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Medical Devices

Transcript for Town Hall Discussion With the Director of CDRH and Other Senior Center Management, September 22, 2011




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September 22, 2011

8:00 a.m.

Embassy Suites

250 Gateway Boulevard

San Francisco , CA 94080


Deputy Director, Office of Communications, Education and Radiological Programming



ALBERTO GUTIERREZ, Ph.D. Office of In Vitro Diagnostics, CDRH

STEVEN SILVERMAN, J.D. Office of Compliance, CDRH



TODD GILLENWATER, California Healthcare Institute

JANE METCALF, Interventional Spine, Inc.


MATHEW THOMPSON, Reduction Technologies, Inc.

MARK DEEM, The Foundry, LLC

RITA REDBERG, M.D., University of California

BERNARD HAUSEN, M.D., Ph.D., Cardica, Inc.






GLENN HAMMONDS, Genomic Guides

ANITA VAZQUES-TIBAU, Californians for Green Dentistry

JAMES TURNER, J.D., Citizens For Health

JOSH MAKOWER, M.D., ExploraMed

NANCY MYERS, Catalyst Consulting


MIKE CARUSI, Advanced Technology Ventures

















MIKE BILLIG, Experien Group






OPENING REMARKS - Jeffrey Shuren, M.D., J.D. 6


Todd Gillenwater 8

Jane Metcalf 11

David Kennedy, D.D.S., and Stacy Case 15

Mathew Thompson 20

Mark Deem 23

Rita Redberg, M.D. 27

Bernard Hausen, M.D., Ph.D. 30

Joleen Chambers 33

Jack Dhuwalia 36

Kenneth Kasper 38

Hugo Campos 42

Birgit Calhoun 45

Glenn Hammonds 49

Anita Vazques-Tibau 52

James Turner, J.D. 55

Josh Makower, M.D. 60

Nancy Myers 65

Kelly Gallagher and Maria Cost 69

Mike Carusi 73


Robert Cartland 78

Paul Kangus 81

INDEX (cont.)


Shelly Trimm 84

Gabriela Anchondo 88

Nedra Heffman 90

Unidentified Speaker 94

Swami Gnanashanmugam, M.D. 100

Lori Roberts 103

Ward Eccles, D.D.S. 106

Liz Lison 110

Joleen Chambers 114

Jack Dhuwalia 121

David Mults 128

Kim Tomkins 131

Unidentified Speaker 133

Ron Bucher 134

Hugo Campos 137

Mike Billig 139

Scott Taylor, D.D.S. 142

Unidentified Speaker 144

Unidentified Speaker 147

Andrew Zacharian, D.D.S. 149

Unidentified Speaker 150

Unidentified Speaker 151

ADJOURNMENT - Jeffrey Shuren, M.D., J.D. 152



DR. SHUREN: Good morning. I'm Jeff Shuren. I'm the director of FDA Center for Devices and Radiological Health. I would like to welcome you to our sixth Town Hall meeting. I actually can't believe we started this about a year and a half ago and committed to hold three Town Halls each year in different places of the country, and this is our sixth and last one for 2011.

We had started this back in 2010 under the recognition that too often we hear from the public if they would like to come out to Washington D.C., and normally it's the context of a public meeting where we pick the topic.

And we said, Well, that doesn't make a lot of sense because many people can't come out to Washington D.C., so we said, Why don't we come out to all of you and make this about what you want to talk about. And that's what's the purpose of this Town Hall, for you to raise issues that are important to you to ask the questions that are on your mind; and we will try to, the best we can, answer them.

I'm going to apologize in advance as it regards answers to questions. So if you're within the Beltway in Washington D.C., you will know that if we're in the midst of considering something, we're developing policy, we don't tend to talk about the specifics. It's not been clear that we have a lot of protocols and we just simply have to abide by that. Sometimes we can't talk about things because they are privileged or confidential, so I may get into Washington bureaucratic speech.

And I will apologize in advance, but we're bound by it. And actually, that's a benefit for all because otherwise we'd start saying one thing and it turns out it changes to something else. It creates a lot of confusion and distraction.

For this morning, first, I'm going to ask if you have a cell phone, to please turn it off. I've been asked to do so because as calls come in, even if you're diligent about trying to cut them off, it can interfere with the recordings. They get a lot of noise here.

Our Town Hall meeting is broken up into two parts. The first are people who have signed up to speak. I'm going to apologize to a number of people in advance. We had far many more people who wanted to speak than we had time to do so, and we tried to assure that we had people speaking on a range of topics.

However, during the question and answer session, which is the second part, anyone can come up to the microphone and ask a question. If you want to make a statement, all I ask is keep it very, very short, really, under a minute. Say it, ask a short question so we have ample time to address issues and concerns or comments by anyone else in the audience who wants to come up.

Joining me here today is ‑‑ and I'll ask them to raise their hand or stand up ‑‑ Steve Silverman, who is the Director of our Office of Compliance, and Dr. Alberto Gutierrez, who is the Director of the Office of In Vitro Diagnostics.

Also helping out is Heather Howell, who is our Deputy Director Office of Communications, Education and Radiological Programming. Heather will be calling up the people who have signed up to speak.

So with that, I'm going to turn it over to Heather. And, again, thank you all for coming.

MS. HOWELL: Okay. Our first speaker today is Todd Gillenwater with California Healthcare Institute.

MR. GILLENWATER: Thank you. My name is Todd Gillenwater, and I serve as Senior Vice President of Public Policy for CHI, the California Healthcare Institute.

CHI is the statewide public policy organization representing California's innovative biomedical R&D community. Our membership includes the state's leading research universities and private biomedical research institutes, venture capital firms, and biopharmaceutical medical device and diagnostics companies in the state.

We're very pleased to welcome you, Dr. Shuren, and the rest of the leadership of CDRH back to California for this Town Hall meeting. California is home to over 1300 medical technology firms employing more than 107,000 people in the state, far more than any other state in the nation. Beyond large multinational companies, the majority of medical technology firms in this state are smaller venture capital backed firms with fewer than 50 employees.

And today, without a doubt, the number one issue and concern of our membership has been the environment at the FDA; more specifically, with concerns of a growing uncertainty, unpredictability, and inefficiency in the FDA's review and approval of medical devices, including both PMA and 510(k) products.

But let me be clear: CHI and our membership support a strong, science-based FDA, and we support strong, science-based safety and efficacy standards. But we do not believe that slower equates with safer. We can and we must have both: high safety and efficacy standards; and efficient, predictable, consistent, and transparent processes to get innovative new technologies to the patients who need them.

With this in mind, I want to briefly address three important items. First, CHI strongly supports the 510(k) process. While it may not be a perfect process, it has a strong track record of meeting the combined needs for protecting as well as promoting the public health.

And we remain in agreement with the Agency and other stakeholders that it can and should be improved. That is why we have supported Agency proposals such as improved reviewer and manager training, but we strongly disagree with the recent Institutes of Medicine's report and its incorrect suggestions that the 510(k) process doesn't evaluate safety and effectiveness and doesn't promote innovation.

And we reject suggestions that the IOM report somehow demonstrates that the 510(k) process is broken or fundamentally flawed. That is simply not the case, which leads to briefly number two.

We do not believe the 510(k) process requires major, fundamental overhaul. And we maintain our concerns with and opposition to questions that were conveyed to the IOM but not addressed, such as combining the terms "intended use" and "indication for use," creating a new Class IIb of products and restricting or limiting split for multiple predicates. The final issue that I'd like to speak briefly: In speaking with our membership, CHI believes that the fundamental issue driving much of industry's concern with recent Agency performance revolves around what we would phrase as Agency/industry or Agency/sponsor communications breakdowns.

For example, the Center has suggested that a growing problem of late has been poor quality submissions, but it certainly isn't in the interests of any company to knowingly and purposely put together and deliver a poor quality submission.

That is why we believe that the problem is more likely driven by Agency communications management and process breakdowns, which leads to industry complaints about moving goal posts, midstream changes in reviewers, and the like.

In fact, we might suggest that the Center itself has acknowledged these issues with recent announcements and mechanisms such as the new Notice to Industry letters and the reviewer certification program.

Regardless, CHI remains committed to working with the Agency, with Congress, and other stakeholders to further investigate this area and find solutions.

To reiterate and conclude, CHI supports a strong, science-based FDA. The issues and concerns I have addressed in no way suggest that industry is looking for shortcuts, but slower doesn't mean better.

Thank you, again, for coming here to California. I appreciate your time.

MS. HOWELL: Thank you. Our next speaker is Jane Metcalf with Interventional Spine, Incorporated.

MS. METCALF: Good morning. I'm here to talk about an issue close to my heart. It's the inequalities that current regulation imposes on small, innovative medical device companies as opposed to the larger well-known companies.

Let me preface my discussion with I believe these inequalities are unintentional, but their effects are devastating on small industry. I spent over 30 years in the medical device industry in both large and small companies. I've experienced firsthand the inequalities that current regulations impose on small companies.

For instance, when I worked for one of our largest cardiovascular manufacturers and I was a director of RA for a tissue heart valve group, I got a call one day from a consumer safety officer, and he wanted to announce five days ahead of time his audit of our facility, standard surveillance audit.

He showed up five days later. He had a microbiology degree. He knew all about our products including our unique glutaraldehyde sterilization process, and he conducted a very thorough three-day audit. He left the facility with a 483 citing one observation.

Contrast that experience with about three years later when I worked for a smaller medical device company doing tissue heart valves. Same type of business, only we had 27 people instead of 350 people. An FDA consumer officer called me on a Friday afternoon to tell me that he's going to conduct a surveillance audit the next Monday morning. He apologized because he said he was juggling his schedule, but this was convenient for him. And I could back out if I wanted to; but you don't want to back out from FDA. So I said fine.

He showed up, didn't know anything about tissue heart valves. We spent a lot of time explaining to him our glutaraldehyde processes and other biological processes, and we spent an interesting three weeks together. But the outcome of the audit was exactly the same.

He made one observation on a 483 and then he left our facility. But the difference was the little company with 27 people in one conference room, we probably spent 1000 man hours to help that auditor complete his audit. At the big company, we spent maybe 200 man hours. Huge impact on a small business.

I want to give you one more example. I want to give you a 510(k) example. With the company I'm at now, Interventional Spine, three years ago they submitted a relatively innovative feature on an interbody spine device. It was called an expandable interbody device.

Under a newly released guidance document, FDA responded, essentially lengthy deficiency letter with a summary on it, essentially saying, We really don't believe you can achieve substantial equivalence with preclinical data. You need to run an IDE clinical study. The company chose not to do that, even though the product was on the market in the United States ‑‑ I'm sorry, on the market in Europe.

Three years later one of our larger competitors submitted the same featured products on a 510(k) and got it cleared. Needless to say, we immediately submitted ours and it's still under review.

I don't want to go into the details because it's still under review, but we've all heard of those little companies that have submitted 510(k)s with innovative features and those 510(k)s have been bogged down in reviewer questions and requests for additional information. And then somehow miraculously the 510(k) is re-submitted by an industrial consultant or some other company that's better known and approved or cleared.

I think that FDA reviewers are skeptical when they see new features on products from unknown, little companies. I think they feel more comfortable when they are dealing with known companies or larger companies that they know or even with regulatory affairs professionals that they've dealt with or that they know of.

I think that these things can be corrected relatively easily. I think they can be corrected by FDA auditors being trained in the products and technologies that they are auditing, even if it means that they call the company they are going to audit and they ask for someone to spend a day offsite or half a day offsite so they get familiar with that technology.

I think the FDA reviewers, although familiar with regulations, really need to be familiar with the use of the product or technology that they are reviewing in a medical setting so that when they do get a new innovation, it's not so scary to them; they understand the impact of that renovation. I think that would go a long way towards reducing their skepticism when they are dealing with a small unknown company with new innovations.

And finally I think that the leadership at FDA should emphasize to their folks the importance of small business and the importance of paying attention to small businesses. If these easy things can be accomplished, I think there will be some dramatic changes in small business.

We'll see refueling because we'll no longer see businesses going out of business for lack of funding of IDEs or lack of ability to get clearances. And in general, the new business will generate employment, and it will provide easier and sooner access to innovative devices for U.S. citizens rather than that access going overseas. Thank you.

MS. HOWELL: Thank you, Jane. Our next speaker is David Kennedy.

DR. KENNEDY: My question is: How is it possible for the FDA to approve a time-released mercury implant that is by far the predominant source of an individual's exposure to mercury.

I practiced employee protected mercury-free dentistry for 30 years. In that time I've seen hundreds of people's lives dramatically improved once these mercury leaking implants were safely removed. I've seen infertile women make a whole family, chronic high blood pressure returned to normal, and multiple sclerosis victims totally recover.

In fact, it's just such a remarkable recovery that started me on this odyssey of trying to get the regulatory agencies of the U.S. government to fulfill their sworn obligation to U.S. the people.

I'd like you to meet another recovered MS victim, Stacy Case, who should not have been poisoned by her fillings except for the dereliction of duty in Washington D.C.

Stacy, tell them your story.

MS. CASE: Thank you, Dr. Kennedy. My name is Stacy Case. I'm a television journalist of 20 years. I anchor the evening newscast in Nashville working on consumer and investigative reports. Prior to joining Fox, I worked at CBS News as a national correspondent.

I've spent two decades helping right wrongs, shining a light on injustice, searching for the truth. I've covered the White House, Congress, the United Nations, and, yes, FDA regulatory hearings always with impartiality.

But today I stand before you not as an impartial journalist but as an injured consumer. Nearly four years ago, I let a dentist talk me into having four 30-year-old silver mercury fillings replaced because he said they were cracked. Your agency at the time, though, the FDA had done nothing to warn me, an educated professional, that this was a health hazard.

This is a great injustice. I had four removed and replaced with four new, shiny mercury fillings because that's what insurance covers. Within a few days I had this heavy metal taste in my month. I kept chewing gum to try to make it go away. As you know from watching Dr. Kennedy's Smoking Teeth video, that emits more mercury vapor which is neurotoxic. Within a few weeks I developed deep, painful headaches.

Within a few months I was experiencing a myriad of neurological symptoms: The sensation of cold water running down my head; pinpricks up and down my arms; having trouble with word recall; cognitive symptoms which, by the way, is a real problem in my profession.

Within four months, blurred vision in one eye, tinnitus, ringing in the ear. Seven months after that dental work, I got out of bed one morning, July 7th, 2008, and could not walk. My husband took me to the doctor, who this time said, Mrs. Case, you either have MS or a brain tumor.

The MS diagnosis came within just a few days. My children were two and three at the time. My immediate concern was will I be caring for them or will it be the other way around. I now know that I and millions of other Americans are genetically pre-disposed to autoimmune disease, and these mercury fillings are the trigger in many cases.

As I'm in the trenches with this disease though, the FDA in 2009 ruled amalgam safe for everyone, once again a missed opportunity.

Thankfully, my journalistic instincts kicked in. I spent weeks on the phone, online, researching MS, researching MS and its triggers. I read several dozen scientific studies. One such study, 1990 University of Denmark, proved monkeys with mercury dental fillings stored it in their spinal ganglia, pituitary gland, and many other organs. This stuff seeps into the body from the day it is implanted. Then one day you reach the tipping point like I did and disease sets in.

In my research I've uncovered plenty of people who've been miraculously cured of MS, all of whom had something interesting in common. They once had these mercury fillings too. So I decided after much thought and prayer to make myself the lab rat. What did I have to lose?

I had my fillings removed. I had my fillings removed using the IAOMT guidelines, the only safe method. Within a week, wouldn't you know it, I was 50 percent better, my body was calming down. I then began IV chelation along with a myriad of vitamins, supplements, minerals, acupuncture, and an anti-inflammatory diet, which is very boring to eat.

And by my first year checkup with my neurologist, I was in remission from MS and have been ever since and am on no MS medications because my neurologist says they aren't necessary; I'm doing too well.

I've spent $35,000 out of pocket on this elective dental work and these alternative therapies that I've just described to you to rebuild my body, and right this wrong.

Thank you for convening a scientific panel to reconsider the safety of amalgam. Your handpicked scientists in 2006 and 2010 have made you keenly aware of the health risks and the disease causation. Please do not ignore them or injured consumers like me any longer. You really want to help this country to get healthcare costs under control, ban amalgam; you really want to see a cure for many autoimmune diseases, ban amalgam; you really want to ensure American moms like me can play chase with their children in the yard, ban amalgam.

After two decades in the news business, I know the truth, and the truth is silver mercury fillings are causing the disease and they are making people sick and keeping people sick ‑‑ so help me, God.

Use your power and position for good, Dr. Shuren. Leave a legacy. Please right this wrong. My website is Thank you.

MS. HOWELL: Our next speaker is Mathew Thompson with Reduction Technologies, Incorporated.

MR. THOMPSON: I'd like to thank Dr. Shuren and the panel for the opportunity to speak. My name is Mathew Thompson, and I'm the founder of a company to develop a non-fusion implant to adolescent idiopathic scoliosis.

I'd like to speak today from three different perspectives: First, as a founder of a pediatric medical device company; second as a member of the medical device company on the whole; and lastly as just a citizen and a person.

I'd like to start with the story of my company so far. Back in 2007, I founded the company based on an idea to treat adolescent idiopathic scoliosis without fusing the spine.

For those of you who don't know, scoliosis hits mostly girls in their teenage years, and the only surgical treatment for it, currently, is spinal fusion, generally 10 vertebrae fused at once in a major surgery that will affect these kids for the rest of their lives. I felt that medical need was great and wanted to do something better.

In 2008, I raised funding from the first two venture capital firms I talked to, which is an oddity, and I know there was some luck in that but it made me feel pretty good. And those firms were great firms. They had a billion dollars under management, and I thought everything was going well.

All of our testing has gone well. Our intellectual property looks great, and there are a lot of excellent pediatric surgeons who are excited by what we have and think that what we have may really be something and might be something really good for these patients.

I've been trying for three years to raise a second round of funding to basically try this idea out in patients in a pilot study and see if it really works or not. And in the past three years, I have not even been able to get a single term sheet from one investor.

I know some of this has to do with the market crash in 2008 and the global recession. I'm not completely unplugged from the world. But the vast majority of the investors I've spoken with have actually money left in their funds and are actively making investments.

And the overwhelming majority of these firms have told me that the number one reason that they're passing on my investment is uncertainty at the FDA for a PMA track device.

As a founder of a pediatrics medical company, I can tell you we have been greatly affected by the changes at the FDA. Pediatric market sizes are usually a lot smaller than adult indications. And investment coming through in pediatric medical devices that's currently making it is for 510(k) path devices and devices that are, by definition, less innovative than a PMA track device.

As a member of the medical device community as a whole, I can tell you that I agree with the feelings of the Minnesota congressional delegation. And while I have not read the studies out of Stanford or PricewaterhouseCoopers, I can tell you that every day I drive by a contract R&D space that is more and more empty as the days go on, that I know guys out there who are looking for work ‑‑ contract work to string them along, guys that have been in startups for 30 years suddenly working for Johnson & Johnson because they don't know what else to do to feed their family.

And you know, it's tough out there, and I feel like investors aren't going to put money in uncertainty. And they are steering the money that is left towards devices that just aren't going to be that innovative by definition.

Finally, as a citizen, I worry that we're losing our competitive edge in medical devices or maybe it's already gone. As the father of an eight-month-old girl, I'm also afraid that she will grow up to have scoliosis and I'll have to watch her get wheeled one day into an operating room. And all I'll be able to do is wonder could I have been able to help her. I don't know. I can't get there.

Could I have helped any of the tens of thousands of children who every year have their spines fused for this condition? I don't know. I truly understand that protecting patients is very serious, and I appreciate that you guys are trying to do that. But we all have to find a way forward that cherishes both the safety of the patient as well as fosters innovation because we just can't keep going the way we're going.

And like I said, I know some of it is due to the recession, but not all of it; and I ask the panel and Dr. Shuren, hopefully we can find a way to work together and keep all of our dreams alive in a way that is as safe as possible. Thank you very much.

MS. HOWELL: Thank you. Our next speaker is Mark Deem with The Foundry.

MR. DEEM: Good morning. Thank you for traveling all of this way to join us in sunny San Francisco. My name is Mark Deem, and I'm the managing partner and chief technologist of The Foundry, a medical device company incubator based in Menlo Park.

Over the past 13 years, my partners and I have started over 16 different medical device companies, which were founded to treat patients suffering from stroke, obesity, heart disease, vision loss, loss of mobility, and hypertension.

I've spoken at prior Town Hall and other meetings about the impact the FDA delays have had on the medical device world. I've described how those delays have impacted our ability to raise capital to continue development of these promising new therapies and given specific examples of companies that were shut down in large part due to FDA issues, most after having received CE marks.

I've described how my colleagues and I are no longer structuring or financing our companies to get clinical trials done within the United States, how we develop our products here in the U.S., take them overseas to conduct clinical trials, and then stay there to commercialize while we make plans and negotiate with the Agency for U.S. approvals. But I'm not going to talk about any of that today.

I'm actually going to defend the job that the FDA is doing. Recent reports by Professor Ralph Hall of Northwestern University, by Dr. William Maisel, then of Beth Israel Hospital and consultant to the FDA at the time, Dr. Steven Nissen and others of the Cleveland Clinic all looked at recall rates of FDA cleared and approved devices. And when compared to the large number of clearances granted, the recall data shows that the FDA's track record of safety is actually very, very good.

For example, Professor Hall found that 99.5 percent of the thousands of clearance decisions the Agency makes every year are free from safety issues. Of the 0.5 percent of devices that do experience a recall, the majority of those recalls would not have been prevented by stricter approval processes or by larger clinical trials. They were recalls due to manufacturing or contamination failures.

I agree completely with Drs. Nissen and Redberg, consumer groups, the GAO and the FDA itself that the Class III devices awaiting classification decision need to be completed. But the GAO's report also found that the 510(k) process is fundamentally doing the job of protecting the public.

The recent conversation by the Institute of Medicine that the entire system is so flawed that it should be scrapped is ludicrous. The IOM should be ashamed of itself. And I, as an American taxpayer, want my $1.5 million back.

Now, I recognize that to a patient who experiences devastating complications due to a procedure or a device failure, the complication rate is 100 percent. And we need to strive to prevent those failures in every way we can.

But in terms of protecting the American public from harm, industry and the FDA are doing a good job. Where we are failing patients and where we are actively harming American patients is in the failure to get lifesaving new technologies to them fast enough.

We concentrate on the harm caused by a failed device, but a patient with no surgical options who dies of aortic valve failure or a patient who suffers a heart attack or stroke due to drug-resistant hypertension or a patient with untreatable, debilitating back pain has surely suffered great harm as well. And today that harm is potentially preventable if you live overseas or if you can afford to travel there for treatment, but not here in America where the technologies that could treat those patients were developed.

Recent reports by several organizations show that therapies developed in America are available to patients oversees almost four years before American patients can benefit from those therapies.

Today in Germany, 30 percent of isolated aortic valve replacements are done without open-heart surgery. Interventional technology capable of significant reduction of high blood pressure where drugs have failed is available throughout the EU.

And outside the U.S., fourth generation artificial spinal discs are routine therapy, while in America, most physicians refuse to even use the available inferior earlier generation systems. We the people, our lawmakers in Washington, and the leadership and reviewers of the FDA need to recognize that improving the efficiency and the speed of review of lifesaving new technologies will prevent harm from many, many more patients than the harm that would be prevented by trying to improve a safety record that already exceeds 99.9 percent. Thank you for your time today.

MS. HOWELL: Thank you. Our next speaker is Rita Redberg of the University of California.

DR. REDBERG: Thanks very much for the opportunity to address this group.

I'm Rita Redberg. I'm a cardiologist at the University of California San Francisco, so I think it's a great location for this meeting. I've been there for 21 years.

I'm also a researcher, and my area of research is medical devices and safety and effectiveness issues, and I'm also the editor of the Archives of Internal Medicine, so I get to review and evaluate a lot of research being done.

As I said, I'm a practicing cardiologist. I've been taking care of patients every day for the last 21 years, and I appreciate, certainly in my patients, the advantages of innovative new devices, but I also appreciate the suffering of patients who have implanted devices who have been recalled.

A lot of these recalls are on devices that have never been evaluated in clinical trials, but devices that have gone through 510(k) such as ICD leads, prosthetic valve rings, and other kinds of like hip implants, so I think the mission of the FDA and my first obligation is to establish safety and effectiveness for my patients.

Many of my colleagues and parents of my kids at school are in the biotech industry in devices. I understand the importance of getting things to market quickly, but getting things to market quickly cannot be done by sacrificing safety and effectiveness. And I submit the only way to establish safety and effectiveness for implanted devices is through clinical trials.

New ‑‑ innovative is not the same as new. Every device that's new is not an innovative device. Innovative has to be demonstrated through clinical trials. Getting things done faster is not always better; getting a device shown to be safe and the effective to my patients is certainly better.

But we can only know a device is safe and effective if it has been studied in a clinical trial, and particularly for implanted devices, which is a lot of what I see in my field of cardiology as well as in orthopedics, these are high-risk devices.

I also sit on the California Technology Assessment Forum where we evaluate new devices in California. A year ago we evaluated the data on metal-on-metal hip implants. This was a device that was approved by the FDA through the 510(k) clearance process. There were no randomized clinical trials. We had surgeon after surgeon, as well as industry, come to us and say this was a fantastic new innovation. It was particularly good, they told us, for young patients.

I asked one of the surgeons how could he know it was such a great device when there were no randomized clinical trials. He looked at me in the eye and said it would be unethical to do a randomized clinical trial on this fantastic new device.

Well, several months later, as you know, these devices were recalled because they were causing pain, suffering, and perhaps mortality in these young patients, that they were ‑‑ tens of thousands that these implants were put in.

And again there are so many examples, but the only way to ensure safety and effectiveness is through clinical trials. I agree there should be consistency and we should speed up the FDA approval process, but the way to do that is to give the FDA the staff and money it needs to do these reviews. The FDA is sorely underfunded. The PMA reviews are incredibly expensive. The users of IC user fees pay at best 20 percent of the cost of a PMA review.

So you know the Medical Device User Fee Act is currently being renegotiated. Industry has opposed any increase in user fees. It's impossible to speed up reviews without having staff and resources to do it. And the ‑‑ I think the way to speed up reviews and get consistency is by giving Congress and medical device industry user fees to reflect the cost of speeding up reviews. It cannot be done by sacrificing safety and effectiveness for our patients. Thank you.

MS. HOWELL: Thank you. Our next speaker is Bernard Hausen.

DR. HAUSEN: Thank you very much. My name is Dr. Bernard Hausen. I'm the CEO of a publicly traded, yet small, medical device company that has numerous products cleared by the FDA and seeking clearance on others.

I'm also a physician and a scientist, which allows me to look at things from many sides. As I'm sure you are very aware, and what we've already heard many times, is that the medical device industry is currently in quite a conundrum.

The extended timelines and with that the uncertainty in outcomes we are experiencing when interacting with your Agency, more so than ever recently, are depleting our precious resources of time and capital faster than we can replenish them. This is a common phenomenon for most CEOs in this room that in my opinion will invariably result in this industry, where the U.S. has been the once world leader, becoming heavily decimated.

Venture capitalists cannot afford to put ever increasing amounts of cash into companies with unpredictable timelines and outcomes. Let me give you a very real but theoretical example of Company X. This company has nothing to do with the company I'm running but is representative, I'm sure, of many of the hundred companies we have in the Bay Area.

By the time Company X has submitted its first 510(k), it has spent approximately three years and approximately 20 million in R&D and pre-clinical work. It has just completed an initial round of funding, which in this environment was extremely difficult and very dilutive.

Now with ten million of cash in the bank and a monthly burden of about 30,000 per day, it is waiting for the FDA to process the 510(k). Ninety days means that if the company is lucky, at the end of the clearance process it is down 30 percent on its balance sheets. That is $3 million.

For de novo 510(k) of young companies, young companies rarely do see things pass within 90 days. One can actually easily double that time. At that point I'm now down 6,000,000; 60% of my cash position to obtain this clearance. For a CO, this is a nightmare because he has to go out and raise money again, more dilution, even unhappier investors. You have the so-called reduced user fees for not yet profitable companies to lighten the burden on the submission fees.

While the tenor of this discount is appreciated, I would rather propose the exact opposite. Allow me to pay you ten, twenty, no thirty times that submission fee enough for you to hire at least one, if not two, FTEs.

With these resources in place, I now ask you to turn my submission around in weeks rather than months through a concerted effort from your teams. As a good leader you can use some of the money to incentivize your employees.

I ask them to work with me to make this happen. Give me guidance, not let me guess what they want to hear or see. Involve the leaders in the review process early to make sure we don't go off on a wild chase for something that really isn't ‑‑ not required.

This fast track review process would initially only be available for not-yet-profitable companies, and while my user fees have just gone up 30 times, I would have clearance within weeks or at least certainty of where I am with my submission by the time ‑‑ it's a win/win.

By the way, this is not a unique program. Many of our notified bodies have successfully implemented fast tracking for years with great satisfaction on both sides, so it clearly can be done.

If you don't implement radical changes within your agency, get better qualified knowledgeable reviewers with real life clinical experience, dramatically accelerate timelines, we won't be able get the funding for our companies. And with that, the industry that feeds the big players within the industry with creative new product will die.

The result, a lot of unemployment, the absence of progress in medical technology, innovation for patients. It's that simple; it's that devastating. Thank you.

MS. HOWELL: Our next speaker is Joleen Chambers.

MS. CHAMBERS: Good morning. My name is Joleen Chambers. I'm a volunteer patient advocate from Dallas, Texas. Yes. I've traveled specifically for five minutes with the FDA. This is my fourth in-person opportunity.

Failed implanted medical devices place patients in medical and legal purgatory, a canary in the coal mine. September 25th, 2010, at the FDA Workshop For Patient Representatives in Washington D.C., I told the FDA that my brother had a failed implanted elbow that required revision surgery removing two components after just four months.

That second surgery did not restore function or relieve his pain. Constant high dose painkillers caused his teeth to disintegrate at night while he sleeps. His insurance provider and the surgeon designer of this device denied him continued care. The FDA knows him as Steven Baker, MedWatch adverse event number 5009052.

A jolting alarm clock: January 13th, 2011, invited but treated as an unwelcome participant at $1700 of my money, I attended the MDUFMA consumer group meeting in Washington, D.C. I stated that patients are not treated as full stakeholders in FDA decisions clearing implanted joint replacements for the U.S. market.

A red flag: March 10, 2011, at the FDA Texas Town Hall meeting, my speech referenced that Medicare is in financial peril and the number one expenditure of Medicare, joint replacements.

The IOM report July 29th, 2011: The Institute of Medicine was charged to review the 510(k) method that's used to clear medical devices for the market. The report concludes that the method is substantially flawed and does not protect patients or ensure that implanted medical devices are safe and/or effective.

The British registry: On September 15th, last week, the New York Times reported that according to the British Registry, Johnson & Johnson DePuy ASR metal-on-metal hips were failing nearly 29 percent of the time. More than 90,000 of these devices were sold worldwide. This means that the U.S. is exporting failed devices on a large scale and relying on a foreign registry for postmarket evaluation.

This petition: Today I present this petition to Congress and President Obama asking that the charter of the FDA be changed to substantially increase implanted medical device patient protection and increase industry accountability to comply with the IOM report on the current 510 system.

The canary, the alarm clock, the red flag, the IOM report, and the British registry are all warning signs. Ignore the warning signs and risk depleting Medicare funds wastefully, losing the public's trust in the integrity of the FDA, devaluing the U.S. export credibility internationally, and endangering valuable domestic medical device industry jobs.

Recommendations: Change the FDA charter to grant full stakeholder voting rights, a patient representative and consumer representative on all FDA implanted medical device advisory panels.

Number two, establish an accessible, international comprehensive registry of implanted medical devices to track all postmarket data; provide realtime quality information that patients and their doctors can use to make life-enhancing decisions such as the information Consumer Reports provides on appliances and automobiles. Require that the implanted medical device industry identify what the life expectancy is for a joint replacement product and warrant a percentage of that period.

This will provide patients speedy and reliable compensation for innovations that fail and a realtime safety effectiveness feedback loop for the industry. Reducing the percentage of failures will encourage quicker innovation since unsafe and ineffective devices will be identified early and be corrected or be denied continued market access.

Number four, revoke the entitlements to the medical device industry that violate patients' rights to basic access to justice in state courts. Focus less on perceived shortcomings of patient messenger or the patients' medium of delivery and more on the message that patients are offering to the Agency, the bureaucracy and exacting requirements of FDA/OSHI are intimidating barriers. Recognize that patients generally don't have nor should be expected to have extensive medical training, graduate degrees in statistical analysis, the physical ability to travel, a substantial travel budget, public speaking skills, computer access, and deep knowledge of FDA regulations, investigate reports of life-altering adverse events by elderly medical and/or financially challenged patients with due respect, and accommodate patients' special needs to provide their full stakeholder participation as a partner with FDA regulators and the medical device industry to the mutual benefit of all. Thank you.

MS. HOWELL: Our next speaker is Jack Dhuwalia of JD Consulting.

MR. DHUWALIA: Good morning. Can you hear me? Yes?

Good morning, Dr. Shuren, panelists and attendees. Thanks for giving me the opportunity. I'm Jack Dhuwalia, president of JD Consulting, an independent consulting firm supporting compliance in the medical industry.

May I suggest five concrete ideas that could work to protect public health and make it predictable for the industry to obtain FDA clearances.

I propose a balanced approach. One, substantial equivalence has been around for a long time for good reason. It's cleared more than 50,000 devices with minimal problems. The industry conducts risk analysis and follows design control for QSR to ensure continued device safety and effectiveness through QMS for the entire product lifestyle. All in all, the data supports keeping it. In essence, if it ain't broke, don't fix it.

Number two, risk-based decisions are appropriate for evaluation. I agree, FDA can and does ask for clinical data to support submissions for low-to-moderate risk devices. Clinical data might be from several sources that are described in the medical device directive, thereby possibly lowering the regulatory burden on the industry.

Number three, postmarket their requirements. MDR is a source of adverse event reports that may serve this purpose on Class II devices without adding a new burden, if used effectively. Another approach, why not work with the industry. The company can be proactive in collecting such data. It's a different mindset. It can work. Serious problems can be addressed quickly. It's in the industry's best interest to cooperate to avoid mandatory mandated postmarket surveillance.

Number 4, I suggest that FDA request risk analysis data summary for low-to-medium risk devices. The companies do that anyway through ISO 14971, an accepted standard.

I suggest, No. 5, I suggest companies provide a periodic update to keep the information current. FDA is often kept in the dark ‑‑ the FDA is often kept in the dark. When the device is cleared after that, nobody knows, goes in a black hole.

In summary, I suggest continuing this standard substantial equivalent, getting the industry involved by working with risk analysis to help make sound, risk-based decisions, to make submissions to the point, easy to understand, and expect FDA to take a gentler, wiser approach. Life will be better with everyone working together. Let's not throw the baby out with the bath water, shall we? Thank you.

MS. HOWELL: Thank you. Our next speaker is Kenneth Kasper with ARK Diagnostics.

MR. KASPER: Good morning, everyone. I'm Ken Kasper. I'm executive director of QA and RA. ARK Diagnostics is a very small medical device company. We make in vitro diagnostic medical devices to measure therapeutic drugs.

In particular, we make devices use their hospital laboratory test chemical solutions to measure epileptic drugs and now methotrexate, which is under review. We have developed assays for retroviral drugs, which are used to treat HIV infection, but these assay methodologies have difficulty reaching the market because of many circumstances.

Therapeutic drug monitoring and the regulatory science for review and clearance of such devices for therapeutic drug monitoring is a challenge, and I think that sometimes the regulatory science can be a roadblock unnecessarily. It is a medical tool comprising one component of an overall strategy to improve health in patients with complex medical decisions.

Imagine driving in your car at night. You usually turn on your head lights, don't you, if it's rainy or foggy. Even the headlights are maybe not quite good enough, but you don't turn off your headlights just because it's more complicated to drive at night under those conditions.

Regulatory science seems to treat therapeutic monitoring in a one-dimensional manner. It is neither a panacea nor a curse to measure blood levels of therapeutic drugs. The argument is not that all drugs should be monitored. It is not an argument that says that the drug branch is releasing dangerous drugs.

However, the concern is that unfounded beliefs determine regulatory science and discourage involvement of IVD medical devices. A specific request is for CDRH to engage fully and regularly with the clinical laboratory community and medical practitioners to better understand this important role of therapeutic drug monitoring for the measurement of the desirable blood levels of therapeutic drugs.

The current impression is that CDRH is unfocused to do so, and TDM is not sufficiently recognized or incompletely understood.

In the area of personalized medicine, no mention is made of measuring desirable blood levels of drugs as a direct marker for indicating whether or not a patient's therapeutic drug regimen is appropriate. Regulatory science initiatives that have been reported by FDA address predictive models either by predictive computer models or biomarker analyses. These are indirect measurements.

While much emphasis has been placed on personalized medicine, and it's part of the innovative branch of clinical chemistry, much of the emphasis from regulatory agencies and popular media is on genetic testing for individualized therapy.

It is important to note that while genetic testing is a key component of personalized medicine, there are still many things that affect drug levels for which genetic testing does not account. We're willing to spend thousands of dollars for a genetic screen, not willing to spend 50 dollars to measure the drug level directly.

TDM is a tool that can assist in the personalization of drug treatment, and we would like to see that the science initiatives include therapy drug monitoring and measurement of drug levels among the other topics for recognizing potential biomarkers.

There is the impression that the difficulty in the risk of measuring a blood result is in the possibility of an erroneous result. There is an example of a drug that would, importantly, have therapeutic drug monitoring tools available: Voriconazole is a drug that treats invasive aspergillosis, a very deadly fungal infection that can have central trauma nervous system consequences. It's often used as a prophylactic therapy for transplant patients.

As an example, reasonable estimates are that a wrong analytical result in a clinical laboratory can occur approximately between one per 1,000 and one per 10,000 results. Compare that to the possibility in public studies that persons who are under therapy for voriconazole, one out of five is likely to have a blood result that is less than desired. So what is the relative risk? I think it's important to understand that the risk in inadequate therapy due to the fact that we don't understand what the blood concentration is for patients is an important perspective when considering the review process and the clearance.

Our company had developed tests for measuring protease inhibitors and discussed the possibilities with the FDA over six years ago, and these possibilities were discounted because we aimed at developing tests that had analytical capabilities of measuring the drug in the range that has been accepted as approvable for drugs. That wasn't good enough, so these products are not available.

I will applaud the FDA for considering the phenytoin regulations for clearance of products that are, not for phenytoin, but other anti-epileptic drugs. I've proposed a number of other suggestions in writing, and I can hand them to you, Dr. Gutierrez, later.

But I'll just simply say if one could use the regulation tools for other antibiotic drugs such as vancomycin as a predicate for voriconazole, this could pave the way for introducing an important new IVD for therapeutic drug monitoring. Thank you.

MS. HOWELL: Our next speaker is Hugo Campos.

MR. CAMPOS: Good morning. First of all, thank you very much, Dr. Shuren and panel, for the opportunity to speak here before you this morning. My name is Hugo Campos, and I'm a heart patient living with an implantable cardioverter defibrillator.

Each year hundreds of thousands of Americans are implanted with pacemakers, loop recorders, and cardiac defibrillators like mine. However, not a single one of these patients has access to the wealth of personalized data that is continuously collected by their implantable devices. I believe it is time for U.S. to change this.

Pacemakers and ICDs are small battery-powered electrical impulse generators. They are implanted in patients with slow heart rhythms or who are at risk of sudden cardiac arrest. In addition to providing lifesaving therapy, these medical devices collect and store advanced diagnostic information pertaining to their normal function and a patient's clinical status. This information is transmitted to a secure and private network owned by the manufacturer of the device. Some of the data collected is made available to clinicians through a secure website enabling them the convenience of monitoring patients without the need for in-office visits. However, this data is not made available to the patient who originates it.

Studies have shown that remotely monitored patients experience a significant reduction in time from clinical event to clinical decision and also benefit from shorter hospital stays and reduced costs per hospitalization. This clearly makes the point that access to information saves lives and saves money.

Yet even in light of such evidence, patients continue to be denied the right to access such useful and incredibly rich data about their bodies. The main obstacle in my view has been the cardiac rhythm management industry itself, which claims that a pacemaker or defibrillator is put into a patient's body for the therapy it delivers, not for the information it gathers, and that making this available to patients doesn't fit their business model.

The types of information collected by a modern ICD, for example, vary from trivial to potentially critical. Among other things, the device monitors its own battery voltage, the amount of time it takes to deliver a lifesaving shock, collects and stores intracardiac electrograms and monitors a patient's heart rhythm, daily activity, arrhythmia episodes, and even the buildup of fluids in the lungs, which is critical to patients dealing with congestive heart failure, for example.

In addition, patients who are at risk for atrial fibrillation and atrial flutter have a higher propensity for stroke and heart failure. Atrial arrhythmias can also cause the ICD to deliver inappropriate shocks, so rapid patient awareness for atrial fibrillation is crucial for those at risk ‑‑ I'm at risk of atrial fibrillation.

Access to our data can do more than just help patients take control of our disease. It may also help with timely identification device-related malfunctions and ultimately contribute to better patient engagement and improve health outcomes. Knowledge is power and a patient privy to his data is an empowered partner in his own health and healthcare.

Access to my device's data can help me track, understand, and manage my condition better, become more active in my care and work more effectively with my providers.

I rely on the FDA to protect me, and I need the FDA to stand with me in this quest for openness, access, and transparency. In the spirit of the new rules proposed last week by Health and Human Services Secretary Kathleen Sebelius that strengthens patients' rights to access their own laboratory test results directly from labs, I would like to ask the FDA to follow suit and publically declare that patients also have the right to the raw data collected and stored by the manufacturers of their implantable devices.

I have the right and the responsibility to care for myself, but cannot do so without information. It is time to fix this and put patients and our families at the center of our own care. And I call on the FDA to help us get there. Thank you.

MS. HOWELL: Our next speaker is Birgit Calhoun.

MS. CALHOUN: I have three children. One of them died last year. All of them have been affected by mercury at one time or another, but because of time constraints I'm concentrating my statement on my oldest son Stefan.

Before Stefan was born, he had 20 amalgam ‑‑ well, before ‑‑ Sorry.

Before Stefan was conceived, I had twenty amalgams and two amalgam root canals. At that time they called everything silver fillings. But anyway, my son Stefan was born in April. He was a healthy baby, but right from the beginning he had a problem sleeping. He had a really hard time falling asleep, staying asleep, waking up in the morning. I got very little sleep myself. He screamed every night for about a year and a half until we found out that he had ‑‑ he was allergic to the butterfat in milk, so we mixed up non-fat dry milk for him every day for many years. That seemed to work more or less.

Before Stefan was three, he had 30 amalgam fillings inserted in his perfectly looking teeth, by the way. I mean he had tiny pinholes of something that looked like whatever. I don't know what it was, but the dentist thought it was cavities.

Anyway, he was ‑‑ he screamed every night for about a year and a half until we found out that anyway ‑‑ yeah. It says that already. Stefan started refusing to eat the foods he had liked before. He disliked odors of any kind, he became cranky, he had less energy, he wanted to be carried all of the time, his sleep problems continued, he still hadn't learned to talk. He started talking when he was three and a half.

And once he started to talk, he always said, I carry you. He did not say, Carry me. He said, I carry you and that was his way of kind of like saying what he wanted to say.

Stefan was very intelligent once he got to elementary school. He had an IQ of 137, but problems started in junior high school. He started to talk about being depressed. He had probably been depressed before that. He just couldn't quite formulate it.

The problems got worse in high school. He was placed in a special noncompetitive environment in Los Altos High School. All the children in that group were gifted, but a little out of the ordinary. Stefan finished high school half a year early, passing the necessary tests with flying colors. He wound up in Who's Who of High School Students. Stefan couldn't have cared less about that. He did not attend his graduation.

By the time he was very ‑‑ by that time, he was very unhappy. He sought help at Kaiser for his depression, but he felt the psychologist didn't take him seriously, so he did not want to go there any longer. Also, in those years Stefan had more dental work done.

After high school, he attended California State University in Northridge. His experience in Northridge was hampered by his increased depression. I tried to keep in close touch. Often, when I called, he told me how he didn't know what to do, he felt so sad and he knew that he had no reason to be sad. He threatened to commit suicide almost every time I talked to him. He stopped going to school.

We had him checked out to find out if anything was wrong with him physically. There was no thyroid problem. He had pain in his kidney area. Doctors checked the kidneys by doing a cystoscopy, I think. None of the checkups helped. Stefan worked at the law library part time for a while, but he was so depressed that he often could not get up in the morning.

Meanwhile I had my two front teeth root canals redone, and my ‑‑ the upper part of my jaw was ‑‑ had a cavitation and I had a bone transplant from here to there and that came from the ‑‑ I got a bill of the amalgams that were put in.

So getting back to Stefan anyway, skip that, somewhere along the line my husband and I decided that the whole family should get rid of the amalgams and paid that out of my own pocket for the removal of 20 amalgams still in his mouth. Anyway, I need to skip that, I suppose, for me.

There were months during the nine years also after the amalgam removal that I almost did not sleep at all because of long exhausting talks I had with my son to keep him from going off the deep end. It was a terrible time. With Stefan some mercury was found high up in his cheekbones. He had to have some root canals done as well.

If my being here can help prevent any of the experiences I've had with Stefan by seeing mercury kept out of dental offices, all of these trials will have been worthwhile. Why do I think it is mercury from amalgams? Looking back as long as I can remember, I've felt bad the day after going to the dentist. I used to think it was the anesthesia. Thank you.

MS. HOWELL: Our next speaker is Mr. Glenn Hammonds with Genomic Guides.

MR. HAMMONDS: So good morning, everyone. My name is Glenn Hammonds, and I'm a native of Tennessee, but I've lived in the Bay Area since 1979 and in Oakland since 1987. And it's a pleasure to be back in south San Francisco where I spent many years, some happy, as a scientist at local biotech companies Genentech and Exelixis.

And I'd like to think CDRH Director Shuren and his staff, and particularly Heather, for arranging the meeting and giving me the opportunity to speak on the subject of direct consumer genomics.

I'm concerned as a consumer, as a scientist, and as a citizen at the prospect of elimination of direct consumer testing. As a satisfied customer of 23andMe, I would be appalled to lose access to the services which I have enjoyed for several years and which I have recommended to friends and family. I've also used Family Tree DNA and am satisfied with their testing, although I don't understand why they have to remove perfectly good data from their reports before releasing it.

As a scientist who's spent a good deal of time in biotech and pharma, I think it's likely that restricting access to these inexpensive and powerful tests could well slow discovery and innovation. I was impressed by the list given by Dan Vorhaus at Genomic Law Report detailing why this might happen, including reduced access to capital, fewer new products, fewer entrances into the field, increased risk of litigation, reduced access to technology, and encouraging movement of the testing overseas.

As you likely know, students and graduates of medical schools today are using DTC genomic data sets, often their own, to learn genomics in a way that's profoundly different from any previous generation. Some of this work is already available online. For example, the Interpretome project from Stanford.

Genomics will continue to transform medicine and biology for a long time. These students are the vanguard of a fully genomic aware cadre of scientists and physicians. Don't stop their growth.

Finally, as a citizen of a nation that values personal freedom and responsibility, I know that a person is not just a patient, a consumer of medical devices, drugs, and advice.

A person's genome is the starting point for all that a person is and contains information relevant to the whole person, not just the patient. Restricting access to information and advice about that most important part of personhood itself is abhorrent and cannot stand.

I'd like to close with a selection of opinions that I gathered from other customers of 23andMe, sent to me after I made a public appeal through their website and announced that I would be speaking here.

Here is the first. It's important that you express the unhappiness, anger, if you will, that has arisen among many who feel that any attempt to regulate DTC is unnecessary and unwelcome.

A second is, in my personal experience, I took my 23andMe results to my physician; and after I explained them to him, he agreed to add them to my medical record.

Another is, the medical profession and individual citizens need education as much as we can help them get about the coming era of personal genomic medicine. Restricting the information that can be learned from DNA testing from individual consumers does not promote better medical care. I don't find the health and trade information on this site compelling and am much more interested in genealogy and ancestry, but I can't support the support the restriction of information to any user whatever their interest. I do not want the government to filter my access to information about my own genome.

I guess that's an angry one.

And finally I want the government involved to ensure that insurance companies cannot use both information to deny me coverage and employers can't use it to not hire me, which I know is not the FDA's genome, so I ‑‑ I just wanted to express my own and many others' opinions that stopping direct to consumer genetic is not a good idea. And thank you for your attention.

MS. HOWELL: Our next speaker is Ms. Anita Vazques-Tibau.

MS. VAZQUES-TIBAU: Thank you. My name is Anita Vazques-Tibau. I'm a Latino and I'm the director of Californians for Green Dentistry. I have been doing advocacy work on dentistry for over a decade. I have been working with local, state, national, and international agencies. I've been around the world.

I've had the opportunity to witness firsthand the devastating impact of FDA's failure to communicate the risks of dental mercury to the Spanish-speaking community. The FDA is charged with protecting the public.

You have this on your website, and yet when it comes to mercury dental amalgam, you seem to be completely ignorant. You are all supposed to be experts in your respective fields, and yet you can continue for decades to let mercury, the most toxic nonradioactive material, go into the mouths of babies.

Seeing this agency that everyone around the world calls the gold standard do absolutely nothing when it comes to mercury in dentistry is contemptible. To say that you are a transparent agency is a joke.

Spanish-speaking people in this country do not have the same access to the internet, making this entire segment of our population vulnerable and exposed. We are taxpayers like everyone else and expect our government to help us. Many have told me that dentists have never ever used the word "mercurio" in any discussion. Instead, mercury amalgam is deceptively called "la amalgam plata," silver fillings.

Dr. Shuren, you told European regulators that quote, "We don't use our people as guinea pigs in the U.S."

But FDA admits that amalgam can cause neurological harm in young children. Their developing neurological systems are more sensitive to the neurotoxic effects of mercury vapor, says the FDA. And FDA admits there is no evidence that amalgam is safe in children under the age of six. No clinical information is available, says the FDA.

So why are small Latino children like Anthony Garcia and Zachary Martinez being used as guinea pigs to test a mercury product. Did anyone tell their mothers it is mercurio?

How dare you sit up there and let this happen to little kids of any race or ethnicity. This child's mouth is ruined, and no one knows what the health implications will be for him. How can you let this toxic material continue to be used? Do you think that any parent in their right mind would allow a dentist to put this toxic poison into their child's mouth just a few inches from their brain if they knew it was mercury?

You have heard the cries of consumers and citizens, you've heard from public officials and now our commander in chief, President Barack Obama said in his address to Congress, I reject the argument that says for the economy to grow we have to roll back protections that keep our kids from being exposed to mercury because of the FDA's failure to disclose this information to our communities.

We have to do your work. We are telling the people what you should be telling us. California cities such as Costa Mesa and Santa Ana have passed resolutions calling on the FDA to ban dental mercury, and they have warnings ‑‑ warnings to parents that say dental amalgam used in many dental fillings causes exposure to mercury, a chemical known to the State of California to cause birth defects or other reproductive harm.

Around the world, amalgam is no longer used in children, even in developing countries and especially in Latin American. They are switching to mercury free alternatives like atraumatic restorative material, commonly known as ART. ART restorations are ideal for children; they cost half as much as amalgam, and according to Pan American Health Organization, they are painless to place, so children cooperate with the treatment and they can be placed outside of clinics and they can do it in schools.

So why are Hispanic kids in America being subjected to dental mercury when kids in Latin America are benefitting from modern alternatives like ART? Has any one of you ever heard the term fiduciary duty, ethical principle, moral values, or even "First, do no harm"?

I am so tired of coming before this Agency and watching the hundreds of people parade before you all saying the obvious, mercury is a poison. So what would I like to see? I'd like the FDA to tell everyone that dental mercury is a neurotoxin that poses health risks and please post it in Spanish, put this on your website on the first page, not buried deep inside an obscure document. When people have limited access to the internet, this is imperative.

And finally just one more thing. Stop implanting mercury and dental fillings in all kids. Gracias.

MS. HOWELL: Our next speaker is Mr. James Turner.

MR. TURNER: Dr. Shuren and Mr. Silverman, my name is James Turner. I'm an attorney and also board chair of Citizens For Health. As an attorney I have shepherded a number of petitions through the device branch. We've been treated well, had good responses, and worked with a good staff.

One of the things that we were successful in accomplishing, which illustrates some of the concerns I have, is the approval of acupuncture needles in 1996. It illustrated that if we could get the FDA to focus, it could make a decision.

But from 1972 to 1996, acupuncture needles were considered illegal by the FDA in spite of 40 state laws authorizing the practice of acupuncture. It's this disconnect that is illustrated by this reality that affects what I'm talking about today, which is mammography.

Citizens for Health has 11,000 members in California and an office in San Francisco and 100,000 members nationwide with an office in Washington, D.C. A number of our members include breast cancer survivors, and they and their groups came to Citizens for Health and asked us to appear to present the points that I'm going to make today.

There are three things that we think that your division should seriously think about doing. One is including significant warnings to women who are undergoing mammography that it does not, in fact, detect all breast cancers and that in fact it provides false positives for many breast cancers and that it is not necessarily the best way for early detection of breast cancer.

Self-examination detects 80 percent of detected breast cancers. That's not, by the way, in any of the FDA's material, one of the things our breast cancer survivors are concerned about. And indeed, our breast cancer survivor group is made up largely of people who had followed the mammography recommendations and nonetheless contracted breast cancer and then engaged procedures to survive.

First point, then, is more information needs to be given to people who are undertaking mammography, and I want to read to you from the National Cancer Institute website about mammography facts that are not made known through the system that provides mammography to women.

This is the National Cancer Institute; screening mammography is also associated with potential harms, including false negative results, false positive results, the diagnosis and treatment of cancers and ductal carcinomas in situ lesions that would not have caused symptoms or threatened a women's life, i.e., over-diagnosis and over-treatment and radiation exposure.

This is information available on the National Cancer Institute's website but not involved in any of the process that the FDA uses to approve ‑‑ what ‑‑ not only approve the mammography modality, but to approve the information that's to be supplied with it. First point, then, is these types of warnings should be done.

Incidentally, I didn't mention that in women 40 to 49 years of age, mammography misses 30 percent of malignancies. That's an important fact for people who are believing that this is a sound screening system, which brings me to my second point.

I think that the division needs to think carefully about the word "screening." Mammography screening is not like pap smear screening. It is not possible for any consumer to know there is such a distinction.

Pap smear screening works at the cellular level, detects deformed cells and creates early treatment opportunities; mammography detects only a lump that has formed, far down the road of early detection of breast cancer. The public hearing screen with a pap smear, screen with mammography hears the same idea; this is a good successful way to get early treatment.

When the FDA presents that kind of information, as it does in its website, and permits the people who provide mammography to present that kind of information to the people who take the mammography, the information being, this is the impression created, this is as good as a pap smear, a serious misleading framework takes shape.

It may well be because of that disconnect that as I said, 30 percent of breast cancers are missed by mammography. Second point, really look carefully at the word screening. We would urge that be changed to therapeutic. It does, in fact, provide a meaningful therapeutic tool in the context of a full range of treatments.

FDA itself says that mammography users should follow their healthcare provider's recommendations for additional mammography. Breast diagnostic procedures including clinical breast exams, breast ultrasound, MRI biopsy, and thermography; that is in an FDA website.

Our argument is that should be provided as a requirement for all deliverers of mammographies so people who come in and are receiving the diagnostic procedure understand this context.

Finally, the third thing that I believe should be done by the division or by the Center and by the FDA in general is to please refrain from saying mammography is still the most effective method for detecting breast cancer in its early, most treatable stages.

That, first of all, is not a true statement; self-exams are much superior. But, secondly, it creates a false sense of security for the people who are going for mammography. Women go and take and get mammography believing that they are having a treatment that's something like a pap smear, but it's in a completely different world and they need to be informed of that.

They need to be informed that it fits into a larger framework, and that in that larger framework they should be thinking of other things besides just relying on routine mammography.

And then secondly, they need to know that routine mammography does in fact carry significant risks. Our entire membership plus the ‑‑ in particular the breast cancer survivors that ask us to make this presentation ‑‑ urge you to provide truthful warnings about mammography and require the providers of mammography to do that, to carefully consider changing "screening" to "therapeutic" for the use of mammography, and finally, to refrain from making statements about mammography that propel it above all other ways of detecting breast cancer, particularly, self-examination.

Thank you very much.

MS. HOWELL: Our next speaker is Josh Makower with Explorer Technology.

DR. MAKOWER: Good morning. Thank you, Dr. Shuren, and colleagues and your staff for coming out here and creating this forum for all of us to give you feedback and also to share your vision and ideas.

My name is Dr. Josh Makower. I am the chief executive officer and founder of ExploraMed, which is a medical device incubator here in the Bay Area, and also a consulting professor of medicine at Stanford.

I'm a physician/inventor/entrepreneur, and I've dedicated my life to creating technologies to help patients, and the companies that myself and my colleagues have created have touched the lives of hundreds of thousands of patients and created almost 800 jobs here in California.

I'd like to start my comments by reminding all of us the impressive record of safety demonstrated by the FDA and the medical device industry. Important recent studies from Dr. Maisel and Professor Hall have confirmed the safety record and reinforced that the systems in place, both the 510(k) process as well as the PMA process, have served patients and physicians well from a safety perspective.

As mentioned earlier by my colleague Mark Deem, 99.5 percent of products cleared by the FDA are free from any problems which would trigger a recall. The most important finding from that work is that when problems do arise, they often come from issues with the quality system, which are things that could not be detected in a clinical trial.

Those that are focused on addressing the 0.5 percent of problems with medical devices with additional clinical testing or more clinical trials are suggesting the wrong medicine for ‑‑ without properly diagnosing this patient.

As an inventor and a physician, it is the sad stories from patients, some of which we've heard today, that motivate me to want to improve the safety of outcomes for patients exposed to our current state of healthcare solutions in the United States.

My colleagues and I work tirelessly to create technologies which we believe will offer new alternatives and bring new innovative solutions to market for patients.

But within the past few years we've faced incredible challenges to navigate the process even though the track record of the FDA has been excellent from a safety perspective.

These hurdles have made it difficult for us to predict where the FDA requirements are going. We've found ourselves halfway down the path with many of these companies without enough money to survive the next round of questions or the next delay.

This has forced me and my colleagues to move overseas with some of our operations, shut down operations, scrap plans for important new medical technologies, and lay off hundreds of workers. I can assure you this isn't good for patients either.

Our mutual goal is to successfully deliver better technologies for patients. And to do ‑‑ and to do this, industry and FDA need to work collaboratively together to create a predictable, transparent, and reasonable process.

One topic to address is the moving goal post issue. Innovators understand that reviewers need to have the flexibility to ask questions pertaining to safety and efficacy of a device.

However, the questions must be based on scientific evidence of realistic possibilities, not theoretical concerns. The draft guidance on risk/benefit needs to include the concept that when proposing some possible risk, data must be presented to suggest that this risk is highly probable and significant.

The level of evidence of that data presented by the review team should support that concern and should be taken into consideration when weighing the possible risks. It's also essential that these issues be brought up early in the review process, preferably in the first review so they can be addressed and it can lead to a more efficient process.

It's also essential that FDA develop a methodology to leverage external experts to assist reviewers as they're reviewing products. I've suggested before that it would be extremely beneficial to have the ability to have a line item reviewed by an independent panel of experts during a review.

In my experience the vast amount of requests from FDA are exceptionally reasonable, but lately they are often one or two major requests which create tremendous burden and challenge for our company. Often these challenges come when a company's own clinical advisors are recommending something that the review team disagrees with.

Yet this review team may not have the expertise to fully understand the issue. It would be highly desirable in these situations to simply raise the issue to a small independent group or panel of experts in a particular discipline of concern so they can inform both the company and the FDA of the proper way of handling an issue, rather than escalating it into a time consuming and politically dangerous appeal, which companies have few resources to afford.

Finally, the FDA needs to do a better job balancing risks and benefits when evaluating new technologies. The law requires the FDA to balance probable risk versus probable benefits.

Today, in many cases, it often appears the FDA looks at probable benefits versus any potential risks. This mindset is causing unnecessary delays and adversely impacting patient care. Industry, FDA, Congress, and others must appreciate that all products have some risk associated with them. However, delaying access to patients can be more harmful than the status quo.

The FDA has served our country well over these years, and we must return to the right balance that will perpetuate that record of safety without damaging innovation or driving it out of the country. We must find constructive ways of working together to better serve patients, but we also must not set expectations for outcomes that cannot reasonably be met.

The only way we win is to win together, and to do so we must preserve the engine of innovation and allow medical solutions to continue to be available for ourselves and our children. Thank you very much.

MS. HOWELL: Our next speaker is Ms. Nancy Myers with Catalyst Healthcare Consulting.

MS. MYERS: Hi. My name is Nancy Myers. I'm president of a consulting firm named Catalyst Consulting. It's a niche regulatory healthcare consulting firm.

Jeff ‑‑ Dr. Shuren and panel, thank you very much for having this public meeting. It is so important for people to be able to hear what others are thinking along with hearing what you all have to say later.

So just for context, besides my consulting firm, one of the things that I do is that ‑‑ and I'm not speaking on behalf of them, but I am currently the board elected president of a group called the Alliance For a Stronger FDA, which is a group of about 180 members working diligently to assure FDA has sufficient appropriated funds to succeed in its mission to protect and promote the public health.

And that is some of the conversation we've had earlier today is one of the important things is making sure FDA is adequately funded. But in preparation for this meeting, I spent time with entrepreneurs, investors, and innovators looking for ways to improve the regulatory process for medical innovation.

They had some very good ideas, but the bottom line is that there is a growing sense of frustration with aspects of the current system and a feeling that investment and product development in the U.S. device space is suffering. I believe with additional focus and a few key initiatives that are hinged on your innovation initiative, that FDA and CDRH can turn this around.

I have four major points. One is that CDRH needs to recognize that it has a significant impact on innovation as it determines its policies and procedures and the interaction that it has at the review level. Leadership and reviewers alike need to own this fact.

If the FDA is caught flat-footed or is overly strict with unnecessary requirements, it will stop investment in the innovative device companies and hinder job creation in the United States. If the CDRH review process continues to be perceived as lacking in transparency, predictability, and consistency, it too will have a negative impact on innovation.

The second point is FDA leadership and CDRH obviously recognize that devices are morphing outside of the CDRH space and their review silo. Although it sounds so obvious, anticipating these changes early, establishing processes to help establish appropriate level of regulatory framework, and crediting reviewers who work across centers to help others understand the technology and the appropriate benefit/risk profile are incredibly important.

If truly dedicated to advancing innovation, CDRH needs to develop a creative program to incentivize reviewers to think progressively about the regulatory review of products. Reviewers should be incentivized to communicate clearly and to help sponsors understand and overcome the regulatory hurdles. Obviously, not compromising the FDA regulatory role. Rolling up one's sleeves and helping a company navigate the Agency would be a wonderful objective.

Fourth, additional federal appropriations are required if we want the FDA and CDRH to keep pace with other regulatory authorities around the world.

So let me focus on point one. CDRH has a significant impact on innovation, and the rules established can create winners and losers. I know there is a debate on how do you define innovation and who should do this.

In my mind, I've taken the broader view of innovation, the one that was espoused in a recent IOM report, which basically says innovation is improving the quality of, efficiency of, or access to healthcare. In the device space, innovation is sometimes incremental, and sometimes it takes the form of a huge leap.

I believe part of the FDA's promoting the public health mission is to design and promulgate policies that encourage innovation while at the same time ensuring the Agency risk/benefit analysis is not constructing unnecessarily high hurdles. This dedication to advancing innovation must come from the top and seep down to the reviewer level.

Point two, as a consultant looking across medical technology industries, I see the world of devices morphing at an incredibly rapid rate. It's really on the leading edge of technology and has been for decades as all those that have invested in California know.

Many innovations of the future look very different from the plastic definition of what a device was in the past. Many no longer sit clearly within the CDRH regulatory silo, and it demands better coordination among the Centers.

I know the Agency's been working on this, but the sponsors that I've been speaking with still think that that coordination needs improvement. Whether it's a combination product, drugs with companion diagnostics, or even something more unique like a combination of a device offering information to a patient through electronic health tools, support by social media, and therefore combining FDA regulated products with non-FDA regulated products, CDRH's leadership needs to stand on its toes.

One of the things I wanted to quickly talk about is the incentivizing reviewers. I think that the reviewers really ‑‑ there tends to be a viewpoint at the Agency. If you say too much to sponsors during meetings, then that information will come back and haunt you. And I think that that relationship needs to change.

It's very clear that the guidance that the FDA believes it's clearly giving to industry is not actually translating very well, and I see this in a number of cases from very sophisticated sponsors to those that are going through it the first time. So that communication I think should be incentivized.

So with that, with FDA, you know, CDRH can't do all of these things that we want to do without additional appropriations. And hopefully, if that's where ‑‑ if anybody in this room wants CDRH to continue to advance, it's one of those things that people should support, making sure the federal government, even in a time of deficit spending, is supporting the Agency. Thank you.

MS. HOWELL: Our next speaker is Ms. Kelly Gallagher.

MS. GALLAGHER: Hi. Thank you. Thank you, Dr. Shuren. Thank you for making this forum available.

My name is Kelly Gallagher, and I'm a five-time Hodgkin lymphoma survivor. I've had a stem cell transplant, I've had 14 months of chemo, I've had over 100 blood transfusions, 11 implants, catheters, and I'm really grateful for all of the medical devices that I've had and all of the treatment that I've had because I'm still on the right side of the grass.

However, my question is if I hadn't had 17 mercury fillings, would I have needed any of that. And I hear, you know, benefit and risk and what I'd like to, you know, have the new mantra for this millennium is cause, not cure. Because if we can get to the cause, we will have the cures and we will make people well.

Having 17 mercury fillings is what's called iatrogenic medicine. It is a cause. It is mercury. It is toxic. We all know it. I ran into a bunch of scientists in the lobby last night that aren't even here for this, and I was just asking them what they thought mercury was about. They are neuroscientists. They are like, oh, it's toxic.

Well, then why did we have it off-gassing in our mouths? And why ‑‑ you know, I was at the 2006 FDA hearing, I was in the 2010 hearings. Why did they say there is no research when Dr. David Kennedy is there with the Smoking Teeth and why we have the science on ‑‑ in the Calgary studies, and all of these scientists have done, you know, the sheep studies, the monkey studies.

I mean what else do we have to study? Children? Yeah, in Portugal that we put mercury into their mouths. They live in an orphanage. Some of them are deaf-mutes. And, you know, who is watching out for them while we put mercury in them with our money from the U.S. and $11 million NIH study.

I don't know, but I think that it's really ‑‑ I've been around the world as a documentary filmmaker on this topic for 10 years; to the United Nations, to the government reform hearings, the same questions, the same stuff. We are wasting a lot of money and a lot of time while people are really sick.

And I've been one of them. I'm 48 years old. I have fought for my life since I was 20. And I thank you for sharing. And I wanted to introduce Maria Cost because ‑‑

MS. COST: I'm also another victim of mercury poisoning and general fillings. Dr. Shuren and I met in Orlando in May, and he really does understand what happened to me. I was struck with double vision and diagnosed with MS, Lupus, and myasthenia gravis seven days after I had an old filling removed and a new one placed.

It's been 14 years. I'm still dealing with the remnants of mercury fillings. I had to give up my business, I couldn't take care of my children, and I realized that the public had to be aware of this, and that's what I've devoted myself to for the last 14 years.

Dr. Shuren, while you assure us that the FDA hears our concerns and listens to us and takes us seriously, the FDA hasn't done anything and hasn't done anything to protect the American public.

In 2010, a scientific panel strongly encouraged FDA to discontinue the use of mercury fillings, particularly for pregnant women and children and to require labeling and warnings for all consumers. Still, nothing has been done.

As Anita Tibau said, even in the State of California, consumers have been warned since 1986, and I quote, dental amalgam causes exposure to mercury, a chemical known to cause birth defects and reproductive harm. Yet in 2009, the FDA ruled unequivocally that mercury fillings were safe for everyone including children and pregnant women.

Our own state department has recently endorsed the eventual phase-out of mercury fillings as part of a global treaty to ban the use of mercury-containing products. Yet despite the years of promises from the FDA, nothing has been done.

Our own president in his recent speech in September, and I quote, said, we have to keep our kids from being exposed to mercury.

Dr. Shuren, it's a no-brainer. Mercury is a poison. It doesn't belong in the human body.

How many more Americans must be subjected to these fillings, the most toxic element on this earth besides plutonium. How many more Americans have to suffer as I did, as Stacy Case did, as the others we've heard tonight or this morning while our government does nothing. Time is running out.

The government is spending billions of dollars to care for people who have these related diseases such as MS, Lupus, Alzheimer's, Parkinson's, and ALS.

Can you tell us when and what FDA plans to do in terms of ridding the dental profession from using mercury fillings? They really have to be banned. There is no use, no reason to continue its use. There are safe alternatives that are being used around the world.

Even in underserved countries, even in this country on Indian reservations, they are using a non-mercury filling. I hope everybody in this audience hears what I'm saying and what everybody else has said. Don't allow mercury fillings to be placed in your teeth or your children's teeth. Thank you.

MS. HOWELL: Our next speaker is Mr. Mike Carusi with Advanced Technology Ventures.

MR. CARUSI: Good morning. Looks like I'm batting cleanup in this morning's discussions.

To begin, I would like to thank Dr. Shuren and his team for hosting this Town Hall meeting. These are incredibly important events to help solicit the views of all of the various stakeholders in our medical device ecosystem.

By way of background, my name is Mike Carusi. I'm a managing partner with Advanced Technology Ventures. It's a bicoastal venture fund which was founded in 1979 and has over $1.4 billion under management. I have responsibility for the healthcare team at ATV and have been at ATV since 1998. I have worked in medical devices and healthcare since 1993, almost 20 years.

I'm here today because I want to stress to the Agency the urgency with which improvements to the medical device approval process are needed. Our industry is in an emergent situation, which if not corrected soon will impact the global competitiveness of U.S. companies and the quality of care Americans receive at home.

There is currently a high degree of uncertainty and lack of predictability when interacting with the FDA. These challenges are being driven by a risk adverse culture which has arisen within the Agency. The pendulum has shifted very heavily towards safety. There is no question, no question, that patient's safety is paramount to us all.

The stories we have heard this morning are tragic and need to be minimized. We don't want these product failures to occur, and I am certain Dr. Shuren and his team do not want these product failures to occur.

With that said, devices cannot be made 100 percent safe. Unlike drugs, there are human factors involved which make it nearly impossible to make devices fail-safe. The FDA, in this regard, should be commended.

Despite the occasional failure which grabs the headlines, the FDA safety record on medical devices is exemplary. You've heard some of those statistics this morning. It is easy to shine a bright light on the suffering patients experience from product-related failures.

It is much more difficult, however, to shine that same bright light on the suffering patients experience from new and novel devices not being approved. When the risk/benefit calculus springs too far towards risk, unintended consequences occur.

These consequences include the delay of unavailability ‑‑ the delay or unavailability of lifesaving devices in the U.S. market and the exportation of our industry overseas. Patients, jobs, and innovations are being negatively impacted. There has been a lot of discussion this morning about safety, yet the bigger challenge our companies are facing is ever-changing efficacy standards, not safety.

It is becoming increasingly difficult to get agreement on appropriate and achievable efficacy endpoints. More often than not, the wishes of the Agency do not align with the concerns of the market, patients, clinicians, and payers. The system needs improvement.

Device development is an iterative process. Ongoing improvements are made in surgical technique, product design, and patient selection. It is evolutionary, not revolutionary. Europe and the rest of the world understand this process. Innovative devices are now available three to five years earlier outside the U.S. At the same time, the safety records in these markets is very good.

The net effect of this dynamic is that medical device investment ‑‑ the area where I focus ‑‑ in startup companies is declining at an alarming rate. For those companies that are funded, every effort is being made to find ways to avoid the uncertainty of the FDA.

The best way to avoid this uncertainty is to target Europe or other markets in advance of the U.S. This is a drastic change for startups; this is not the way it used to be. These young dynamic companies are now making strategic decisions to delay or in some cases even forego the U.S. market altogether.

As a result of these decisions, lifesaving devices are becoming unavailable to American citizens, and companies are exporting jobs overseas. These jobs include manufacturing, sales, clinical organizations, and in some cases now even the corporate headquarters.

A brain drain is occurring in our industry. The practice of medicine is becoming more innovative outside of the U.S. than within our own country.

At one time people from around the world came to the U.S. because of the quality of our healthcare. More and more, however, U.S. citizens are now finding it necessary to travel to gain access to the latest medical technologies. We are losing our competitive edge.

It is not too late to reverse this trend. My colleagues and I are willing to help. We would like to engage in a dialogue, to help find the right balance between risk and benefit, regulation and free markets, caution and innovation, so as to help make these devices available to patients in a thoughtful and careful way while allowing the U.S. to gain its footing as a worldwide leader in the medical device industry.

I thank you for your time.

DR. SHUREN: Well, thank you all. This concludes the first part of the Town Hall meeting. We are going to take a 15-minute break. We'll come back at 10:15, and then we will open up the mics for Q&A.

(Off the record.)

(On the record.)

DR. SHUREN: Just ask everyone to take their seats. Last person in their seat will have their user fees doubled on the application. People are moving very quickly right now.

So for the next about an hour and a half, we are just opening up the microphones for people who want to ask questions. Again, I ask to please keep the questions short so that there is not ‑‑ there is an opportunity for everyone who wants to get up to do so.

If you do want to come up to the microphone, there are two of them on either side of the room. I'll ask you to come up, and we'll alternate between the microphones.

MR. CARTLAND: Hi. Thank you very much. My name is Robert Cartland. I'm an engineering physicist from Southern California. We heard a lot today about dental amalgam and the FDA approval process.

And ironically, dental amalgam never had to undergo that process. In December, there was a meeting to discuss dental amalgam. I became interested as a patient and a scientist to write a paper on that based upon that debate at that meeting, and I'm happy to share it with anybody here.

At that meeting we heard dentist Ahmed Ismail say, We have to find ways to recognize that there are some patients that cannot and should not have amalgam. We heard a toxicologist from the EPA, Susan Griffin, say, I want to echo my concerns that there does appear to be a very susceptible subpopulation to immunological effects. We heard the pediatric neurologist from the Mayo Clinic, Suresh Kotagal, say infants and children need to be addressed separately than adults because of the increased risk. And I think there really is perhaps no place for mercury in children.

Dentist Van Thompson agreed, definitely not in pregnant women and definitely not in those below six years of age.

The Swedish government has created a commission in 2004 for those suffering from amalgam-related illness. They have actually banned amalgam. Their commission still says that those who relate their symptoms to dental amalgam or other dental materials still feel they are getting nonchalant responses in the care services and not receiving the treatment they believe they need.

These patients who often have a long history of illness have undergone many courses of treatment with only limited effect on their symptoms. Many have, in due course, had their fillings removed. In some cases, they have recorded mitigation of their symptoms as a result.

At that meeting, many dozens of us reported the same thing, and there have been at least five peer-reviewed studies showing sometimes with hundreds of patients mitigation of health problems following amalgam removal.

Anthony Watson ‑‑ this is my last quote ‑‑ of the FDA concluded the meeting saying, We're going to go back as I mentioned and really hit this and hopefully we'll come out with something that everyone can be proud of.

My question is: When will the FDA come out with something that everyone can be proud of?

DR. SHUREN: So when I came to CDRH, and this was in late 2009, we had received concerns about our assessments of our ‑‑ of the evidence on dental amalgam, and one of the things I did was I reconvened the advisory panel.

And we had that meeting in December, as you know, 2010. We've gone back and we looked at the evidence, and what I can tell you is we intend to come out with an announcement by the end of this year.

MR. CARTLAND: And what will that be?

DR. SHUREN: You see, if I was saying that, then I'd be announcing it today. But in all seriousness, no, we are coming out with ‑‑ that is our intent ‑‑ coming out with an announcement by the end of the year. And then we'll explain things at that point, but we're wrapping up on that.

UNIDENTIFIED SPEAKER: Why don't you tell us now?

DR. SHUREN: Because it's not finished going through with the process.


DR. SHUREN: So we will, by the end of the year, make an announcement. And I appreciate folks raising their concerns coming here and talking. We've gone back, looked at the science, we've taken the concern seriously, and like I said, intent is by the end of the year we'll make an announcement. So thank you.

MR. CARTLAND: And if anybody is interested in my review, if they're new to the subject in particular, I'd like to give them a copy. If they are friends, I'll e-mail it to you.

DR. SHUREN: And you're also welcome to give us a copy too.

MR. KANGUS: Hello. My name is Paul Kangus. I'm with radio station KPOO. I have a question for the members of the FDA here plus for the whole audience.

How many of you have children that have been vaccinated and how many of you have children who have autism because as ‑‑ if you read the press in California, for those of you coming from Washington, D.C., the autism rate in California has gone up 2000 percent. Funny. The vaccination rate has gone up 2000 percent.

So is there anybody in the audience who has children who have been vaccinated? Nobody? Oh, good. My children went to high school and school in San Francisco, and I knew the law enough to know that you don't need to get vaccinated. All the schools must allow the religious exemption. So there is a little blue card you get from the principal's office and fill it out.

Being an atheist, it wasn't hard for me to get a religious exemption, but it's an important question that the FDA needs to look at. You're here in California. Do you know the statistics here of vaccination of autism and California? It's a 2000 percent rise. Thank you.

DR. SHUREN: What I can say is vaccinations ‑‑ I hate to always do this ‑‑ is handled by our center for biologics. So we're not the folks.

But it is an issue that the Agency has looked at, and I think you'll find the Agency's position out on the web. It's been talked about very publically and hasn't found a relationship between the vaccinations and autism. And that's been looked at fairly thoroughly by many institutions as well.

UNIDENTIFIED SPEAKER: But that's not true. The Simpsonwood report at CDC absolutely indicates that mercury is a problem and ‑‑ although the courts haven't ruled in that way, when you remove the mercury from the autistic kids, they get well. I did a film on the subject. I've studied it for five years.

And by the way, mercury when delivered to the dentist has to be delivered in a biohazardous container. They are not portion controlled. And when it leaves the mouth and goes into the waste, the waste has to be filtered, and yet the dentists are still putting it in the mouth. I've been living with this thing for 20 years. I've done 20 books on the subject. I've done five films.

And nothing seems to get done. And one of the main reasons is that the people who run the FDA, particularly the woman in charge now, Dr.  Hamburg is it, is on the board of the Schein Company, the largest manufacturer of silver fillings in America. So there is a conflict of interest.

So what I'm saying is that mercury is definitely a poison. When thimerosal is used on the bottle of the vaccines, when it was used, it was a skull and crossbones on that bottle. It's poison. So I just wondered about the conflict of interest with Hamburg and Schein company.

DR. SHUREN: Dr.  Hamburg actually doesn't engage in discussions on dental amalgam.

UNIDENTIFIED SPEAKER: But she's on the board of the Schein Company.

DR. SHUREN: I don't know that she's still on the board.

UNIDENTIFIED SPEAKER: If she wasn't, she was. I mean isn't that a conflict of interest? I mean it shows that the president of the United States ‑‑ what I'm getting to is this: Until we take back our government from the corporations, until we have campaign reform where money doesn't talk, we're killing our population.

In 1970, autism was one in 10,000. Today it's one in 70 in certain areas in this country. And why doesn't the FDA find out what's causing it? It's a matter of national security. One in 70 kids. Can you imagine the amount of money that's going down the line? It's going to bankrupt this country.

MS. TRIMM: My name is Shelly Trimm with RCQ Consulting, and one of the things my clients and I are dealing with is the changing of the reviewers and the depth of knowledge they have. And we understand how hard it is for the FDA to retain reviewers and get them to the level that industry does. Industry moves very fast. We learn very quickly, and it's very hard for the FDA to keep up with us.

One of the programs you've come out with is a training program. Could you give us a little idea on the depth and on how that is being implemented and when we can start seeing some consistency between our reviewers and division chiefs.

DR. SHUREN: So this issue about the experience of reviewers, and I'd say the turnover of reviewers, is a very important one. We've done our own analyses on the impact of what happens when a reviewer changes, or even more so a medical officer or the firstline supervisor, and we know that leads to longer review times. So we try to drill down into what the causes are.

And, in fact, this same problem befell our Center for Drugs and our Center for Biologics. They were experiencing the same trouble. And much of it was due to higher workload for the number of people and much more of a sweat-shop mentality, insufficient number of managers have management oversight and also the managers having too much of a workload, and not paying people for the jobs that they were doing.

And they solved that. They wound up getting the people to do it, having the managers and changing the pay appropriately for people, and their retention has increased. So they've dramatically lowered their turnover rate.

That's what's befallen us now, so our workload goes up. We have gotten some more resources and we've grown the program, but not quite in proportion to the volume of work coming in. We do not have a sufficient number of frontline managers. I have two premarket review offices; one has a ratio from manager to staff of 1 to 14; the other is 1 to 27.

Anyone who knows good management practices, that's a prescription for disaster. And particularly for frontline managers. We pay them less than comparable positions in other centers. It's been an issue that we think is important to resolve, so we'd like to cut down on that turnover because right now most of my reviewers have four years experience or less.

And for my frontline managers, it's about three years experience or less, very hard to keep frontline managers; worst job in the sector, it really is. So we need to have the funding for that. That's one issue. We've got many to deal with.

Training is just as critical. So you raised the rearview training program. We just have implemented, for the first time, required training for all new reviewers. That didn't exist beforehand. But as of now, starting in September, all new reviewers as of July will have to go through that program, get standardized course work.

It's mandatory review of certain kinds of applications with oversight, and we will review their work and grade them to ensure that they are well trained. And we are actually going through all of our key disciplines and setting up core competencies for each one of those. And that will be required training for them moving forward.

I'm going to continue on this point for a moment, though, because it goes to also those are on the basics. What about for understanding technology? As much as we talk about resources, the answer isn't just have all of the people at CDRH. That's unrealistic and not the way to handle things.

We need to have an adequate number to get the job done, but we need to do a better job leveraging expertise outside of the Center. You heard that in some of the comments today about need to touch outside. We had already proposed to do that and committed to do that, and in the next few weeks we will be putting out an SOP on establishing what we call a network of experts so that we can reach out to appropriate experts to help us address important scientific questions and to do it in a timely way.

And we're going to start with some pilots for some healthcare professional and scientific organizations to reach out to appropriate experts to address it.

The last piece I'd like to raise, and just to follow on, but to make that work isn't just the ability to in a timely way find those experts and use them. It's that I need to have in-house the people with the appropriate scientific disciplines and healthcare and medical disciplines to have an informed dialogue.

I'm a neurologist. You're not going to have me talk to an orthopedist. In fact, even with orthopedists, you have subspecialties. My brother is a hand surgeon. If we have an issue regarding hands, he's a good person if he was at the Center to reach out and to talk to someone. But if it's a spine issue ‑‑ what's that.

UNIDENTIFIED SPEAKER: Left hand or right hand?

DR. SHUREN: He's an equal opportunity hand specialist.

UNIDENTIFIED SPEAKER: (Off microphone)  ‑‑ rare breed.

DR. SHUREN: But then you go for spine too, and there are subspecialties. What we'd like to see in the Center is that we have the sufficient cadre of experts to be able to talk to the experts outside of the Center, and we're not there yet.

Last point on training, we are also setting up what we're calling a residential learning program, the opportunity for our reviewers and managers to go to manufacturing sites, manufacturers' sites, healthcare facilities, research facilities to get real-world experience. And that will set up in a more formalized program in 2012.

We're already starting to have some of our reviewers go out now. We just did that in the past few weeks to some of the companies, and this will also be a resource-dependent function because it's not only the ability to send them out and pay for it, but it's their time away from doing review work, and then the work just backlogs.

So we need to also have the people to do the work to allow our people to take the time off to go out and get the real-world experience. We'd like to see all of it done.

MS. ANCHONDO: Hello, Dr. Shuren. My name is Gabriela Anchondo.

I'm a regulatory specialist for a medical device company in California, and my comment and question is regarding interactive communication. And I start on a positive note.

We have a lot of work with a lot of your reviewers in your different branches that are extremely collaborative, very accessible, so we really appreciate that. So I wanted to make that comment. They are very accessible via phone, via e-mail, and that really has a positive impact in early collaboration before submissions and during submissions in addressing deficiencies.

On the same note, there are other reviewers not as collaborative or as accessible, so my question is: Outside from the plans on training and guidance pre-IDEs, how can you foster and improve that work ethic of interactive communication with manufacturers and regulatory specialists like myself?

DR. SHUREN: First of all, I would agree with you that our performance on those interactions is inconsistent. Part of it is we need to settle on what are sort of the right points for the interaction. On the one hand, interaction is good; if you have a lot of it, and it's not value added, it eats up time, it becomes highly inefficient.

Those are issues we're actually talking through as part of our user fee reauthorization. But in the interim, we're already setting up to do tracking within the Center on if we did a review, did we actually have that informal engagement with the company on it or not, so we can have a better handle on where we may be seeing reviewers who should be engaging and they're not engaging.

We will also be talking about clarifications on roles and responsibilities, expectations, and then also building it into performance plans. One of the things we're doing now is as we look to improve our premarket review programs, where do we need to build in the right expectations for reviewers.

You don't want to have, you know, a list of 30 to 50 expectations because they are going to be all over the place; and how do you incentivize people for doing the important work. And we're going through what those priorities will be and make those into performance expectations for our reviewers.

MS. ANCHONDO: Thank you.

MS. HEFFMAN: Hello. Thank you for this forum. My name is Nedra Heffman. I live in Southern California and I work in regulatory affairs for a company that has facilities in Northern and Southern California. I know right now for the 510(k) process, that you're getting input from several sources, including industry and people who want to respond with comments.

My question is kind of two parts, but very closely related. I'm just wondering about current thinking in the FDA regarding the input so far about the 510(k) process and particularly about clinical, clinical evaluation for the 510(k) process.

For example, that might be a subset of products or product codes or all encompassing. So that's my question in general and also specifically clinical.

DR. SHUREN: So in terms of feedback we've been getting, it's been exceptionally helpful. When I mentioned I came to CDRH in fall of 2009 and actually came in an acting capacity and was told very clearly because I was asked if I would take the job, you're welcome to compete, but you'll go through the process. In the interim, you're acting.

And one of the things I said coming in the door was, If I'm going to be acting, I don't want to be a caretaker. There are issues we need to address. I'd like to address them.

And one of them was concerns I was hearing about the premarket review programs. At the time, in particular, 510(k) ‑‑ concerns coming from the industry that the program, and this goes beyond 510(k), PMA as well ‑‑ was not providing adequate predictability, consistency, and transparency.

But I was also hearing from some of the consumer groups and healthcare professionals and third party payers that the 510(k) was letting some unsafe devices on the market and also not providing adequate information to make well-informed treatment and diagnostic decisions because you make a decision on substantial equivalent, as an indirect way of showing that a device is safe and effective, as opposed to an independent demonstration of safety and effectiveness. That was the concern raised.

And even my own staff were saying that the current implementation of the program was not well suited for some of the emerging technologies we were seeing. So my sense was with all of these presented to us, we needed to do an assessment. You need to figure out what are the problems, but also what are the root causes because from that you can figure out what the right solutions are.

So we set up two working groups. One focused on 510(k); one on how we use science and regulatory decision-making, which got to aspects of our other premarket review programs, and we engaged in a lot of public outreach.

We heard about this in Town Halls like this in 2010. You think about 2010 was about assessment. We had two public meetings. We had open public dockets, and we put out two reports in August 2010, and one of them just focused on 510(k) with findings and recommendations. And again, we got public comment on that.

And based on that input, in January we announced 25 actions we would take this year to improve the predictability, consistency, and transparency of our premarket review programs and have since then announced additional actions. And many of those are already underway, and that's based upon the kind of input we were getting from the public.

So a longwinded answer to say is it helpful. It is exceptionally helpful, and that's why we do these kinds of forums and other kinds of forums because it truly does inform our decision making.

Clinical data was your other.

We ask for clinical data in the small subset of devices with one exception, and that's in vitro diagnostics. Clinical data you can think about as not just big randomized trials. It could be taking specimens from a patient. It could be a blood sample. We consider that clinical too.

And for in vitro diagnostics, generally you have some kind of clinical data, but for all the other devices for 510(k), the majority of them, around 90 percent or so don't have clinical data. It's a subset.

And in guidance that we'll be putting out in the next few weeks we had committed to do on clarifying the 510(k) paradigm is to provide better explanations under the circumstances where we might ask for clinical data. But clinical data, as I mentioned, runs the gamut. It could be a few patients; it could be a more formalized study.

MS. HEFFMAN: My main question is when is the right kind of science being used. I didn't mention that I have another son who died last year. He was psychomotor retarded and he never talked. He was also mercury affected.

And whenever I hear about science being done as far as vaccines, or for that matter dental things go, children who are severely or sort of mildly affected tend to not be included in the large group of who is being tested. Like they exclude anybody who is sort of not quite right. They only want to use normal, quote unquote, people in order to find out what might be wrong with dental amalgam or any other kind of device that might be used.

Now, it seems to me some of these children may have been exposed at birth, and so these children should be included in any of these kind of investigations. Thank you.

DR. SHUREN: One thing I will say. I ‑‑ I empathize with the concerns you raise, and it sounds like you have had a lot of misfortune for your family, and I'm sorry to hear that. We always try when we make decisions to base it upon the best available data we have, and I emphasize the word "available" too.

One of the big challenges is that science is not only always changing, it's oftentimes incomplete, and yet there are concerns and issues always before us, and we try to make the best decision we can based upon the best available information. I know people don't always agree we've got it right, but that is certainly the intent by which we're motivated by.

UNIDENTIFIED SPEAKER: Good morning, Dr. Shuren. It's good to see you again. I'd just like to reinforce some of the things said this morning, and you've said it several times during your comments now, and that is consistency. I think there is one other part to consistency, and that is the commitment to the advice you give while you're being consistent.

And I have a different view than I might have had three years ago in seeing some of the companies that I've worked for. I'd just like to give some perspective about what lack of commitment to the advice given means to some companies.

There are two different kinds of examples. One company, for example, had two pre-IDE meetings with FDA. I worked out a clinical protocol for their 510(k). I might add that it was a clinical study that had never been done for that kind of device before, did everything the FDA asked, filed their 510(k), got to the very end of the review process.

The staff changed. The new staff didn't like the old device, denied the 510(k); the investors walked away from that company. The company is on the verge of shutting down. Did everything it was asked to do.

Another company filed ‑‑ had a pre-IDE meeting with FDA. FDA said that this device, if you don't have this design feature or this design feature or this kind of clinical study, you're not going to see a clearance here in the U.S.

The company changed its whole strategy and went outside the U.S. Three years later the FDA approved two competitive products in the U.S. without any of those design features, and the principles behind those competitive devices were exactly the same.

So lack of commitment to the advice given creates unlevel playing fields in the marketplace, or in some cases brings companies to their very knees. So to turn that into a question: Do you see places where you can add a commitment ‑‑ what can you do in the area of commitment to advice given?

DR. SHUREN: So the first thing is we have come across those cases, and that does occur. It shouldn't occur. Here are the things we're doing about it: So one is in the context of a meeting before you're submitting something to the Agency, just for the rest of the folks, which is a pre-submission meeting.

It may be before a clinical trial, it may be before an application that comes in. We are working on guidance; also we've committed to get that out by the end of November. It's my hope we'll still do it by then, but it will be pretty close.

And one of the things we'll address is this issue about if you come into a meeting, what do we expect from the company to provide and what should you expect from us. And one of the things is if we are providing advice, we're writing it down now and standing behind it, unless there is a change being made by the manufacturer that would change the device. You want to change your intended use for device, we may need to change our advice. But that would then formalize it, put in writing, and stand behind it. That would be the expectation.

The other is, let's say you've done a clinical trial, you come in with the data; you were told one thing and you get new reviewers and they want to make a change. We are also putting in place our SOPs for who gets to make that decision.

One of the challenges we have faced is that oftentimes these kinds of decisions may be made just at the review team level. And that's where you may be changing the bar on a particular product or you may be changing it across a type of product.

We have already set up what we call the Center Science Council of our senior managers. All of us sit on it and are experienced scientists to which certain critical issues will be brought. One of them is if you want to change the clinical requirements across a type of device, that has to come to this council. It's not going to be made in the lowest part of the organization, and it's not fair to my people that they should be left with that responsibility.

It's a decision that should be made at the highest level of the organization within a forum in which the scientists, the staff, the managers can all get together and talk about it and work through the science and try to make the best informed decision.

And for other kinds of calls, laying out at what level within the organization at management level those decisions need to be made. And I'm hoping that ‑‑ it's our sense that will start to provide that greater level of consistency. Also, there will be SOPs about even when a reviewer change, what the new reviewer would have to do if they want to go different from what we've committed to do with the company previously.


DR. SHUREN: So those are all going into place. So thank you for that question.

Before I turn to the next person, let me put something in context because sometimes it gets lost. What is going on with our premarket review programs?

We have looked back at the data and the signs for concerns actually began around 2002, 2003. You can actually see the data and everything starting to take off from then.

In our analyses, we concluded there are three things we need to deal with. First of all, the Agency, and I'll say the Center, has not done as good of a job as it should running the program. Period. There is a lot we need to do to fix it. We've identified those issues and already put out the actions we will take to improve it. It's a lot of work, but it's critical we do it.

The second piece is something that was raised by Todd Gillenwater in the first ‑‑ and I broke my own rule about not turning off my cell phone. It's the first time I've been ejected from the movies. So sorry about that.

The second piece is, you know, we do receive from some companies poor quality submissions, and that impacts the efficiency of our review. Different from a drug and biologic center, we accept pretty much everything.

There, if you don't have a quality submission, they throw it back, pus the onus on the sponsor to get it right. We haven't done that. And we're used to dealing with a lot of small companies. We're used to providing more hand-holding than our counterpart centers for that reason.

But at the same token, that allows anything to come through, and it has an enabling ability. That needs to change. And we are working with industry on setting up what that bar should be for what we throw back, if you will, so there are clear expectations about the quality coming in. That can lead to greater efficiencies. So there's things we need to do. There are some things we are working with industry on to do better.

And the last is we need adequate resources to get the job done. There is only so far we can go with the changes we're going to make. They're going to help, but if we don't have the people to do the work, if we don't have the managers to have the oversight, the concern about inconsistency, how are you going to address inconsistency when you don't have enough of the managers and they're going to stay there to assure that the right decisions are being made.

All of that needs to get done, and I think if we address all three of those, then the U.S. remains the world leader in medical device innovation, patients get to have safe and effective ‑‑ and I emphasize "effective devices" ‑‑ in a timely manner. And that's a win for everybody, so I just want to lay that as a context for the things we'll talk about.


DR. GNANASHANMUGAM: Thank you for that. Thanks, Dr. Shuren, for being here today. My name is Swami Gnanashanmugam. Like you, I'm a fellow graduate of the Feinberg School of Medicine at Northwestern. I actually just finished my third year of surgery residency, and I'm here in California doing a research fellowship at Stanford focused on medical innovation.

My question is this: You know, in this entire process of me sort of choosing my career, I think in some ways I represent the future. I've been inspired by various physicians and mentors that I've worked with since I was 19 years old, and this is what I wanted to do. I started a program in Northwestern that teaches medical innovation that's in its fifth year that involves law students, engineering students, business students, and sort of recruits them into what I think is the greatest industry in the world.

Where else do you have an opportunity to touch the lives of so many different people? I've recently lost a number of colleagues, though, who are in this arena, engineers, for instance, to other industries. One of the major concerns that they raised when asking them about that is the FDA process.

I'm wondering kind of what are you doing to ensure that this is still an area that I can go to my colleagues, that I can, you know, talk to other engineers about, that I can recruit people to ensure this is going to be a viable future for them. And I'm also wondering, you know, what can I do as someone who sort of has an organic leadership role, if you will, in recruiting other people into this area. What can I do, what can my fellow physician colleagues do to help you also to make sure that this continues to stay that way.

DR. SHUREN: Well, we'd like to see the medical device industry here thrive. We think ultimately that's in the best interests of patients. And at the end of the day, that's our driver: What is in the best interests for patients. And we think that things that are good for industry can also be good for patients. There doesn't have to be a dichotomy in that perspective.

What I would say for helpful is, we've been out there talking about all of the things we're doing for improving the program. You know, we spent a lot of 2010 about the problems; we're spending 2011 on the fixes. Those are going to take some time as they start to kick in and to do.

One of them is the challenges about being an Agency of the federal government. I can't just simply do something. I change some of these policies. I put them out for public comment. That is a good thing. You all get to weigh in. Here is the downside. It takes a heck of a lot longer to get it done. But we're moving forward at a fairly fast pace. In fact, I've had some of the device trade associations have called and complained that we're putting out so many things there is too much for them to review and comment on. I consider that a measure of success in some respect, so I don't know any of those phone calls.

And I'm putting these guys under tremendous pressure too as we both handle the day-to-day workload and try to make improvements to the program. But I'd say the first thing is start looking at the things we're doing and let people know, because if those are the right stuff, then say they are heading in the right direction. It may take a little time to kick in, but they understand the issues and they are doing the right things.

If we are missing things ‑‑ missing some of the things we need to do, you have got to tell us. And for those who are in companies, we want to hear about what the experience is but not at the high level. It's just not been predictable. It's inconsistent. Walk us through the specific cases so we can go back and look. And some companies have done that, and we've made some changes to our processes based on that very specific input.

So that's the other thing I would take back to those who are in industry as well.


DR. SHUREN: You're welcome. But what I would say is hang on; help is on the way. But the same token, industry needs to work with us, and one of the things I think is harming this is all the rhetoric that is going on in Washington, D.C., because right now too much of what is going on is getting taken over by lobbyists and becoming political. And that is the wrong way to solve these problems. It is absolutely the wrong way to do it. We can solve it together, but when you deal with rhetoric and lobbyists in Washington, D.C., that is a prescription for ending up doing the wrong thing.

MS. ROBERTS: Hello, Dr. Shuren. Thank you for having this, and panelists. My name is Lori Roberts, and I'm a regulatory affairs professional with a medical device company in Central California. Compared to everyone else, it probably doesn't sound really difficult, my job. I'm the regulatory affairs person for wheelchairs.

However, it is really important. We change people's lives. We make probably in excess of 300 semi-custom wheelchairs a day. They are customized to each person, and many of them are pediatric, and they really do change people's lives.

One of the things you can do with a wheelchair is modify it. And so my job at my company, I always say, is to keep them out of trouble. I'm there to keep them in compliance with FDA regulations. And a lot of times people don't think there are regulations for wheelchairs, but actually it's Class I, and if it's a power chair it's Class II. So there are a lot of things for us to think about.

One of the main things you can do with a wheelchair is modify it. So I was very happy to see in the summer we came out with 510(k) device modifications, deciding when to submit a 510(k) to change an existing device.

In order for me to kind of rein in my engineers and keep us in compliance with the FDA, I need to understand this, and so I've been scouring through it, and there is one sentence that my colleagues and I are kind of stumped on how to interpret it because if you interpret it directly, it's going to mean we're sending in a lot more 510(k)s, and I'm going to have to say to my engineers, unless you're changing the paint color, we're going to have to file.

The sentence is on page 6 and it says, Manufacturers should scientifically justify their conclusions that modifications individually and collectively could not affect safety or effectiveness.

To me, that's impossible to prove a negative statement like that. You can't prove something does not exist, so I'm sure you've had some feedback on this or thought about it, I hope.

DR. SHUREN: Yeah. So one thing I would encourage you to do is send us written comments so we can have it in our record. It's so critical that we have an administrative record. That issue has been brought up. It's something we will be looking at as we go to final.

So there is the value of public comment on the documents going forward, but our intent in the modifications guidance, which is an update on existing guidance to clarify those circumstances under which you would submit or not submit a 510(k) when making a change to your device, which we decided to do because we were encountering a number of scenarios with oftentimes it was newer technologies where we had not provided guidance in the past as to what to do, and companies weren't sure, and there were cases where they should have submitted.

And it's not good for the company if they get caught in that circumstance ‑‑ and sometimes because they just didn't know. And then you've got a product out there and people are, What do we do with it; do you take it off the market, do you submit the 510(k)? We usually work with the companies then. We often leave it on the market unless it's a big safety concern and work it through. And we thought the way to minimize that is with guidance.

It is so critical though ‑‑ and sorry for rambling ‑‑ and our intent was not about raising the bar. It's truly about just providing clarity. But we know in any of these cases where it's fairly complex, sometimes in how we communicate it or draft it, we may not get it just right. And getting the perspective back from the people who this affects is so important.

So please submit the comments. If there are other parts of the document where there is lack of clarity or you don't think we have it quite right or you're sort of questioning what you were really trying to get at or what the implications would mean for our company if applied this way on how to interpret, it will be helpful to us in finalizing that document.

DR. ECCLES: Hello, my name is Ward Eccles. I'm a dentist across the Bay in Livermore, a traditional dentist for many years until about 31 years ago I decided a lot of things have to change.

One of the things that triggered it is I had a son who was six years old that was perfectly healthy, and in three days he was gone from Reye's syndrome. And they did all they could do it diagnose quickly, and I later ‑‑ well, it's a brain inflammation, so I began to learn from my study what causes this kind of a problem.

And I realize every day in my practice, I'm working with a neurotoxin which is mercury, and so I began examining then and realizing, hey, I'm doing something pretty bad here. I was taught traditionally, hey, it's an alloy, safe, it's covered with saliva in the mouth, don't worry about it, there's no problem.

Well, first of all, it's not an alloy. There is no shared electrons with dental amalgam; a lot of things mixed together.

And, secondly, mercury comes out of that restoration every single minute of the day and even much more when you raise the temperature. Now, when that mercury was delivered to my office, it was pretty darn toxic, and we've already heard this.

And when it's in the mouth, well, it's just supposedly safe. But when I take it out, it has to go in a plastic toxic waste dump. If I throw it in the garbage, the garbage becomes a toxic hazardous waste. There's a lot of protocol now to protect the environment from this mercury, but it still hasn't been put on the environment in the mouth.

And that's what I'm concerned about. I switched a couple of years later, stopped using the mercury filling, the mercury amalgam. I started treating a lot of patients with systemic problems, one of them in particular in the eighties was called candida, and it was a systemic form.

They didn't get better until they got the mercury out of her body and got the parasites out of her gut. There are so many systemic effects from mercury. So my goal was to remove the toxins. Safe practices is a great procedure in dentistry where we take the mercury out of people in a safe way to reduce the exposure that they have.

So if someone in here is responding to this sensational holistic approach or announcement, don't run out and get your mercury out. Learn about how to do it safely, so you're protected by safe practices and a dentist that's trained in that. It's very important that we know how toxic this material is.

And my question is, you know, I think there is a maximum on what we can ingest or breathe each day of 30 micrograms a day, yet we poop 150 mean grams per a day, so there is a lot of exposure out there and a lot of it is coming from dental amalgam.

My question is: What requirement will you put as to how many micrograms a day are you willing to be okay, to expose the consumer to? What will the FDA say is okay for the consumer to be exposed to? Now, there is a great paper that Dave Kennedy has. I don't know if you're going to talk about it.

I'm just going to comment on a few things. It's an article that just came out in 2011 in the Journal of Clinical Hypertension and the title is, "The Role of Mercury Toxicity in Hypertension, Cardiovascular Disease, and Stroke." There is a lot of evidence showing it's significantly involved. It binds to metallothionein and substitutes for zinc, copper, and other trace metals, reduces the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction.

Have you heard that with the girl who had autism, and, oh, it wasn't caused by mercury, it was caused by mitochondrial dysfunction. Well, mercury induces mitochondrial dysfunction. Increased oxidative stress and reduced oxidative defense are common. Selenium and fish containing omega-3 fatty acids antagonize mercury toxicity.

The overall vascular effects of mercury include increased oxidative stress and inflammation, reduced oxidative defense, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction. You can go on and on and on about the pathological effects of the most toxic material beside the radioactive materials. You have to look at it, have to have better regulation.

So my question was: Is there going to be a standard or a maximum dose to which a consumer can be exposed to other than the 30 micrograms per day we can ingest or eat because we poop a lot more.

DR. SHUREN: So here I go back to Washington, D.C. speak. It's our intent to make an announcement by the end of this year.

MS. LISON: Hello my name is Liz Lison. I'm an independent regulatory affairs consultant here in the Bay Area, and I work exclusively with in vitro diagnostic companies.

I have a two-part question. I understand, and this may not be a correct statement, but I understand that the office of in vitro diagnostics did not participate in the activities which led up to the Institute of Medicine report on the 510(k) process, and I think that working with the OIVD we have perhaps some industry-friendly practices in that they do publish summaries of their 510(k) clearances, quite detailed summaries, from the reviewers.

They seem to have been able to use the de novo 510(k) process effectively. And in conversations with my medical device colleagues, IVD seems to be more collegial and responsive in the pre-IDE process.

So were any of these perhaps more industry standard practices or industry-friendly practices taken into consideration by the IOM before they came to the conclusion that 510(k) process didn't work?

And then the second part of my question is: In diagnostics it is possible to bring a test to market without FDA oversight, and could you comment or update on when either the existing system or any new regulation may be brought into effect over those tests?

DR. SHUREN: So I'll let Alberto address the second part. I'll quickly hit the first part. I sat down, and I heard you say in vitro diagnostics. I figured Alberto is on, I get to take a break. But oh, well. The Institute of Medicine, we don't ‑‑ I mean they took ‑‑ they did their own deliberations, and they decided what they would look at.

That's an independent process from us, so I don't know all of the things they look at, and we're not privy to that. It stays completely separate. We write the check, we set the scope of what they look, of the task then, and then they decide.

I will say regarding, and Alberto will say thank you, too, for the kind words, but the things you raise about putting out summaries of our decisions and on de novo, I just want to then take and talk about our other premarket review office, our Office of Device Evaluation.

We are starting up to do the same thing regarding summaries for the devices that they review. We've already done that for the some of the like PMA 180-day supplements for some of the divisions, and we're moving from there, and we'll start to scale up to put more of those summaries from FDA out there, so you're hearing directly from the Agency.

The second is on de novo. De novo has been a broken process for a long time. There's some reasons why it's a little bit easier to work through for diagnostics than it is for other kinds of devices.

But the fact that the de novo doesn't work well and these are for devices that are more innovative but they are moderate, lower risk, so they may be innovative, they don't have a predicate on the market, they can't take advantage of the 510(k), but they're not high risk where you'd want them in a PMA category.

So de novo is another mechanism for getting on the market and then ultimately get classified Class II and be subject to a 510(k) for subsequent iterations.

We are also putting out, in the next few weeks, changes to the de novo process to streamline it and, we think, get this back on track. This has been a longstanding problem that needs to get fixed because we have some of these devices and trying to shoehorn them into the 510(k) program doesn't work and people raise ‑‑ why are you asking for this, when in reality it should be de novo and you're sort of building this de novo through 510(k). We need to get in the right pathway to make sure the pathway works.

DR. GUTIERREZ: So I think Jeff's comment on the IOM was Washington speak for telling me that I shouldn't talk about the IOM. I will, though, point out that at least one of the IOM members knew in vitro diagnostics well, so I'm sure that was part of their discussion, one way or another. Thank you for the nice comments.

I do want to point out that, again, when we're talking, or everybody is talking, about all of CDRH and we have done our own internal assessments and we have put in ‑‑ we're putting processes in place to become better at running our regulatory program.

The CDRH is actually quite large, and there are pockets that have good practice and pockets that don't. And so when we go through and identify problems, problems are not necessarily all across the board, but processes that we put on to make sure everybody comes up to, you know, similar processes that are good practices for everybody.

And clearly best practices apply to everybody, and everybody tries to incorporate them. So yes, we have looked internally. We know areas that are there are groups that have good processes, and we tend to propagate those to the entire Center as much as we can and when they are possible to do. What was the second question.

UNIDENTIFIED SPEAKER: The unregulated tests.

DR. GUTIERREZ: Yeah. The laboratory developed tests, I'm going to go into Washington speak. And yes, we had a meeting last year for in vitro diagnostics. There are really two paths to market: One is submitting to the FDA and being regulated through the FDA. The other one is for laboratories to develop their own test and put them out in the market, and now with ability to ship samples across the nation and go through the internet, that clearly is a viable model that competes with the in vitro diagnostics in some areas.

And there has been a perception now for almost 20 years that there are regulatory gaps that need to be dealt with for laboratory developed tests. The Agency had a meeting last year, and we proposed to put a regulatory framework on the table, we said that we were thinking of proposing a way forward, we are still planning on proposing a framework but haven't yet done that yet. It's a process that takes time.

Again, it takes time to go through the whole process, and we're hoping to be part of a solution here of a problem that has been identified, not just by us, but by a lot of people in this area.

MS. CHAMBERS: Again, I'm Joleen Chambers. At my own expense I came from Dallas, Texas to speak today. And I think it's point for the regulators and the industry to know this that when we come, we come for a reason. I'm wearing all brown, 99 percent of me is brown. The tiny bit of me is the yellow that means there is a problem here.

And even now as a patient advocate, I don't feel particularly embraced by either the regulators or the medical device industry. And if we treat medical device industry and what we're doing here much like the aviation industry, we should be intrigued, we should be looking at what happened, and let's improve it. Don't treat me as an outcast. Treat me as somebody that's a partner.

I notice with a lot of medical device and industry meetings, there is a lot of collaboration between industry, or the regulators coming to speak to the industry. I don't see a lot of the industry inviting us, the patient advocates, to come.

When you invite us, give us a scholarship, give us a place to stay. We would like to come and partner with you. And think about that, when you're talking about us giving us the lip service of being stakeholders. We're really not. In the medical device advisory committees, we're not stakeholders. There is somebody that OSHI picks to be in that position. That person does not correspond with me or with other consumer groups I'm involved in.

And I wanted to say one thing about the meetings in Dallas. We had a lot of women who are of my certain age who talked about surgical mesh, and they've had some real successes with surgical mesh, and it was very satisfying today, here, today to see people are still talking about dental amalgam, and hopefully there is going to be some change with that.

I hope with the implanted devices that I'm speaking of, and I'm speaking particularly the way my brother and the orthopedic devices, we need traction, we need the public to be aware of what's going on to realize when I come here with my yellow to say there is a problem.

It's not that I ‑‑ my brother believed in the medical device industry, and I think the industry has to realize this. Twice he went to the same surgeon that was the designer for this care. And now the Mayo Clinic and the doctor designer both said we won't give you anything but federally mandated care. And his insurance company has backed out.

So when you talk about your investment and how you touch people, this was not a very caring touch, and my brother has not sued anybody, but he is financially in really bad straits because of this. And this impacts his children and their children.

So just know you are touching human beings and the way that you touch them. The other thing is that some of these smaller manufacturers that are saying it's so important that, you know, you get recognition for what you are doing, look at some of the bigger companies and how you're being represented.

Now, AARP, which I'm a consumer member of, this is on page 11 of this month's AARP magazine, they are not involved as far as I can tell at FDA in approving these implanted joints, but they are involved with their magazine accepting this kind of ad that says Johnson & Johnson DePuy. These are not the ones that failed, you can ‑‑ there is a very young man ‑‑ appears very young and very virile who got a hip implant and he's riding bicycles competitively. What does this say? This is not who they're putting in hips generally for, but they are trying to get much younger people to think that these joint replacements are an alternative for them when in fact they are only planned to work for about 15 years and there is no warranty on any of these products.

And it says real life tested. What does that mean? Real life tested? That means you're the guinea pig. So just be aware that some of these consumer groups that say they are representing you as a consumer might not and that the industry itself is using pretty aggressive tactics to get people into having these hip and joint implants when in fact our medicare system really can't afford to keep doing this and have so many revisions. So please get involved and pay attention when someone says there is a problem. We're not the problem. Okay? We're just trying to raise our hands and say let's get in this together, and let's help figure this out.

And next time if we can get a room that doesn't have so many pillars, we might have a ‑‑ I was sitting in the second row behind a tall person, and I missed out on a lot in the second row, so whoever is planning the meetings, that will be helpful next time. I'll be there next time. Thank you.

DR. SHUREN: Thank you. I will say regarding patient perspective and input, we've actually been working with dozens of patient advocacy groups under the auspices of NORD, the National Organization of Rare Disorders, the National Health Council about mechanisms and opportunities for great engagement by the community. So that is underway, and there are some proposals they're going to be sending our way fairly shortly.

This also factored into a guidance we put out a few of weeks ago. You heard about setting the right line and making benefit/risk determinations. Because no device is ever going to be risk free. We know that. We know that, but setting where that balance is and that benefits outweighing the risks and what factors you take into account is still critical in decision making. What we decided to do is to give the public a look under the hood, so we put out draft guidance that says here are the factors we would use in making that kind of a decision.

I will tell you I've been at the Agency on and off for over a decade; nothing like this exists for any other center. It's the first time the Agency has done it with an intent that we will be consistent in our approach and that we take these factors into account; and secondly, we document them in the record.

All of our reviewers will be filling out a template to answer those questions. It allows for a dialogue within the Center on those points. It allows for a dialogue also with companies on those factors.

And one of those is taking into considerations patients' perspective on risk because ultimately it is how much risk you want to tolerate isn't just an issue for the reviewer; it is for the patient who is going to get that device. And we need to do a better job factoring that in. That is one of the issues that we put front and center on the table in the benefit/risk determination guidance, which is out for comments. So I encourage you to please take a look ‑‑

Actually, let me ask how many people have read that guidance. Not a lot of people. So I encourage you, look at that. Look at all of the guidances we've put out, and please provide input because that's the best way we're going to put out the right policies.

So that one is out there, and as I mentioned, many more guidances to come. So keep your Kindle ready. We're seeing if we can have them downloaded, maybe get them on a Kindle, people will look through them.

Go ahead.

MR. SILVERMAN: I've had the opportunity to hear you talk on a number of occasions about your brother's experience, and I'm sorry about the hardship that he's dealt with, but I think it's an opportune moment to talk about our orientation. I want to be very clear because I think that you raise important points about the FDA's relationship with the medical device industry. My orientation and the orientation of everyone with whom I work in CDRH is a patient-based orientation.

And I say this in all sincerity. We come to work every day and attempt to do our best to promote patient health. We do it on the premarket side through supporting the review of often lifesaving technologies. And in my case we do it on the postmarket side by holding the manufacturers and marketers of those technologies accountable for requirements with ‑‑ I should say for compliance with good manufacturing practices, with appropriate labeling and with appropriate advertising and promotion.

There are many ways to enhance patient well-being. We don't see our most viable option as pitting ourselves in opposition to industry because, as Jeff said, we believe that there can often be a win-win outcome when we facilitate appropriate device innovation, production, and distribution.

Where appropriate, we do take a more hard line, more traditional enforcement-based approach and will continue to do so, but in terms of hearing messages from the patient and healthcare community, I have to say having spent time in other parts of the Agency, I think that the work that's going on within CDRH is unprecedented.

There is no other center that has done what CDRH has done to provide outreach and venues for input, not just from device stakeholders but from patient and practitioner groups as well. And I think that this meeting, the meeting in Dallas, the meeting in Orlando, the meeting in Boston, the meeting in Minnesota, and the meetings that will come are very strong evidence of that commitment to hearing from all stakeholders.

DR. SHUREN: And I'll throw one example. You've mentioned surgical mesh was raised at the meetings. Well, concerns were raised by healthcare professional organizations and by patients, and we looked into it, and folks probably know we called an advisory panel meeting specifically on that for surgical mesh and pelvic organ prolapse and also talked about neurological slings as well.

I blew you off the last time. Sorry.

MR. DHUWALIA: Yes, you did. Thank you. I'm Jack Dhuwalia from JD Consulting, and I have been threatened something terrible is going to happen to me if I use the word mercury, so I won't.

I would like to ask Dr. Shuren about two different things. I see difference in those. One is a premarket submission process, approval process, clearance process, and one is once it's marketed for ten years, nine years, whatever, the product goes into the market and now the quality system, the surveillance people take over.

I see some differentiation between the two, so with that background, my question is: How much ‑‑ what is FDA's opinion about when does the device start giving problems in a number of years after it has been submitted after it has been released, approved, cleared? In general. A very general question. Is that quickly, or is it a year, is it five years? What do you folks see?

DR. SHUREN: So we look to take best advantage of the information that we learned in a postmarket setting to better understand what the risk/benefit profile is of a device on the market, and also about how that product is being made and there is a continuing to be made in a high quality form.

We've actually been going through some internal looks about shall we be making changes in the organization to facilitate that stream of dialogue and information flow between the premarket and postmarket side.

In fact, for our priorities, we have four strategic priorities. One of them is on total product life cycle and integrating information across the life cycle. A second one is actually facilitating innovation. There was a comment this morning that innovation has to start at the leadership level.

Well, when I came in the door, I made that one of our four top priorities. In fact, innovation was something CDRH was talking about, about a year before the rest of Washington caught on to it. So we take that very seriously. It's part of our mission. We protect public health, ensure devices are safe and effective; we promote public health by facilitating innovation.

Your point about, also, the postmarket side and what we do and incorporate is actually an issue that got raised in the IOM report. So there has been a lot of focus about their recommending getting rid of the 510(k) program, and you know, we have said publicly we do not intend to scrap the program. We are making some changes to improve it, we're open to other ideas, but we do think it provides value.

But they also said maybe you should be looking at the postmarket side and how you can actually integrate that with premarket. And here is something we should be having a dialogue about. What should the postmarket world look like in the U.S.? Because you could think about if we had a very robust system here, the following things happen.

One is when there are problems, you can identify them more quickly, and if you get on top of them more quickly, you get away from the big news splashes, everyone focusing on that would really get down to what the issues are. And if there are appropriate mitigations, get them in place, deal and move on, and get that information out there.

The other is getting better information we can use to inform premarket review and maybe reduce the evidentiary burden on the premarket side, but that would take this better integration and having the right systems in place, postmarket, to do so.

MR. DHUWALIA: Actually, I see that as a crystal ball, premarket, you're looking at today in trying to predict what's going to happen here two years, five years down the road. And for a reviewer, I'm imagining it must be ‑‑ they are between a rock and a hard place that if they are approved, they release the product and a year down the road there is a problem, it doesn't look very good, does it?

DR. GUTIERREZ: Let me address that. Actually my office was created in 2003 as a pilot program in which we brought the postmarket and the premarket together to see whether regulating in a more holistic form entire product life cycle worked and whether we could gain some experience in doing so.

And I think overall it has been a pilot that has worked. We actually can clear or prove devices, and then the same people sometimes, some people actually are not premarket reviewers but are part of the team, some do both, go back and actually look for post-market problems.

And unlike what the fear is that a reviewer that reviews something and cleared it, that they would feel guilty or that they would feel bad or that they would look the other way if there was a problem because they didn't want to be faulted with actually not having done a good job in the premarket, we find that actually not to be the case most of the time.

Because reviewers are people who are extremely committed, who are committed to making sure that the devices that are out there are safe and effective and they take ownership of them, they know them well and they can usually identify the problems early on when something begins to go wrong, and actually it's one of the strengths that our postmarket people understand the devices extremely well and understand what kind of issues they see over and over. And it translates later on what kind of things they ask in the premarket.

MR. DHUWALIA: I have a follow-up question on the postmarket. MDR process has been around for a long time. It seems that it's a very large piece of information going to the FDA. And I have a suggestion and a question. The question is how can it be made more efficient.

And my comment is that is it possible to have a category differentiating between a serious problem that is happening in the field, and then potential problems could be in another file. So you're looking at ‑‑ you're focused on deaths and serious injuries that have happened and the rest would be somewhere else. So I feel that maybe you might be able to focus on real problems.

Nobody wants to take that?

DR. SHUREN: We're negotiating over this.

MR. SILVERMAN: Exactly. If anybody in the crowd is an attorney, I could use some representation.

Okay. So I'll talk briefly about MDRs. We ‑‑ the MDR program is administered by CDRH's Office of Surveillance and Biometrics, but within the Office of Compliance we rely on it very heavily. It's a critical information source. In terms of modifications, I'll kind of speak at a general level, and I'll talk about how we rely on it. I think that there is ‑‑

MR. DHUWALIA: What is an MDR?

MR. SILVERMAN: Oh, sorry. It is a medical device report which is a report that is required to be provided by manufacturers of medical devices when information comes to them about problems associated with their devices, and then as part of a larger medical device reporting program, we also receive reports from other sources such as healthcare providers and patients.

What is important to note is that the threshold for submitting a medical device report is, for example, any death or serious injury associated with the device. So it would be inaccurate, I think, to say that the submission of a medical device report means that there has been a device quality problem. It means that there was an incident and therefore there was information about that incident submitted to the Agency.

The Office of Surveillance and Biometrics aggregates these reports and has, I think, a very deep analytical expertise, and when they see signals, they develop those signals and in some cases they feed the signals to premarket reviewers to factor in what they're seeing into the premarket evaluation of products.

And they also send their signal to the Office of Compliance. From our perspective, that's incredibly helpful because we struggle with applying our compliance resources in areas that represent the most immediate and significant risk to patients.

So when we get these kinds of reports, especially where we're seeing signals that are associated with complex or lifesaving devices or even more everyday devices but where there is significant injury, it helps us to calibrate where we focus our effort.

To your point, inherent in the medical device reporting construct is a differentiation between information about deaths or serious injuries associated with a device and information about defects, if they were to recur, that could result in deaths and serious injury. So some of that differentiation already occurs, and then within the group that's responsible for monitoring these devices, I know they are constantly looking to refine their data gathering and analytical capabilities.

And one additional point, I think related, is that we've been doing a lot of work as a Center with the unique device identification system, where each individual device is tracked as it moves through commerce.

And I think that when we have those types of identifiers in place, it will further enhance our ability to understand how devices are performing in the marketplace and then to use that information to inform our pre- and postmarket regulation.

MR. DHUWALIA: There is one box, the same box applies to both date of injury occur and is it possible for it to occur in the future. Same box. To me, it aggregates everything in one.

No. No. I'm asking. That's what I meant.

MR. SILVERMAN: No. No. I do think that in terms of how we review the information ‑‑


MR. SILVERMAN: How we evaluate there is different.

MR. DHUWALIA: Thank you.

MR. MULTS: Hi there. My name is David Mults. I work in device development for drug delivery systems for a pharmaceutical company. And my question actually relates to human factors.

One of the things that we do, we do interact with a lot of different centers because we're doing a lot of combination products and definitely appreciate the leadership that CDRH has provided on a number of fronts, human factors being one of them.

And with the emergence of more patient self-administration of therapeutics and patient interpretation of diagnostic results, as with the two earlier, there is a lot more importance of human factors in the safety and efficacy of devices and therapeutics and diagnostics.

And so my question is: You've got a small staff of human factors experts at CDRH, and you're increasingly being called upon to work with CDER and CBER and probably other centers as well to evaluate human factors.

Is there some sort of mechanism that is available to create a broader remit for that group and create a way to think about human factors and the impact that we as designers and developers have on the products in the way they are being handled by users in a much more holistic fashion so that it's not being treated differently by different centers and that other centers who may not actually be even really aware of human factors engineering as a discipline and as a science, that they can use that as something to help guide their thinking and approvals of the products they deal with?

DR. SHUREN: So we completely agree with you, by the way, on how human factors is becoming increasingly more important as a field with devices and, in fact, when we did a look back on adverse events at MDRs, we were finding that I think it was almost a third of the cases where we were true ‑‑ finding there was a problem with the device ultimately turned out to be a human factors issue.

It wasn't as much an issue with the person who used it. There were design issues in that technology, that then ‑‑ and for folks, human factors usability is that interface between man and machine, understanding how people use a technology.

And ultimately you want to design a technology that takes into account how people will use it so you minimize the likelihood of a problem occurring and that they can effectively use that technology, and as technologies move into the home, need to factor in it's not a healthcare professional who is using it, it's a patient.

One of Commissioner Hamburg's efforts recently was to bring in a deputy commissioner for medical products and tobacco to actually help on these issues of better coordination, particularly with the medical product centers on things like combination products or delivery devices. And I think that will start helping in terms of education on some of these disciplines that may be more well-known to one center but not as well understood by another.

And we, as you know, just put out draft guidance on human factors. We'll finalize them in the next few months. We're also going to make some changes in adverse event reporting to try to better capture human factors issues, and in fact, we recently set up a laboratory on human factors at CDRH as well, and then more engagement with the other centers, I think coordinated with the new deputy commissioner.

MS. TOMKINS: Hi. Kim Tomkins. I'm with the medical device industry at a start-up down in Southern California. I would like to thank all of you for being here. I know this is not an easy job to get up here in front of all of us, and I especially appreciate you, Dr. ‑‑ Mr. Silverman stating that we're all here for ‑‑ to try to get the most safe and effective devices out on the market. And I think we all agree with that.

I'm especially interested in the concepts of consistency and predictability especially in a collaborative way. The reason I'm standing up here is to really kind of follow up on a comment that you made earlier about if you want to change the requirements for a device class, that it has to go to an internal counsel.

So I guess my question is: How is that communicated back to industry? And to follow-up, if decisions similar to that, if there is any indication that those kinds of decisions are being made at the branch level, is there any visibility to that by the council so that you can be involved in that process?

DR. SHUREN: So two things. One is for those council decisions on whether or not we would change what we'd asked for, clinical data across a type of device, you would ask, how would we communicate that?

In two ways. In the past you would learn about it either because we put out draft guidance or you learned about it when you came and you spoke to the Agency about that particular device. And it may even be when you submit that application and you learn about that change when the application comes in, and you'd find out our expectations have changed and you need to go back and do something else.

In response to those concerns, we have put out an SOP on a new communication tool we call a Notice to Industry letter. And that when we make that kind of a change, first of all it goes up to the council for decision, so council would say, yes, we should do it. And then the next is, is this a change we need to make right away? You know, we have big safety concern, you couldn't let this device go on the market unless you address it. It's important enough. Then we would notify industry with this letter. You can think about it like a mini guidance.

It says here is the problem. We're going to be asking for other clinical data. Come in and talk to us. You will be notified right away. If it's really within two to three weeks of our making a decision, about three weeks you will know about that change.

If it's something where ‑‑ no, we do not need to make this change now, it would benefit from public input, we would move forward and do a guidance and then not make a change in our policy at that point. That's how we would move forward.

MS. TOMKINS: And in reverse, if those kind of decisions are being made at the branch level, do you have visibility or it's just not being made at the branch level?

DR. SHUREN: So this is across the type of device that's being communicated down to the staff. We are also putting in place a rationing ‑‑ we are requiring of ourselves something we require of you, which is CAPA. And we're starting with our Office of Device Evaluation with a system that if issues get flagged, we see potential problems, we're tracking them, we're assuring there is appropriate intervention, and we're monitoring. That along ‑‑ these would be the kinds of thing we would be looking for as well.

MS. TOMKINS: Thank you.

DR. SHUREN: You're welcome.

DR. GUTIERREZ: We're also putting an SOP into practice that tells the branches already what the expectations are at the different levels when these kind of questions come up.

UNIDENTIFIED SPEAKER: I apologize. I thought that you were finished. I just have a quick yes or no question. I'm wondering when you make your announcement on silver mercury amalgam fillings this year, will people like me be happy with the announcement? Just yes or no. Even a maybe ‑‑ even a "maybe" would be good.

DR. SHUREN: I don't know. I don't know.


DR. SHUREN: I feel like, by the way, I'm up testifying before Congressman Dingell. If any of you have watched, Congressman Dingell only asks yes or no questions, and he sits there and goes, just answer yes or no. And he's asked some questions where, so how much does it cost to do the following. Yes or no. So I feel like I just got a Congressman Dingell.

MR. BUCHER: My name is Ron Bucher, and I lead customer support groups. I've been doing that for the last quarter century and got into this industry in 2006. And you know, I see this struggle to get a balance between safety, efficacy, and innovation.

And I've attended literally dozens and dozens of medical device conferences and speaker events over the past five years, and so I've probably heard hundreds of investors and CEOs and doctors expressing their frustration that we don't have the right balance between those things.

My experience with turnarounds ‑‑ this is a management question and an open-ended question, not a yes or no. My experience with turnaround situations, one of the things that's really important is to change the incentives of the individual employees.

So my question is: What changes have been made and what changes are going to be made in the incentives of all of the CDRH employees with regard to incentives for compensation, for job performance, and for career advancement?

DR. SHUREN: So that is one of the things we talked about a little bit earlier is we're looking at what should be the important things that they are focused on and then to design performance expectations around that. And that goes to incentives, so we're working through that.

A little leery about paying people for certain kinds of ‑‑ it depends on the kind of performance, but that's one of the issues that we're talking about.

But we want to work through all of the different changes we're making and then as part of it saying, okay, if this is what the program is looking like and these are expectations for our people, then aligning performance evaluations in ways that people know this is what's going to be most important, this is how you're rated on, and this will then determine, you know, advancement and other things that come from it, and that's the way to build in the incentives. But we're going through that now over the next few months.

DR. GUTIERREZ: You know, one thing I'd like to let you know that for the most part, most of the people that work at the Agency are extremely committed, and that a lot of these issues are more us setting clear expectations or us setting the correct expectations and getting them there. They want to do it.

They know what's important for public health and study the issues, and they are extremely committed people who typically joined the FDA not for financial reasons. They are not getting paid the highest salaries. So if we do our job and we set expectations correctly, you can expect that we can get them to do the right thing.

DR. SHUREN: And I will say that point of striking it right, as you heard in testimony today, some people think we set the bar too high, some think we set it too low, some say we're doing a good job on safety, some say we're not doing a good job on safety. Welcome to our world.

Striking that right balance is so important but incredibly hard to do. And when asked what will people react to when we come out with an announcement later this year, I don't know because people have different perspectives. It's near impossible to come up with a program that everyone is going to be happy and think that we get right.

What we are trying, though, is to set up a program that does the best job it can and is nimble and adaptable to make changes based upon new experience in emerging technologies because where you set that line will get modified over time, and we need to adjust and do it in a smart way. And that's what we're about.

MR. CAMPOS: Dr. Shuren, thank you. Again, I'm Hugo Campos with the ICD User Group, a group of patients with implantable defibrillators and pacemakers. We're going through a very exciting time in healthcare as we transition from a paternalistic model into more a participatory model in which patients are engaged, are asking to be empowered, and are asking to even be equipped to sort of, like, use the e‑patient kind of concept to really take care of themselves and step up. And we are an untapped resource.

I realize the FDA is ‑‑ that's what we hear: The FDA is strapped for resources. And there's an incredible amount of people like me who are interested in participating and engaging in my own care. My question is exactly about this.

What is ‑‑ what is the FDA doing or particularly the Center for Device and Radiological Health doing to equip and empower people like me and, again, sort of in the context of data access to these silo networks that hold our data, all of these things, all I'm asking is to let me help myself. So that's my question. Thank you.

DR. SHUREN: It's a great question because patients are becoming increasingly more savvy and involved in their own health, and that's great, and we need to do what we can to help them have the tools and have the data they need to make smart decisions.

We're trying to do what we can with the data that's in our possession, and that's why I think you're seeing the whole transparency initiative from the Agency. Still work in progress, but for what we have, we're trying to put more and more out there and in a usable fashion. We have put up on our website even a tool to make it easier for the public to start bringing in data on different devices. We call it experience adverse events.

Then comes a question about what happens when the data is owned by someone else, if you will, collected by someone else. And that's where we have less of the ability to impose, but we are looking for ways to facilitate, and things like the technologies that will allow patients to get access to information and make better-informed decisions.

I think you can see that reflected in a policy we put out recently on mobile applications and those that would be a device we are calling mobile medical apps where we try to strike a right balance between those types of applications, that maybe it's a medical device, but we don't need to put ‑‑ impose a lot of oversight and requirements on to let a lot of things innovate, but where those things are much more like traditional devices to assure that they are truly are safe and effective.

And that's one of the places where we're working, trying to make sure the technologies are out there to enable ‑‑ to help patients.

And the next thing is something I'm going to take back to our people about is there more we can do about making it easier to get information about you, that's collected about you, available to you.

MR. CAMPOS: If I may ask just a quick follow-up question regarding data ownership. I obviously feel that the data that is collected by my implantable device and transmitted over network to Minneapolis and stored in servers over there is my data. That is not what medical device industry sees as it is acting ‑‑ is technically apparent. It's in a gray zone. I don't even understand it. So maybe you can help clarify for me: Who owns this?

DR. SHUREN: Some of that goes beyond our purview, but I'll tell you as a patient myself, I view the data on me, it's my data about me. So the point you raise is something we're going to take and talk about at the Center.

MR. CAMPOS: Thank you.

MR. BILLIG: Mike Billig from Experien Group. We all appreciate you coming out and having this dialogue. I think it's very helpful. I think it gives a lot of ability to make things better and improve on what we're doing together.

I've been doing this since '73, so I've been in pre-amendment days and have seen a lot of things happen over the years working with FDA. I think we're at a juncture right now where there is a lot of opportunity and challenges, call it what you do, but I think two areas I'm finding quite difficult these days has to do more with the IDE process and the statistical review.

And I know you've had problems with your reviewers and you have a very ‑‑ unfortunately a turnover that you want to improve on. And the statistical area is one of the real difficult areas, certainly, because that's an important area making sure that the studies are well designed and you get the proper endpoints and you get the proper results and we put the right product on the market. So that's one area I'd like you to comment on.

The other one has to do with the process that I've talked about before with you is the de novo process. And I know that's something we've all recognized as deficient, needs to be improved, much more so than, I think, most of the areas that you're working on today. And I think it's also an area that can show a lot of opportunity for future products because there is a lot of those low risk products are able to bring to market if in fact we could get a process where you didn't have a direct predicate but you have an ability to bring that forward. Thank you.

DR. SHUREN: So for de novo, we will be putting out in the next few weeks, a draft guidance to streamline that process, and we think that will get de novo back on track. It will be out for public comments, so critical folks weigh in to let us know if we got it right or not.

And you know, based upon feedback, if there are changes to make, we'll move forward and make appropriate changes to the policy. But we consider that a high priority too. And like I mentioned, the next few weeks we'll have that out.

Regarding our statisticians, I actually think we have excellent statisticians at CDRH, and I actually view our people there as some of the leaders in statistical analysis. They're doing some amazing work on developing innovative statistical methods to try to, if you will, get more ‑‑ to turn lemons into lemonade, in some respects, and to get the most out of the data that's out there.

In the device arena, unlike some of our other products, we deal with what I call "dirty data." It can be very challenging to set up sometimes for clinical study, where you can control a lot of the biases there because if you get an implantable device, it's very hard, you know, in some cases for someone not to know that they have something put in their body. We're used to that all the time, and it's forced our statisticians to think about, then, what do you do in those circumstances so you can make the most of what you get and have data you can really rely on and make a well-informed decision.

It's why we have a large cadre of epidemiologists, so that we can actually rely on real world experience from observational data, where sometimes in the Center, people sort of put that aside, we will use that to a lot greater extent. So I think our statisticians actually do a very good job.

What we need to do is make sure we have the right policies in place. And one of the issues we have that comes up with clinical trials we think is so important to deal with is to set up the grounds where those studies can occur earlier in the device development process than they have before.

If we can bring clinical studies back here to the U.S. and start them here earlier or first, then we'll keep the technologies here in the U.S.

So, again, in the next few weeks, again, watch the websites, look at news reports. There will be much to read. We will be putting out new policy on early feasibility studies. And that includes first in human studies. For circumstances where they can start earlier and opportunities where you can make changes to the device and not have to come back to the FDA first on that protocol, we'll try to take it into account beforehand. So stay tuned.

DR. TAYLOR: Dr. Shuren, my name is Scott Taylor. I'm a general dentist. I practice in Morro Bay, California. I just heard a murmur.

I want to first of all let all of you know that I'm glad I came today, and I had no idea there were so many people involved with making medical devices and that you are all were putting so much time and energy and emotion and money into trying to develop these products. And there are days where I'm trying to run a solvent dental office, and I wish I would have opened up a coffee shop instead. And honestly, now that I'm seeing your lot, I'm glad I'm a dentist.

DR. SHUREN: I wish I had opened a coffee shop.

THE WITNESS: Anyway, my point is going to be short. I'm looking forward to the FDA's decision later this year, and I'm hoping when you said earlier you weren't sure what your response would be, I hope that means a decision is still open.

And I don't have a question as much as I have a request, and I would just ask you to consider ‑‑ well, first I want to let you know I realize it's difficult to draw a relationship between some of the personal stories that we've heard today that some people feel mercury toxicity has played, you know, in, you know, that they feel there is a direct causal relationship between mercury toxicity and some other their difficulties that they have had, you know, chronic inflammatory diseases, other neurological things that are going on.

I've had mercury fillings in my mouth for many years, and I have a robust, healthy body, and I tend to have a genetic predisposition to metabolizing and excreting mercury well.

And so I hope we won't try to draw a relationship between whether or not it causes disease but rather whether amalgam filling emit unacceptable levels of mercury into our bodies. That's our only ‑‑ my only request. Thank you.

DR. SHUREN: Thank you.

UNIDENTIFIED SPEAKER: Thanks again for giving me the opportunity to speak earlier. I have a general question that covers the regulatory compliance arena for IVDs.

And I want to use the Canadian medical device regulation with respect to low to moderate risk IVDs in regard to the use of a certified quality system and self attestation root for licensing IVD medical devices. So this is somewhere between the CE marking for self attestation for low risk medical devices and what the FDA does in terms of reviewing 510(k) submissions.

And is there any thought within CDRH about rewarding companies that have strongly compliant quality systems? And I notice there are regional directors here in the Office of Compliance sitting just below me.

I've never met them, but you know, I'm sure they might have ‑‑

So it's one thing to get certified to ISO 1345, which we've been able to accomplish without non-conformities. Is some avenue of this kind a possibility in the in between the medical device industry and particularly IVD medical devices?

MR. SILVERMAN: Well your question is incredibly timely, so thank you. I'll give you some FDA paraphernalia after the conference, notepads or maybe a carryall bag, something like that.

There are a couple of points I'll make by way of response. First of all, we view the steps we are taking with respect to ISO 13485 as part of a progression towards supporting a single audit initiative. So one of the things that we recognize is that as we operate in a rapidly and increasing global marketplace, FDA can't be everywhere that we would like to be.

Our capacity to inspect firms outside of the United States at this point is something like on the order of once every nine years for firms located outside of the United States. That's an unacceptable model, and in the resource-strapped times we're operating, we're not going to get anything close to the resources that we would need to make significant improvements in that area.

Although for those of you who may be speaking to your congressmen, we'd love to have additional appropriate resources. But the reality is we're going to have to do more to partner with foreign regulators and trusted third parties and find methodologies to rely on the information that they are providing based on what they're seeing with inspection models that may go beyond ISO 1345, but don't necessarily work in lockstep with our quality system regulation.

Additionally, one of the initiatives that I have been heavily involved in over the last year, this is actually an initiative that Jeff was at the forefront of, was a champion for, is working with industry to identify what are best quality practices and to understand how device manufacturers can incorporate best manufacturing practices throughout their operation, because what we have found is that firms that are quality leaders realize kind of bottom-line profit benefits that go beyond avoiding FDA enforcement.

They are able to get their products to market more quickly, they are able to keep their products in the marketplace more effectively, they have enhanced customer loyalty. And so one way to really drive quality in the market place is to have a dialogue and a shared understanding between the Agency and industry about what quality looks like, to ask industry what it can do as a collaborative unit to implement quality practices across manufacturers, and then also to look inward at our current regulatory construct to ask whether there are practices that we apply today that have the unintentional effect of preventing firms from implementing best quality practices. If we are applying, for example, a very specific and inflexible construct. And what that means is that firms feel uncomfortable trying to find new ways to enhance product quality, that's a bad outcome for industry, it's a bad outcome for patients, it's a bad outcome for us.

And so we have hope, to have in this spirit of tremendous information from CDRH a report out by the end of the year on the work that we've done so far on best quality practices. And it's going to be an ongoing initiative.

DR. GUTIERREZ: And a more different perspectives focus to a certain extent. We are looking to see how we can actually also promote best practices in the premarket, so that we actually let those firms that give us high quality submissions, we somehow get those submissions through either in an expedited form or get a different type of look.

And so the ‑‑ my boss here is pushing me to set up another initiative which is we're going to be triaging our submissions as they come in, our 510(k)s as a pilot project in OIVD sometime next year. What that triage will look like, we haven't settled yet, but one of the hopes is that quality of submission will be part of that triage, so we encourage companies to give us quality submissions.

UNIDENTIFIED SPEAKER: I do have a follow-up question about dental amalgam. And given that you're coming to a decision towards the end of the year, my question is ‑‑ and I have a background of many decades working in materials and material science.

And I know Dr. Eccles mentioned, dental amalgam is not really an alloy; some people consider it a solid emulsion. And it can contain up to seven different metals: mercury, copper, silver, tin, and sometimes zinc, palladium or indium. And there is numerous studies that show the amount of mercury released depends heavily on those formulations. And sometimes, even if they use the same formulation, it can depend on the size and shape of the particles.

And Boyd Haley did a very controlled study in a controlled environment ‑‑ Boyd Haley is a professor emeritus in chemistry from the University of Kentucky ‑‑ and he found that variation as high as a factor of four depending both on the dentist who placed the filling and on the manufacturer. And there was no clear trend, and some individual dentists had large variation even when they were using the same formulation.

So my question is: Will the decision that the FDA is coming to, will they consider all of those various formulations? One, will it require manufacturers to report how much mercury is released based on the formulations?

And, finally, how will it apply to future formulations? If the FDA determined every formulation on the market today was safe, who is to stop someone tomorrow from developing a different alloy not being required to report the amount of mercury released and it's not really regulated.

DR. SHUREN: I always hate to do this. As you know, we're looking to put out an announcement by the end of the year. I almost feel like there should be a wax figurine of me with a little ripcord on the back, and you can just pull it to get the same answer. I apologize. These will be the last three. If we can keep it very, very, very brief.

DR. ZACHARIAN: I am Dr. Andrew Zacharian. I'm a dentist in San Diego. I'm also a former dental researcher at IDR. I wanted to know how your administration will differ from past groups because I want to know what safeguards you've used to guarantee that the consensus that you come to at the end to make a decision is fairly based because a lot of dental people are trained that in this subject of dental amalgam, mercury is safe, and when you rely on individuals from one group, you don't necessarily get the consensus.

I have a second little B question. Will you be saying anything ‑‑ making a decision about mercury thimerosal?

DR. SHUREN: Mercury thimerosal, no, we're talking about dental amalgam. We're not talking about mercury that may be used in vaccines. It's a different center.

Our decisions: we have an open policy on people to talk. We have very open frank dialogues. We also put in place a process that if someone differs from a decision that we're making ‑‑ this is within the Center ‑‑ they can actually go through that process to sort of raise the issue up to assure that their perspective is taken into consideration, so we built that into our program as well.

DR. ZACHARIAN: You're inviting people from both sides of the issue.

DR. SHUREN: Oh, yes. Absolutely.

UNIDENTIFIED SPEAKER: Hi, Dr. Shuren. One more torturous question. I think I forgot to mention that I have radiation-induced cardiac disease, which has required a new heart valve, a ring on my tricuspid, and just a gurgling, whatever, mitral valve.

I just received my fifth pacemaker in July, and part of the reason they thought I had so many is I'm allergic to titanium and some of the things that were in the pacemaker.

And I had to do some evil integrated medicine, some laser therapy to get my body to accept it. So my question is with whatever your answer is at the end of the year, could it be possible that we would have a required allergy test or a heavy metal test like the MELISA test that they do with AstraZeneca in Europe, so people getting a hip replacement or dental amalgam or whatever, you know, when I had dental amalgam and a pacemaker, my body was having an oxidation problem.

So I just wanted to see if maybe possibly we could have part of the protocol be that we get tested before we have these things if we're going to have them.

DR. SHUREN: All right. Last question.

UNIDENTIFIED SPEAKER: It's more of a comment but also refers to this upcoming announcement by the end of the year. And earlier this week I attended a city council meeting in Southern California, and although we have one side of people that say that mercury is really, really bad and the scientific evidence is obvious and I've been around the world for the past 11 years and that really is confirmed, and the other side who are mercury-using dentists who are still trying to keep this in the marketplace.

My question is: Will you be able to seriously look at the science and evaluate it so the strong-arm tactics of mercury-using dentists will be eliminated and you don't go on the side of just an industry point because they are the only industry in the world, as a United Nations stakeholder in this upcoming mercury treaty, I am and they are the only industry trying to protect mercury, the only one in the world.

Everyone else, batteries, cell batteries, lights, nobody else is fighting to keep mercury in play, except the dental industry. And I do hope you evaluate on the science and not on the industry that says it's safe when they've never proved to me it was. Thank you so much.

DR. SHUREN: Well, thank you. Thanks to all of you for coming today. We really appreciate the input and the open dialogue. So enjoy the rest of the day.

(Whereupon, at 12:09 p.m., the meeting was concluded.)


This is to certify that the attached proceedings in the matter of:


September 22, 2011

San Francisco , California

were held as herein appears, and that this is the original transcription thereof for the files of the Food and Drug Administration, Center for Devices and Radiological Health, Medical Devices Advisory Committee. ____________________________


Official Reporter

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