did you go through this separate rule making. One thing we can do, and we've talked about, is kind of this over-arching rule, but then we can pick appropriate special controls and not have to -- and just kind of do it on the spot, if you will, rather than going through a whole another process. But if that's where we end up, that rule making may take a little bit of time.

We think there is some things we might be able to do administratively in the interim, though, that can speed it up. So I don't have a set answer for you. Our goal is to do things as quickly as possible. Some things we may be able to do in the coming year. Some things may take a little bit longer. But it may have enough of an impact in the next year that it will be worthwhile.

MR. BILLIG: And then lastly, do you think user fees are any contributing factor? I mean, is that a problem, the fact that they do not apply in this particular case? And so, I mean, it stands to reason that without user fees, if I were reviewer, I would be hard pressed to pick something up and put it on the pile, when, in fact, I've got a lot of things that I'm going to be zinged on.

DR. SHUREN: So user fees are not influencing what the reviewers are doing. Getting the fee doesn't. And I will say it's -- when I first came to the Agency, it's actually the first project I got for the drug program, was to get into it. And then I have been into it on the device side.

Fees coming in, our reviewers don't know from one or the other. The check never comes to them. The check goes through a system. It doesn't matter. They've got a workload. That's all they know. That's all the managers know. They've got a workload.

Now, what we do is we design our business process around our goals. And if our goal is a certain number of days, here is the percentage of time, we'll -- the percent that we will hit that goal, you design a process where you think you're going to meet the goal. Right? It's not on each individual case, oh, we're at this particular day and, therefore, you have to wrap it up. You always build within the system that for some 510(k)s, for example, will be more complicated than others and may take more time. And that's how you get to what you think will be the right performance goals. You design around it.

De novo doesn't have the MDUFMA commitment in terms of timeframes. Does that matter? Maybe yes and no, but it's not the way to go about it. You can put goals in place, but if you are not positioned to meet them, it's sort of irrelevant. I mean, there are goals that are in the statute on PMA. Right? It doesn't matter, because we couldn't get to 180 days straight on a lot of those cases anyway. It doesn't.

What really matters is -- and maybe in the next round of MDUFMA there will be a goal on de novo, and we'd come up with something -- is that you'd also have to make sure you're resourced to do that. And that's kind of the lesson. And in return, though, we'll put the transparency on it. We'll have the performance measures in place. But if you don't have the adequate funding, it really doesn't matter.

And we know in coming in the next round of reauthorization, things are challenging with the economy. I think everyone knows the device industry got hit with an excise tax. There were a lot of challenges out there. At the same token, wherever we end up FDA is still the ones there who are looking at the products. And if the FDA is not well resourced to do it, the people who suffer ultimately is industry and patients and healthcare professionals.

You could get rid of the user fees tomorrow. They actually only make up -- they make up less than 20 percent of the MDUFMA program. Namely the activities covered by user fees, they are only about 15 percent of the medical device many program. You could get rid of it tomorrow, and the FDA is still going to be there.

But companies -- and maybe some people who are sitting here will not be in business. Technologies that may be safe and effective and could be game changers may never get to market. So this is a conversation industry needs to have with -- you know, inside, is FDA worth the return on investment? We think it is.

And there was a comment earlier about, well, money went into the center and, therefore, we haven't seen all these fantastic benefits. It was wasted money. The question is, what would have happened if the center didn't get the money? And while it does make up a small percent, we did get extra people on board. And what would have happened it those people were not there?

MR. BILLIG: Thank you.

DR. SHUREN: You're welcome.

Well, we are just about at the time to stop. I'm going to take three minutes just -- well, maybe three and a half, just to hit a few other things for clarification, because as we're going through the comments, we have seen questions raised about a number of the recommendations. I'm just going to put this out here to explain our rationale, because obviously some of the things, as we wrote in the documents, maybe were not clear.

So just so you know -- and I will take personal responsibility for any lack of clarity in the reports. In fact, I'll take personal responsibility for all the device failures and everything else. I'll do it. I'd also like to say that I'm Spartacus.

Off-label use came up, and this is a statutory change. We put this in here not to engage in -- get involved in practice of medicine. We do stay out of this. But practice of medicine is about a healthcare practitioner's decision about what to use a medical product for. And that we wouldn't look to change.

But we have -- and these are rare cases, where a company comes in the door and they say this is the intended use of the device, but that is not the intended use that they're intending. This is about manufacturers' intents, not doctors' intents. And so there have been cases, manufacturers will say, oh, we put it right here on the labeling, but that's not what they're coming in the door for. And it hits the market and it is not what it gets used for. That's what we're going about. Because then when we did the risk/benefit determination, it was on the wrong use. That doesn't serve anyone well. That's what we will address.

Predicates. We are not looking to limit the number of predicates that you can cite. I've seen some comments about that. There's no intent about that. What -- because a predicate is old, therefore you can't use it, that's not the intent either. If we were going to say some predicates would not be able to be used, we think it's a small number. It's more over -- if something came off the market for safety concerns, the company took it off. We're not going to rescind the -- normally rescind the 510(k). Maybe that's something we'd think about doing. Maybe no one would challenge it. But as long as a 510(k) is out there, even if the device is not, it can be used as a predicate. That's what happens. I mean, we've not otherwise addressed it.

So, yes, you can come in the door. That device is off because of serious safety problems. And if you're substantially equivalent, you could say arguably then you have to be cleared, because 510(k) is there.

Multiple predicates. We support multiple predicates 100 percent. We're just looking to clarify circumstances, because there's even been differences of opinion internally. So that clarity we think is helpful.

Split predicates is where we have an issue. And there's been difference -- people interpret split predicates, we've heard, on the outside a little bit differently. For us we're talking about you use one device to say we have the same intended use, and you use another device with a different intended use to compare technological characteristics. There is no such thing out there. That's different from multiple, where you may have several components, and each component is compared to a predicate.

Here you're taking different parts of the 510(k) pathway, and you're splitting out intended use and technological characteristics. Where it's different and where I've heard questions raised is suppose, though, you've got two devices, same intended use. They're the same technological characteristics, except maybe you're using a different material, and that will material was used in another device in a similar circumstance and there weren't safety concerns. Well, there we would be using that experience with that other device to help answer the safety question. That, to us, wouldn't be a split predicate. That's not a true split predicate.

So that's why we were talking about not using those. And first of all, in OIBD they don't use them. There's no split predicates. In ODE, actually some branches, review branches, occasionally do it, and some never do it as a matter of policy. There's actually an inconsistent internal policy in the center. But the reason we have concerns with it is, it's a chimera. You're not doing a real comparison to the predicate. That's not what the law was ultimately about.

Summaries of safety and effectiveness, safety and effectiveness data. What we've said, to provide to us what you know or reasonably would know on safety and effectiveness data and studies. The reason for that is many times when we go back to ask questions, those could be answered with information that's already out there. So it's helpful to us that we don't go down rabbit holes if we don't need to go down rabbit holes.

Now, maybe it doesn't need to be more every single device, and that's -- that's an issue, as well. But clearly in a number of cases that could be helpful information. The intent is not to do all this extra work. It's work that you otherwise would have done or one would say should have done. You developed the device. You're going to want to know what information was out there about it. That's good due diligence. What we're saying is summarize it and let us have it. That's all. You're going to have better informed decisions.

I think that covers -- preclearance inspections, some folks have raised in comments. We don't intend to do many of these at all, but we do have the legal authority. Our proposal was simply to clarify when we would actually exercise that authority. That's it. That's all the recommendation was about. It puts a little bit onus on us.

Bill already talked about class 2B. The intent there was not expanding the universe, but to clarify it up front, to the extent that we can, recognizing what's in that class will change. Some things may go in when they're new. Some things may come out over time as we better understand them.

All right. Any other questions folks have? Well, then on behalf of CDRH, I'd like to thank everyone for coming out today and for really the terrific comments and questions.


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CSR NO. 13526