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Medical Devices

Transcript for Town Hall Discussion With the Director of CDRH and Other Senior Center Management, June 22, 2010




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June 22, 2010

8:00 a.m.

Hilton Boston/Woburn

2 Forbes Road

Woburn , MA 01801



MARKHAM LUKE, M.D. Office of Device Evaluation, CDRH

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

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


PAM WEAGRAFF, Quintiles Consulting, representing MassMEDIC


MAHA SALLAM, VuEssence, Inc.

ZVI LADIN, Boston MedTech Advisors


PETER STEIGER, Optasia Medical

MATTHEW PRICE, Centurion Medical Products



CHAS BURR, Regis College


ERIC BORNSTEIN, D.M.D., Nomir Medical Technologies





ARTHUR RANKIS, AA Rankis & Associates, Inc.

JOEL WEINSTEIN, BioSphere Medical Inc.

NATHANIEL SIMS, M.D., Massachusetts General Hospital


SHEILA HEMEON-HEYER, Boston Scientific Corp.


ERIC KUPFERBERG, Northeastern University

BEVERLY LORELL, M.D., King & Spalding


ART RANKIS, AA Rankis & Associates, Inc.

MARK LEAHEY, Medical Device Manufacturers Association

PAM WEAGRAFF, Quintiles Consulting

TIM MOON, Sparta Systems

MARIA GARRIGAN, Bayer Healthcare Pharmaceuticals

JOHN NEUGEBAUER, Koning Corporation

BRIAN SHOEMAKER, ShoeBar Associates

PETER OHANIAN, Philips Healthcare


MAHA SALLAM, VuEssence, Inc.

BRENDAN O'LEARY, Prism Ventures






OPENING REMARKS - Jeffrey Shuren, M.D., J.D. 5


Pam Weagraff 8

Richard Eaton 12

Maha Sallam   15

Zvi Ladin 19

William Christianson 21

Peter Steiger 23

Matthew Price 27

Gerald Brecher 31

Barry Sands 34

Chas Burr 42

Konstantin Goranov 45

Eric Bornstein, D.M.D. 48

Eric Ankerud 52

Paul LaViolette 57

Dan Goldsmith 61

Randel Richner 66

Arthur Rankis 69

Joel Weinstein 73

Nathaniel Sims, M.D. 77

Jeff Secunda 80

Sheila Hemeon-Heyer 84



Eric Kupferberg 89

Beverly Lorell, M.D. 93

Paul Schrader 96

Art Rankis 100

Mark Leahey 110

Pam Weagraff 115

Tim Moon 119

Maria Garrigan 119

John Neugebauer 120

Brian Shoemaker 124

Peter Ohanian 126

Rosina Robinson 127

Maha Sallam 128

Pam Weagraff 130

Brendan O'Leary 134

Konstantin Goranov 136

Tom Sorreno 137

Bob Zoletti 139

ADJOURNMENT - Jeffrey Shuren, M.D., J.D. 142


(8:00 a.m.)

DR. SHUREN: Can everyone hear me? That's good.

Again, good morning. It is a pleasure to be back in Boston, a place I called home for several years. In fact, I married a woman from Watertown, so I am tied to the area forever after.

I'd like to take a moment to introduce my colleagues from the FDA Center for Devices and Radiological Health, CDRH, and I'll ask them to stand when I call their name. They're going to help me address your comments and questions.

First, Dr. Markham Luke, Deputy Director for Clinical Office of Device Evaluation; Dr. Alberto Gutierrez, Director of the Office of In Vitro Diagnostics; and Mr. Steven Silverman, Senior Advisor, Office of Compliance.

We're happy to be listening to you today. This is our second town hall meeting. As many of you know, we held our first meeting in Minneapolis in May. More than 500 people attended that meeting. We had over 600 registered for today.

I think this kind of Center public interaction is unprecedented and, at least, for us, invaluable. It provides us with insights on how we can do our jobs more effectively and creatively, and I hope you find today's town hall useful.

I think that you, the industry, the healthcare community, patients, and other members of the public impacted by our actions can view these town hall meetings as a clear indication of how we will continue our communications with you, open, public and transparent.

We've heard two big themes consistently, not only at the Minneapolis town hall meeting but at other public meetings that we've held this year. The need for predictability has been both the central theme in almost all of the presentations and discussions at recent public forums. I've heard a clear message from you. The FDA needs to provide industry with clear, predictable pathways to approval and clearance. I can tell you that we hear you, we agree with you, and we are on it.

Providing clear, predictable pathways to market will also help foster innovation, which is another theme we've been hearing. We agree with you on this front as well. Therefore, as part of our strategic priorities for 2010, we've been looking at concrete steps we can take to be a smarter FDA by adapting a balanced public health approach to assure the safety and effectiveness of devices and to use our enforcement tools wisely while also facilitating innovation and fostering a culture of quality and prevention among industry.

One such step is to make available our experts to help industry solve problems, not just identify them. For example, we've been collaborating with the University of Pennsylvania on open-source software for external infusion pumps that manufacturers can build on or use to benchmark their own products. In fact, we've offered to perform diagnostics on infusion pump software at any stage of development even before the device lands at our doorstep. The intent is to help manufacturers identify problems early in the device development process rather than late in the course during pre-market review.

Also, this Thursday we are holding our first workshop specifically to discuss what the government can do to encourage innovation in medical device development. This meeting will be chaired by members of the Interagency Council on Medical Device Innovation, which is comprised of the FDA, the Centers for Medicare and Medicaid Services, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Department of Defense, and the Defense Advanced Research Projects Agency. What we want from this meeting is your input and ideas on the ways government can minimize or even remove barriers that may hinder the development in medical devices that address unmet public health needs.

I hope that many of you here today are planning to attend or submit comments. We can't identify these needs and work to address them without your help.

This is a new approach for CDRH, but one that falls squarely within the scope of our mission to both protect and promote the public health and one we believe is responsive to what we've heard so far in our dialogue with the public.

Today's agenda is very simple. For the first half of the morning, we're going to have registered speakers come talk to you. We have 21 people who have signed up. They each have five minutes. When you come up, Heather Howell, who has helped coordinate this meeting, will be in the back and she will signal you if you are running out of time. So I ask to please stay on time as a courtesy to others speaking.

We'll then take a very short break, and after that, the session is wide open. Anyone can ask any question or make any statement they want. I would ask if you're going to just make a brief comment, to please keep it brief so that others can talk. But you can ask anything, and to the extent we can answer it, we're here to answer your questions.

With that, let me call the first speaker up to the lectern, Ms. Pam Weagraff. Good morning.

MS. WEAGRAFF: Heather, I'm watching you.

Good morning, everyone. Good morning, Dr. Shuren and other CDRH and FDA officials here. It's a pleasure to greet you in our region.

My name is Pam Weagraff. I'm a principal consultant with Quintiles Consulting and the regulatory advisor to the board of directors of the Massachusetts Medical Device Industry Association -- Industry Council, fondly known as MassMEDIC.

Previously, I've held marketing, regulatory, clinical and quality executive positions in large companies, as well as small early stage startups. In 1993, I had the very great opportunity to serve a fellowship with HEMA, now known as AdvaMed, and during that one year, I valued the opportunity to work very closely with FDA reviewers, FDA branch chiefs, FDA division directors and other FDA personnel, and I've continued this spirit of collaboration with the Agency and industry throughout my career.

I thank you for this opportunity to speak before you, and on behalf of the members, the directors, and officers of MassMEDIC, I'm honored to welcome you to our region again and thank you for your interest in learning more about the FDA programs with respect to the impact that they have on operations of medical device companies.

Mass Medical was founded 14 years ago to create a united voice for the medical device industry in the state and to promote the unique interests of this sector. As you probably know, this state is home to the second largest concentration of medtech industry activity in the nation. Since 1996, MassMEDIC has grown to 400 members from Massachusetts and around the region and has become the largest regional medtech organization in the nation.

MassMEDIC is very proud of its long history of interaction with FDA and CDRH. At the inauguration meeting in 1996, FDA Commissioner David Kessler spoke. Since that time, we have hosted three other FDA commissioners at special forums that were hosted by the late Senator Kennedy. In addition, we have welcomed every CDRH director to our annual FDA update program, and we are especially pleased to extend an invitation for you to join us at our next session on December 1st later this year.

MassMEDIC has also sent representatives to Rockville and now to White Oak to discuss a number of pending regulatory issues, and we have always maintained the closest working relationship with FDA's district office in Stoneham. And it's a pleasure to see Gail and the new acting director of the district office here today.

What I want to do is share some of the comments at a high level of the MassMEDIC member concerns, and these are, from your comments, very likely concerns that you've heard before, but I would like to just scope those out from the perspective of MassMEDIC.

First, to the 510(k) program, MassMEDIC applauds FDA for its review of this very important program. We eagerly await the publication of the Institutes of Medicine analysis. As there is no industry participation in this project, we do ask that medtech company representatives and other stakeholder organizations such as MassMEDIC be given the opportunity to participate in the review and comment on any of the study's findings before changes are implemented in the program.

As we know -- as you know, the 510(k) program has been the workhorse process for over 30 years, clearing thousands of medical devices and providing a steady flow of innovation to improve clinical care of patients. MassMEDIC supports the Center's goal to improve policies and procedures that ensure only safe and effective devices are available to patients and healthcare providers. And while safe and effective devices are paramount, we urge you at the same time to equally challenge proposals that needlessly lengthen the review and approval process and serve only to delay patient and provider access to some of the most innovative technology available today.

Product reviews for Class II and Class III devices are understandably more complex due to the fast pace of technology developments. However, member companies are seeing an emerging pattern in the increasing number of questions and the scope of the questions and requests for additional information. The root cause of this pattern, of course, is unclear to us, but regardless, the impact is one of reduced predictability and transparency during the application review and delays getting new devices into the hands, again, of patients and providers.

MassMEDIC members also report an increasing reluctance on the part of Center management and reviewers to engage in meaningful, thoughtful, and substantive discussion with industry and a reticence to discuss alternative solutions during presubmission meetings if these solutions have not been spelled out in the official meeting request.

MassMEDIC members are struggling as well with shifts in Center interpretation of guidance, shifts that are not being communicated readily to industry. In short, the Agency seems to be in decisional gridlock from a MassMEDIC member perspective.

Through MassMEDIC and forums such as this, many small and early stage medical device companies have had an opportunity to learn more about FDA policies and priorities. MassMEDIC wishes to build upon this relationship and would welcome the opportunity to work with you and your staff as you review the Center's operations.

In closing, I thank you for your kind consideration of these comments and appreciate your willingness to listen.

DR. SHUREN: Thank you. Next, I'd like to ask Mr. Richard Eaton to come to the microphone.

MR. EATON: Good morning. My name is Richard Eaton. I am industry manager at the Medical Imaging and Technology Alliance, called MITA, in Arlington, Virginia. We are the largest imaging trade association. We represent manufacturers of all kinds of imaging products, including radiation therapy, ultrasound, nuclear medicine, medical imaging, informatics devices, MR devices, and a whole panoply of x-ray and CT devices.

I want to thank Dr. Shuren and FDA for holding this meeting. I was at the meeting in Minnesota in May and hope to be at the meeting next -- well, in the next couple of days in Gaithersburg. These meetings are extremely important and they need to continue.

I'm going to echo a few themes you've already heard in past meetings, but I think they bear repeating. First of all, good communication depends critically on transparency. Now, what does "transparency" mean? It means several things. It means the timely communication of existing FDA policies and practices regarding regulatory requirements and their underlying rationales and communication with regard to plan changes in these requirements. It also means communicating the dates when proposed rules, guidances and other critical regulatory documents will be issued, and, if applicable, if they are delayed, what the reasons are for their delay. Thirdly, communicating to applicants on the status of their product submissions on a frequent ongoing basis. All of these are critical to good communication.

Transparency is also important in terms of maintaining an essential smooth and efficient regulatory process. We've had a number of issues which I want to bring to your attention: lack of predictability of regulatory requirements. This can take the shape of either no guidance for a product clearance process or unclear or confusing guidance. CAD is one example.

A second issue: changes in FDA policies and practices that are not made public. An issue here that we have seen is in software data requirements.

Third issue: unduly onerous regulatory requirements which are not connected to a risk assessment of a device. And here, we can point to clinical data requirements.

Now, we have a few proposals which we hope will improve the communication process. Number one, we would ask FDA to issue the CAD guidance. Number two, to reconcile the 2005 general software guidance with the International Standard IEC 62304. Third, to share changes in FDA policies and practices with the public. Fourth, ensure the regulatory requirements for clinical data are based on the risk assessment of the device under review, and also to create FDA communication performance goals.

Finally, in conclusion, I'd like to say that transparency in communication is essential to creating an efficient and streamlined regulatory process. It has been mentioned many times before, but I don't think it can be overemphasized, FDA and stakeholders need to aggressively seek out opportunities to establish, maintain, and enhance two-way communication. We've heard it said in a number of these public meetings that we must find a way to dialogue, and MITA couldn't agree more.

Again, thank you, FDA, for holding this meeting today, and we hope to participate in the future. And MITA stands ready to work with the Agency in facilitating two-way communication.

DR. SHUREN: Thank you.

Ms. Maha Sallam.

MS. SALLAM: Thank you.

Good morning, everyone. My name is Maha Sallam. I'm the founder and president of a start-up medical device company. I also serve on the board of directors of a medium-sized public company in medical devices. I have been involved in industry for about 14 years and have interacted with the FDA extensively over that period of time.

I first want to applaud the recent initiatives undertaken by CDRH and the transparency fostered by this meeting and other recent public meetings, as well as the strategic priorities that are published by the Center show a real commitment to improving the process.

FDA actions greatly impact the industry on several fronts, and perhaps the most important is the review of pending submissions. One of the most important issues that face the industry is uncertainty and unnecessary delays in the review process even when submissions contain extensive supporting data that closely meet FDA guidance. It is clearly important to allocate appropriate time for conducting thorough and careful reviews to ensure safety and efficacy; however, there are several sources of unproductive delays that do not contribute to safety or efficacy but nonetheless have been hampering, delaying the review for the past several years.

In the past, experienced FDA personnel were able to apply fair and balanced assessments in reviewing submissions. However, in recent years, it became clear that the review process is susceptible to strong views and opinions driven by issues that are personally important to some reviewers. Reconciliation between these views and others that may be more balanced within the Agency cause unnecessary delays.

CDRH recently updated the standard operating procedure for resolving internal differences of opinion within the Agency. The procedure is thorough and systematic. However, it does not protect submissions from unnecessary delays because it allows for an interactive process that can be escalated several times.

I would like to urge the Agency to consider streamlining the process by limiting the number of iterations or total time allowed for resolving these differences of opinions. I would also like to urge the Agency to consider resolving all the submissions that have been held up by the delays in this process.

In my experience, FDA reviewers have always been challenged -- FDA reviewers have always been challenging and thorough. It is very common for reviewers to request additional information and ask challenging and probing questions. These requests and questions are part of the normal review process and should be allowed to take their proper course. However, in recent years, the questions raised by the Agency have become increasingly academic, disproportionate in scope to the submission at hand, and often misdirected at a particular submission as a reaction to a well-publicized controversy. I would like to urge the Agency to implement a process for screening the questions raised during submission reviews. This process must ensure that concerns and questions raised are well-founded and the theoretical concerns are balanced with practical issues.

The arguments and data presented in submissions are often complex. In the past, the Agency was more interactive and more open to constructively discussing the issues as they were raised. This gave companies the opportunity to address questions and to clear any misunderstandings in real time, allowing the review to move forward more effectively.

In recent years, the Agency has become increasingly reluctant discussing pending submissions or presenting companies with opportunities to address issues raised during the review. As a result, valuable time is lost through prolonged formal communication cycles typically separated by weeks that lack any substantive progress on submissions. I would like to urge the Center to adopt a mechanism for allowing review teams and companies to utilize informal meetings, teleconferences or e-mails early on in the review process that will allow for discussing questions and concerns that are raised at that stage.

When appropriate, FDA must take definitive actions to change submission standards for new or existing products based on new safety concerns that were not known previously; however, it is not reasonable to pursue such changes when the concerns are speculative or are not fully supported by data. It is also not reasonable to arbitrarily apply these changes across the board when the concerns arise due to a single product or product use.

I would like to urge the Agency to continue to move forward with product reviews based on existing procedures and precedence as it works on updating the processes going forward. When changes in submission review standards are necessary, I urge the Agency to provide informal guidance as soon as possible and to allow for appropriate transition periods, absent any immediate safety concerns.

In closing, I want to emphasize that the various stakeholders understand and support the fact that the Agency's overriding responsibility is to protect public safety. However, as a regulatory agency, the FDA also has a responsibility of basic fairness to the industry it regulates. These responsibilities are by no means incompatible, and I believe the Agency can achieve both.

Thank you very much for the opportunity to speak.

DR. SHUREN: Thank you.

Mr. Zvi Ladin.

MR. LADIN: Good morning, Dr. Shuren, members of FDA Center for Devices and Radiological Health, members of the New England medical device industry.

My name is Zvi Ladin, and I am a principal at Boston MedTech Advisors, a consulting and service company that serves the medical device industry on regulatory clinical studies, reimbursement, and business and market development issues.

I would like to share with you some observations regarding the review process of de novo submissions. The de novo submission route, established in 1997 following the enactment of the FDA Modernization Act, was intended to provide a regulatory route for new technologies whose risk profile does not justify classification into Class III, yet due to a lack of predicate device, could not be classified into Class II and cleared under the 510(k) process.

The de novo regulatory path involves two phases: an initial standard 510(k) process, followed by a review of the risk level of the technology, the de novo review. In FDA's guidance document describing the de novo application, the Agency committed to completing the second phase, the de novo review, within 60 days.

We recently completed a comprehensive analysis of all de novo devices cleared by FDA during the period 1998 through 2009. A total of 54 such products were cleared by FDA during that period, and the review times of all devices were tabulated, including the review time of the initial 510(k) submission and the review time of the de novo application. We have identified a clear change in the review process that took place in 2007.

Until 2007, the average review time of the initial 510(k) application was 196 days, about six months, followed by the de novo review that took 62 days, in line with FDA's 60-day commitment, leading to an average review duration of about eight months. However, devices cleared since 2007 experienced an average initial 510(k) review time of 279 days, about nine months, followed by an average de novo review period of 240 days, eight months. That led to a doubling of the average total review time from 8 to 16 months. Such a long period significantly exceeds FDA's commitment for the duration of the review process of even most panel-track pre-market approval, PMA, devices.

Interestingly, even though the number of devices cleared per year under the de novo track amounts to 0.1 percent of all cleared devices, it constituted 5 percent of all complaints reported by CDRH's ombudsman in 2009.

Thank you.

DR. SHUREN: Thank you.

Mr. William Christianson.

MR. CHRISTIANSON: Good morning, Dr. Shuren, and welcome to New England, and hello to the local FDA staff.

My name is Bill Christianson. I'm the vice president of regulatory affairs with DePuy Spine, a local medical device manufacturer, and I'm here today representing DePuy as an organization.

DePuy has a long history of developing products in the field of orthopedics, spine and neuroscience, and neurovascular products. DePuy has been manufacturing safe and effective products to treat the American public since the 1890s, and we have a very sophisticated regulatory staff, R&D staff who participate in many national and international societies and standard-setting organizations.

We sell our products in 51 countries around the world and employ over 1,000 people. We have manufacturing plants here in the U.S., in three sites in Europe, and a manufacturing plant in China as well.

Typically, our products are released in the U.S. first because it is our biggest market, followed by the introduction in the rest of the world, and in a typical year, DePuy produces 15 to 25 new products for such release. However, due to changes that we've seen in the Agency in recent years, many of our new products are now released outside the U.S. first, and that has been a change that we've just seen in the last year and a half.

Clearly, reviewers are asking for more information, frequently clinical information, to make a substantial equivalence determination for a Class II device, and it's not obvious to us that the questions being asked would result in a safer product. We're not aware of any data that would suggest that products released under the 510(k) process in the U.S. have led to unsafe or ineffective devices being available to U.S. citizens. We think the 510(k) process is robust and effective for reviewing such products, and, of course, these are all Class II products.

This became evident to us, as I said, about one and a half years ago, but it has been increasing in frequency, and the questions have been increasing in more recent times, particularly in the last year. And many products that my company produces that would have previously been a typical 510(k) product now find themselves blocked or delayed from release in the U.S. and, as I said previously, are available, in many cases, outside the U.S. first.

In essence, when a reviewer asks for clinical data in a Class II application, it has the effect literally of raising the bar to a Class III product, and, again, we're not aware of data that would suggest that that level of review and scrutiny are necessary for the review of these Class II products. If a statistical hypothesis is being developed and clinical studies are being designed, it doesn't matter whether it's a Class II or a Class III product; the statistical questions are the same. So in the context of a randomized controlled trial, which is frequently what's being asked for in these Class II reviews, that again raises the regulatory bar from Class II to Class III for these products. And I do want to remind the Agency that there are other methods of developing valid scientific evidence, as outlined in 21 C.F.R. 860.7, and we would like to urge that other forms of clinical data development be considered when these requests are being asked.

I'd like to applaud FDA for holding these public meetings. I think they're very important. We welcome the chance to address you today and would be happy to answer any specific questions, if the Agency has them, regarding specific individual products.

Thank you.

MR. STEIGER: Good morning. I appreciate the opportunity to speak here. My name is Peter Steiger. I'm CEO of Optasia Medical.

Optasia is a venture-backed startup who makes software that facilitates the reading of x-rays for the management of musculoskeletal diseases. Our lead product, which is CE marked and sold in Europe, is Spine Analyzer. Spine Analyzer is a PACS DICOM workstation software for the assessment and documentation of vertebral fractures and osteoporosis. Spine Analyzer's 510(k) file is currently under review by the FDA.

I would like to share with you our case study just as a personal anecdote of how several of the things we're talking about today has been affecting us as a company, and I'd like to start with a brief history of our submission, which was filed on September 5, 2008, over 21 months ago, and we still have no decision.

About 60 days after the submission, things started well enough. We received our first request for additional information, to which we responded within 10 days. In December of 2008, we received our second request for additional data, requesting clinical data. After a teleconference with the review team in February, we submitted our response to the second AI request in April of 2009.

From April through July 2009, we had a number of discussions with two different statisticians and the review team, which resulted in additional data analysis that we submitted in July 2009. In that response, we requested a face-to-face meeting in order to receive clarity on some of the Agency's instructions and to understand the relevance of those instructions within the context of existing regulations, published policy and precedence.

In September 2009, we received a request to submit additional clinical data not requested before, and that request did not acknowledge our query submitted in July and ignored our request for a face-to-face meeting. Again, we requested a face-to-face meeting. Since then, we have had no formal communications with the Agency, that is, since September 2009.

After the radiology branch moved to the Office of In Vitro Diagnostics in January 2010, we started receiving informal updates on process through our regulatory consultant, which were very helpful. These updates, however, did not address any of the substance of the submission but suggested that the Agency was reviewing our existing file and working on coming to a decision. As of today, almost 22 months after our initial submission of our file, we still have no decision and no clarity of what we need to do to obtain approval.

We empathize with the Agency's difficult position and its responsibility for ensuring that marketed devices are safe and effective. We recognize that this position has become even more difficult in light of recent controversy. We understand that regulations, guidance, and the law is subject to interpretation. We acknowledge that there can be differences in opinion. We are willing to be good corporate citizens, to be flexible and to comply with the instructions provided by the Agency. We observed that under new management, the Agency is making great efforts to better understand the public's and the industry's perspective, and we applaud those efforts. We believe that the CDRH's fiscal year 2010 strategic priorities are well chosen and highly relevant. However, I do have to express our frustration over the Agency's behavior. We do not understand why we cannot get a face-to-face meeting with the review team to collaboratively work through the problems; why, after almost one year, has our request to meet not even being acknowledged?

Over the course of the review of our submission, there have been disagreements between the Agency and us, and apparently also disagreements within the Agency over how predicates, regulations and guidance applies to our product. Why can there be not more transparency about what those disagreements are? After 21 months and counting, we do still not understand them.

We are willing to meet FDA's expectations, but the Agency's requests need further clarification. How can we meet those expectations if the Agency is unwilling to commit to a meeting?

This is up close and personal for a company like ours. This is about survival. We believe that our products, like those of many other venture-backed startups, make an important contribution to meeting unmet medical needs in a cost-effective way. In order to survive, companies like us depend on raising capital. Venture capitalists are walking away from investment opportunities that involve a regulatory approval process that is unpredictable. Optasia Medical and many companies like us will be out of business soon if these problems cannot be resolved.

These town hall meetings are helpful. The CDRH's strategic priorities are good. It is time to walk the walk because time is running out for companies like us.

DR. SHUREN: Mr. Matthew Price.

MR. PRICE: My name is Matthew Price. I'm the director of quality assurance and regulatory affairs for Centurion Medical Products.

The message that I bring to you today, Dr. Shuren and the rest in CDRH, is not so much focused on pre-market clearance and pre-market approval as it is about what happens after that.

My message is probably going to be received and perceived as frustration because it is with the ongoing inspections that the medical device industry is really exposed to and has to undergo. We talk about a lack of transparency, and this extends into the investigation process with a lack of transparency associated with purpose, scope, and duration for these inspections, especially with what seems to be a tendency for more and more directed inspections coming from the Agency and industry not being given any notice and being subjected to the whims and the wills of the investigators. It seems as if it's an open-ended process at times, leaving medical device companies feeling like the passengers on the tarmac for eight hours in the Detroit airport.

The focus seems to have shifted from confirmation of compliance to a search for opportunities for observations. We experience investigators taking liberties, deciding that rather than confirming the substance of the Code of Federal Regulation is satisfied, it's deciding to judge style and taking issue over style.

There's been an influx, as needed by the Agency, to bring in more investigators, but it has resulted in an influx of inexperience such that the medical device companies spend exorbitant amount of time trying to educate the investigators on our business, on our products, on our processes, and feeling at times that if the investigator doesn't understand it, their response is, "Then it must be wrong," almost like, "We will do what we want to do and you have no say." The results seem to have been an over-focus on procedure at the expense of a loss of sight of purpose.

Recently, Jonathan Sackner-Bernstein, the associate director of post-market operations, was reported at a meeting to the RAPS, Regulatory Affairs Professional Society, as saying one reason industry seems to have been holding back in the past has to do with the riskiness of bold revolutionary scientific leaps and the relative safety and comfort of much smaller evolutionary steps in product advances. But that's not a good reason to deny public health what it deserves, he said. Now, I may have read this through jaded eyes, I admit, from experience, because the way I read it was essentially the Agency saying to industry: You're not doing enough; we either falsely deny or flat out don't recognize that at the root is our own unreasonableness, aggressiveness, perhaps lack of experience in actually designing and manufacturing that which we're regulating, and the misery and expense we put you through to actually get something new approved and manufactured, and yet it's your fault. Very discouraging to me.

Now, I know it's easy for me to come up here before you, Dr. Shuren, and complain, but hopefully it will be more beneficial with recommendations that I have for you and the Agency. Much like those passengers sitting on the tarmac in Detroit, I would recommend a medical device industry bill of rights, either administratively or legislatively, providing more clarity to us and effective checks and balances to those performing the inspections. Elements of this industry bill of rights could include greater transparency to purpose and to scope, really turning the Form 482 into something that's usable, specifying these things from the beginning, that there would be requirements associated with the frequency of inspection and their duration; utilizing a defined formula based on things like establishment size, nature of inspection and unambiguous risk ranking of the products and the companies that are being investigated.

I would require in this bill of rights improved training and experience for investigators and proper control of them. I would require disclosure of inspection data by industry type, by inspection type, by district office -- because working for a company who is affected by many districts, there is a notable difference in these things from one district office to the next -- and an understanding of the proportion of inspections that are performed based on the number of medical device companies within that district; and, finally, a more credible industry complaint mechanism with believable anti-retribution protections.

Now, I have more ideas but, unfortunately, only five minutes. But those are just some of my thoughts on the matter. If you can't tell that I'm passionate about this, Dr. Shuren, then I've failed in this presentation.

Now, the first motivation for my passion is probably the most obvious, because I'm on the front line. I'm the director of quality and regulatory. The not so obvious is my personal motivation. I'm a 37-year-old man who was diagnosed with Type I diabetes at nine years old. So the people in this room representing the companies that they represent are largely responsible for not only my life sustenance but my life enjoyment and the quality of my life and its improvement. So you can see why I'm so passionate, hopefully.

These experiences upset me. It's not -- for as hard as we're working and as much as I personally have at stake in this industry, it upsets me to be treated or at least be made to feel as a criminal. Something has got to change.

Dr. Shuren, I was raised by an incredible man who taught me to believe that if you see a piece of paper on the floor and you just walk by it without picking it up, you might as well have dropped it there yourself. My piece of paper today is the thought, the initiative, the effort and the courage to stand before all of these people to deliver this message to you. With the utmost respect, your paper is to take it from here with the understanding that the road to two-way communication will lead to nowhere so long as it's viewed as a one-way street.

DR. SHUREN: Thank you.

Mr. Gerald Brecher.

MR. BRECHER: Good morning. I'm Gerry Brecher, CEO of EndoEvolution, a startup medical device company located in Chelmsford, Massachusetts. I want to thank you for the opportunity to share my experiences and observations based on three decades in the world of startup medical device companies.

First, let me say that the FDA and CDRH are to be commended for holding these town hall meetings. At a time when the relationship between industry and regulators has become highly problematic in other sectors, I believe that a fundamentally healthy relationship between FDA and the medical device industry remains a good thing for the public and also for industry.

My own experience is limited to the 510(k) pre-market notification process, but it goes back a long way to when the 510(k) application fit on a single sheet of paper, and if the Agency didn't say no within 90 days, you were free to market your product. In 30 years of doing this, I don't recall a single instance where our ability to bring innovative products to market was impaired by the 510(k) regulatory process.

Four different companies that I founded introduced a series of 510(k) products for minimally invasive surgery from simple mechanical devices to complex electro-optical imaging systems, and in each case, these were first-of-a-kind products representing true innovation, yet in every instance, FDA accepted our explanations and cleared our products as substantially equivalent without undue delay or burdensome process. So from my perspective, the 510(k) process works, and it works well.

I don't claim, however, that my experience is universal. I know other companies that have gone into the 510(k) process and never came out. Perhaps it was the nature of their products or perhaps it was poorly conceived and inadequately executed regulatory filings that in the end failed to achieve the desired results. But is it not fair to say that the 510(k) process also works when the answer is no? In that regard, I wonder if we would all be sitting here today if it were not for the ReGen matter. And that's why I want to quote at a little bit at length from FDA's own report: "Although inquiries from members of Congress about FDA's handling of a constituent's product application are not unusual, interviewees describe the congressional involvement in the ReGen matter as highly unusual not only in the members' persistence but also in members' interest in specific, substantive aspects of the device's review. The Director of FDA's Office of Legislation described the pressure from the Hill as the most extreme he had seen and the Agency's acquiescence to the company's demands for access to the Commissioner and other officials in the Commissioner's office as unprecedented in his experience. Congressional interest in the ReGen matter and the unusual responsiveness of the Commissioner to that interest initiated a chaotic new phase in the Agency's handling of the 510(k) submission for the CS device."

My concern is that the backlash from ReGen has and will result in a 510(k) process that will be considerably more complicated, more difficult, more time-consuming and more expensive, none of which is a good thing for a startup company or even for a large established company. A more arduous process will certainly mean that fewer new -- certainly, it will certainly mean that fewer new and innovative products will find their way to market, but it's not at all certain that a more arduous process will inevitably lead to better products. And why is there this backlash? ReGen was simply an instance of an applicant company not at all willing to take no for an answer but all too willing to enlist every politician it could find to bring to bear every political pressure it could muster to get the Agency to reverse its repeated denial of 510(k) clearance. And why does this episode mean that the 510(k) process is flawed and in need of major overhaul? Why isn't the lesson of ReGen that the 510(k) process is fundamentally sound? After all, CDRH staff reviewed the Menaflex application repeatedly and each time turned it down for rational and defensible reasons. The process worked. Political interference and perhaps, maybe -- probably, a lack of backbone at FDA is clearly the culprit. And why should the rest of us face an even steeper and more tortuous regulatory path when we play by the rules, something ReGen was clearly unwilling to do.

The uncertainties of healthcare reform, the perilous condition of the economy, and the shrinking availability of capital make it difficult enough to launch new ventures in the medical device space, but these new ventures are the fertile ground from which disproportionate numbers of useful and innovative devices sprout, to the ultimate benefit of patients everywhere. My plea to FDA is that the fundamentally sound 510(k) process will not be recast in such a way that our efforts at innovation will be stalled and eventually wither.

Thank you.

DR. SHUREN: Thank you.

Mr. Barry Sands.

MR. SANDS: Good morning. My name is Barry Sands. I'm the president and founder of RQMIS, a consulting company in regulatory, clinical and quality, just located north here in Boston.

And I'd like to cover five principal topics: One, just to explain my background and perspective and where I come from with some of my comments; I think it will be somewhat similar to what you've already heard this morning. Also to highlight the fact that this is not the first time the Agency, in particular, the medical device area, has gone through this pendulum swing of review and more critical analysis of submissions and compliance activities. I'm just going to highlight just a sample of current events that we've personally experienced with clients or past companies that we've worked with, and I'm going to highlight certain concerns with the current regulatory review process, and then finally wrap it up with the recommendations that I hope the Center will take and seriously consider.

My background is actually seven days -- seven days -- seven years at the FDA. It definitely did not feel like seven days. But it was first working in the field in the Boston District here in Winchester at the engineering and analytical lab, and then the balance of those seven years, five years at the Office of Device Evaluation being a scientific reviewer. During that period of time, I did get to see the first pendulum swing when Dr. Kessler took over the reigns as commissioner. Since leaving the Agency, I've spent 17 years actually running the regulatory clinical study design as well as compliance activities in both the startup world as well as in the middle-size medical device company.

One of the things that I have learned in living and breathing on both sides of this equation is that clearly the company as well as the FDA has responsibilities when they come to the table and they negotiate and discuss getting a product through the regulatory review process. One of those -- and let's start with the company responsibilities. It's very clear that it's the companies who should and does understand their device, the clinical environment it's being used in, and the risks associated with that use. They should come to the table with a good understanding in risk assessment of their device. They should also have a clear understanding of what they believe is a solid verification and validation plan for that device, and they should also have, hopefully, a clear understanding of the regulatory process and the requirements thereof. This, of course, is what we're talking about today.

But on the FDA's side, it's also equally important that they provide consistency in the review; they provide predictability; and they also afford a level playing field from company to company -- open communication is critical in all of those aspects; and also, and most importantly, to provide good science and reasonable risk management in submission reviews. This is where we get reasonable assurance. And you'll hear risk management as a common theme.

The pendulum swing. As we all know, back in the early '90s when Dr. Kessler became commissioner, there was a reevaluation of the medical device review process. There was a stagnation of the review, a complete slowdown in the review, and spent two years in that process before joining private industry. What we experience today is somewhat analogous to exactly that same scenario back in the early '90s. Multiple events caused that first pendulum swing. I won't go through those now. But we're going through similar concerns that are occurring in the field that's causing the second pendulum swing.

The problem is when we go through these swings, predictability goes out the window. When predictability goes out the window, startup companies in particular are harmed. They have a limited cash flow. They have a limited timeline to live by. To be able to live in an environment that's not predictable makes it very challenging to not only raise money but to stay alive and to continue to raise money to execute and fulfill requirements that are constantly changing over that development period.

Some issues that we've personally gone through as a consulting firm as well as working in previous companies, going through an IDE process in which pre-IDE meetings were held, pre-IDE submissions were reviewed, original IDEs were submitted and initially disapproved, and only a year later on these first responses to the disapproval was there a thorough analysis of the data analysis plan. That analysis resulted in a request to change the plan so significantly that sample size went up two to three times of the original agreed-upon sample size and, therefore, timelines dramatically affected as well as the amount of cash necessary to execute.

Level playing field, another example. Very frustrating for a startup company who is trying to do the right thing, fulfill the IDE requirements to perform clinical studies and go through a PMA process when they see a competitor on the field who is marketing a device for another use but is truly marketing it for an off-label use. Very challenging to explain that to a board of directors, and it's very challenging to survive in that type of environment.

Open communication issues, another important issue. I have had mixed results in this. I've had reviewers that have been outstanding at returning e-mails, returning phone calls and having discussions. However, I've had the opposite. When the data analysis plan changed so significantly that it was going to impact the timeline dramatically, there was initially an absolute refusal to have a face-to-face meeting, and only a face-to-face meeting was going to accomplish the discussion and negotiation that needed to occur.

Education. Maybe not the most primary interest of everyone here today, but I think education is important. The process to go through regulatory review, compliance activities, clinical study activities is not a simple process, and more education needs to be available. FDA clearly does not have the resources to do this nationwide, but there are third parties, like the World Medical Device Organization, that have eLearning suites that can assist in this, and it would be good to see a partnership with it between FDA and these third parties to provide that education.

So issues, concerns. I'm going to throw out some statements that I've heard amongst the industry, amongst our clients, that I think have already been echoed, but some of my responses from the standpoint of living on both sides of this equation:

"The pre-market review process, meaning the 510(k) review process, has caused all of the issues that are at the forefront of our concerns today." My response to that is no, that is not true. If you look at all the issues that we have seen, there's a multitude of issues. There are compliance issues; there are off-label promotion issues, issues that I do not believe are most directly affected by a pre-market review process.

"The 510(k) process is too flexible." Again, I would say no to this because I think this flexibility is absolutely required when you're dealing with such a multitude and range of products that are particularly in the Class II arena. You must have this flexibility. I would say, though, that a more defined use of risk management techniques be used in the 510(k) process to make that review process more quantitative and more open in communication because you will clearly call out what the issues are, the risks involved, and it will also cause the FDA to say, "You didn't list all the risks" or "You viewed this risk as insignificant; we don't. We do view it as significant." And you get away from just reviewers coming up with their concerns. Although maybe legitimate, they're not objective.

"The 510(k) process is flawed because predicate devices that are being used were not adequately reviewed at the time that they were put on the market." With this, I do believe there is some truth. There is some truth that during the period of FDA over the past 20-some-odd years and the level of review fluctuating, that this process has allowed devices that have gone through a less critical review. However, I don't believe that this is a good enough excuse to cause the system to be so unpredictable that you don't know why a particular predicate device is not appropriate for the 510(k).

I do believe that the Agency should use risk assessment again if they see where predicates were not properly evaluated. State it, identify it publicly, explain why and the actions that are truly necessary to address it. I think we have 21 devices right now that are under that category and which calls for additional data or clinical information are currently pending or required.

I'm getting the Heather wave, so I'll wrap this up very quickly.

Another interest that is very, very much on the forefront of a lot of clients is the constant referral and need for clinical studies in 510(k)'s. Yes, in some cases, I think it's absolutely relevant to have the clinical evaluation, but what I do see is a serious concern or belief that a clinical study will answer all questions or it's the shotgun approach to evaluate a device. Please recall clinical evaluation will not address all issues, and, quite frankly, performance testing on a bench will challenge that device to a much larger range of issues and scenarios that the clinical study will never evaluate. So balance that appropriately.

I've gone back and looked at ventilators, for example, which are Class II products just like infusion pumps that go through the 510(k) process that are critical devices, but yet there hasn't been a Class I recall of those devices in the past four or five years. The 510(k) process must be working there, but I don't see the requirement of clinical studies for those submissions.

The last point I'll make is to distinguish what's the best approach to manage risks. I think there needs to be a clear understanding that the pre-market review process is the first opportunity for the Agency to review risks, mitigate risks appropriately. That is their mandate and they should be doing that job. But they should also recognize that you'll never mitigate risks of any product to zero. Impossible. This is particularly true with medical devices because you have a user interface issue between the doctor actually using that device. It doesn't mean doctors are not educated or not intelligent, but you have a multitude of ranges of training and experience. And you need to understand that the pre-market review process will mitigate risks to a level, but just like with drugs, you must review ongoing use in the post-market environment, analyze failures when they occur, properly investigate them from a compliance, quality standpoint, issue CAPAs where necessary, and when those CAPAs result in absolute design changes addressing safety issues or labeling changes, then a regulatory submission is necessary, and the feedback loop can occur, and we can all improve the process of reviewing and approving devices.

So just in closing, one of the bigger topics that is facing the industry today, there's a lot of litigation involved with it, and that's with off-label use and off-label promotion. This is a good example where the pre-market review process is truly not the most precise tool to address this issue. It is the compliance side that I think is better equipped to deal with off-label use. Review of 510(k), as labeled, as intended, make sure the labeling is clear for the user to use it, but if a company, of course, chooses to market it outside of that approved use, then it's the compliance folks that should probably address that issue.

Thank you.

DR. SHUREN: Thank you.

Mr. Chas Burr.

MR. BURR: Good morning, and thank you to FDA for this opportunity.

My name is Chas Burr. I have been in medical technology and medical engineering my entire career. In 1986, I fell down the rabbit hole and entered the world of device regulation and have worked in management, regulatory and quality management, and in consulting with both large companies and small. For the last eight years or so, I have, in addition to consulting, been teaching, and I am currently the program director for Regis College's master of science degree program in health product regulation and a fellow of the Regulatory Affairs Professionals Society.

I want to very much applaud FDA's efforts and the many very good suggestions here for increasing predictability, and with predictability will come timeliness of the review process. I want to plant some seeds for long-term change because it is my firm belief, based on experience, that the history-based classification inherent in the current law, the search for the predicate device does not allow ultimately flexibility and transparency. What I am proposing that you look towards is evident now in the Global Harmonization Task Force proposal and the processes in the European Union and in Canada in which there are rule-based risk classifications, not history-based classifications, and in which there are graded appropriate conformity assessment methods appropriate to the risk of the device.

The concerns I have where the current law does not provide a basis for flexibility -- and before I go into the weaknesses, let me absolutely acknowledge that for decades, we have worked with the 510(k) process. It can be made to work. But on the other hand, ultimately the law is not providing the philosophic basis based on risks that would allow true flexibility and transparency. Under the current rules, a limit -- a low or moderate risk device that has no predicate must default into Class III PMAs or, as has been described earlier, an onerous and untimely de novo 510(k) process. There is not the flexibility to just recognize it based on reasonable review. This is a low to moderate risk device and deserves a shorter conformity assessment.

At the other extreme where we have a predicate device, we have experienced the situation where FDA reviewers take us aside and say we're not letting you compare to that predicate anymore -- you, in industry. The predicate remains on the market, remains legally marketed, which means, per the law, that we can compare to it, and yet we're being told in the corridors by reviewers you can't do that. That provides the segue into transparency, certainly this idea that what you can compare to is something to be done in the hallways rather than in a transparent means. Ultimately, the comparison of your device is to the 510(k) of the predicate device, a 510(k) that, at most, is available to us in a redacted format, and the decision process of FDA remains opaque.

We are told that we did not compare favorably to a 510(k) that we're not allowed to see, and I'm all in favor of confidentiality, would not expect to see it. What I would expect from FDA is risk-based decisions that can be explained.

The final argument that I would make in favor of going to a rule-based class -- risk classification with flexible conformity assessment is global harmonization. FDA has paid more than lip service. Congress has provided funds. Industry is very interested in global harmonization. A history-based and particularly an FDA-centric history-based system will not make it. It's a nonstarter in global harmonization.

So for the goals of flexibility, transparency, and harmonization, please continue what you're doing in the short-term to make the 510(k) process work, but also start the groundwork for thinking about what must follow the 510(k) process. It is not the proper basis for a risk-based product approval system.

Thank you very much.

DR. SHUREN: Thank you.

Mr. Konstantin Goranov.

MR. GORANOV: Good morning. Thank you for the opportunity to express my opinions and be involved in the ongoing process of regulatory affairs.

I'm Konstantin Goranov with Salutaris. My company is involved in developing of new medical devices. We do have several platforms for infection control. In the past several years, we developed surgical masks and respirators for intense protection against clinical pathogens.

COURT REPORTER: Can you move closer?

MR. GORANOV: Yes. Can you hear me better now? COURT REPORTER: Yes.

MR. GORANOV: In the past several years, we developed a series of respiratory devices, surgical masks and respirators for intense protection against clinical pathogens. In the process, we collaborated with FDA and were very pleased to find their willingness, really, to go through all the regulatory approval process and new changes in the guidances regarding incorporation of -- equipment.

We had definitely great cooperation, but then I think the 510(k) process has certain historical issues which are very difficult to implement in today's fast-pace development. Being an innovative company, we're definitely faced with the challenge to bring the products very quickly to the market and at relatively reasonable effectiveness and cost-effectiveness. In this process, the regulatory process is way too long. And not to share all the disappointments, we had to withdraw the application because of the delays and lack of interest from the investors.

In recommendation, I will say the process may have some different format. In general, it is very difficult to create a new device, to come up with all the bells and whistles, and to really stick with the rules and regulations which are already preset. And that's what the current 510(k) process actually provides. We do have a framework we have to work with and particular guidances based on historical product devices. Those are old products. And that's our predicament. We do have an old history and we have to invite something new. It's virtually impossible. And I think that's why we've seen so much frustration among participants here because it's difficult to design a product, bring old innovative technologies in place, and then find out that we have to prove the availability and the risks and the effectiveness. Yes, we can provide all this evidences and have provided a lot of tests, but it do take time and money, and that's not very doable these days.

I think a resolution -- and that may be something the FDA already considered -- to really help the innovators early in the process, before I'm sure the product is already in final shape, to help people involved in the innovation to define most specifics of their equipment, of their particular devices, to guide them through the innovation process and bring the innovation step by step into compliance with the FDA regulations. I think this approach will save a lot of time for consecutive evaluations, for reviews, for going back and forth between different tests and different forms of evaluation.

This group could be independent of FDA. It could be in conjunction with the established structures with FDA, but this process of staging the developments, staging the innovations, and having the feedback from FDA early on before the final device is made will bring great, great advantage.

Thank you for considering my opinion.

DR. SHUREN: Thank you.

Mr. Eric Bornstein.

DR. BORNSTEIN: Ladies and gentlemen, my name is Dr. Eric Bornstein, and I'm the chief science officer and founder of Nomir Medical Technologies, a startup company. In the last seven years, I have been the primary author of numerous peer-reviewed papers in the laser and photobiology world, where the explanations and data that I have presented have led to three different 510(k) approvals for laser devices.

Thank you for the opportunity to speak at this forum concerning the state of CDRH in today's difficult business environment. If I were speaking today to another well-known government agency, I would start my remarks with, "Houston, we have a problem."

My company's laser technology was developed to offer patients an alternative to currently available medications for toenail fungus, most of which presents serious systemic risks. Because our energy delivery is local, it carries no risk of the systemic adverse effects. The design of our pivotal trial was based on two years of bench studies, three animal studies, one cadaver study, three pre-clinical trial studies, extensive literature reviews, and direct consultation with FDA. Inclusive in our literature review were three seminal FDA advisory meetings in 1994, 1999, and 2004. The key points from these meetings were that toenail fungus is a chronic condition, that low-risk treatments are recommended because the condition lasts for such a long time, and that a cure is not always a feasible outcome.

Our draft protocol was presented to the FDA for review and comment. The FDA replied back to us that, quote, "A 3-millimeter or greater clearing of fungal nail at six months with negative mycology were valid endpoints," which we then included in our protocol. We then sought a pre-IDE meeting and were counseled by the FDA that there was no other guidance they could provide for us.

Next, we proceeded to execute our study following the FDA's recommendations. In our trial, both clinical endpoints were met in the predetermined time frame of our study, and our device was highly successful, surpassing its objectives and delivering effective treatment results in a manner that was convenient for patients, consistent with our study, and there was no adverse events. Given this success, we expected a 510(k) approval. However, in December of 2009, we were instead given an NSE letter.

Remarkably, the reviewers were now erroneously comparing a nonsignificant risk device to substantially longer follow-up time frames for the drugs that treat this disease. Baffled by this NSE letter, we attempted to explain to the FDA that a difference in follow-up times from the drugs is supported because of the highly favorable risk-benefit profile of our device. We also volunteered to limit our claim of effective treatment to exactly the period of our study, six months. We finally pointed to our adherence to the FDA suggestions that six-month follow-up in our pre-IDE process were the suggestions. All of these arguments fell on deaf ears.

This flawed comparison by the FDA abjectly fails to recognize some clear science, namely, that anti-fungal drugs remain locally in a mycotic nail for months after their ingestion and that our laser offers a completely different and nonsignificant risk therapy. I absolutely reject the notion that drug studies alone hold a special and protected time frame of reference in which to judge data from a device study. Such an opinion in data analysis is an aberration and does not hold merit on scientific grounds, as drug uptake into a nail is wholly absent in the light-based therapy. This is not due process. This is mistaken process.

Finally, in a teleconference with the FDA in February of this year, our examiner explained that the FDA was in the process of reconsidering globally the endpoints for toenail fungus treatments. This, to me, is unconscionable. How can CDRH justify the fact that apparently the laws governing drug studies are now post-facto being applied to data analysis for nonsignificant risk devices where the risk-benefit ratio is so profoundly different?

A fundamental problem here is the uncertainty with respect to the scientific requirements for FDA approval. To the investors in my company, it has become increasingly clear that pre-stated and pre-negotiated rules of the game can now capriciously and arbitrarily be changed and that good science no longer suffices for FDA clearance.

When a company conducts years of bench, animal, cadaver, and preclinical studies and then attempts to solicit FDA feedback on pivotal study requirements directly through the pre-IDE process, then implements the FDA feedback that we got in its testing protocols, executes those protocols successfully with no unexpected safety or effectiveness problems, there should be a reasonable certainty of 510(k) approval. To now move the goal post at the end of the game after a company has done all of these things responsibly simply because opinions change within the FDA about optimal study design is extraordinary. These actions do not serve the public health. They do not create an environment of certainty, and they stifle innovation. This drives investment away from medical technology, and it destroys capital.

In my own company, as a result of the FDA's decision driving this investor uncertainty, I have now been required to lay off 75 percent of my workforce.

I will finish my statement in the same manner that I started. "Houston, we have a problem."

Thank you.

DR. SHUREN: Thank you.

Mr. Eric Ankerud.

MR. ANKERUD: Good morning, Dr. Shuren, and others in the audience.

My name is Eric Ankerud. I'm executive vice president of clinical regulatory and quality for INCEPT, a medical technology incubator-type organization with a consortium of companies, some based here in Boston, others on the West Coast, innovating novel technologies to serve unmet clinical needs.

Over 25 years ago, I joined the medical device industry as an in-house legal counsel for a small medical company, and sitting in a conference room with the 20 other employees, the president announced that FDA was coming in for a GNP [sic] inspection -- or GMP inspection, I should say. Having an economics degree, I raised my hand, saying, "I know what that stuff is. Gross national product, of course." And he said, "Fine. You're in charge." And so from that time and learning, I've had the privilege of working for a number of large medical device companies as well as startup companies and collaborating with FDA to gain approval, both through the 510(k) clearance process as well as the PMA process of some fairly novel and innovative and unique medical products, some of which have been used on my family. And so I certainly appreciate the process that FDA has of protecting public health while allowing companies to move forward with these innovative technologies to serve these medical needs.

I support a number of the position of previous presenters on some of the topics that are most important for these town hall meetings, and our motto is thinking through the communication, collaboration, and predictability issues as they affect our startup companies within the INCEPT organization.

And so what I thought I would do is just share a little bit of our own company experience, as some of the previous presenters have done, to give a flavor for what those three topics mean to our companies.

We've had some very good successes working with FDA, and we thank FDA for collaborating with us on innovative technology and new ideas for clinical studies, specifically in the PMA world, where some of these ideas are unique. And FDA has been very helpful in thinking through some of the issues that would help us design clinical trials to support the PMA process. And in my experience, it seems that it's the individuals at FDA that make the difference in working with companies to gain some of the successful product approvals.

However, from our first foray into the field with a novel hydrogel technology, we were able to gain approval for a neurosurgical application of that product. We've spun off other companies using the same technology and run into obstacles working with FDA that I'd like to talk a little bit about over the next couple of minutes.

We've had one of our companies work with FDA through the pre-IDE process where we've gone through four pre-IDE reviewers over the course of a 12-month period of time, and we certainly appreciate the challenge that an FDA reviewer faces in trying to understand technology that we spend 20 hours a day thinking about and they only have a few minutes to try to engage the technology in a way that's meaningful.

In addition to the number of pre-IDE reviewers that we've had to educate and work with, we've now gone to a second branch within CDRH. And so after spending nearly 12 months working with one branch, we're now starting from scratch with a second branch. And although the FDA review team has been appreciative of the time, in a startup company, as you all can imagine, time is money, and money is not easy to come by in today's economy.

Similarly, we've had one of our companies kind of uniquely go down the 510(k) path -- and I know there's been a lot of talk about the 510(k) process this morning -- where we've gone through a pre-IDE review with FDA again trying to build a collaborative effort so that we're doing the right thing, and we really have an objective of handling our development process the right way to put out a safe and effective product. In the case of this particular company, we did submit a 510(k). We made it very clear that the pre-IDE information was very helpful in designing our preclinical studies. Unfortunately, for this company, there was no human clinical data required to support the 510(k) submission. Unfortunately, when the deficiency letter that was anticipated came, it became very clear that FDA forgot about the pre-IDE communications that had taken place over the last six months and was gracious enough to acknowledge the fact that they had missed the fact that agreements had been made out of the preclinical studies. That's great, and we appreciate FDA's honesty and collaboration and transparency. Unfortunately, again, it's a loss of time, and that's critical to our startup organizations.

And the last example that I wanted to share is in regard to a product that deals with our hydrogel technology that has a pretty long experience as a safe medical device. We're putting it into a new indication and therefore have to demonstrate clinical efficacy for that device. But having gone through the pre-IDE process again with FDA, we learned that FDA had changed its mind at the last minute. In going through the last two and a half years or so of the regulatory process, we were geared up for, in this case, a 510(k) clearance. And I stand here thinking most of the products that we put on the market are PMA devices. But since we're kind of addressing the 510(k) regimen, I thought this example might be of interest to FDA.

We were days away from anticipating FDA clearance, having a very good working relationship with FDA, and although the communication was not as efficient as we had hoped, there was not a period of silence so we had a pretty good idea of what was going on. At the last minute, when we were expecting that 510(k) clearance, the wall of silence occurred and FDA stopped talking. We didn't hear from FDA for days, and those days turned into weeks, and those weeks turned into months. And then finally we got a communication from FDA saying, "We've reclassified your device to a Class III. You now need to submit a PMA."

Again, predictability is the issue, not so much that we were surprised, because I think most of us in the regulatory world know that when the silence starts to occur, usually good things don't come out of that silence. And so we were disappointed by the fact that FDA had changed its mind, and it was quite clear in communicating with the Agency that others became involved in the review process that had not been involved over the past 12 to 18 months, and, therefore, inputted different information. Had we known it was a PMA process -- we're a very experienced PMA team -- we would have gone down the PMA route from the beginning. But now we've lost time, and, again, time is money.

In closing my comments, I wanted to reiterate some that previous presenters have made. In the startup world where time is money, money is also people. And in one instance where the 510(k) that a company had submitted went into what I described as the black hole, we couldn't figure out what was going on, by the time the clearance came, 30 people in the company were let go. The venture capitalists walked away and the 30 people joined the unemployment ranks in California. Similarly, where the direction for the regulatory path had changed from a 510(k) to a PMA, just yesterday five people lost their jobs in Boston. And the value that I place on employment is so high that it's painful to see people go because of time.

And so as much as we've had some very, very positive experiences with FDA, we wanted to share some of the issues that we think are challenging. And as we look at the 2010 strategies that CDRH has put forward, we applaud those strategies and are very willing to offer FDA any support and assistance that as a startup organization and our representation of numerous companies we can offer.

Thank you very much, and thank you to Dr. Shuren for making this opportunity at the town hall meeting.

DR. SHUREN: Thank you.

Mr. Paul LaViolette.

MR. LaVIOLETTE: Thanks, Jeff.

My name is Paul LaViolette and I'm with SV Life Sciences, a leading healthcare venture capital firm. I've been actively involved in the medical technology industry for 30 years, both running some very large companies and investing in many startup companies, including some represented by prior speakers this morning, that have contributed to some very important medical innovations. I'm currently a director for nine medical technology companies.

My remarks today are endorsed by the National Venture Capital Association, and SV Life Sciences is a member of that group.

I would also like to join others in thanking Dr. Shuren and the FDA leadership team for accessibility and commitment to continued process improvements. I appreciate the opportunity to comment on some of the challenges emerging growth companies are experiencing with the FDA pre-market notification process for medical devices and how these challenges are impacting investing, which is, from venture capital sources, the predominant source of funding for emergency growth companies in the United States.

Medical innovation has been a hallmark of American medicine. Quite simply, these innovations have revolutionized the practice of medicine worldwide, and most of these innovations were developed by venture-backed startup companies.

We have witnessed a disturbing trend in the medical device industry that is impeding patient access to innovative technologies and is disrupting critical U.S.-centered research and development. The trends of increasing regulatory uncertainty and inconsistency are delaying medical device approvals to the point of bankrupting emerging growth companies. This, in turn, greatly reduces our ability to invest in this sector. Venture capital investments in the U.S. have declined by over one-third in the past two years, and medical device investments were down 29 percent in the first quarter of this year. Many of the most important and innovative venture-backed companies now routinely pursue approval and commercialize their technology into routine medical practice outside the U.S. before even initiating regulatory review in the U.S.

Now, venture capitalists completely accept the risk that if they fail to demonstrate the safety and effectiveness of an innovative device, then most or all of their investment may be lost. However, unpredictable FDA decision timelines and the enormous added costs of inefficient reviews are factors that are difficult to accept. In 2009, 510(k) review times grew by another five percent, and uncertainty about future changes in the 510(k) process are a cause of great concern to all of us in the industry. While all device companies face these factors to some extent, these challenges are compounded for small venture-backed companies which simply do not have the financial capacity to absorb such inefficiencies.

We believe that the Agency needs to improve by attacking process uncertainty, particularly regarding the regulatory process for novel technologies. As we know, review times for expedited review of breakthrough products are longer than for conventional reviews. To address this, I would recommend first that early-stage device companies need a special refined regulatory pathway for truly novel technologies, and that pathway must be robust, collaborative, and predictable. FDA should produce a definition of "novel" and should also determine if devices either meet or do not meet that definition within 30 days of an application. To fortify review of these novel devices, the sponsor could and would volunteer to submit a second incremental user fee to enable FDA to assemble a concentrated team of high-level review resources, including outside consultants to review the submission. Investors would readily fund more expert resources rather than watch the passage of nonvalue-added time.

Second, access to content experts is an essential element of proper technology evaluation. Given the limited number of individuals who may possess the clinical or scientific knowledge to understand novel or disruptive medical technology, FDA should consider new ways to access these individuals, including characterizing current FDA experts by specialty rather than just by their division so that scientific experts can be appropriately assigned to novel reviews. FDA should also tap outside specialty research institutions which offer a wealth of conflict-free advisory and review talent.

Third, innovative devices should be regulated based on the actual levels of risks they present and not on whether they fall into a risk category based on legal precedent. The current de novo system does not function this way and is unnecessarily burdensome to the Agency and industry as a result.

Finally, the current review system is increasingly unpredictable. Innovative devices require that FDA and sponsors work together in premeetings, as we've heard, to determine the best testing and review regimen, and then to stay focused on issues that legitimately influence device safety and effectiveness. Too often, the agreements reached in premeetings fail to carry through to the final approval requirements for the devices in question.

In summary, we expect a review system that is rigorous and uncompromising in determining safety and effectiveness, but also one that is transparent, predictable, attentive to the needs of innovation and a model of process effectiveness. The health and survival of America's medical technology development ecosystem and patients' continued access to the benefits of novel technologies depend more than ever on this effort.

Thank you very much.

DR. SHUREN: Thank you.

Mr. Dan Goldsmith.

MR. GOLDSMITH: Good morning. My name is Dan Goldsmith. I am the president of X-Laser USA, and we are a proudly compliant laser light show manufacturer based out of Maryland, actually. Being a laser light show manufacturer, we're going to take an abrupt left-hand turn from the entire rest of this meeting thus far.

We are here today out of a deep and growing concern for the not only quantity but quality of products that are being illegally imported from China in the laser light show market sector. Many people who are with the CDRH are aware of this problem, but we feel that perhaps they are not fully aware of the scope of this problem. With a lot of eyes and ears on the ground, we're here today to provide some context and also some recommendations for what might be able to be done.

There are two main parts to this problem. One is quantity and one is quality. In this limited time format we don't have time, of course, to go through our methodologies, but we have the full report we'd be happy to provide you all with that, shows a lot more of that information.

Based upon our estimates, we're looking at an import quantity of about 107,000 units a month, or about 1.2 million units per year. These are being distributed through major retail outlets, and one of the largest single providers of these units is eBay. And if anybody wants to have a good time, go to eBay and type in laser light show as a search term to search titles and descriptions, and as of this morning, there were 29,621 noncompliant laser products that were posted on eBay for sale to the United States as of this morning.

The second problem that is of great concern is the quality of these units. These units are produced en masse without any real regulatory oversight, and they are sold and used by individuals who have really, honestly, no business using them.

I brought one just as an example today. This is slightly ridiculous, but it is actually much more the rule than it is the exception. For those of you who are involved in manufacturing, you might want to prepare to be slightly horrified. This device is marketed as a Class IIIa laser product. That means it can be sold without a variance. It is, in fact, emitting 37 times the limit of IIIa radiation. It is assembled with plumbing strap, recycled wiring that's been pulled from other fixtures, glue that the U.S. distributor believes to be toxic and is, in fact, built into a piece of cut-down five-inch PVC water main.

This is quite reflective of the products that are coming into the United States right now, often fraudulently. They're imported as stage lighting equipment or disco lighting to avoid FDA overview, and they are coming in en masse. The manufacturer of this product was actually cited in October for providing noncompliant products. This product was released in January, and they claim to have sold 5,000 units in the first quarter of 2009. In fact, I saw one of these just this past May at a high school dance being shot at a bunch of high school kids.

This is a significant problem for us, and we have a few very, very simple, what we feel are very, very simple recommendations to try and help combat this. The full list of recommendations will be in the report we'll be happy to provide for you, but I just want to give you three to start.

The single biggest problem is that people in our market segment don't believe that the FDA has regulatory jurisdiction over radiation products. There are also a large portion of our market that don't believe that lasers are radiation products, but that's another problem entirely.

The FDA has a number of actions that it takes for imports, but it is absent in the public mindset. We'd like to see the FDA become more visible in enforcing its regulatory obligations. To that end, we'd like to request the creation of an auto letter that can be sent out whenever a report of noncompliance is made. That letter can clearly state that the FDA has not evaluated the claim but at least make the person who is the subject of that report aware that the FDA is looking into it and that may begin to clue them into the regulatory responsibilities and make the FDA more present.

Second, presently, there is no method of report at all. If we find a noncompliant distributor of laser light show products or an illegal laser show occurring, regardless of the severity of that event, there is no mechanism whatsoever for reporting that incident for FDA to follow up on other than e-mail, which is frequently not returned.

And, lastly, we would like to see the FDA publish a very simple summary of responsibilities of laser light show manufacturers. All these findings, by the way, are endorsed by the International Laser Display Association, which is sort of heavy lift in and of itself, but there is no one source for us as a regulated industry to point someone to say, "Your product is noncompliant. Here is why." It's scattered about through many, many documents and laser notices and so on and so forth. And it's good that the information is out there, but there's no one place to go to where we can say, "Here's the definitive authority. Check it out," and then let people make their own decisions from that point forward.

In conclusion, I would just like to say that the folks who are in this room make medical products that substantially impact people's lives. The products in our market segment are designed and intended to be shot at people. And these are not ending up in people's basements. They are ending up in high school dances. They are ending up in local bars and nightclubs and that sort of thing.

There is a certain quality of problem in the quantity of product, and we would like to see the FDA take a more proactive role in regulating these products.

Thank you very much.

DR. SHUREN: Thank you.

Ms. Randel Richner.

MS. RICHNER: Hello. Thank you for the opportunity to speak to you today, Dr. Shuren and the FDA.

I am Randel Richner, president and founder of a Boston-Washington-based consulting firm that specializes in reimbursement, health economics, and healthcare policy advocacy, and I represent a variety of medical technology, biopharmaceutical and diagnostic companies.

While many of you know that I am an advocate for, or some would say rebel rouser for, payment reform in CMS issues, today I'm specifically addressing the barriers and significant regulatory burdens imposed by the FDA on a company seeking to expand indications to include pediatric patients. As we all know, few drugs and/or device manufacturers had any incentives to expand indications to children due to many factors, none the least being the additional study requirements to provide -- to prove efficacy and safety.

In 2007 all were encouraged by the passage of the Pediatric Medical Device Safety and Improvement Act, providing specific authority to the FDA to allow extrapolation of adult data to support a pediatric indication, providing the course of the disease and the effects of the device are sufficiently similar in adults and pediatric patients. Nonetheless, many companies are still required to produce numerous studies to obtain label expansion.

Today I am referencing a well-established company with a therapeutic device used in children for over -- for at least the last decade. I'm not at liberty to name the company nor the indication due to fear of repercussions from the FDA. So having said that, this company in particular does not promote the device for children in the U.S., even though there are few available treatment options for patients with this unnamed severely debilitating disease.

Over the years, the company approached the FDA to try to find a solution to expand the indication. Unfortunately, the studies that the FDA suggested are far more complicated, lengthy, and costly to run today than the original pivotal studies that were conducted to obtain FDA approval. Today, conducting the prospective clinical trial in this patient population will be extremely difficult, if not impossible, with the product on the market and reimbursed by commercial insurance companies across the country. It is unlikely that parents would enroll their child in a clinical trial where they would be subjected to delay in treatment during extended periods or possibly being randomized to a sham control arm.

The FDA has published several guidance documents that detail how to use published literature in support of establishing clinical data for new indication for use. In this particular example, there is extensive published peer-review literature on the device's safety and efficacy in children, easily meeting the FDA guideline requirements based on a thorough literature review framed on protocol design and a priority protocol for analysis. Unfortunately, the submission was held to a standard FDA established before the passage of the 2007 Act. As everyone acknowledges, this older standard makes submission of peer-reviewed literature nearly impossible to use, and also the impetuous for passing the Pediatric Act. So the company is at a crossroads. They are now forced to conduct an IDE study that will likely fail due to lack of participation, or they do nothing.

Further, this critical device is approved throughout the world for use in children. The international regulatory authorities have accepted the available clinical data through systemic review of peer-reviewed literature or by extrapolation of pivotal studies to use in children.

We would ask that the FDA consider those technologies that are clearly widely used with a proven safety record be considered more liberally for use, for the FDA to evaluate options to seek ways for this manufacturer or others to receive the indication that it's clearly reasonable and safe for pediatric use. This barrier is an inflexible policy. We wonder why leading experts globally accept published literature and evidence as sufficient for their children, but children in the U.S. are not eligible. We would like to see the FDA consistently embrace the spirit of the Act and work with manufacturers to find a way to make the system work, not requiring repetitive and large studies that are likely to fail, a really unnecessary use of healthcare dollars and resources that we can't afford right now as a country.

The actual process of device and procedural innovation is highly iterative with many feedback loops based on learning from clinical practice. Technological innovations require active and continual interaction between practicing clinicians, biomedical engineers, scientists and researchers. We need to have the kind of creative approach and flexibility by our regulatory policy makers to support sound policy, but be reasonable in the enforcement of the rules. To help our great innovators ‑‑ and all these people in the room that represent innovation -- and I've been in healthcare for over 35 years and I love innovation. Believe me, I want to live a lot longer, so I believe in this technology, and we all want to make it accessible to us. Help our innovators and our companies to get our products to patients in America first, not last in the world.

Thank you.

DR. SHUREN: Thank you.

Mr. Arthur Rankis.

MR. RANKIS: Good morning. I'm delighted to be here, and I thank you for the opportunity to speak.

My name is Art Rankis, and I've been working with medical device companies on 510(k)'s and GMPs since before there were 510(k)'s and GMPs. Today, I am a consultant to medical device companies and, frankly, have to thank the FDA because my business is doing very well. Companies come to me because of the unpredictability and inconsistency and confusion that occurs these days, and we've heard a lot about that today.

My time is short. There are many things we could discuss. I'm a hands-on guy, so I will make two points and then give you a couple of examples demonstrating those points. The first one is simple. For 510(k)'s, FDA needs to use substantial equivalents to predicate devices as the basis for their clearance. And that's it. The second point is FDA needs to be aware that their policies and decisions result in very significant competitive advantages to some companies and undermine the commercial viability of others. I'm sure that's not FDA's intentions, but the results are very real and the same.

So here are my examples. Orthopedic implants, knees, hips, joint replacements. Surgery requires an instrument set. These instrument sets are sterilized by the hospital, steam sterilization. They're reusable and they're prepared. The common cycle is four minutes long, 135, 132, 135 degrees centigrade, and there are many sets in the marketplace for which a valid sterilization cycle takes longer. They're out in the market. They're being sold. If you submit a 510(k) today with a cycle longer than four minutes, it will be blocked. Questions, speed bumps, different kinds of arguments, it's blocked. The fact that there are many predicate devices that are still on the market being sold makes no difference. The companies that are already in the market continue to thrive and sell their sets; the new company, the company with the 510(k), can give up. They can reconstruct their kit and tell people to break the kit down. It's constructed in a certain way so the surgical procedure can go move effectively and safer. They can break it down and go into smaller compartments and do it in a four-minute cycle, and someone has to reassemble it. And with reassembly comes risks. I can bet that it will not always be reassembled exactly the way it should be. Or as we've heard today, the companies can say, "Well, we'll just bring these new novel technologies to our patients outside the U.S."

The second example. There are hundreds of thousands of people today that are treating their diabetes with insulin pumps. When you have an insulin pump, there's a disposable component with the set. It's sterile, and you have to replace it every 3 days. A lot of people don't replace them in 3 days, but that's a different story. Okay. So every month, this patient gets 10 sets. A month has 30 days; they get 10 sets. They submit that to their reimbursement company and they get reimbursed. If you try to do that for the product on the market today, you'll be told two days, and there's all kinds of wonderful reasons that it's blocked. Okay.

Now, if you go to a healthcare reimburser and say, "Look, I've got this great new set and I'd like you to also add us to your reimbursement scheme and we'll need 15 of these every month," and the other product needs 10, they're not going to reimburse the 15 because they see that even though it may give clinical advantage to the patient or it may be better for the individual, they're not going to give it to them. So you have to pay because obviously there's a difference -- a significant difference in price.

The companies in the market continue to thrive. The 510(k) company has the same options, they can give up or they can put their product on the market elsewhere. Again, in both cases, safety and efficacy is an issue, then everyone should be doing it, not just the new guy on the block.

I could go on and on, but I don't think that's necessary. I believe the situations I have described are a recent phenomenon. They can be undone as quickly as they have been implemented. Certainly, I don't think no new laws, regulations, or study committees are required to reverse the trend.

I heard my colleagues suggest that a risk-based approach would help. I have mixed feelings. I like it. Half of me says that's a good thing because we'll both share an understanding of what the risks are involved, and half of me is terrified because in today's environment, adding something else that people can come and put up as roadblocks and speed bumps in the way of the progress of the thing could -- be careful what you ask for. Okay. It could be a great tool. It could also be difficult in today's environment.

In closing, I do not want to believe that the Agency has intentionally abandoned the substantial clearance to predicate device requirement. I do not want to believe that the Agency intentionally wants to give companies business advantages over other companies. I do not want to believe that the Agency intentionally wants to increase risks to patients or make technologies available to patients elsewhere, the new ones. And I don't want to believe that the Agency is there to bring me more work. I do want to believe that the people in the Agency, such as yourselves, are genuinely concerned, are interested in the consequences of their policies and decisions, and want to improve healthcare for Americans first without favoring one company over another.

Thank you.

DR. SHUREN: Thank you.

Mr. Joel Weinstein.

MR. WEINSTEIN: Good morning. My name is Joel Weinstein. I've spent 30 years in the medical device industry. Believe me, if I took my jacket off, you'd see I have the scars to prove it.

I'd first like to thank CDRH for the opportunity to address this very timely town meeting.

In life, usually things work right, but sometimes they don't. So let me tell you a story. BioSphere Medical has developed the QuadraSphere, a novel, minimally invasive technology for the treatment of liver cancer. QuadraSphere is an embolic material delivered arterially that shuts down the blood supply feeding the tumor and simultaneously delivers chemotherapy directly to the cancer site. With today's best practices, fewer than 25 percent of the 21,000 patients who are diagnosed with primary liver cancer in the U.S. each year are eligible for curative surgery, a tumor ablation. For the remainder, the standard of care involves the off-label use of embolization using injected particles either with or without chemotherapy. Neither of these treatments and no embolic device is currently FDA-approved for hepatocellular cancer. Note that even though doxorubicin has been used to treat cancer for over 40 years and is the most common chemotherapy for hepatocellular cancer, its use for liver cancer is also not approved. This means that although many guidelines, including the American Cancer Society, Society of Interventional Radiology and the National Cancer Coalition Network, identify chemoembolization as the standard of care for patients with unresectable HCC, physicians and patients have no FDA-approved embolic options and must resort to off-label use. So we at BioSphere felt strongly then and continue to feel strongly now that a product properly validated and approved for the treatment of these patients would both serve the public health and benefit the patients. So a year ago, we embarked on a course to seek IDE approval to conduct a randomized trial and pursue an indication for the use of our QuadraSphere product for chemoembolization with delivery of doxorubicin in the treatment of primary liver cancer in patients who are not eligible for curative therapy.

Now, as background, QuadraSphere, which is designated as HepaSphere outside of the U.S., is currently approved for use in the treatment of liver cancer with and without delivery of doxorubicin in the EU. Clinical trials conducted in Europe presented at professional medical meetings published in the peer-reviewed literature and shared with the FDA showed that compared to conventional treatment, HepaSphere demonstrated excellent effectiveness in terms of tumor response and a better safety profile. Accordingly, we submitted pre-IDE materials to the FDA a year ago, followed by a full IDE application to undertake a Phase 3 study comparing the off-label, quote, "conventional treatment" with QuadraSphere.

Because our device would be used to deliver a drug, the review group included members from both CDRH and CDER. Unfortunately, it does not include any interventional radiologists, who are the physicians who understand and treat this category of liver cancer patients. We responded to numerous questions and suggestions from the reviewers for nine months and finally had a face-to-face meeting with the Agency to agree on, quote, "the final question of survival" as an endpoint in the study. And so it came as quite a shock to us when having agreed to this, quote, "last issue," FDA introduced a completely new requirement for the study nine months into the process, requiring a third arm to the study.

Now, because this study would have confounds built into it and this design would therefore require that the confounds be addressed, we believe it is highly unlikely to demonstrate a clear outcome. Our repeated requests for further discussion with CDRH over two months ago have received no response whatsoever. So in the meantime, the trial has not moved forward for over a year, and every day those who are diagnosed with liver cancer are continuing to be treated by an off-label, less-effective, and less-safe method.

As the 510(k) and PMA processes are reviewed, we urge FDA to develop criteria that are reasonable, predictable, consistent, determined with reviewers with appropriate medical expertise, meet the test of least burdensome as required under law, and to ensure the training and monitoring of staff for conformance to those criteria so that market access is not arbitrarily denied, as has been the case in this example.

Thank you.

DR. SHUREN: Thank you.

Mr. Nathaniel Sims.

DR. SIMS: Good morning everybody. It's amazing we seem to be on time. I'll try to be quick.

I'm Nat Sims. I'm a physician at Massachusetts General Hospital, been there for 30 years, and I'm speaking to you as a cardiac anesthesiologist with perhaps 10,000 hours of experience in the cardiac operating room trying to safely deliver intravenous drugs safely to patients that are up to 10 or 12 infusions receiving coronary care. I also am a member of the board of directors of AMI, a standards development organization, and academic co-chair of one of the standards committees involved with infusion devices. Therefore, it's probably no surprise that my remarks today are directed at the infusion pump improvement initiative that was publicly announced in April of this year by the FDA, an event which we really would like to celebrate in every possible way.

The details of that initiative are well spelled out on the FDA website under Medical Devices, and the full transcript and videos of the two-day workshop in late May are also spelled out there. I highlight that to your attention because to some extent -- and I ask Dr. Shuren to nod if he agrees that this initiative around a particular medical device is actually just a harbinger of a very broad-based restructuring of the 510(k) process into the total life cycle approach and represents to some extent a major shift in device assessment by the FDA from a history-based to a rule-based and a safety assurance-based approach to medical device approvals.

I really only want to highlight one -- a couple of concerns amid the enthusiasm for this initiative and an expectation of its broad impact for all medical devices, coupled -- first of all, the initiative was announced in the context of FDA's understanding that there have been about 56,000 adverse incidents, 750 patient deaths, and at least 85 major device recalls in the drug infusion pump space in the last five years, clearly a matter of concern and one that echoes my involvement as a physician advisor to biomedical engineering struggling with inadequate technology in the drug infusion space with respect to patient safety for almost 30 years. Therefore, the appropriateness of picking this area for an intense focus is absolutely right.

The only point I want to do in our short time here is to focus on the parallel compliance activity that was also announced in the late-April time frame in which FDA has not unreasonably requested the destruction of about one-fifth of the fleet of drug infusion pumps used throughout our 5,500 hospitals here in the U.S., 200,000 devices at a value of about $3,500 each is a sort of 700 million-dollar initiative, and the risks to the public health is considered sufficiently great, but the initiative is to be completed in 18 months or so.

There are three premises to that announcement that we want to make sure are being adequately tested. The first one is that there's sufficient manufacturing capacity among the remaining drug infusion pump manufacturers to meet the requirement to make an additional 200,000 devices in 18 months. While there are a lot of drug infusion pumps, perhaps a million and a half in the United States, 50,000 of something a year is relatively low-volume manufacturing, and it's not all that easy to turn up the dial on manufacturing as one would for, say, an iPhone. So the first question, then, sufficient manufacturing capacity, is it really there?

The second one is that it was announced at that meeting that the FDA had inquired of foreign regulators to see if there were any foreign devices not currently approved for sale in the U.S. that could address this, a gap in the requirement of filling 200,000 devices, and that the answer from foreign regulators had been, no, there weren't any. Well, sitting under my chair in the third row is one of 100,000 infusion pumps made a year by a European manufacturer, which we have just over the last number of months been testing to find out that it does seem to fulfill the requirements for safety and efficacy in our clinical environment. And so the question is how could we get into a very difficult situation where we're having to replace 200,000 devices in 18 months but with a qualified foreign manufacturer that manufactures and sells these devices in almost every country in the world except the U.S.? Not being able to get in to participate in that activity, it creates a sense of anxiety on my part which I just don't know what to do with.

A related topic is the role of the standards groups, and it was mentioned many times at the FDA meeting that it is the expectation that AAMI, the standards organization, in rewriting infusion pump standards to be more rigorous can effectively translate all the ideas in the FDA guidance document into a new standard. As an academic co-chair of that committee, I'm very challenged by understanding the process of how we can best work collaboratively to do that in the short time frame required, and so look forward to continuing interaction around how to do that very challenging thing.

Thank you very much for your time.

DR. SHUREN: Thank you.

Mr. Jeff Secunda.

MR. SECUNDA: Good morning. My name is Jeffrey Secunda. I am vice president of technology and regulatory affairs at AdvaMed. AdvaMed is the Advanced Medical Technology Association and is the largest trade association representing the manufacturers of medical devices and diagnostics. AdvaMed supports the efforts of the FDA to seek feedback from stakeholders through these town hall meetings. We appreciate the opportunity to speak at this meeting.

AdvaMed supports the FDA development of the CDRH strategic plan. The CDRH plan is consistent with FDA's mission to protect and promote the public health by assuring the safety and effectiveness and quality of medical devices by fostering innovation and by providing the public with accurate science-based information about the products overseen by CDRH.

I want to focus my remarks on three areas, the 510(k) process, the transparency initiative, and FDA's new science initiative.

FDA believes that -- excuse me. AdvaMed believes the 510(k) review process is well designed to assess the safety and effectiveness of low and moderate risk medical devices whose characteristics and risk profile are well understood from previous experience. While we think the basic structure of the 510(k) process is sound, we recognize that every process can be improved. We believe that regulatory requirements should balance FDA's dual mission of protecting the public health while facilitating innovations that benefit patients. Patient safety, however, is the number one priority of the medical technology industry.

The 510(k) program has worked well for more than 30 years. 510(k) submissions include documentation based on bench testing, animal studies, conformance to FDA-recognized standards and additional requirements as specified by FDA. The Agency has the legal authority to request as much data and information, including clinical data, that is necessary to make pre-market notification determinations. The FDA alone makes the final decision whether a medical device can be marketed in the U.S. The safety record for 510(k) devices has been strong, and FDA's substantial post-market controls have contributed to ensuring that these devices meet their clearance specifications and are made under quality systems that ensure the manufacture of consistently safe and effective products.

Turning to transparency. AdvaMed supports FDA's general efforts to improve communication and increased transparency with external stakeholders to maximize the public health benefits of its regulatory decisions as well as to increase the public trust and confidence in FDA. A number of FDA transparency proposals, while well-intentioned, would have a number of negative effects. For example, the public release of information in product applications and the exchanges of information between reviewers and sponsors before FDA makes its decisions are very concerning. They would undermine intellectual property rights. They would disadvantage originator companies, especially small companies, relative to competitors. Most important, they would reduce the attractiveness of early-stage investment in novel, breakthrough products and ultimately harm the public health by reducing the development of new treatments and cures. The public health benefits alleged from releasing proprietary information while a product submission is under review are minimal or nonexistent. The argument about investors being able to use limited research dollars more efficiently is puzzling. Since the proposal is opposed by both manufacturers and venture capitalists, it is likely to result in less innovation. It is hard to see on what basis FDA would make this argument.

When considering new science in regulatory decision-making, the FDA should bear in mind the relative risks and benefits of devices whose decisions it may affect. AdvaMed understands there may be situations in which anecdotal or observational data such as MDR reports may highlight potential critical safety issues and may require an expeditious response. In these instances, FDA should promptly perform risk-benefit analysis to determine next steps in consultation with affected companies. In general, however, FDA should conform safety signals through scientific investigation. If FDA decides to pursue changes in device-specific requirements or broad regulatory changes, it is critical that FDA be transparent by documenting the changes and to make them available to all device manufacturers as quickly as possible via updated guidance or notice and comment rule-making as appropriate.

In conclusion, on behalf of AdvaMed, I would like to reiterate our support for FDA's current risk-based approach to medical device regulation. We look forward to working with FDA to improve the 510(k) process, to enhance transparency of FDA's regulatory processes in a manner that will have a direct impact on public safety, and to improve regulatory decision-making on statistically valid scientific information.

Thank you very much.

DR. SHUREN: Thank you.

Ms. Sheila Hemeon-Heyer.

MS. HEMEON-HEYER: Dr. Shuren, Dr. Luke, Dr. Gutierrez, and Mr. Silverman. My name is Sheila Heyer, and I am vice president of global regulatory affairs for Boston Scientific Corporation. Thank you for the opportunity to appear before you today.

Boston Scientific is a major medical device company headquartered in native Massachusetts with locations throughout the United States and internationally. We focus on delivering less-invasive medical therapies for treatment of a wide variety of conditions in cardiovascular, cardiac rhythm management, endovascular, neurovascular, neuromodulation, endoscopy, urology and women's health.

Over a 30-year history, Boston Scientific has successfully brought more than 500 new medical devices to market through the 510(k) and PMA processes ranging from simple surgical tools to complex life-sustaining permanent implants, including drug device combination products. This successful history was possible and can only be sustained through positive partnerships with FDA as well as all other regulatory agencies throughout the global marketplace. In these partnerships, medical companies and regulatory agencies must work together to assure that patients come first. We must recognize that we all have the same ultimate goal, which is to provide our customers with the treatments they need to help patients, treatments that provide clinical benefits without unnecessary safety risks. But we must also accept that medical devices are not risk-free, particularly life-supporting and life-sustaining medical devices intended to treat serious illnesses. We must do what we can to minimize risks but still enable innovation and timely delivery of valuable medical therapies to those in need.

My colleagues before me today have raised many important issues and offered valuable suggestions for facilitating communication between FDA and the medical device industry, so I won't repeat what's already been said. But I do want to emphasize that two-way communication early and often is the key to success. The ongoing evolution of technology and changing regulatory requirements present challenges for both industry and FDA, and it's only by working together with open communication that we can best meet patient needs.

I'd like to discuss two fairly new CDRH programs -- they are related -- that would benefit from improved communication, and these are the signals escalation and corrective fixes programs. These programs, to my knowledge, have been in operation for around a year, but with very little public visibility.

Under signal escalation, again, it's my understanding that anyone at CDRH can raise up a concern about a product. Signals are assessed, entered into a signals database and tracked. Signals can be for specific company products or may broadly impact a product type across companies. CDRH may take action when concern reaches a certain threshold. Actions have ranged from publishing safety alerts to requesting the companies conduct product recalls.

Corrective fixes is related to signal escalation in that pre-market submissions for device changes may be flagged as potential signals. If MDRs have been filed for the device at issue, CDRH may conclude that the change is a correction and classify that change as a recall. If CDRH concludes that the unchanged device presents a safety risk relative to the modified device, then the company may be requested to remove the unchanged device from the market.

While each of these programs are certainly within FDA's authority and mandate to protect public health, the concern lies in how these programs have been executed. There's been very little communication to industry as to the criteria for signal escalation, what signals are being tracked or the threshold for CDRH action. No guidance has been issued as to what information should be provided in pre-market submissions for product changes to address Agency concerns that may relate to corrective fixes.

Medical device companies are continually modifying their products for many different reasons, including the desire to add new features, increase manufacturing yield, respond to physician preference feedback or, yes, to improve functionality. And this may be in response to internal evaluations or to external complaints. Companies must be able to make product changes and improvements without fear that these changes will be seen by the FDA as corrections requiring recall of the unchanged product on the market.

Unless a marketed device presents a clear public health risk, companies should not find themselves on the receiving end of a call from FDA to immediately recall a device without the opportunity for dialogue. If FDA has concerns about a device, the company should be contacted early and given an opportunity for meaningful discussion, including access to FDA's health hazard evaluation to be sure that each side is considering all relevant information and weighing both benefits and risks to come to the appropriate conclusion.

The medical device industry shares FDA's focus on patient safety, which is why we need to work together on these important issues. Clear FDA guidance on the criteria used to make decisions regarding signal escalation and corrective fixes will help to align industry actions with FDA expectations. A clear understanding of how FDA differentiates product improvements from product corrections will enable greater consistency and predictability for companies planning product modifications. Absent an eminent public health risk, an opportunity for meaningful two-way dialogue before FDA performs a conclusion about a signal will help both industry and FDA arrive at solutions that best serve patient needs.

Boston Scientific appreciates your efforts to engage with your stakeholders, provide opportunities for dialogue, and listen to our input. We hope that this dialogue will contribute to meaningful and sustainable improvements to assure the timely and continued availability of safe and effective medical therapies in the United States.

Thank you.

DR. SHUREN: On behalf of CDRH, I would like to thank all the individuals and organizations who came up to speak. We do appreciate the input.

It is now 10:17. We are pretty much on time. Let's take a 15-minute break. We'll meet back at 10:32, and we'll go ahead and start from there with the open session.

See you in a few minutes.

(Off the record at 10:17 a.m.)

(On the record at 10:32 a.m.)

DR. SHUREN: We're going to go ahead and get started with the open public session.

If you have a short comment or you have a question, what I'll ask is that you come up to the microphones. There's one in either aisle. And we'll just go back and forth between the aisles, if there are people lined up. But, again, you are welcome to make any comment that you have. I ask if it's just a comment, to keep it short, and you may ask any question that you have. Please identify who you are when you come up to the mic. So let's go ahead and get started, please.

MR. KUPFERBERG: My name is Eric Kupferberg. I am the director of the masters in regulatory affairs program at Northeastern University. We have 900 students in the regulatory affairs program there. I am very happy that we brought about 15 of our students here today.

I kind of wished this morning there was a representative of patient advocacy groups and/or trial lawyers. It seemed as if -- okay. I had said that I had wished this morning we had had a representative from patient advocacy groups or trial lawyers. It seemed as if this morning we heard pretty much one perspective. And in lieu of that, I'm hoping this afternoon that you might have -- or this morning you might have a few moments to explain the rationale again for the changes. If these meetings are about transparency and clarity, it would be nice once again to hear why these changes are taking place and what the FDA hoped to benefit from these changes.

DR. SHUREN: Just -- I'm going to ask you just to clarify "changes." I will say, yes, we'd be delighted to hear from patient advocacy groups, trial lawyers. We open this up to everyone. And our district office was actually out making phone calls and contacting a variety of different groups, and whoever wanted the opportunity to speak or to come was given that chance.

MR. KUPFERBERG: That's terrific.

DR. SHUREN: But just want to ask, in terms of changes, were there particular changes that you wanted to --

MR. KUPFERBERG: Well, there's been a response today about a variety of different changes that the manufacturers and AdvaMed and MassMEDIC had seen, and it was a little unclear as to the other side of the argument. So what I was hoping for is in addition to the link to the website, the FDA website, that in this meeting I had hoped that you or someone else representing for the FDA had a chance either to set up the problem this morning or to reply in some way.

DR. SHUREN: Well, let me take a moment to talk about the 510(k) program because there's been a lot of questions on that, and why we had undertaken the evaluation in the first place. I know there was one question raised did we do this because of ReGen. And the answer is no.

The report that came out does mention we should do an assessment of the 510(k) program, given what was found in that evaluation, because in addition to concerns about what happened specifically with ReGen, there were questions about how the 510(k) program was being implemented at the Agency generally. But those issues about the 510(k) program were circling around for a while, and it's really in response to concerns raised outside of the Agency -- some of those you've heard today, questions about predictability, about the questions that are being asked, the need for clinical data -- and also concerns raised inside the Agency as well about whether or not the 510(k) was appropriate and adequate for addressing some of the devices that were being brought forward to us.

The 510(k) program has been around, as you know, since 1976, and it's quite true when it first came into being, you had to submit about one to two pages. But back then, it was a different program. It was just a process. It was a check on the system to make sure that you've actually come back to consider the risk of that product and where it may fall in classification. That's all it was.

Over time, the Agency has tried to adapt the program to use it as a pathway to market for moderate-risk devices. In fact, what the Agency had implemented administratively was ultimately adopted by Congress in 1990 in a change in the law. Since then, the scope of devices that have fallen to 510(k) has continued to grow and the Agency has made an attempt to try to be flexible to squeeze as many devices under there as seems to be appropriate. But as you can imagine, as the technology continues to evolve, that prior system may not be in the best shape to address the newer technologies. And we're at a point now where we're conducting a reassessment: How good is the current program and the implementation of that program meeting its two goals of assuring that devices that get to patients are safe and effective and that we are facilitating innovation?

As mentioned before, it's not the first time we have done it, and I will tell you it probably won't be the last time that we do it. This world will change, and we need to make appropriate midcourse corrections.

I'll end this part by saying that we are fairly close to issuing, we hope in the coming weeks, our report on the 510(k) program and on the use of science in regulatory decision-making. They will both come out together, and they will be preliminary findings and recommendations that will be available for public comments. We're not going to do anything until we hear back from the public. If we hear fairly strong support for particular recommendations, we may start to implement them at that time. For those recommendations that may be very controversial and may benefit from additional input, we'll put that over to the Institute of Medicine.

As you know, we've got two assessments going on. We have heard the concern that if there are changes to be made, some of the changes need to be made more quickly. Companies feel that they cannot wait a long time, and that's why you're seeing the Agency move quickly to do its assessment, get it out there, and if there are steps we should take now, we can start doing it in 2010. If there are other broader changes for the program more fundamental, we may wait for the Institute of Medicine, because that report is not coming out until probably the summer of 2011, and until we vet that, get input on potentially some additional steps to take, we may not be making any changes until later in 2011, which we have heard from industry and from others may be too late. And that's why you see this two-part assessment.

DR. LORELL: Thank you. First, thank you to FDA for this great meeting today. I'm Dr. Beverly Lorell. I'm a cardiologist and Massachusetts physician and also the senior medical and policy advisor for King & Spalding in Washington, D.C.

I have two questions. One relates to FDA's changing review of the 510(k) summary statements, and the second is a quick question regarding 510(k) devices and home use. On the 510(k) summary issue, FDA has recently signaled that it is now paying more attention and scrutiny to 510(k) summaries. Probably for both industry innovators and for patients and physicians, it's very important to have transparency and consistency in how the 510(k) summary statements are handled and reviewed by FDA.

So, Dr. Shuren, my first question to you is what processes is FDA putting in place to ensure consistency and transparency in how the FDA reviews and manages the important 510(k) summary?

DR. SHUREN: First, the 510(k) summary is a very good question. If you were looking at devices under review at our Office of In Vitro Diagnostics, there that summary is going to be ‑- if you can think about it as the work product of that office, because they have reviewed, they made changes, or if they've written something themselves, it is a good reflection of what the office took into consideration in making a decision and the basis for its decision. If you're looking at devices that were reviewed by the Office of Device Evaluation, those summaries are typically coming from the manufacturer. They may not be an adequate reflection of what the office, in fact, reviewed or ‑- in fact, in some cases, and I've looked at them myself, they sometimes look more like a marketing tool, certain devices.

This is an attempt for us that when there's a summary up there and we put it out for the public, you can actually have confidence that this is what the Center actually relied on to make its decision and the basis for its decision, and, therefore, it's going to be more useful to manufacturers because it would more adequately reflect our decision-making, where currently that is not the case. In that sense, too, the summaries will be more transparent of what the Center, in fact, did.

DR. LORELL: My second question deals with 510(k) devices and home use, and I'm thinking specifically about really the enormous innovation that is occurring of physicians and patients moving some very complex devices, not just infusion pumps, but intermittent respirators use in the home or, what would be another example, nocturnal dialysis. FDA has provided some information about where it is going and thinking about this, including a survey, and can you provide a little bit more insight as to what the next steps will be, the timeline for clarifying how FDA is going to respond to home use of this level of 510(k) device and also whether the survey that's been cited many times is going to be transparent and put out in the public domain.

DR. SHUREN: The next big step is to work on guidance. We need to be more clear about what our expectations are if you are developing a device for use in the home because the circumstances may be different, depending upon that technology and when it is used in a healthcare facility setting. But we have not been clear about our expectations and we need to do that. That, again, will go through traditional guidance development. It will be out there. We will get public input before we finalize anything, but at the moment, we have not yet done that. And that's a critical step.

We are also working with some of the home care accreditation groups to educate them about the safe use of medical devices in the home. Some of these technologies were designed for a healthcare facility. The instructions are for practitioners. They may not be adequately designed for the unique situations in a home setting. Like in the case of dialysis, we've had examples where materials, things from pets, hair from cats have ended up in the systems because they were not designed in a way to keep those out, or the instructions may not be adequate for use for the lay caregiver. We need to be clear about it. But a home healthcare agency can be helpful. If they understand those differences, they may be able to then train or assure that home healthcare agencies are accredited to understand how to use those technologies in the home and assure safe use.

In terms of the survey, a question of discussion, because we're also talking about what additional information needs we will have and whatever we're going to base any decisions on, we'll make sure that information is available for the public.

MR. SCHRADER: Paul Schrader from Philips.

A question about one of the Agency's goals for this year, which has not had a lot of public discussion, and that's the reclassification of Class III products. I suspect part of that is because they are linked in some way to the 510(k) -- overall 510(k) process. So I'd appreciate an update. And I have some specific questions that may follow.

DR. SHUREN: The good news is, it's not held up with the 510(k) review. So a reclassification is under way, and it will probably fall into, you know, the three buckets: the devices that we call sort of the fallen angels, those that are just not out there anymore; those that may be subject to a PMA; and those that would be subject to a 510(k). That is moving forward as quickly as we can make the process move along.

I'll turn -- if folks have any additional comments? No?

MR. SCHRADER: Maybe I can help them with specific questions. In terms of is it the Agency's intent to release all of them or -- the decision all at once, or will they phase the decision, given that the fallen angels I would think would be pretty straightforward?

DR. SHUREN: Yeah, it'll -- when we're ready to come with a decision, we'll make the decision. We're not going to hold up to do everything at once.

MR. SCHRADER: Okay. So is the framework -- I mean, the data was provided last August. It's 10 months since then and, here again, it doesn't seem like there's been a lot of progress, so I'm wondering what the transition rules are. For example, if you have a product that's being submitted at this point and say a month from now the Agency makes a decision, what thought has been given to the transition rules, if any?

DR. SHUREN: That's one of the -- that is one of the considerations that we have, what the implications will be; if we were to change the status of the particular device, what that means for devices that are coming before us. And we have that same issue -- and I'm telling you as much as I can tell you at the moment. Folks should realize sometimes in government, you can say only so much when they're still under consideration because we've not made a final decision. So it is not an attempt to be evasive; it truly is the most I can say right now. But the issue you raise is a fundamental issue. It's not just limited to this reclassification. It's actually at the heart of an issue that was raised earlier today about what happens when the Agency's regulatory expectations change. And even if it's legitimate for that expectation to change -- say, we have a new safety concern -- what do you do with the application that's sitting before you today that you're about to make a decision on? What do you do with the technology that's under development? What do you do with the technology that you just approved or cleared two days ago and is now on the market? These are fundamental questions. Because on the one side, yes, we do have to protect patients, but on the other side, we've got to be -- also think about what are the implications for the development of safe and effective technologies, and if we make the wrong steps and we lead to unnecessary delays or burdens, that also hurts patients who don't get those technologies. And those are the exact considerations that we are grappling with right now. We're going to try to provide a little bit more clarity when we come out with that report on the use of science and regulatory decision-making.

MR. SCHRADER: And one final specific question. We were involved with a reclassification petition associated with one of those products, and I think, by rule, you have 180 days to respond. I'm just wondering if that will ever be addressed in any fashion, given that it seems like there's going to be one announcement. If you could speak to how you're going to handle reclassification petitions that went in?

DR. LUKE: Did you say it's one and -- it'll be -- I think there'll be each individual product area we'll be looking at in time, and we'll look at the science basis for any change in classification, should one be warranted.

MR. SCHRADER: Understood. But I'm under the impression that the announcement for all 20-plus products will come at one -- and I'm not really clear what the process is once the announcement is and what the transition rules are, et cetera. There seems to be a lack of clarity in that area.

DR. LUKE: I'm not sure what you mean by an announcement. There was an announcement regarding the docket being open for comments.

MR. SCHRADER: No, the final decision, I guess. Right now, you have to make a decision on reclassification for 20-plus products, and each of those will be considered in turn. Okay.

DR. LUKE: And as part of that, then there's a reclassification petition that will be addressed as part of that process.

MR. SCHRADER: I'm not sure exactly --

DR. SHUREN: Yeah, if it's part of the submission for the docket, then it may be included within that determination.

MR. SCHRADER: Okay. Thank you.

MR. RANKIS: Hi. I'm Art Rankis. I spoke earlier, and I'm back. But my question is the background -- we heard this morning and I think we're all aware that there have been a lot of changes at the Agency, organizational changes. One speaker mentioned that he believes that a cause of that has been a reaction to the Menaflex issue. There's been other changes. People have spoken about not being able to communicate with the Agency, big periods of silence. Obviously, at least to myself, there have been a lot of changes. The question is what do you guys see as the driver behind those changes; is anything being done to rectify some of those more immediate changes that we're seeing today, and has a change in thinking occurred -- more important, has a change in thinking and policy occurred that's going to carry over to the revised 510(k) process?

DR. SHUREN: Well, first of all, very good questions, but a lot of things on the table. So let's take each of them.

ReGen. ReGen is an unusual case, and it should be viewed as an unusual case. That's where there were concerns about undue pressure from outside the Agency on the pre-market review process. That's why the Agency undertook its own investigation and it came out with a recommendation to do a reevaluation of the administrative record for the ReGen Menaflex device to decide what the status of that device should be. Conclusion was made that there was insufficient information to determine whether or not that influence truly affected the final decision that was made in the case of the device. That is separate. ReGen is separate.

I will say on the flip side, what it does show is the Agency has a commitment to maintain the integrity of that pre-market review process, that we keep the people, the experts who are reviewing a submission, separate from any political influences. And that's what it shows. That's what ReGen shows. But it's a unique situation.

In terms of what are we doing for the issue about consistency in decision-making, you're going to see what our findings and what our recommendations are pertaining to that in these two reports that we're going to issue in the coming weeks. I don't want to get into it because they're not -- they are not public yet. But it is an attempt to address those concerns and I think, as raised, this has been going on for a few years; there's an impression that this may be increasing as time goes by. We take that very, very seriously. And I think you'll see in these reports that we have done our own evaluation and we have a number of things on the table in terms of what to do.

For changes in organization, there have not been major fundamental changes made as of yet in the Center. There are some that are under way and there are some that are being contemplated, and it is important to address this issue about assuring that we are consistent in what we do and to ensure that we are the most efficient in what we do.

So, for example, when I came into the Center, it had a very -- it was a much more siloed organization. The folks here can disagree with me, so I will let them chime in as well. But we had essentially eight different offices. One office was the office of the Center director. It had its own small little pockets of programmatic function, but it did not have much capacity for oversight of the other offices and for a sort of central-wide strategic policy development. That is something that I have tried to change since coming in the door.

One thing we are doing is bringing on two deputies and taking the science programs and bringing together under one deputy Center director for science, have greater alignment across our pre-market review offices and with our programs for both compliance, post-market surveillance, and our laboratories because we do need to do that and have that better coordinated. That is in the works.

We are also contemplating more fundamental reorganizations within the Center to actually break down some of those walls between the offices. The way the Center did it before is it created a matrix structure. It had what they called network leaders, an individual who was responsible for a particular product line, and when an issue might come up, they would try to connect the different people in different offices to address it. A matrix structure can be very challenging to maintain and very hard to be successful.

We did an internal assessment of that matrix structure, and we concluded it's probably not the best organization we should have right now, and so we're exploring other options. We are going to come out in July, by the end of July, with what we are considering for potential organizational changes at that time.

MR. RANKIS: What about the more day-to-day issues of people who can't get a response, people who have a de novo process which suddenly takes two or three times longer, people who have commitments made to them in the pre-IDE process, and those seem not to be those changes, but they have certainly occurred, and my biggest concern is that whatever the thinking within the Agency is today, if that carries over to the new 510(k) process, I'm not sure it's going to solve those issues as opposed to perpetuating some of them.

DR. SHUREN: In terms of what's happening today, first off, is when problems arise, is that if you're not -- if things are not getting resolved down at the reviewer level, they do need to be elevated. They do need to be elevated. And I've heard from companies, sometimes companies are fearful for doing that because they think it's going to be taken out on them by the reviewers. If you don't raise it up through the ranks, people don't necessarily know. And as a result, you may be allowing staff to have more of a control on it than may be maybe appropriate.

Now, on the flip side, I will tell you there are times when I've looked into it where a company has raised a concern and the review staff and the branch are absolutely correct, backed them. And other times, we have found that no, we disagree, and we start to make changes. But it's got to be raised up so that we understand it.

I've been very clear with my managers, you have to manage; that's what you are there for. Congress -- I'm going to go on for a moment because I feel very strongly about this. Congress gave the authority on our Agency, first, for the Secretary of Health and Human Services. That was delegated to the Commissioner. The Commissioner delegated some of it to me, and I've delegated it to some of my managers. That's as far as the delegation goes. Below that, there's no congressional authority. You've got to let the managers know.

You're going to see in the reports that come forward -- and I know people want change immediately, but to change an organization takes a lot of time and effort. There are about 1300 people to do that. We have gone through -- and if we're going to make changes, we're going to make it based on the best data we have, and we've been going through that process now, trying to get beyond just anecdotal reports, which we take seriously and we'll look into, but we've got to understand how big of an issue are we dealing with and do we have them all on the table so we make the right changes. We will address in those reports steps regarding consistency, and we're going to address the de novo process and what our thinking is about the de novo process and what we would recommend doing on the de novo process for making changes, and everyone in this room is going to get an opportunity to weigh in on what we found and what we recommend before we do anything.

DR. GUTIERREZ: I also feel strongly, so let me address some of the issues. You know, not only in this meeting but in Minnesota, we've heard a lot of complaints, and clearly there are some issues here. There's no question. And there are some companies that have been treated not in a way that we would like them to be treated. That's a lack of communication and files that have gone too long. But the truth is that, you know, there's going to be pockets of having things you'd like.

If you -- if we looked at data that we do have, for example -- and I'm going to speak mostly to OIVD because that's the one I know. We actually do a survey every year of all the manufacturers and we try to see what's going on. We ask about fairness. We ask about how you were treated. We ask about timeliness. We ask whether the process was something that was good or not and the data for the CRA, and they look almost exactly like the one from the year previous to that and the year previous to that. Most of what we're doing seems to be good.

Now, there are pockets, I know, because some of the complaints that happened to it now happen to be under my office, and I know that there are issues with some companies at some point not having been treated correctly and that we do have some managerial issues that we need to deal with. I'm not trying to deny that. But, in general, I think also that there are also some good things. There are lots of very passionate reviewers on both sides. I can tell you probably my most passionate people who tell me about not -- not actually over-reviewing are a lot of my reviewers. A lot of them have come from industry. They actually understand industry. They actually help us figure out how to do things.

So at CDRH, we have a lot of different issues. We have a lot of different areas. Some of them probably have issues that we need to deal with. Some of them are performing well. And we need to look at the whole -- at everything that we're doing and we need to make changes rationally. We don't actually want to make changes in those divisions that are working well and actually break something that isn't broken.

MR. RANKIS: Thank you.

DR. LUKE: If I could also comment on the pre-IDE submissions and the pre-IDE meeting? Pre-IDE meetings are intended to be a sharing of information, a dialogue between the Agency and industry prior to submission of a product submission for an IDE. The pre-IDE meetings that we have, we don't always make commitments. I think the notion of a pre-IDE commitment may be overstating the actual discussion that is had at the pre-IDE meeting. Remember at the pre-IDE meeting, we don't get the full submission. We don't know what you have exactly in mind for a clinical trial. And oftentimes, we often see that there isn't the expertise in the room from either the sponsor's side or the FDA's side to address certain issues. And so those are -- it's an exploratory meeting to have that discussion.

And the pre-IDE meeting is only as good as the actual submission that's presented to the Agency prior to having the meeting. So make sure that you have a proper submission package for us to consider when you schedule a pre-IDE meeting. And we do encourage having these meetings simply because it allows us to learn about your product before you submit it and for you to learn a little bit about what some of our expectations are.

Thank you.

UNIDENTIFIED SPEAKER: I have what I think, I hope is a fairly simple question. There's an old expression in my family that 99 percent of the problems happen when someone gets surprised. And a lot of what I've heard from this room today and what we've experienced in our industry is that there's a lot of surprise when the formal methods of communication through FDA, which are very well established, come back with a result that is something other than what we expect.

My question would simply be there is value in being able to have informal lines of communication with the people who are regulating industry, and there are specific members of CDRH staff who are responsible for interfacing with members of industry. Would you support a policy within the Agency that those members of the staff make themselves available for some limited period of time, perhaps each week, that they are going to be there and be able to be responsive to informal requests for guidance from industry?

DR. SHUREN: We have guidance for our staff on interactive review to encourage them in terms of the use of informal communications, whether it be e-mails or phone calls. How well that is followed or instituted has been variable.

In part, by people -- in part, I will say on the flip side, too, we are finding in some cases with workload, too, the workload for our staff has been going up over the past few years. They are seeing their plates just get taller and taller orders, and the same token, getting requests and inquiries coming in from companies. We would like to be in the position where we have much more of the back-and-forth, try to address questions, not get away from the formal communications as much as possible, to give updates on where we are. There are things that we need to do better. There are some things where we're going to hit a limit just because of how much work is on the table. And I will tell you on the flip side that perspectives sometimes of companies -- some companies, not all companies, but some companies, has also been unrealistic. Because I've had that in my case with companies who come in the door, demands that we need to hear this and we want that, and if you haven't done it, you're terrible, you're horrible. And, you know, their expectations are just in the wrong place. There's a lot of work for us to do on both our ends. But I think we have a shared interest in -- getting to what you've at least put on the table generally, about more of that informal back-and-forth to try to solve issues.

I think the other challenge with technologies are do we have a good understanding of it for our side? And, of course, when we deal with a newer technology, it's less likely we're going to have the in-house expertise. What we absolutely need to have are the experts who can talk to the experts outside of the Agency and understand it.

One of the commitments we have made in our priorities is to set up for a network of experts so that we can tap the understanding and the knowledge and the experience of people outside of the Agency, particularly when we're dealing with newer technologies. But to be able to do it, you need the right experts inside to have the dialogue. In many cases, I may have one person in a particular medical field; in some cases, I have none. And you can imagine -- I'm a neurologist. You do not want to send me to have a conversation regarding orthopedics. You can, but I'm not going to understand it in the same way as an orthopedist will, particularly when I'm dealing with newer technology. So that's one of the challenges I have to deal with as we move forward.

MR. SILVERMAN: I think that the points that Jeff makes about the challenges that we face in receiving information and, in particular, receiving information about problems that industry members are encountering in the course of their own work are entirely valid.

One thing that I think that's interesting, though, is the opportunities for FDA to work collaboratively with regulated industry when we decide that there's an area where we want to engage.

There can be tremendous, tremendous benefits from partnering in some contexts, for example, with information sharing. So to your point in your presentation about letting folks know what FDA's expectations are and using industry members as a conduit for providing that type of information, I think there are real benefits to be gained. And so while we do face challenges in terms of putting the information in and deciding where it is that we're going to stake out our areas of concern on how to decide to act, we do look for opportunities to communicate and to bring about change by partnering with the folks who we are regulating.

MR. LEAHEY: I'm Mark Leahey with the Medical Device Manufacturers Association.

First, again, I want to thank the CDRH leadership for your willingness to participate today and across the country and in Washington. I think the level of engagement has been very helpful given some of the challenges that we heard about today.

I just have two brief recommendations and then a question. First, in the kind of notion of transparency, kudos to FDA for the new transparency website. I think there's a lot of good information out there for the industry. Recommendation would be for programs like the corrective fixes or the signal escalation in which, you know, industry had heard rumblings for, you know, a few years that this was going on but really no confirmation. I think that would be a great platform to, in real time, provide information about the rationale for these new programs so that industry has a better sense about what's going on and what the intent is, how they can work collaboratively versus just guesswork, I think, that occurred with a couple of those programs.

Second recommendation, I think that OIVD survey, that was actually the first I've heard of it, and maybe something comparable on the ODE side as well so that, again, we can get a sense about what people's experiences are. That, hopefully, will give more visibility not just in OIVD but across all CDRH about the industry's experience.

And the question I have relates -- and, Jeff, you had just talked about the expertise in kind of a thin bench. I think one of the areas that our members have faced challenges -- and you all, to your credit, are trying to address this now -- is dealing with the FDA panel process, and part of that lies with the, I think, panel composition and changes in the law, FDAAA, about expertise waivers that can be granted through conflict of interest, and yet there seems -- so there seems to be an erosion of the scientific expertise for the real specialists, perhaps because of the conflict of interest requirements, and yet new FDA policies are moving away from the approval/nonapproval vote within the panel to something that's more science-based and not regulatory-based. And so how do you reconcile a move focusing the panel away from approval or nonapproval to more science-based, and also with the environment in which, again, your hands are tied in some respects of getting the necessary expertise you need on those panels?

DR. SHUREN: So, again, always the very simple questions with no parts to it, so I appreciate that.

Signal escalation, just so folks know, it is a work in progress. This is really an attempt for the Agency to be much more regimented about deciding what is a signal that merits further follow-up, and then what ultimately constitutes, rises to the level where we should take an action and what action should we take. We're still in the stage of working that through.

We've got a pilot ongoing right now. There's nothing that's been done. It's actually not the case of anyone ‑- the Agency just throws anything in a database and we're going to then act on it. It's actually the exact opposite so that we move away from that kind of model. But we are much more regimented and have criteria for what constitutes a signal and how we act on it. We're going to talk a little bit more about it -- I hate to keep going back to these reports that you can't see because you probably find that unbelievably frustrating. If we held this meeting in a few weeks, we would probably be talking about a whole bunch of other things. But we'll talk about it a little bit there, and we will have more to say about signal escalation over the upcoming months. But that's a way for us to actually be better about determining when we should be doing more and making better use of the information that we get. So it's not just, "I have a few MDRs and therefore I'll do this." Well, what other experiences are relevant? And we can put it together and have a better understanding of the risk-benefit profile for the particular device or kind of device we're dealing with.

Corrective fixes, we'll actually talk about possibly can we put out more clear guidance about what we would put in that category of, "You should have made this a recall and not handled this as a 510(k)," because it did get set off with companies where, in our belief, these were cases of it classically would have been a recall, and, instead, the company, from our perspective, opted to just submit a 510(k) instead, and said, "Oh, what we're really doing is we've decided to improve the product." You had a problem with the product and you're now fixing it, but you didn't do the recall as should have been done. That was the basis. But we will talk about maybe providing greater clarity on that because we understand that point.

The panel -- the panel is challenging. First off -- I mean, we agree there need to be appropriate conflict of interest rules in place. Obviously, the rules of the road changed recently, and Congress changed those rules, and it creates challenges for us. I think the issue about the kinds of questions that the panel answers is irrelevant as regards the conflict of interest rules. The people we bring on board are to address scientific questions, not regulatory questions. They're not the regulatory experts as to what is the standard for PMA approval and, in the cases where we use a panel for 510(k), for them to be experts on making substantial equivalent determinations. Heck, if anything, people are sort of complaining are our own people sufficiently expert in making those decisions and not the academics that we may be pulling from institutions to sit on the panels.

So one of the changes we've made is to make sure we get the scientific experts focused on scientific questions. The ultimate determination on whether or not to approve or clear a product still is one that the Agency has to make. We'll take the advice that comes from the scientific experts on the panel into consideration.

Having the right experts on a panel is itself a challenge, as you have raised. We are looking at ways to take that into consideration and to try to address other questions that don't have to be in an advisory panel setting by looking to other experts that may be outside of the panel process. We're not going to circumvent the panel process when it's appropriate to use and the kind of questions that go to them, but we can make better use of experts out there particularly to better understand new technologies, and those kind of questions we can ask without going through a panel process. And that's one of the priorities we have for the Center.

MR. LEAHEY: Thanks.

MS. WEAGRAFF: Dr. Shuren, Pam Weagraff, Quintiles Consulting. I have -- everybody knows who I am? Good. Okay. Pam Weagraff, Quintiles Consulting.

My question -- first, I'd like to make a recommendation, and then I have a question, and I promise it just has two parts. The recommendation is the Office of In Vitro Diagnostics routinely publishes the decision rationale for 510(k)'s when they are cleared. That does lend a certain amount of transparency to industry in terms of what FDA's current thinking is with regard to clearing a particular IVD. It would be lovely to see ODE adopt a similar practice as aiding transparency and then more readily communicating what the Agency's current thinking is in reaching their decision of substantial equivalence.

To my two-part question, it has to do with conflict resolution, and there are two key pieces to that. Number one is perhaps a short -- the short part, which is with regard to the CDRH ombudsman. Understandably, Les Weinstein has moved on, and I wish him all the best, but we're missing someone with his wisdom and capability to approach to resolve issues. Could you comment on what the status is with instituting a new CDRH ombudsman?

DR. SHUREN: So to the first point about ODE issuing 510(k) summaries, have the rationale much like OIVD is doing, you're going to get your wish. We've committed to do that. We're going to start doing that this year.

MS. WEAGRAFF: Great. Thank you.

DR. SHUREN: So both will be doing the same thing.

DR. GUTIERREZ: Can I take that for a second? Well, to be fair, the reason that OIVD was able to do that was because we actually have very good regulations in terms of labeling. So it was easy to transfer the labeling into a template that we could do the reviews that we could post without having to worry too much about allowing data that the companies would consider proprietary. And so OIVD has been doing this now since 2004. It is time-consuming. It is especially time-consuming on our management because they have to make sure that nothing that is proprietary to the company goes up on the web. So it does create some work for management that I think OIVD is going to find difficult to do.

Since we have a division that has moved from ODE to OIVD, we're actually committed to begin doing that and trying to lay the groundwork for ODE to be able to do that, but it's going to take a little work for ODE to be able to follow suit with what OIVD has been doing.

DR. SHUREN: And it also requires some degree of cooperation from the manufacturers, and I think you'll be hearing about that soon.

MS. WEAGRAFF: Count on me being able and ready and willing to help my clients do that.

With regard to the ombudsman?

DR. SHUREN: Yeah. So the ombudsman. Right now, we have a person acting in that position, a Dave Buckles, who has been at the Agency for many years and is very, very knowledgeable on CDRH's work in a number of offices, and he's got, I think, the right mindset for the job. But he's in an acting position. We are looking to fill that permanently.

MS. WEAGRAFF: Okay. And the second piece on conflict resolution, there is a guidance document that talks through when reviewers disagree, how to resolve those differences, and it goes up the chain of command. And what I've experienced through multiple clients multiple times is that the branch chiefs, multiple branch chiefs, and, in fact, some division directors are much more hands-off, and, therefore, the kind of back-and-forth is going on and on and on. And, again, you know, not knowing what the root cause is for some of the delays you've heard about today, I wonder if you'd be able to comment on that conflict resolution process as it seems that the check-and-balance that was between management and the reviewers is no longer functioning as it did a few years ago.

DR. SHUREN: I see two pieces to it. The issue about managers being managers was one that I heard rolling in the door to CDRH. That we are working on, and that's, in part, some of the changes that we are making in terms of management structure and organization to address that because they have to be managers. They are responsible for their decisions even if the reviewer says -- you know, the review team comes to a conclusion. When you sign off on it, it's your decision, period.

The process we have in place we modified because the older process had weaknesses, and what we've done is made changes that are actually more in alignment with what goes on elsewhere in the Agency. We're much more consistent in what we do there. We're more consistent in terms of what we do as compares to other agencies. In fact, we had an outside consultant take a look at it and thinks that the processes now are actually fairly robust, that we may have gotten it right.

Now, I understand the concern about it's these many layers or the opportunity for it, isn't this going to lead to unnecessary delay? It's something we're monitoring to see what the impact will be. We do have the opportunity, though, to sort of jump the queue, if you will, under certain circumstances where it can be elevated directly to me. I will tell you, though, since we put it in place, not one single instance of it's being -- for when it's been used has it ever risen up to my level. It's all been resolved before ever getting to me. So in that respect, maybe it's having some success, but I think it's too early to tell. And if we need to make changes, we'll make those changes. We'll do it.

MR. MOON: Hi. Tim Moon from Sparta Systems.

Any updates on the eMDR initiative?

DR. SHUREN: On eMDR, we need to finalize regulations on that, and that is moving forward. I can't give you the time frame other than hopefully it's going to be more on the order of sooner rather than later. But once a rule is out for review outside of the Agency, I have no control on that process, absolutely no control.

MR. MOON: Thank you.

MS. GARRIGAN: My name is Maria Garrigan from Bayer Healthcare Pharmaceuticals, and my question has to do with personalized medicine and the in vitro diagnostics or the tools that are used to select patients for treatment with drugs. I was just wondering if you can comment on when you expect the guidance to be finalized that describes the criteria for approval tools, and also how do you envision the interaction between CDRH and CDER in the approval of the drugs and the IVDs, who would take the lead and how is that communication coordinated?

DR. GUTIERREZ: This is an issue that has been on the table now for many years. We originally put out a white paper in 2004, 2005 on co-development, and it has not been an easy road. We really -- it's been -- CDER does things differently than what we do, and getting the two regulatory paradigms to coincide, it's been difficult.

Now, Dr. Hamburg promised that we would be publishing a co-development or some type of guidance this year. I'm actually right now very hopeful that this is moving. We actually have a group of people from CDER, CBER, and CDRH working hard on coming out with some form of guidance in the near future.

Even without the guidance, though, I can tell you that the number of submissions that we have seen in which a drug is now depending on a diagnostic has increased tremendously, and we are -- we have many, many consults or many thousand which we are co-reviewing with CDER at this point. And I do think that that, if nothing else, would lay the groundwork as to how this will work, and things are at this point moving fairly well.

MS. GARRIGAN: Thank you.

MR. NEUGEBAUER: Yes. Good morning. John Neugebauer -- I wouldn't make that name up -- from Koning Corporation.

First, a comment and then a question. One of the speakers this morning spoke about the ReGen situation and mustering congressional support and whatnot, and I'm really not going to talk about ReGen, but what I do want to say is that when communication comes to a standstill, many of these companies really have no place else to turn. And I'm not suggesting that Congress should get into your daily business, but it becomes a point where how can the communication begin to get started again. So if we want to avoid congressional interference or whatever from outside activities or people, we've got to fix the whole communication thing.

And the second question is basically the radiology producing products have been moved into In Vitro Diagnostics, and I just would like to know if you could give us some rationale for that, and will that change later on and go back into the radiology branch, or am I misinterpreting how that's taking place?

DR. SHUREN: In terms of communications, you know, as I mentioned, if there are issues, they need to be raised up, you know, within management within the Center. If we're getting to the point where there are problems beyond that, it's further up within the Agency. And, quite frankly, when I hear of, you know, if there's been an issue or problem and I'm learning about it because some congressional member is coming complaining to the Agency, then I'd say the company maybe didn't pursue it in the best ways. You've got to raise it up to us first. And I think some companies who have been willing, that when things have not been -- if they feel they're not getting some answers and they've raised it up, we've actually looked into it. Sometimes it's led to or is leading to changes in how we're approaching that technology. Sometimes we may be reaffirming. But communication is critical along the way that we're doing that one right.

In other cases, there may be decisions made, and then we have more formal processes for how to go about it. I will tell you my perspective on that is we've got to stick with that process, those processes, and not go around it. If we go around for one, we've got to do the other. And one of the issues has been all these exceptions being made, and that's created not only more confusion, it's actually led to my staff having mistrust about some of the more -- you know, about management for the Center in some cases. And that's something I'm trying to address by we'll be open within our Center and we'll stick with those processes.

In terms of the move to -- I'll be frank with you about the move to OIVD. There were concerns raised by some of the staff at the time of that branch regarding their interactions with management, and I have been looking into that. You are probably all well aware that some allegations on criminal conduct and wrongdoing were referred to the Office of the Inspector General. The OIG came back and concluded their investigation and they found no criminal wrongdoing. But as this was going on and concerns were raised, I went to the staff and I went to managers and said, here's what I can do: I can move that branch to another part of the organization, and here's where I'll move them and here's why. But I can do that if, as we're going forward in our investigation, there are concerns about those interactions and people having fewer retaliation. And there was uniform agreement by both the staff and the managers to make that change. And so I made that change.

The reason they're over in OIVD is that in many cases for the radiological technologies we're dealing with, the way of assessing them is actually more in alignment for how we review some of the diagnostics over at OIVD. So the mindset was not all that different. There are some technologies that are reviewed more traditionally for many -- as many of the other devices in ODE, and that's an issue that we deal with. But putting it over there actually for a number of reasons, in fact, made sense, and I think that transition, in terms of the approach, has, to date, worked relatively well. I don't know if you want to opine a little bit more?

DR. GUTIERREZ: Not on that part, but I'll opine on the first part. Actually, if there's a breakdown of communications, it may be the companies are afraid to bring it to upper management, the issues to upper management, either because they think that they are going to be retaliated against or for whatever reason. If that is the case, I can tell you I want to know if there's an issue in my office, and if I can't assure you that there's not going to be any retaliation, I'm not doing my job. My job is to make sure that the office works, that we are fair, and that we don't retaliate. If there is an issue with timeliness, I want to know about it, my division directors want to know about it, I want to know about it. If you don't bring it up, we can't fix it. And unless you bring it up, you know, we're not going to be able to do anything. It may take some time. Sometimes those issues are difficult to fix. We will try to keep you updated as to what we're trying to do, how we're trying to do, and we'll -- you know, we will try to move things along.

MR. NEUGEBAUER: Thank you.

MR. SHOEMAKER: Good morning. Brian Shoemaker, ShoeBar Associates, a software validation consulting and software quality consulting.

A few weeks ago at the software design for medical devices conference in San Diego, Rick Chapman of OSEL mentioned to us that there's a change in expectation at least in some kinds of 510(k)'s to a different sort of organization, more the assurance case, safety case kind of organization. Not that I'm disagreeing with that at all. I think there's a logical organization that makes a lot of sense for approving the safety of a device; however, it's a pretty deep and fundamental change in the overall organization of the kind of documentation that needs to be pulled together, which I'm sure is of great interest to a number of people who are on the ground doing these kinds of things in this audience. Can you comment on whether that's going to become a more general expectation in 510(k)'s moving forwards, or is that something we should be expecting as part of the reports?

DR. SHUREN: So we went ahead and we did make that change in dealing with external infusion pumps to use the case assurance approach, and it is a way of pulling together the information and making a case for that technology. And we think, certainly in the case for infusion pumps, that can be very helpful. One of the things we have found is that important information can be in different places in a submission, and you've got a reviewer who now has to pull it together and then tries to understand what was the company's thinking and then has to go back to the company and ask, much better than -- pull that together.

You're basically making your -- stating what your case is, giving your evidence and sort of arguing it. That's really the structure that is put together. And that might actually reduce the need for follow-up questions and issues about, "Oh, that information? Oh, it was sticking on page," you know, "335," even though the thing you were originally looking at where you thought it would be would be on page 27. So that's the potential value. And, yes, it may be something that you can see for consideration in the report when it comes out.

MR. OHANIAN: Thank you. Peter Ohanian from Philips Healthcare.

Two questions. About a year and a half ago, FDA published a proposed classification for medical device data systems. Can you provide a status of that? And, second, what are your plans to classify and regulate electronic medical records?

DR. SHUREN: So for the MDDS rule, we are continuing to move forward on the regulation to try to finalize it. That is in the works. I don't have a specific date other than it's moving forward through the process.

MR. OHANIAN: Is that a priority?

DR. SHUREN: Yes, it is because we know this area in terms of, you know, technology for the electronic transmission and compression, analysis of data is of great interest to industry and we are -- and to patients and to healthcare practitioners, so we are moving forward on it.

In terms of electronic medical records, there is this ongoing dialogue right now about what, if any, role FDA should play. I think we have been clear in the past we view them as medical devices, but we have not asserted our authority generally in those circumstances. We have been part of a dialogue that's being coordinated by the Office of National Coordinator for Health Information Technology, and they have been looking at what role the Agency might play. They established an HIT policy council committee that has been opining on that issue. Their recommendations are out there for the public. And now the government is sort of trying to come to a conclusion about what, if any, role that may be, and I think in the broader context of how do we facilitate innovation and adoption of EMRs, but also assure patient safety in moving forward.

MR. OHANIAN: Thank you.

MS. ROBINSON: Good morning. Rosina Robinson, MDCI.

My comment and question has to do with the issue of predictability. For someone that's been in regulatory for a number of years, as you can tell by my gray hair, it used to be that when we submitted a document to the FDA, we could be fairly certain of the anticipated response time frame, not necessarily absolutely predict the review time, et cetera, but we were sure of the Agency's expectations and we could counsel our clients on what they should anticipate one way or the other. It seems like right now when we develop the regulatory strategy, it's the eight-ball strategy, you know, shake the eight-ball, look at the response.

There have been changes in increasing unpredictability in even things like 513(g), request for classification submissions. I've been involved in two that are now close to or past the 90-day mark, and the statute indicates a specific review time, and the only response that I get is the branch isn't finished yet.

DR. SHUREN: So -- I mean, I think there's been a lot of discussion today about predictability, and I hope it's evident to everyone here we take those concerns very seriously and that we are going to be talking to that in the coming weeks. 513(g) and everything else, much of this has been caught up with, in part, the workload and, in part, some of the uncertainty within the Agency itself as we move forward and where things will ultimately end up with a variety of the different programs that we have under review at the moment.

MS. SALLAM: Maha Sallam, VuEssence.

I would like to take us back a little bit to the question of review processes that take, you know, an undue amount of time and very prolonged. The submitter is often in a very difficult position because they are trying to work through the process with the branch or at the reviewer's level and, you know, they try to accommodate FDA request questions. They move through the process as much as possible, and at some point it becomes, you know, six months, eight months, whatever it is past the regulatory review period, and we're still kind of trying to work through that submission. And it's very difficult sometimes to elevate the issue because you don't know if you're really close to the end and you're going to disrupt that process by elevating it, or you should be elevating it because you're not going to get to the endpoint because there is some fundamental issue that you're not aware of and it can't be resolved. Would you consider doing systematic reviews perhaps of submissions that are way past due? I'm not talking about something that's just past the 90 days or whatever it is, but maybe a 510(k) that's been under review for approaching a year. Would the Center consider doing systematic reviews consistently of all submissions that reach a certain level beyond the statutory guideline and consider assessing the status of those submissions proactively versus waiting for a submitter to come in and approach a higher level to where they feel they may be jeopardizing their existing relationship or process they're undergoing at the moment?

DR. SHUREN: So to answer your question, yes, we would consider that, you know, for individual cases as they go forward. I will tell you the ones that do take longer, things are monitored, and, in fact, we are currently doing an assessment of 510(k)'s that are much farther out from the time frames to kind of see are there characteristics, what is it about in those circumstances that actually led to the longer review times? Was it things on FDA's part? Was it something on the company's part? Was it something about the technology? What actually are the factors? Is there something different about this group of devices, the people who dealt with it, than the ones that we reviewed in a more timely time frame?

That said, I will also tell you that generally for the time frames that we have under Medutha (ph.), for the most part, we are actually meeting those time frames. There are some places where things aren't quite there, but for the most part, the data showing in the majority of cases, we're actually doing pretty well. And it's in a smaller subset where there are kind of the questions, and in terms of the program, for the most part, things are moving along pretty well.

I'm going to back up on another point when we talk about clinical data. You know, on the OIVD side, most of the submissions have some kind of clinical data. That's been going on a long time. And interestingly enough, for the most part, we don't get a lot of complaints or concerns raised on that. On the ODE side, it's only about 8 percent of the 510(k)'s in which we request clinical data. Over 90 percent, there's no clinical data at all. And we understand, though, the need about can we, ourselves, be more predictable and clearer about those expectations, and are those expectations appropriate for what we're asking for. But I do want to make sure folks are aware that we're talking about a smaller group of devices, whereas the majority, time frames and things are moving along, at least from the data we have, fairly well, and most of them are not involving clinical data at all.

But your suggestion is a very good one. We'll take that back.

MS. WEAGRAFF: A quick discussion or continue the discussion around informal pre-IDE meetings versus the formal collaboration meetings, determination meetings, early agreement meetings. On the pre-IDE meeting side of things, it's understood -- and I certainly counsel clients on a daily basis that it's an informal setting. The information provided is not legally binding on the FDA, and as new information is collected, that that may, understandably, if its safety or effectiveness around the device, alter the Agency's thinking. However, on the flip side of things, if a company, large, small or somewhere in between, chooses to go the formal route -- in the past, I've done that on a number of occasions, and the Agency has more consistently than not recommended not going the formal route because of the burden it places on the Agency, et cetera, et cetera. So the conundrum is, there is a mechanism in place to get legally binding input from the Agency, but it takes a long time -- the agreements tend to be very conservative versus the pre-IDE. So what's a company to do?

DR. LUKE: With discussion of agreement meetings, there is a mechanism and there's actually a regulation about how we can have a formal agreement with a company prior to you starting your investigation or program, as to what the informational needs are, in order for us to eventually get to a marketing decision for either approval or disapproval. It's not necessarily the product be approved because you don't know what the outcome of the clinical study is. Of note, very few companies take that route. In my experience, I've only seen one or two companies over the last two years take that route. So formal agreements are a rare bird.

MS. WEAGRAFF: But the conundrum is not getting an assurance that the product will be approved, but rather getting an assurance that the Agency agrees to the study design, the study endpoints, inclusion-exclusion criteria, et cetera. Specifically, in the Bayesian statistics guidance document, it recommends companies to seek formal agreements with the Agency. So I'd be curious to know how many companies have actually pursued it in line with Bayesian statistics designs.

DR. LUKE: Along the lines of statistical agreements, you get into a priority decision-making for how you want your clinical trial analyzed and you need to come up with a specific statistical plan to have an agreement. These are all trying to control the various variables prior to approval or prior to having the particular study go forward before you actually do that study. And there is significant risk to that, and I think companies that are willing to take that risk will go that route. But along with that risk comes predictability because you know that I'm willing to put so many dollars into the study, I know that it's going to have sufficient statistical rigor and clinical trial design to meet the level of evidence that the FDA would require for a firm decision on approval or nonapproval of the marketing application.


DR. LUKE: Very few, very few. And the reason may be -- and this is very different from the CDER environment where there is a process for SPAs, special protocol assessments, whereby you can have, coming into -- I don't know how many folks here work in the drug regulatory environment, but I know some folks are pretty -- can work in both areas. In that area you come in with a clear expectation of this is my clinical trial design, this is my statistical plan, can we go forward with this; and you get a prior agreement, then you get really good predictability.

That's not something that device companies have been willing to pursue, although the route is available, and we would encourage companies to come in and explore that possibility. I don't think we've ever dissuaded a company from going that way, that direction specifically. I think if a company feels that the particular information or pieces are too onerous for their development in the program and they want to pursue a different route, then there is a different risk set that they need to understand. It's all about risk and decision-making.

DR. GUTIERREZ: So let me see if I can help. Essentially choose your poison. I guess the place where I could tell you there is some experiences, that CBER actually also regulates some in vitro diagnostics and they actually have formal meetings. Companies tend to prefer not to have for us -- at least with us, it tends to be, again, you can get predictability, but then we tend to be very conservative. In the end, I think that, you know, the question is what confidence do you have that whatever commitments the Agency made in the pre-IDE meeting that was not formal, whether the Agency will keep those commitments or not. And we should. And in most cases, unless we have a very, very good reason as to why we don't keep the agreement -- you know, whatever we ask, whatever we came to an agreement with the company, we usually try to keep to those. We should not change that.

There are times when there are good reasons why we don't. Whether you give the company a lot of flexibility to -- because if they don't make a commitment, many times the companies don't actually follow through exactly with what the commitment was, and they come in and we look at their data without any regard as to whether they actually kept the commitment or not, and we look to see whether the data actually backs the claim they're making. That's the benefit and the risk of what you do.

MR. O'LEARY: Hi. I'm Brendan O'Leary. I'm from Prism Ventures, an early stage venture capital firm.

My question is actually very related to the SPA question. We do both drugs and devices. On the drug side, many companies take advantage of the SPA process. You know, probably more should, but, you're right, it is fairly onerous to go through the process. On the device side, even though now many of the trials resemble drug trials both in terms of length, cost, potential patient benefits, et cetera, novelty, many do not.

I would say that from our perspective, the perception is that the level of commitment and agreement that you would get from CDR about the SPA is greater than what you would get at CDRH with the formal agreement process and that there's still concern that you could go through all of the -- jump through all the hoops, submit a great plan with complete statistical backing, but then four years, $40 million down the road, the goal posts have shifted. I think in many cases maybe that's -- technology advances probably a little faster on the device side than the drug side, so, you know, new data has come up, et cetera, and, you know, maybe there are some good reasons for that. But the perception really is that you could go through all this, spend all the money to get the agreement, and then at the end of the day, it didn't matter. So maybe there could be some comments about that, about how you think about your commitment to the formal process because I think if there's more information about that, more people would take advantage of it.

DR. LUKE: I don't think enough companies have gone through that agreement process for us to make any insinuations that the product -- that that agreement process does not work. I think we have not seen it not work. I mean, it's something that companies should -- if they're willing to invest the resources and the pre-work that's involved in getting one of these in place, that's something that they should think about considering.

MR. O'LEARY: Just a quick follow-up on that. So with the new guidance that's coming out with the realization that many drug trials ‑- I'm sorry -- device trials are becoming much more expensive, longer term with higher risks associated, and with the whole science-based initiative, is this going to be addressed further in the new guidance?

DR. SHUREN: In terms of formal commitments?

MR. O'LEARY: Formal commitments, you know, again, the whole theme of predictability, transparency.

DR. SHUREN: Well, formal commitments won't be addressed because we have the process in place. I think what Markham is saying is we're not seeing a lot of companies take advantage of it to even have a good idea of is it not the right process in the first place. If you've got cases where there was a formal agreement under this process and then we turned around and at the end didn't honor that commitment, that we should talk about.

MR. O'LEARY: Okay. Thank you.

DR. SHUREN: And if you have a case, I would raise that.

MR. O'LEARY: Okay. Thank you.

MR. GORANOV: Konstantin Goranov, Salutaris.

Thank you so much for all the comments and clarifications on the current process.

(Off-the-record comments.)

MR. GORANOV: Anyhow, considering all these changes, what do you think will be a good time to resubmit or submit a new application, 510(k) application? In a month? In three months? This fall?

DR. SHUREN: Do you want me to respond to that?

MR. GORANOV: Go ahead.

DR. SHUREN: For right now, it's still business as usual in terms of any fundamental changes. Even when we put the reports out, there's going to be a public comment period. We're going to look at the comments and we'll move forward. If we're going to go ahead and make any changes to the program, it's not going to start until probably a little bit later in 2010, and some of those may not have ramifications for later.

I can tell you this. We are not coming out with a finding that says the 510(k) program should be replaced. That is not going to happen, so you do not -- that's not on the table.

MR. GORANOV: Thank you.

MR. SORRENO: Hi. Tom Sorreno from --

Nobody has mentioned anything very much about comparative effectiveness research and how that's going to play into this, because I think certainly on the diagnostic side with the OIVD particularly ‑- and Alberto and I have had these discussions before -- a lot of the things that we do end up being a direct comparison to things that are standard of care. And perhaps that doesn't really extend to other parts of devices, but it seems to be that quite a few of my customers are very, very concerned about how that may impact not just the size and cost of trials but where their market position is. So anything you guys would like to say about that?

DR. SHUREN: I can just say generally all the things that happen with comparative effectiveness with healthcare reform legislation is not impacting what we're doing on pre-market review. It's not -- I will tell you honestly within the Center, it's not even a part of the conversation, really is separate. But you're right that in terms of certain technologies that we review, they're reviewed in terms of a comparison. Actually, the 510(k) program, its very hallmark is a comparison. It's not a comparison along the lines of what people think about the comparative effectiveness, but it's always been a comparison between technologies.

I should tell you, anything where we're playing a bigger role with comparative effectiveness is more on the regulatory science side with the tools that can be used to assess drugs and devices. That's, from our perspective, things that we think are important in the normal pre-market review programs anyway. We are looking for better ways to assess safety and effectiveness of drugs, devices, biologics so that we get more information and we can do it more efficiently. But that is probably our biggest role. And then those tools are available for any kind of study, including comparative effectiveness, not ones that we would conduct.

We haven't talked much today about regulatory science, but I will say this is a place where investments -- and we're seeing a little bit more investment by the federal government in that -- can really pay huge dividends for the development and the assessment of technologies and maybe help bring some devices to market more quickly and at lower cost.

MR. ZOLETTI: I'm Bob Zoletti. I'm with OMNI Life Science.

And I know there's a lot of changes happening right now, and I can tell you that in discussions I've had with management at FDA in review branch, they seem very unsure about what FDA policy is in some respects. And one of my concerns is with the changes coming, that when a draft comes out, they'll be even -- they may even be more unsure, or be thinking, "Well, do I have to start to implement this? This is going to affect my thinking." So what will be the process at FDA to make sure that doesn't happen because there'll be a review period for the changes, so what's -- I'm concerned that during this review -- during the review process, that the changes will be sort of creeping into the system, and what is your process for preventing that happening? What's the training at FDA? You know, I mean, I guess you need to consider what the training is going to be to prevent this from happening.

DR. SHUREN: So if there are going to be changes made, we've been very clear -- we've been talking as managers and then going back with staff, and I've been doing this actually in meetings across the Center. I actually meet with all the staff either by office or division level about once a quarter to go over issues, to take any questions they have. They get their own town halls, if anything. And I've been going around, the other managers are going around to make very clear nothing has changed at this point, and we'll be very clear with our staff when things should be changed. If we make any changes, you can anticipate that training is going to be a part of it. And I'm going to elaborate on training for one moment, too.

I'll tell you one of the issues I faced coming into the Center is that there was a need for greater training generally within CDRH. You know, there was actually no training, formalized training for new reviewers coming into the Center. That was one of our priorities for this year, and we've actually set up for a training program for our lead reviewers and for our medical officers, and that program is getting under way now. And I think you're going to anticipate seeing a lot more of that at the Center, that we have clearly set training programs and we have means to actually certify people for meeting those training requirements. You can anticipate that if we make changes to a program, there's going to be training involved in that as well and training about when something is implemented and we make changes.

MR. ZOLETTI: You know, we all appreciate that. Because I think the more consistent FDA is, the more consistent the training is, the more it's going to help us because right now, I think, as almost everybody has expressed here, there's so much uncertainty, and so -- things have changed and I'm worried about -- again, just hopefully this is a heads up that we're seeing this huge change and there really hasn't been any change at FDA. So take that -- I'm sure you're taking that into account.

Thank you.

MR. SILVERMAN: You know, your points are well taken. I also want to just build on some of the points that Jeff made by way of response. In the same way that there has been intensive communication with stakeholders, including industry, there's been a tremendous focus since Jeff's arrival in CDRH on internal routes of communications. So I think that there's information flowing in both directions.

As Jeff said, there is tremendous emphasis on clarity and transparency in terms of where the Center is headed, what's coming down the pike, and when those changes may be initiated. Many of the conversations that we've been having with you and many of the decisions that we are undertaking are also being informed by feedback and input that is appropriately being provided to us from staff, which is another mechanism that's very useful to assure that there is an aligned view within the Center about the direction in which we're headed and when it's an appropriate time to actually roll out those changes in comparison to a time like the time that we are in now where we are identifying potential directions in which we may be headed but soliciting input from stakeholders outside of and within the Center.

DR. LUKE: I wanted to also address just one piece about the IDEs. There were some questions about when you receive an IDE and you're proceeding along and doing your IDE study, that if your IDE letter says it's a conditional IDE, those conditions, those should be met before you go and do the study. So if you receive a conditional approval letter, that's not the same thing as an approval letter for your IDE. And just to be clear, oftentimes we see companies coming in with a submission with none of the conditions met that were in the conditional approval letter. And so that is a concern. And that may be a reason for some of the lack of predictability that some of the companies have been seeing.

There were some presentations earlier about -- some questions about IDEs and getting those studies approved, but the question is were they really approved or was there a conditional approval and were those conditions met?

DR. SHUREN: Well, let me thank everyone who came out today to participate in this meeting. We here at the Center truly appreciate it. I hope you found it useful.

Let me ask you was it worthwhile having a session like this?

Okay. Well, we will continue to do so. Obviously, we're trying to hit different parts in the country. You are also welcome, too. If folks are going to come into D.C., and particularly we like it as kind of groups of people because, as you know, we have lots of meeting requests and, obviously, we're not getting to all the meeting requests. But we are very interested to continue to hear from people in terms of issues and your ideas, so let's keep the lines of dialogue open.

Thank you again.

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


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


June 22, 2010

Woburn, Massachusetts

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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