U.S. FOOD AND DRUG ADMINISTRATION







                                    THIRD ANNUAL



                    CENTER FOR DEVICES AND RADIOLOGICAL HEALTH/

                    CENTER FOR BIOLOGICS EVALUATION AND RESEARCH



                   MEDICAL DEVICE USER FEE AND MODERNIZATION ACT

                                      (MDUFMA)

                                STAKEHOLDER MEETING









                               Gaithersburg, Maryland

                            Thursday, November 17, 2005







                                                              2


           1    PARTICIPANTS:

           2

           3       MARK BARNETT

           4       DANIEL SCHULTZ

           5       JESSE GOODMAN

           6       LINDA KAHAN

           7       JOANNE LESS

           8       DIANE MALONEY

           9       ROBERT YETTER

          10       MARTHA LOUVIER

          11       DONNA-BEA TILLMAN

          12       DON ST. PIERRE

          13       TIM ULATOWSKI

          14       MICHAEL MARCARELLI

          15       STEVE NIEDELMAN

          16       GINETTE MICHAUD

          17       PATRICIA LOVE

          18       STEVE SYKES

          19

          20

          21

          22




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              3


           1    PRESENTERS:

           2

           3       MARK LEAHEY

           4       JANET TRUNZO

           5       BOB BRITAIN

           6       MARLENE VALENTI

           7       CLAUDIA MILLER

           8       MARLENE KEELING

           9       PATRICIA SHRADER

          10       DIANE WURZBURGER

          11       LINDSEY WADE

          12       NAOMI HALPERN

          13       ANTHONY BLANK

          14       JACK LASERSOHN

          15       DIANA ZUCKERMAN

          16       MAC McKEEN

          17       DENNIS HAHN

          18       ROBERT DURGIN

          19       ALAN TOTAH

          20

          21                       *  *  *  *  *

          22




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              4


           1                   P R O C E E D I N G S

           2                                             (9:08 a.m.)

           3              MR. BARNETT:  Okay.  Welcome to

           4    this third annual public meeting on the

           5    Medical Device User Fee and Modernization

           6    Act, which everybody knows as MDUFMA.  I'm

           7    Mark Barnett, Assistant Director for

           8    Education and communication -- who else is

           9    that talking there?

          10              MS. KAHAN:  I'm sorry.  Hold on one

          11    second, Mark.

          12              MR. BARNETT:  So much for the

          13    stereo portion of our broadcast.  Now we're

          14    back to mono.  Anyway, as I was saying, I'm

          15    Mark Barnett; I'm the Assistant Director for

          16    Education and Communication in FDA's Center

          17    for Devices and Radiological Health.  And I'm

          18    going to be your moderator today.

          19              A quick piece of housekeeping.

          20    When you registered out there today, you

          21    should have received a package which contains

          22    the meeting agenda and a list of the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              5


           1    attendees that are going to be here, a list

           2    of the guidances that we've issued under

           3    MDUFMA so far, some important web addresses,

           4    information on how to get transcripts, and

           5    most importantly, information on where to get

           6    lunch.  And so if you didn't get that

           7    package, you can get one during the break.

           8              Well, as we all know, MDUFMA

           9    authorizes the FDA to collect fees from

          10    manufacturers to help offset the cost of

          11    reviewing applications for new medical

          12    devices.  And it also has some important

          13    provisions about things like third-party

          14    inspections and special requirements for

          15    manufacturers who reprocess devices that are

          16    labeled for single use.

          17              Now, as everybody in this room also

          18    knows, MDUFMA is going to expire on

          19    October 1, 2007.  And so today's meeting is

          20    particularly important because it's going to

          21    serve as a vehicle for us in the FDA to get

          22    your input and recommendations on what any




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              6


           1    reauthorized MDUFMA legislation ought to look

           2    like.

           3              Specifically, we want to know what

           4    you think has worked well with MDUFMA so far,

           5    and whether there are things about MDUFMA

           6    that ought to be changed in the future.  And

           7    so this meeting is basically a listening

           8    session for the FDA.  There are familiar

           9    faces out here, so I know that many of you

          10    know that this is not the first MDUFMA

          11    listening session that we've had.

          12              We've held similar public meetings

          13    in 2003 and 2004, and in fact, we based many

          14    of the actions that we took in implementing

          15    MDUFMA on what you told us during those

          16    meetings.  So today, we're going to continue

          17    that commitment to listen.  As before, this

          18    meeting is going to be transcribed so that we

          19    can review what was said here today, and

          20    we'll use what we learned from this session

          21    as we prepare for the possibility of new

          22    legislation.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              7


           1              Let me say a few words about the

           2    format for the meeting.  It's going to

           3    consist of six separate sessions, each one

           4    covering a different aspect of MDUFMA.  Now,

           5    during the entire day, there's going to be a

           6    standing FDA -- actually a sitting -- but

           7    we'll call it a standing FDA panel, sitting

           8    up here, and I'll introduce them in a few

           9    minutes.

          10              And then also during each of the

          11    six sessions, one or more FDA subject matter

          12    experts are going to come up and sit with the

          13    other panel and listen to presentations from

          14    stakeholders who have registered to speak in

          15    advance.  Each of these registered speakers

          16    are going to have up to 10 minutes for their

          17    presentations, and I'll give a little signal

          18    when there are two minutes left, and then

          19    again at the one minute mark.

          20              Now, I might mention, if you are

          21    one of those registered speakers, you were

          22    told in advance about the 10-minute limit,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              8


           1    but if you didn't receive the information,

           2    and you know now that your presentation is

           3    significantly longer than 10 minutes, this

           4    will be a good time to kind of mentally edit

           5    it down so that you can fit the time limit.

           6              After each one of the speakers,

           7    there's going to be a few minutes in which

           8    the FDA panelists are going to be able to ask

           9    the presenters for clarification or for

          10    additional information.  We want the FDA

          11    folks to understand what you're saying.  It's

          12    important.  And so if they have any questions

          13    for you, that's the time they are going to

          14    ask you.

          15              Now, at the close of each of the

          16    six sessions, we're going to open the floor

          17    to those people who may have registered to

          18    speak this morning when they arrived, and

          19    after that, we will open the floor to

          20    comments from anybody in the audience who

          21    wants to speak.  But one important ground

          22    rule about speaking from the audience, and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                              9


           1    that is that the comments ought to address

           2    only the subject matter of the panel that we

           3    just had.

           4              In other words, we just had a panel

           5    on the third-party inspection program, your

           6    questions or comments ought to address that

           7    topic and not something else.  We've also set

           8    a time limit for the comments from the floor

           9    so we can stay on time and allow everybody to

          10    speak.  So on the comments from the floor

          11    we're going to go no more than five minutes.

          12    And again, I'll give a reminder when there is

          13    one minute left and then call a halt when

          14    it's over.

          15              Okay, so much for introduction.  At

          16    this point, we do have some words of welcome

          17    from Dr. Dan Schultz, who is Director of the

          18    Center for Devices and Radiological Health,

          19    who could not be with us today, but he is on

          20    video; right?  And we're going to show the

          21    video now.  Is that how it works?  Okay.

          22              Dr. Dan.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             10


           1              MS. RICE:  I need to get in here.

           2              MR. BARNETT:  You got to get in

           3    here?  Okay.

           4              MS. RICE:  And I need the laptop.

           5              MR. SCHULTZ:  Good morning.  My

           6    name is Dan Schultz, director for the Center

           7    for Devices and Radiological Health.  I want

           8    to take this opportunity to thank all of you

           9    for coming to the annual MDUFMA stakeholders

          10    meeting, and to assure you that while I can't

          11    be with you in person, I am certainly with

          12    you in spirit and committed to the mission

          13    that you are embarked on.

          14              Our mission, getting safe and

          15    effective devices to market in a timely

          16    fashion, is certainly essential to the

          17    purpose of this meeting.  Over the last year,

          18    we've hired a number of highly qualified

          19    engineering, medical, and statistical staff

          20    to enhance the expertise of the Center in

          21    evaluating new devices.

          22              We've also been able to increase




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             11


           1    professional development as well as

           2    increasing the use of outside experts to

           3    assist in our mission.  We held a record

           4    number, more than 500 pre-meetings with

           5    industry, which as you know, is a vital part

           6    of getting good submissions and an efficient

           7    review process.

           8              We've performed very well against

           9    MDUFMA goals, both 510(k) and PMA in the

          10    areas of cycle goals and decision goals.

          11    We've also worked hard on the other

          12    commitments in the Secretary's goal letter,

          13    such as developing GMP and BIMO inspectional

          14    timeframes, issuing many device-specific and

          15    special control guidance documents and

          16    updating our IT infrastructure, especially in

          17    those areas designed to increase the

          18    efficiency of the review process.

          19              During the last year, we've also

          20    started to work on developing a more focused

          21    and proactive post-market program that will

          22    enhance the pre-market review process and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             12


           1    improve the efficiency of that process by

           2    allowing our staff to consider and use

           3    information when evaluating device

           4    modifications and new devices.

           5              This will also allow us to move

           6    more quickly to identify post-market issues,

           7    to act on those issues and resolve them, and

           8    quickly notify the health care and patient

           9    communities to improve the safety and

          10    effective use of those products.

          11              We recognize that MDUFMA user fee

          12    revenue is tagged to improvement of the

          13    pre-market review program.  But we need to

          14    make sure that we don't lose sight of the

          15    importance of the post-market program to

          16    fulfill our mandate to ensure the safety and

          17    effectiveness of medical devices throughout

          18    the product life cycle, and to maintain the

          19    confidence of the U.S. public in the products

          20    that we regulate.

          21              Information we learn from

          22    post-market on how a device works in the real




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             13


           1    world, when and how it may fail, is critical

           2    to our pre-market review process.  We've also

           3    been focusing on several important critical

           4    path initiatives, including development of

           5    simulation-based engineering and medical

           6    imaging technology that will help in the

           7    assessment of new stent designs; developing

           8    clinically relevant animal models to improve

           9    the prediction of device toxicity on injured

          10    tissue in critically ill patients; working

          11    with our trade associations and academic

          12    communities in the development of new

          13    statistical models for predicting the

          14    effectiveness of cardiac stents; and to be

          15    able to measure and improve long-term safety

          16    of these devices.

          17              I want to stress the importance of

          18    your participation at this critical point in

          19    the MDUFMA process.  Next spring, we'll be

          20    starting re-negotiation for MDUFMA 2.  We

          21    need to hear from all of our stakeholders.

          22    Unlike previous years where FDA provided




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             14


           1    updates on our implementation progress, this

           2    year is dedicated as a listening session for

           3    the Agency.

           4              As Mark mentioned, there will be

           5    several main topics for which we would like

           6    your feedback.  This is your opportunity to

           7    tell us what you liked and what you didn't

           8    like about MDUFMA.  We need you to be as

           9    specific as possible with your

          10    recommendations for MDUFMA 2.

          11              Together, we have the opportunity

          12    to use the knowledge and experience of the

          13    last three years to make a good program even

          14    better.  I have no doubt that with all of our

          15    resolve and commitment, we will accomplish

          16    that goal.

          17              Thanks very much, and have a great

          18    meeting.

          19              MR. BARNETT:  Okay, thank you, Dan.

          20    Our next speaker is live.

          21                   (Laughter)

          22              MR. GOODMAN:  I think.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             15


           1              MR. BARNETT:  We think he is.  Dr.

           2    Jesse Goodman, who is Director of FDA Center

           3    for Biologics Evaluation and Research.

           4    Jesse.

           5              MR. GOODMAN:  Sure.  Good morning

           6    everybody.  We really do appreciate your

           7    presence here, and I'm really just going to

           8    briefly echo, I think, Dan's comments.  You

           9    know, I think it's remarkable, the progress

          10    we've made in the last couple of years.  I

          11    think I speak for both the centers, but I

          12    have the most knowledge specifically about

          13    ours.

          14              And I think it's also particularly

          15    remarkable that MDUFMA has enabled us to do

          16    that in a time when resources have otherwise

          17    been quiet constrained for the agency.  From

          18    my point of view, first of all, I want to

          19    thank the people who have worked with us on

          20    that.  And that includes the industry

          21    associations and specific companies who I

          22    think have been very helpful in identifying




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             16


           1    issues where we can work together better, and

           2    have also been responsive when we've raised

           3    our issues.  So I thank you for that, and we

           4    sure look forward to that continuing.

           5              The other comment I was going to

           6    make is that I think some of the improvements

           7    in the performance measures, review time and

           8    number of cycles, are terrific, and they help

           9    achieve the goal that Dan mentioned, which is

          10    getting safe, effective products to benefit

          11    people more quickly, and I think that has

          12    really happened.

          13              But I think something that is a

          14    little harder to measure has also happened,

          15    which is quality and consistency have been

          16    maintained, and in many cases improved.  So I

          17    think those are very important, we're very

          18    proud of it and the MDUFMA resources have

          19    been really critical.

          20              The other thing we've done, and

          21    this has been cultural within the FDA, but I

          22    think the resources have also helped with




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             17


           1    this, is we've been able to turn our

           2    attention to our internal processes and our

           3    collaborations.  And I think CDRH and CBER

           4    are working together very well in a

           5    bidirectional way, and we're relevant, we're

           6    getting, I think, high quality guidances out

           7    that are meaningful across the industry.  So

           8    I think those things are good too.

           9              Dan mentioned the post-market, we

          10    too are more and more trying to integrate

          11    that with the pre-market process in the

          12    approval, and again, we do look forward to

          13    discussing that as part of continuing MDUFMA.

          14    And finally, I would like to say, in our

          15    area, the tremendous promise of devices, I

          16    mean, everybody -- it is very graphic when

          17    you have a new defibrillator or a prosthetic

          18    device, et cetera, et cetera.

          19              But we have many devices that are

          20    absolutely essential for the well-being of

          21    the American people and for dealing with some

          22    of our public health threats.  You know,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             18


           1    whether it's new infectious agents that

           2    threaten the blood supply, BSE, or

           3    confronting issues like mass vaccination, and

           4    the promise of devices for meeting those

           5    needs.

           6              Another area that is relevant to

           7    the critical path that Dan mentioned is in

           8    combination products and tissue-engineered

           9    products, and I think that's a perfect

          10    paradigm where we and CDRH are working

          11    together to make things easier for innovation

          12    and bring future products to people.  So you

          13    know, we just do look forward to your input,

          14    and I think even more than that, to

          15    continuing to work together.

          16              I think it's a very productive

          17    interaction between FDA and the industry.  I

          18    think consumers benefit and are another

          19    important group to provide input, and we just

          20    thank you all, the industry and consumers,

          21    for your support and trust in this.

          22              Thank you.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             19


           1              MR. BARNETT:  Thank you, Jesse.

           2    Let me now introduce the permanent panel

           3    that's going to be up there all day, and as I

           4    introduce them, I'll ask them to raise their

           5    hand, because people in the back can't see

           6    their name cards.

           7              Linda Kahan is Deputy Director of

           8    the Center for Devices and Radiological

           9    Health.  Joanne Less is Associate Director in

          10    that Center for Clinical Research and

          11    Government Affairs.  Diane Maloney is

          12    Associate Director for Policy in the Center

          13    for Biologics Evaluation and Research, and

          14    Bob Yetter is Associate Director for Review

          15    Management in the Center for Biologics

          16    Evaluation and Research.

          17              And I'll ask Linda to just say a

          18    few words of introduction if you would.

          19              MS. KAHAN:  Thank you.  Can you

          20    hear me?  First of all, let me tell you that

          21    Dan has been to Taiwan, and he actually cut

          22    his trip short.  He may be able to make a




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             20


           1    guest appearance today later in the meeting.

           2    He was getting back last night.  And he

           3    really did want to be here, and he may still

           4    be able to do that.

           5              I wanted to also echo what Dan and

           6    Jesse have said, and thank you for coming to

           7    the meeting today.  As Dan suggested, this is

           8    a little bit different than the meetings

           9    we've done in the past.  But I don't want

          10    anyone to think for a minute that we are not

          11    willing and able to provide information.  And

          12    one of the reasons that you've gotten the

          13    handouts that you have is that we have put

          14    all the information that we've been

          15    constantly making available on our websites.

          16              And most of you are veterans of

          17    using that tool, but in case you haven't had

          18    an opportunity to do that, please make sure

          19    that you do take advantage of all the

          20    information that's out there, including the

          21    guidances that have been put out as part of

          22    the implementation of MDUFMA, and the reports




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             21


           1    that are available right through the website.

           2              I wanted to also echo something

           3    that Dr. Goodman said about what it means to

           4    get resources in this fiscal environment.  I

           5    think that all of us are painfully aware of

           6    the natural disasters and the international

           7    unrest that have plagued the world and our

           8    country over the last years.  And it is

           9    really a very bleak situation for most of the

          10    government in terms of fiscal funding and

          11    resources.

          12              And as you know, before MDUFMA, the

          13    medical device program was one of those

          14    programs that was continually losing

          15    resources.  Even when we had supposedly

          16    steady funding, we were in fact losing

          17    resources because of inflation.  So the fact

          18    that we are now visible, and that we're one

          19    of the programs that gets funded and gets

          20    thought about when limited resources are

          21    being distributed really is a tribute to the

          22    work that our stakeholders have done to make




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             22


           1    this possible.

           2              And we're very appreciative of that

           3    and we hope that that's going to continue,

           4    because it's made a huge difference in the

           5    way we can work, and in our ability to work

           6    with the industry to get safe and effective

           7    products to market quickly.

           8              I wanted to just also point out

           9    that this is just the beginning of the

          10    process.  We are very anxious to hear from

          11    people today about what's happened over the

          12    last couple of years that they think has

          13    worked well, and as Dan said, things that

          14    need to be done differently and better in the

          15    next iteration of MDUFMA.

          16              We here at the FDA kind of have a

          17    two-pronged job over the next two years.  One

          18    is to continue to work on the commitments for

          19    the goals and the other things that we have

          20    promised to do through the Secretary's letter

          21    until '07; and at the same time, we need to

          22    gear up for what we can plan to do hopefully




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             23


           1    when MDUFMA is reauthorized in '07.

           2              So we're kind of working on both of

           3    those tracks.  And the purpose of this

           4    meeting is to really get input from you about

           5    how to work that second piece of it based on

           6    the three years of experience that we've had.

           7    I also want to remind people in case you

           8    didn't realize that there will be another

           9    public meeting in the fall, at which we will

          10    be able to talk about these things again, and

          11    have another year of experience to put under

          12    our belts.

          13              And I also wanted to let people

          14    know that under the statute, once we work

          15    with our stakeholders to actually come to

          16    some tentative agreement about what ought to

          17    be in the next version of MDUFMA, that will

          18    be made publicly available through a Federal

          19    Register notice, and people will have chance

          20    to comment on that.

          21              And as Jesse pointed out, the

          22    importance of having consumers and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             24


           1    practitioners and health care professionals

           2    give us some input is a big help to industry

           3    and to the FDA, because everybody is

           4    interested in that same goal, which is to get

           5    good products out there as quickly as

           6    possible.  So with that, Mark --

           7              MR. BARNETT:  Okay.  Thank you,

           8    Linda.  I think we're ready now for

           9    Session 1, which is on the "User Fee

          10    Structure," and I'm going to ask Martha

          11    Louvier to come up and sit with us.  She is

          12    from the Office of Management in FDA.

          13              She is taking the place of Frank

          14    Claunts, who was going to be here but could

          15    not make it.

          16              MS. LOUVIER:  Good morning.

          17              MR. BARNETT:  Now that she is

          18    seated, we have the full panel.  Let me call

          19    in our first speaker, who is Mark Leahey, of

          20    the Medical Device Manufacturers Association.

          21              MR. LEAHEY:  Thank you, Mark.

          22    First, I want to begin by thanking




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             25


           1    Dr. Schultz, Dr. Goodman, the staff at CDRH

           2    and CBER, and Cindy Harris for putting this

           3    meeting together.  I think it is a great

           4    opportunity for all of the stakeholders to

           5    get together and talk about what is working

           6    and what improvements need to be made.

           7              And I'm pleased, this is my third

           8    year at the meeting, and I'll have to say

           9    that I think some of the issues that we had

          10    address in the past have been remedied as

          11    part of the MDUFMA trigger fix in August.  So

          12    hopefully it will be an opportunity again to

          13    identify those things that need some tweaking

          14    and improving the future.  But I think three

          15    years into the program, we are in a better

          16    shape than when we started, and I think

          17    that's a tribute to everybody in this room.

          18              So again, by way of background, let

          19    me just start off by saying that I'm the

          20    Executive Director with the Medical Device

          21    Manufactures Association.  We're a trade

          22    association based in Washington, representing




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             26


           1    hundreds of medical technology companies,

           2    many of which are small- to medium-sized

           3    companies, and I think that's indicative of

           4    the industry itself.

           5              Prior to the trigger fix in August,

           6    the user fee system was volatile and

           7    unpredictable for the industry.  I think this

           8    is evident by the fee increases that we

           9    saw -- just in the first two years of the

          10    program, we saw fee increases jump between 55

          11    and 60 percent for both 510(k)s and for PMAs.

          12              You'll see here, the PMA fee, which

          13    started off at $154,000, jumped to $239,000

          14    and change in just two years, and the 510(k)

          15    fee jumped from $2187 to more than $3500 in

          16    just two years.  And this is something that I

          17    think the entire industry voiced concerned

          18    about, these types of dramatic fee increases

          19    that I think, to everyone's credit, there was

          20    a recognition that these fees were not

          21    sustainable.

          22              Another issue that I think we had




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             27


           1    prior to MDUFSA is the fact that the

           2    structure allowed FDA to collect more per

           3    submission if they saw a decline in

           4    fee-generating submissions.  Certainly, we

           5    understand the need for FDA to have a stable

           6    source of revenue, but the industry also

           7    needs that stability.

           8              And the structure prior to the

           9    trigger fix did not provide that.  And again,

          10    these increases were unsustainable for

          11    99 percent of the industry.  And if we want

          12    to continue to develop innovative, safe, and

          13    effective products for America's patients,

          14    it's vital that the entire industry has the

          15    ability to innovate.

          16              Another note:  Prior to MDUFSA, and

          17    hopefully we'll see a reverse here, there was

          18    a dramatic drop in the number of

          19    fee-generating submissions after the user fee

          20    was created.  So hopefully -- there could be

          21    many reasons for that, but I think the

          22    numbers indicate that there was a dramatic




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             28


           1    drop, and hopefully that the lower fees or

           2    the stabilized fees will provide an

           3    opportunity for those submissions to

           4    increase.

           5              So where are we now after MDUFSA?

           6    Fees are much more predictable for the

           7    industry.  And I think this is the biggest

           8    success under the program moving forward,

           9    that for the first time, the elements -- the

          10    compensating and work load adjustments

          11    that -- a large portion due to the dramatic

          12    fee increases we saw in the first couple of

          13    years -- are no longer in place.

          14              The fee increases are capped at

          15    8-1/2 percent annually.  I think that the,

          16    industry was hoping for something along the

          17    lines of inflation, but recognizing that we

          18    still wanted to provide FDA resources to fund

          19    them without needing dramatic cuts, it was

          20    settled on an 8-1/2 percent annual increase,

          21    which I think in the long term, it's still,

          22    I'll have to see if that's the acceptable




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             29


           1    rate of increase, because that may be

           2    difficult to sustain long-term, but we can

           3    take a look at that.

           4              I'm also very pleased that it

           5    eliminated the workload and compensating

           6    adjustments as I just spoke of, and this is

           7    something I'm sure many of you will be happy

           8    to hear.  During the first MDUFMA

           9    stakeholders meeting, I talked ad nauseum

          10    about the need to eliminate these.  During

          11    the second, I did as well.

          12              Now I can congratulate everyone

          13    here for making those decisions.  I think it

          14    was something that was shared by many.  And

          15    we're just pleased that we now have, again, I

          16    think, the right equation for developing the

          17    fees moving forward.

          18              And the final important point that

          19    was made as part of our provision, as part of

          20    MDUFSA, is the fact that it provided greater

          21    fee relief for companies under $100 million

          22    in annual revenues.  You know, this is




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             30


           1    something prior to the development of MDUFMA,

           2    back in 2002, MDMA was trying to push for a

           3    number higher than $30 million.  We were

           4    unsuccessful, but we're pleased that now we

           5    have this $100 million threshold.

           6              We know for certain that there are

           7    companies out there in that $30- to

           8    $100 million range that were withholding

           9    regional PMA submissions, PMA supplements,

          10    because it wasn't in their regulatory budget

          11    to file, and now they're moving forward.  So

          12    I think to FDA's credit, the revisions that

          13    were made under MDUFMA hopefully give them

          14    the resources they need to move forward, but

          15    also allows the industry to move forward and

          16    innovate.  And I think that's the ultimate

          17    goal of this program.

          18              So user fees, what's ahead?  I

          19    think we need to evaluate the value of user

          20    fees.  Now what do I mean by that?  Well, I

          21    think two things are important to this

          22    component, the first being what the actual




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             31


           1    fee amount is.  And that's something that we

           2    need to address.  The other is something I'll

           3    address on a later panel, which is, what does

           4    that fee provide in return as it relates to

           5    ensuring the patients have safe and effective

           6    products more quickly?  And that relates to

           7    performance goals.

           8              So I don't think in trying to

           9    determine what a reasonable fee is, I don't

          10    think you can just look at a dollar amount,

          11    alone in and of itself.  You have to look at

          12    the dollar amount in conjunction with the

          13    performance that's being achieved.  Again,

          14    this goes along with fees being reasonable

          15    and rational, look at fees and performance

          16    together.

          17              We also need to ensure that fees do

          18    not increase at unsustainable rates.  I think

          19    that again, we took a huge step in the right

          20    direction in dealing with eliminating the

          21    workload and compensating adjustors and

          22    having that 8-1/2 percent cap in place.  And




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             32


           1    I think the industry will get together and

           2    determine what is a sustainable fee increase

           3    moving forward.

           4              There also needs to be an

           5    understanding that the fees are meant to be

           6    additive to appropriations and not

           7    substituted.  And this is something that I

           8    think shouldn't be looked over.  Again, when

           9    everyone got around the table and the

          10    industry agreed to pay I think almost close

          11    to -- generate almost close to $80 million in

          12    the first three years of the user fee

          13    program -- this was meant to be additive to

          14    hire new employees to help enhance the

          15    process.  But unfortunately, we saw the

          16    congressional appropriations that were

          17    promised under MDUFMA and committed to under

          18    MDUFMA were not delivered in the first couple

          19    of years of the program.

          20              And I think there is a concern that

          21    a lot of the user fee dollars again that were

          22    meant to be additive were actually used to




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             33


           1    supplement the congressional appropriations.

           2    And again moving forward, we really need to

           3    make sure, and I know a lot of this falls

           4    outside the ability of FDA to guarantee that

           5    the monies are there, but do what we can to

           6    ensure that the user fees aren't just used to

           7    plug in a drop in congressional

           8    appropriations.

           9              I think the final thing we need to

          10    do is determine FDA's actual resource needs

          11    related to the pre-market review program.

          12    And again, to FDA's credit, they worked with

          13    Dr. Geiger to try to get at some of this

          14    information, and Dr. Geiger recently put out

          15    his report.  I think there is some good

          16    information to be gathered there, but I think

          17    there are some shortfalls related to really

          18    flushing out what the resource needs are on

          19    the PMA side, between PMA -- original PMAs,

          20    PMA's supplements.

          21              But again to FDA's credit, I think,

          22    that they have put some internal data




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             34


           1    collection mechanisms in place that will

           2    hopefully provide better data to be collected

           3    on, again, what the resources are for

           4    original PMA, what they are for the 188

           5    supplements, and hopefully now that they are

           6    in that process of gathering that

           7    information, we will really get a better

           8    understanding of what the resource needs are.

           9    And then once we can determine that, I think

          10    it has to be understood that the user fees

          11    are not meant to cover that entire cost of

          12    that, that the user fees again should be

          13    supplemented with the Congressional

          14    appropriations and should play a part in

          15    assisting FDA but not the overwhelming

          16    majority.

          17              MR. BARNETT:  Two more minutes.

          18              MR. LEAHEY:  Well, here we are.

          19    User fee, what's ahead?  Looking forward,

          20    we're looking forward we're looking forward

          21    to working with FDA, the folks within the

          22    other industries and the Hill to ensure that




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             35


           1    patients have timely access to safe and

           2    effective medical technologies, and that

           3    smaller companies continue to have the

           4    ability to innovate.  And I think again, the

           5    stakeholder meeting today is certainly a sign

           6    that there is an element of a partnership

           7    involved here that Dr. Schultz spoke of last

           8    year.

           9              I think we look forward to working

          10    with everybody.  Again, MDMA is committed to

          11    making this program work, so long as we can

          12    ensure that smaller companies aren't harmed

          13    and that patients ultimately are the winners

          14    with safe and effective medical products and

          15    they get access to that in a timely fashion.

          16    So with that, I will conclude, thanks.

          17              MR. BARNETT:  Thank you, Mark.  And

          18    let me ask the panel, before you step away.

          19    Is there anyone that needs clarification on

          20    that or has any questions for Mark?  If not,

          21    thanks very much, and let me ask our next

          22    speaker to come up, Janet Trunzo of AdvaMed.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             36


           1              MS. TRUNZO:  Good morning, my name

           2    is Janet Trunzo.  I'm the executive vice

           3    president for technology and regulatory

           4    affairs at AdvaMed, the Advanced Medical

           5    Technology Association.  We represent over

           6    90 percent of the medical devices sold in the

           7    U.S., and we're the world's largest medical

           8    device trade association.

           9              First of all, AdvaMed would also

          10    like to thank FDA for providing stakeholders

          11    the opportunity to comment on the various

          12    aspects of MDUFMA.  AdvaMed also would like

          13    to recognize Dr. Schultz and Dr. Goodman and

          14    all of the CBER and CDRH staff for all the

          15    hard work and effort they have made in

          16    implementing the provisions of MDUFMA.

          17              My comments today are going to be

          18    limited to two areas:  The elements of a

          19    reasonable user fee program; and also, I'm

          20    going to make a few comments about FDA's cost

          21    analysis study.  First, I would like to talk

          22    about the elements, make a few statements




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             37


           1    about the fundamental elements of a user fee

           2    program.

           3              First and foremost, medical device

           4    user fees are additive to the FDA's device

           5    budget, and never are or have been intended

           6    to supplant FDA's base device budget.  In

           7    fact, Section 101 of MDUFMA states the

           8    following: "Congress finds that the public

           9    health will be served by making additional

          10    funds available for the purpose of augmenting

          11    the resources of FDA."

          12              In fact, under MDUFMA, the

          13    additional resources provided were a

          14    combination of industry user fees and

          15    congressional appropriations.  The user fee

          16    program in fact was designed intentionally,

          17    such that the industry contribution was

          18    intended to not exceed 15 percent of FDA's

          19    entire device base budget.  And indeed this

          20    is the case and remains so.

          21              So what does the medical device

          22    industry expect from user fees?  Well, it's




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             38


           1    quite simple.  We expect reasonable fees.  We

           2    expect that the fees will not increase

           3    drastically from one year to the next.  We

           4    also expect adequate appropriations from

           5    Congress.  Last, but definitely not least, we

           6    expect improved performance for the industry

           7    contributions.  Representatives from AdvaMed

           8    member companies will be commenting later on

           9    performance during the later panels.

          10              Turning now to FDA's cost analysis

          11    study:  In September of this year, FDA issued

          12    its cost analysis study on determining the

          13    unit cost for the process of medical device

          14    review.  And I don't know if any of you got a

          15    chance to look at it.  It's quite a lengthy

          16    report.

          17              But after reviewing the report, and

          18    also after hearing some presentations from

          19    Dr. Geiger, who is the author of the report,

          20    I would like to offer the following comments:

          21    First, there are some limitations in the

          22    data, and those limitations were noted




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             39


           1    actually by the author himself.  Data in this

           2    report reflect the '03 and '04 activity.

           3              And although FDA recently trained

           4    its staff on making improvements to the time

           5    reporting system, data collected in '03 and

           6    '04 were not precisely collected, such that

           7    the time spent on original PMAs and the

           8    various types of PMA supplements were clearly

           9    delineated.

          10              Second comment:  In reviewing the

          11    calculations for determining the unit costs,

          12    it appears that FDA used information from the

          13    FY '03 and FY '04 financial reports that it

          14    makes to Congress under the requirements of

          15    MDUFMA.  And it shows -- if you look at those

          16    reports themselves, those financial reports,

          17    it talks about the budget and how much of the

          18    FDA budget was used for device review

          19    activities.

          20              So that information from that

          21    report is combined with the cost analysis

          22    study.  Please note also that device review




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             40


           1    activities encompass a lot of activities.

           2    They are not just the time that the FDA

           3    reviewers spend on the actual review of the

           4    application; they also include the support

           5    activities, center-wide expenses, including

           6    rent utilities, field investigations, and

           7    general agency and administrative costs.

           8              In the cost analysis report, FDA

           9    allocated both indirect and direct costs to

          10    the various types of applications, and then

          11    divided the number of applications completed

          12    during the time reported in the report,

          13    that's '03 and '04, and came up with the unit

          14    cost.  When using the data from this report

          15    in the future, we must bear in mind that the

          16    reported unit cost represents a fully loaded

          17    cost, and in their totality represent a

          18    significant portion of the FDA's total base

          19    budget for devices.

          20              I also would remind the agency as

          21    it contemplates using this information in the

          22    future, and drawing upon what I said earlier




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             41


           1    in this presentation, that the device user

           2    fees are intended to augment the FDA's device

           3    base budget.

           4              In closing, we very much look

           5    forward to working with FDA for the

           6    re-authorization of MDUFMA.

           7              We look forward to designing a

           8    device user fee program that incorporates all

           9    the basic elements of a workable user fee

          10    program that I noted earlier, and at the same

          11    time, provides FDA with the additional

          12    resources it needs so that patients have

          13    timely access to safe and effective medical

          14    technology.  Thank you.

          15              MR. BARNETT:  Thank you, Janet.

          16    Let me turn to the panel now and ask if any

          17    one has any questions of Janet.

          18              MS. KAHAN:  I wanted to ask, is

          19    there another presentation for this panel?

          20    I'm going to wait; can we ask questions at

          21    the end, if we have some?

          22              MR. BARNETT:  Okay.  All right




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             42


           1    Janet, stay tuned then.  And our next speaker

           2    is Bob Britain, of the National Electrical

           3    Manufacturers Association, or NEMA.

           4              MR. BRITAIN:  NEMA, we represent

           5    manufacturers of medical imaging equipment

           6    and radiation therapy equipment.  So we have

           7    a very special part of the medical device

           8    manufacturing community.  And again, I echo

           9    the thanks of Mark and Janet, the panel, FDA,

          10    putting this all together.  I wanted to

          11    specially thank Ms. Less for moving this

          12    program into November, out of December.

          13    Remember, I have never been able to get to

          14    this because of the RSNA in Chicago.  Thank

          15    you.

          16              Something else special about this

          17    industry:  We've worked very hard with FDA

          18    when we were first negotiating MDUFMA to have

          19    an exemption from user fees for manufacturers

          20    that use third parties for 510(k)s.  So many

          21    of our manufacturers actually use third

          22    parties and do not pay the user fee.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             43


           1              So the other thing special about

           2    this part of the industry is that we're

           3    mainly 510(k); very few products go to market

           4    in medical imaging through the PMA process.

           5    So we have not been, so to speak, hit as hard

           6    as many of the other medical device

           7    manufacturers that put their products through

           8    the PMA process.

           9              So therefore, I essentially support

          10    everything that Mark and Janet have said.

          11    The increases in 510(k)s have been

          12    substantial, if you look at the percentage

          13    increase, but if you look at the total, going

          14    from 2000-something to 3000-something hasn't

          15    been too hard on the industry.

          16              I support the predictability.

          17    Things -- increases have to be predictable.

          18    You know, industry works from budgets, too.

          19    And we can't be taken by surprise.  We do not

          20    support trying to backfill on shortfalls from

          21    the year ahead to the previous year.  And I

          22    think that's not supportable, it's not right.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             44


           1              You've got to do the best job you

           2    can in predicting the number of PMAs and

           3    510(k)s coming in.  You are going to hit the

           4    mark sometimes and you are not going to hit

           5    the mark at other times.  But when you're not

           6    hitting the mark, it usually means that you

           7    don't have the numbers coming in, you don't

           8    have the numbers of supplements and PMAs and

           9    510(k)s that are coming in -- so you're doing

          10    less.  You're not expending the resources

          11    that you thought you might have to spend.

          12    Gee, forgot to put my -- all that is to say

          13    that in the last three years, the 20 to 30

          14    percent increases have been quite excessive.

          15              We are thankful that AdvaMed and

          16    MDMA were able to negotiate a cap, which was

          17    8.5 percent last year, and we support that.

          18    Long-term, however, I'm not sure that is the

          19    right number.  8.5 percent a year seems like

          20    a lot to me going forward.  So we need to

          21    establish some reasonable formulas going

          22    ahead.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             45


           1              The other thing I'd like to say is

           2    that throughout this day, from the three

           3    trade associations, you're probably going to

           4    hear a lot of concerns, issues, but probably

           5    not going to hear a lot of solutions.  We're

           6    going to be working this spring, we're going

           7    to be sitting down with FDA, trying to work

           8    out solutions to MDUFMA 2 in 2007.

           9              So I think we have to be careful

          10    what we can say today in how to fix things.

          11    So what you're going to hear today is

          12    concerns more than solutions.  Thank you.

          13              MR. BARNETT:  Bob, thank you.

          14    Again, let me ask the panelists if they have

          15    any questions.  Linda, you had a question

          16    that you wanted to ask.  Do you want to do it

          17    now?

          18              MS. KAHAN:  Let me start.  One

          19    question that I had, and I guess maybe Mark

          20    could be the best person to try to answer

          21    this, but I think that one of the things that

          22    we've struggled with and that we'd sort of




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             46


           1    like some ideas about -- and I realize that

           2    you're not offering solutions, but what are

           3    the tools that we, meaning all the

           4    stakeholders:  Industry, consumers, Congress,

           5    FDA, can use to figure out when a fee

           6    situation creates a disincentive for small

           7    businesses, for industry?

           8              I think one of the concerns that

           9    you have put on the table, as has AdvaMed,

          10    NEMA, and everybody else, is that we want to

          11    make sure that nothing in this program

          12    undermines innovation or limits the ability

          13    of small companies to get on the market.  I

          14    guess I was wondering if you have any ideas

          15    about how we get to that.

          16              MR. LEAHEY:  The first answer is to

          17    ensure that the fees are reasonable, and I --

          18              MS. KAHAN:  Well, that's my

          19    question.  My question is how do we --

          20              MR. LEAHEY:  I think probably the

          21    fee increases that we saw the first two years

          22    were unreasonable, and that's one of the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             47


           1    reasons why we saw a dramatic drop in the

           2    number of submissions.  So I think that

           3    there's some evidence that the current system

           4    was not working as intended, that it was

           5    having a stifling effect on innovation.

           6              I think the other issue may, you

           7    know -- oftentimes, you hear, well, these

           8    folks are in business, and it's the cost of

           9    doing business.  I think the response that

          10    many of them feel is, again, if the

          11    government would like to regulate an

          12    industry, it certainly has that right to do

          13    so.  But the government needs to fund those

          14    regulations.  And this was never something

          15    that was initially a burden for these

          16    companies for the decades and decades of

          17    innovation, and this is something relatively

          18    new on the horizon.

          19              And one of the things that the

          20    industry was told -- I guess this was part of

          21    the pitch from folks -- was that this is a

          22    sound business decision.  This will result in




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             48


           1    faster reviews, enhanced performances et

           2    cetera.  And quite frankly to date, that

           3    hasn't played out.  That I think the jury's

           4    still out as to whether or not user fees are

           5    a sound business investment, and I think

           6    that's what we really need to do and look at

           7    over at the course of the next two years to

           8    determine -- these folks are innovators, and

           9    they do run businesses.

          10              And again, it goes back to one of

          11    my slides, I think, about last year, the

          12    benefit of the bargain.  We need to look at

          13    what are we getting for the user fees.  And

          14    so I think it's hard to determine -- to say X

          15    number of dollars is unreasonable.  I think

          16    it's very easy to say that X number of

          17    dollars with no enhanced performance is

          18    problematic, because there, the company would

          19    not would view it as, again it is diverting

          20    resources from the R&D and other areas.

          21              MS. KAHAN:  Thanks.

          22              MR. BARNETT:  Anyone else on the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             49


           1    panel want to question?  Anyone in the

           2    audience want to respond to what they just

           3    heard?

           4              MR. LASERSOHN:  I have something.

           5              MR. BARNETT:  Come on up to the

           6    mic.  Please identify yourself, first.

           7              MR. LASERSOHN:  I am Jack Lasersohn

           8    from the National Venture Capital

           9    Association.  I want to strongly support what

          10    Mark just said.  The question of

          11    reasonableness for these fees cannot be

          12    looked at in the abstract.  Our company spent

          13    millions of dollars a month in the start-up

          14    phases to get products through the FDA.

          15              So even fees of $100,000 or

          16    $200,000 or $300,000 for a key PMA in the

          17    context of that is not problematic.  What's

          18    problematic is not having performance results

          19    that justify the payment of the fees.  So I

          20    think that is the balance at least the

          21    venture funded medical industry would really

          22    like to strike:  Rather than a particular




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             50


           1    concern on the absolute level or the absolute

           2    level of increases, we would be happy to pay

           3    for increases if they are commensurate with

           4    performance increases.

           5              MR. BARNETT:  Thank you.  Is there

           6    any one else in the audience who wants to

           7    respond to anything they've heard.  Mark?

           8              MR. LEAHEY:  Again while the

           9    venture community is very important, I think

          10    we need to also be careful that there are a

          11    lot of companies out there without venture

          12    funding.  So to increase the fees across the

          13    board without that sensitivity is something

          14    that we need to look at the entire landscape

          15    of the space.  And recognizing again, when we

          16    move forward here, it's important to look at

          17    all elements of the fees, the performance,

          18    and look at all the different folks who are

          19    participating, small venture backed, large

          20    medical technology companies and those

          21    companies that aren't venture backed.

          22              MR. BARNETT:  Thank you.  Before we




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             51


           1    close out this panel, anyone else?

           2              Bob Britain, step up.

           3              MR. BRITAIN:  This has nothing to

           4    do with what's been said, but I think it

           5    should be said.  And that is this -- the user

           6    fee process, whether it's here in the United

           7    States or in Japan or China or Canada, is a

           8    cost-shifting process.  Somebody's got to pay

           9    for it; somebody pays for the user fees.  The

          10    cost of medical devices increases because of

          11    them.

          12              Medicare pays for your user fees;

          13    the whole health system is paying for the

          14    user fees.  I didn't want to leave here

          15    without saying this because the whole world

          16    is looking at you and saying, "user fees are

          17    okay," and the whole medical device industry

          18    is faced with a worldwide user fee system

          19    which is dearly going to cost patients,

          20    Medicare systems, third-party payers, a lot

          21    of money.  So just keep this in mind when you

          22    want to consider your increases year after




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             52


           1    year.

           2              MR. BARNETT:  Thank you, Bob.

           3    Janet Trunzo --

           4              MS. TRUNZO:  AdvaMed represents

           5    small, medium, large manufacturers, and I

           6    just would like to reiterate a point that I

           7    made in my presentation, that companies --

           8    and it kind of builds on what the

           9    representative from the National Venture

          10    Capital Association said, is that paying a

          11    user fee, there is an expectation that if a

          12    company pays a user fee, that there will be

          13    improved performance.

          14              And that philosophy and that

          15    expectation is an expectation not only of

          16    small companies, medium sized companies and

          17    large companies, all companies expect some

          18    return in the performance and predictability

          19    in the performance as a result of a user fee.

          20    Thank you.

          21              MR. BARNETT:  Thank you, Janet.

          22    Anyone else before we call it a close for




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             53


           1    this panel?  Then I'll say going, going, gone

           2    for this particular panel.  I guess we've all

           3    talked ourselves out here, right?

           4              Then it's time for a break, 15

           5    minutes.  It's now 10:00, so why don't we be

           6    back here, at 10:15.

           7              Thank you.

           8                   (Recess)

           9              MR. BARNETT:  We're ready to start,

          10    so please have a seat.  Thank you.

          11              We're ready to begin now with our

          12    session 2, which is on premarket review

          13    performance goals, and up with us to join the

          14    permanent panel are two FDA subject matter

          15    experts, Donna-Bea Tillman, who is Director

          16    of the Office of Device Evaluation in CDRH,

          17    and Don St. Pierre, who is with the Office of

          18    In Vitro Diagnostic Device Evaluation and

          19    Safety with CDRH.

          20              And our first presenter is Mark

          21    Leahey, again, with the Medical Device

          22    Manufacturers Association.  Mark?




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             54


           1              MR. LEAHEY:  Thank you, Mark.  And

           2    unlike years past when I had the pleasure of

           3    speaking five times during one of these

           4    meetings, I'm pleased to note that I'm only

           5    speaking three times, and we're halfway home

           6    after this, or more than that.

           7              Again, we spoke a little bit about

           8    performance in the first panel.  Again, the

           9    importance of not looking at fees isolated,

          10    but looking at fees in relationship to

          11    performance.  And I think that this is

          12    something, probably one of the more critical

          13    elements of MDUFMA 2 if we're to get there

          14    that needs to be addressed, because again, it

          15    goes to the heart of the value of the user

          16    fee.

          17              So performance issues.  The goal of

          18    MDUFMA was to ensure patients' timely access

          19    to safe and effective medical technologies.

          20    Now, back in 2001, there were a lot of

          21    attempts to try to enhance FDA through

          22    various reforms short of a user fee, but then




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             55


           1    ultimately the user fee component entered the

           2    equation.  And one of the things that we

           3    heard consistently from FDA and from others

           4    was that if you a pay user fee, it will

           5    enhance review times by approximately

           6    25 percent.  And again, I think when you talk

           7    to a lot of CEOs, if they're told that things

           8    will improve by 25 percent, then a reasonable

           9    fee is something that they consider to pay.

          10              The problem was that the goals were

          11    developed with limited data, and this is no

          12    fault of anybody's other than just time.  You

          13    know, when you're trying to get a sense as to

          14    where FDA -- what their performance criteria

          15    were, what the data was, back in 2001, when

          16    there weren't necessarily the proper ways to

          17    collect that data, I think it caused a

          18    problem, and people just put their best guess

          19    out there as far as what they thought would

          20    represent 25 percent enhanced performance.

          21              However, three years into the

          22    process, we certainly have more data that is




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             56


           1    available.  And I think it's evident when you

           2    look at the data that the goals

           3    themselves -- and this is not -- again, I

           4    want to clear that I make the distinction

           5    between FDA's actual performance and the

           6    goals -- because to FDA's credit, they've

           7    exceeded the goals in many many cases, and

           8    exceeded them substantially in some cases.

           9              But when we're talking about the

          10    MDUFMA goals in comparison to the actual

          11    performance from FDA in the years leading up

          12    to MDUFMA, it's not clear that they represent

          13    enhanced performance.

          14              And I think when you look on a

          15    percentage basis of the total number of

          16    submissions, 510(k)s represent about

          17    90 percent, and PMA supplements represent

          18    about 8 or 9 percent, and PMAs represent

          19    about 1 percent.  It's clear that in most

          20    cases, those FDA/MDUFMA decision goals didn't

          21    necessarily reflect enhanced performance.

          22    But as I said again, they're exceeding these




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             57


           1    performance goals.  So there is some good

           2    news here.

           3              But I think as we move forward to

           4    MDUFMA 2 and re-evaluate the goals, I think

           5    they should be that; goals; something that

           6    you strive for, not something that you're

           7    already achieving.  And remembering that the

           8    ultimate goal is an efficient and effective

           9    review.

          10              We need to keep the focus on the

          11    final review times.  The cycle goals are

          12    certainly important, but something that I

          13    know we've spoken to -- the entire industry I

          14    think has shared some concern about the

          15    efforts to maintain or meet -- cycle goals

          16    may have a -- may have an adverse impact on

          17    meeting the decision goals.  And I think we

          18    need to find a balance that still ensures

          19    that we are monitoring FDA's early

          20    performance in the review process as far as

          21    meeting certain time goals of getting

          22    requests for additional information and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             58


           1    certain letters out.  But we can't lose sight

           2    of the ultimate end goal here of performance

           3    in ensuring that a patient has access to that

           4    technology.

           5              Here are just a couple of slides

           6    that I put together to illustrate.  Again,

           7    this is not looking at FDA'S actual

           8    performance, this is solely looking

           9    at -- it's looking at FDA's actual

          10    performance prior to MDUFMA, and then

          11    comparing that to what the MDUFMA goals lay

          12    out.  And here, you're dealing with the

          13    percentage of 510(k) decisions, FDA decisions

          14    within 90 days.  And again, looking at the

          15    numbers here, in 2000, 2001, 2002, FDA was

          16    reviewing between 77 and 80 percent of their

          17    510(k)s within 90 FDA days.  The goals laid

          18    down in MDUFMA allow FDA to review, I think,

          19    75 percent in '05, 75 percent of the

          20    submissions in '06 in 90 days, and then it

          21    goes up to 80 in '07.

          22              And again, to their credit, I think




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             59


           1    86 percent or so was the number for '03-'04.

           2    So they are exceeding these goals, but as we

           3    look forward to MDUFMA 2, I think we need to

           4    ensure that the goals highlighted in

           5    the -- there's a second goals letter in

           6    MDUFMA 2, an actual enhanced performance.

           7    And I think 25 percent, you know, that was

           8    the number that was thrown out in MDUFMA 1.

           9    That's a good place to start.

          10              And then, you know, whether it's

          11    90 -- I don't know what the actual goals

          12    themselves need to be, but it's something we

          13    need to look at.  Again, looking at 180-day

          14    PMA supplements which represent I think

          15    another decent segment of the submissions

          16    that FDA reviews, prior to MDUFMA between

          17    2000 and 2002, there were anywhere between

          18    90-94 percent of 180-day supplements -- were

          19    receiving an FDA decision within 180 days.

          20              However, the goals under MDUFMA

          21    allowed that number to drop to 80 percent in

          22    '05, 85 percent in '06, and 90 percent in




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             60


           1    '07.

           2              And again, I think FDA is meeting

           3    and exceeding the goals in many cases, but I

           4    think there's an inherent problem when the

           5    goal that was established under MDUFMA that

           6    was talked about at 25 percent enhanced

           7    performance in many cases actually

           8    represented a decline in performance with the

           9    status quo.  And I think this is something we

          10    need to address moving forward; are these

          11    realistic but also aggressive performance

          12    goals, in conjunction with a reasonable fee.

          13    And that's going to be the way I think this

          14    program succeeds moving forward.

          15              Original PMAs.  Again, prior to

          16    MDUFMA, looking at the baseline between

          17    2000-2002, 86 percent of the submissions had

          18    an FDA's decision within 320 days, and

          19    90 percent had an FDA decision in 347 days.

          20    So that's kind of the baseline in which we

          21    were operating prior MDUFMA.  And I think

          22    it's important to note that over the course




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             61


           1    of first three years of this program, the

           2    industry has contributed close to $80 million

           3    in user fees.  Congress has appropriated

           4    approximately $30 million, with hopefully

           5    more to come.

           6              So it's not an insignificant amount

           7    of resources that are being invested into the

           8    FDA here.  And then when you look at that

           9    investment coupled with the goals that are

          10    laid down in MDUFMA in FY '06, the goals

          11    state that 80 percent of the decisions need

          12    to have an FDA decision in 320 days.  Again,

          13    this allows for a drop from 86 percent.  And

          14    then in '07, 90 percent need to have an FDA

          15    decision in 320 days, representing

          16    approximately a 4 percent improvement.

          17              So these are things that we need to

          18    take a look at, and certainly, again, we

          19    appreciate FDA's efforts to exceed the goals.

          20              By no means do I think that they

          21    are only trying to work to achieve the goals

          22    and move on.  I think the evidence indicates




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             62


           1    otherwise, that they have taken steps to

           2    improve that.  But again, I think even the

           3    steps to improve probably don't come anywhere

           4    close to the 25 percent enhanced performance

           5    that the industry was I guess promised or

           6    committed prior to MDUFMA.  That's something

           7    we need to work on moving forward.

           8              MR. BARNETT:  Two minutes, Mark.

           9              MR. LEAHEY:  Perfect.  I think we

          10    need to re-evaluate both the cycle and the

          11    review goals.  Again, as I said earlier, we

          12    do not want the cycle goals to impede the

          13    process.  I think they are important to

          14    measure kind of the process, and ensuring

          15    that there is communications early on in the

          16    process.  But we don't want the fixation on

          17    the cycle goals to detrimentally impact the

          18    overall review process.

          19              And I think the goals should

          20    reflect more than the status quo.  So that

          21    would I think clearly indicate that the

          22    current goals need to be enhanced.  And we




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             63


           1    need to work with FDA, Congress and the

           2    stakeholders to determine real and reasonable

           3    goals.  And this is something I look forward

           4    to over the course of the discussions this

           5    springtime.  I think we all have to remain

           6    focused that the ultimate goal here is to

           7    enhance patient care.  And I think if we keep

           8    that as a primary focus, hopefully everything

           9    else will fall into place.  So thank you.

          10              MR. BARNETT:  Thank you, Mark.

          11    Anyone on the panel wants to ask Mark a

          12    question?  Okay.  If that's the case, let's

          13    go on to our next speaker, Marlene Valenti,

          14    with AdvaMed.

          15              MS. VALENTI:  Good morning.  I'm

          16    Marlene Valenti, and I'm the vice president

          17    of Regulatory Affairs for Cordis Corporation.

          18    And as Mark indicated, I'm also an AdvaMed

          19    representative.  I actually am the

          20    chairperson for that PMA task force.  And as

          21    I told some of you during the break, I'm also

          22    a very happy hurricane survivor from Wilma.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             64


           1              As we all know, MDUFMA mandated

           2    user fees, and we've heard over and over this

           3    morning in regards to one of the key

           4    objectives, and that was to reduce cycle

           5    times from the time of submission to getting

           6    that product onto the market.  And that it

           7    obviously includes both cycle goals as well

           8    as performance goals, decision goals.

           9              And we would like to commend FDA in

          10    regards to the fact that have met most of

          11    their 2005 performance goals, and based on

          12    the numbers, actually most of the 2006 goals

          13    also.

          14              With that, and as Mark indicated

          15    before, we are very happy that those goals

          16    were met, but we have to go back to looking

          17    at the key objective in regards to this

          18    provision.  And several FDA officials have

          19    recently publicly stated in regards to

          20    whether or not it really has met that

          21    ultimate intent of that regulation, they've

          22    indicated that in some cases, yes, and in




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             65


           1    some cases with unintended consequences.  And

           2    I think when they speak to that point, what

           3    they're talking about is that in some cases,

           4    FDA is managing by the cycle times and the

           5    decision times rather than pulling back and

           6    looking at the big picture in terms of the

           7    overall time from submission to market

           8    release of that product.

           9              If you talk to industry, I think

          10    they would definitely agree with that

          11    position.  And in fact, I think industry

          12    would say that the objective is very

          13    infrequently met.  In terms of industry,

          14    here's some perspective in regards to first,

          15    the PMA supplement non-approvable letters.

          16    And if you look at the numbers that came out

          17    in fiscal year 2003, it was about a

          18    15 percent where we were receiving

          19    non-approvable letters; that went up to over

          20    40 percent in 2004.  And that is very

          21    significant in the aspect of obviously

          22    getting the product to the market as quickly




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             66


           1    as possible, and also allowing us to have

           2    predictable review times.

           3              We don't have the numbers for 2005

           4    yet.  I know AdvaMed has asked for those

           5    numbers, but in terms of looking at the

           6    preliminary numbers that were published, and

           7    also just conversations with our members, we

           8    do suspect that it's not any better, and it

           9    may actually be higher than the 2004 number.

          10              In addition, we've had some

          11    conversation with the 510(k) working group

          12    that was just headed up by Catherine Beath.

          13    And they are indicating that they're seeing

          14    an increase in NSC letters that are not

          15    substantially equivalent.

          16              So again, it seems from our

          17    perspective that the FDA is managing to the

          18    cycle and the decision goals rather than

          19    pulling back and looking at the overall time

          20    from submission to market.  Now, in regards

          21    to the path forward, I'd love to stand here

          22    and say that we have all the answers and be




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             67


           1    able to provide those to you today.  We can't

           2    do that, but what we can say is that in

           3    discussion with our members, we strongly feel

           4    that more guidance documents are needed, and

           5    that that will facilitate the review cycle,

           6    and that these guidance documents need to be

           7    kept up-to-date and really reflect the

           8    current thinking of FDA, so that when a

           9    manufacturer goes through that guidance

          10    documents, uses that for an application, that

          11    they are putting in that application what FDA

          12    is looking for and therefore not receiving a

          13    non-approvable letter.

          14              And one of the key ones that I know

          15    we have been working with FDA for many years

          16    on is the PMA change guidance document.  And

          17    I'm very happy to hear that FDA is treating

          18    that as a priority to get that out.  But we

          19    really feel that is an important document for

          20    us, because it really will provide

          21    transparency on what type of submission is

          22    required.  In addition, AdvaMed is extremely




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             68


           1    willing to work in a collaborative manner to

           2    help develop innovate ways to improve the

           3    process, and also in regards to the guidance

           4    documents.  We would love to be working with

           5    FDA upfront.

           6              I think one case that we can point

           7    to in terms of what did work was working with

           8    Dr. Gross' group, with OSB, in regards to the

           9    conditions of approval.  And we met with him

          10    several times before he actually published

          11    the guidance document.  And I think having

          12    that opportunity to provide to him what

          13    worked and what didn't work allowed him to

          14    put out a guidance document in a very, very

          15    quick manner in terms of getting it out

          16    there.

          17              And it's something that pretty much

          18    reflects most of the opinions that we had put

          19    forward in terms of the key elements with the

          20    conditions of approval.  So if we were to

          21    cite an example in terms of what would work,

          22    I would encourage you to look at that




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             69


           1    process.  Thank you.

           2              MR. BARNETT:  Thank you, Marlene.

           3    Again, anyone in the panel who want to ask a

           4    question or some clarification?  If that's

           5    the case, let's go to our next speaker,

           6    Marlene Keeling, who's with the Chemically

           7    Associated Neurological Disorders.

           8              MS. KEELING:  Good morning.  I'm

           9    Marlene Keeling.  I am president and a

          10    founding director of Chemically Associated

          11    Neurological Disorders, or CANDO.  I want to

          12    thank the FDA for the opportunity to speak

          13    before this stakeholder meeting.

          14              I'm here representing consumers of

          15    medical devices.  In particular, I will

          16    address the approvable letter with conditions

          17    recently sent by the FDA to the manufacturers

          18    of breast implants.  My concern is not with

          19    the time it took the FDA to respond to the

          20    manufacturer's PMA application, but the

          21    science behind the decision to approve this

          22    Class III device.  My concern is with the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             70


           1    proprietary or secret conditions as set forth

           2    by the FDA for ultimate approval.

           3              The Washington Post quotes a cover

           4    letter recently sent by Mentor to plastic

           5    surgeons stating: "In anticipation of a final

           6    gel breast approval, the FDA is requiring

           7    that study doctors send a letter to their

           8    study patients to remind them of the

           9    importance of their commitment to continue

          10    their one-, three-, and five-year follow-up

          11    visits."

          12              Does this mean that the FDA is only

          13    going to require the manufacturers to follow

          14    the breast-implanted patients for five years?

          15    In networking with thousands of

          16    breast-implanted patients, we know that often

          17    it takes seven years or more after

          18    implantation for symptoms of systemic disease

          19    to appear.

          20              The most common local complication

          21    of implants is encapsulation.  It is

          22    well-recognized that this is an inflammatory




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             71


           1    response in the body's attempt to wall off

           2    this foreign material.  Recently, there has

           3    been much written about inflammation and its

           4    role in systemic disease.  Common sense tells

           5    me that after a number of years, and when

           6    these implants start to degrade, it

           7    overwhelms the immune system and

           8    detoxification ability of the human body.  I

           9    would like to briefly review the record of

          10    the FDA and breast implant manufacturers.

          11              Seventeen years ago, the FDA

          12    classified all breast implants into the

          13    Class III category because of reports of

          14    adverse events in the medical literature.

          15    Fourteen years ago, PMA submitted by the

          16    manufacturers did not contain sufficient data

          17    to warrant a review by the FDA.

          18              Thirteen years ago, FDA decided to

          19    allow silicone gel-filled implants on the

          20    market only under controlled clinical

          21    studies.  Nine years ago, FDA sent a letter

          22    to manufacturers detailing information needed




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             72


           1    for core studies.  This year, FDA sent

           2    manufacturers an approvable letter with

           3    conditions after reviewing only one, two and

           4    three years of data.

           5              My understanding is that the

           6    current third generation implants being

           7    considered for approval had been manufactured

           8    since 1988.  The question then becomes why

           9    did the manufacturers not have 13 years of

          10    data, or even 9 years of data?  I believe I

          11    know why, after networking with thousands of

          12    breast-implanted patients.

          13              The incidence of complications

          14    becomes too high of this non-life-saving

          15    device, and the women are not being followed

          16    in many cases as required by the FDA,

          17    especially after they develop local

          18    complications or systemic disease.

          19              In 1997, when I filed my first

          20    Citizen's Petition regarding breast implants,

          21    the manufacturers were being allowed to quote

          22    a 1 percent rupture or failure rate, and many




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             73


           1    women were being told that their implants

           2    would last a lifetime.  This was the

           3    information that women were using to make a

           4    decision as to how much risk they were

           5    willing to take.  After independent MRI

           6    research by the FDA, it was determined that

           7    the rupture rate was 77 percent, with

           8    silicone seen outside of the scar capsule

           9    21 percent of the time.

          10              Manufacturers then changed the

          11    wording in the product insert to simply say,

          12    "Implants may not last a lifetime."  As

          13    stated by the Washington Post: "Some of the

          14    major reservations voiced by the FDA

          15    scientists and 2005 advisory panel experts

          16    involve the relatively limited amount of

          17    long-term information about the implant's

          18    effect on women's bodies."

          19              Paul Wooley, director of research

          20    for orthopedic surgery at Wayne State

          21    University, recently stated: "It's been

          22    suspected for at least a decade that heavy




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             74


           1    metals used in manufacturing of implants

           2    might cause problems for women who receive

           3    these implants."  Independent research by the

           4    FDA published after the IOM review in 1999

           5    found an increased incidence of fibromyalgia

           6    in breast-implanted women.  Independent

           7    research by the NIH, also published after the

           8    IOM review, found an increased incidence of

           9    some cancers in breast-implanted women,

          10    including brain and lung cancers as well as

          11    others.

          12              I find it curious that when the

          13    manufacturers pay for studies, they do not

          14    find an increased incidence of systemic

          15    disease for the most part.  Former Mentor

          16    employees reported to the New York Times that

          17    data was falsified regarding breast implants.

          18    One employee, who was a former product

          19    evaluation manager from '96 to '98, said

          20    Mentor never met basic quality standards for

          21    implant manufacturing while he was there.

          22              One employee who supervised




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             75


           1    Mentor's complaint department said she

           2    received about 6000 complaints of ruptured

           3    implants in each of her three years at the

           4    company.

           5              However, in a recent filing with

           6    the FDA, Mentor stated that it received a

           7    total of 8060 rupture complaints from 1985 to

           8    2003, or approximately 400 a year.  How can

           9    the FDA rely on any data submitted by Mentor

          10    under these circumstances?  Inamed stated at

          11    the 2005 FDA advisory panel hearings that

          12    their gel implants did not leak platinum.

          13    Mentor stated that their implants did leak

          14    platinum, but that it was in a zero valence.

          15    CANDO submitted data to the FDA after that

          16    advisory meeting on a woman with 1997 Mentor

          17    third generation gel implants, and her

          18    4-year-old son born after implantation.

          19              Both were found to have significant

          20    amounts of ionized platinum in their urine,

          21    with a valence up to +4.  Ionized platinum is

          22    on the suspected list as being a




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             76


           1    neurotoxicant, immunotoxicant, respiratory

           2    toxicant and a sense organ toxicant.  Dow

           3    notified the EPA in 1996 of substantial risk

           4    to their platinum catalyst used in the

           5    manufacturing of breast implants.

           6              Any detectable level of ionized

           7    platinum is a health hazard.  The more, the

           8    worse it is.  Several families with children

           9    born after implantation testified at and sent

          10    documentation to the FDA of significant

          11    platinum urine levels up to 382 parts per

          12    billion per liter of urine.

          13              In an ongoing research project,

          14    CANDO has now tested the urine of 20 children

          15    born to breast-implanted mothers.  Why is

          16    this research being ignored by the FDA?

          17    History will reflect that it was under your

          18    administration that these devices that

          19    rupture at an alarming rate and spill

          20    chemicals and heavy metals into a woman's

          21    body were approved.

          22              MR. BARNETT:  Two minutes, please.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             77


           1              MS. KEELING:  Sure.  Due to the

           2    combined lobby effort of the chemical

           3    companies, the manufacturers and the plastic

           4    surgeons -- these are the beneficiaries who

           5    have the money to do clinical trials -- it

           6    would be negligent should the FDA allow these

           7    manufacturers to follow these women for only

           8    five years.  It would be negligent for the

           9    FDA not to require the manufacturers to

          10    follow-up on any children born to

          11    breast-implanted women enrolled in a clinical

          12    study, or not to require platinum urine

          13    testing.

          14              Because the chemicals and heavy

          15    metals used in the manufacturing of medical

          16    devices are considered proprietary

          17    information or secret, consumers must rely on

          18    the FDA to protect them and advise them of

          19    potential risk.  If approval is given, will

          20    consumers be advised that their implants may

          21    leak heavy metals, and these heavy metals, if

          22    ionized, may cross the placental barrier and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             78


           1    brain barrier?

           2              I would consider it grossly

           3    negligent of the FDA not to require the

           4    manufacturers to inform consumers of this

           5    important information when making an informed

           6    decision on how much risk they are willing to

           7    take when implanted with these devices for

           8    many years and during their childbearing

           9    years.

          10              Thank you.

          11              MR. BARNETT:  Thank you,

          12    Ms. Keeling.  Does anyone on the panel need

          13    clarification or question?  If that's the

          14    case, we go to our last speaker, Bob Britain

          15    of NEMA.

          16              MR. BRITAIN:  I'd like to welcome

          17    Dan Schultz to the meeting.  You made it from

          18    Taiwan?  You want to say, "What's in a

          19    number?"  Thirty years ago, the Medical

          20    Device amendments came out, and there was

          21    established 90 days and 180 days -- does

          22    anyone in the room know how those figures




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             79


           1    were established?  Anyone?  Other than a

           2    political decision?

           3              How many resources and hours we

           4    have spent trying to defend those numbers is

           5    amazing.  I think 90 days is pretty good for

           6    510(k)s; I think 180 days is probably short

           7    for PMAs.  It's hard to get a PMA through the

           8    process with advisory committee meetings and

           9    scheduling and that.  But I want to leave you

          10    with a good note, at least from the medical

          11    imaging industry, since we're mainly

          12    510(k)-oriented.

          13              The 510(k) process is working very

          14    well for us.  Most of our 510(k)s are getting

          15    through in 90 days.  Also, the third-party

          16    review process is taking under a total of 90

          17    days, so we're feeling pretty good about

          18    this.  We probably had some ups and downs

          19    trying to get digital mammography devices

          20    through the PMA process, but that was a very

          21    high profile -- at times very touchy issue,

          22    and we had to be very careful about the data




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             80


           1    and how it was derived.  And FDA needed to

           2    take some time to make those critical

           3    decisions for those PMAs.

           4              So on the whole, basically, it's

           5    fun to be the last person on the panel,

           6    because I can say that we certainly agree

           7    with everything the first two speakers said.

           8    And I'll leave it at that.

           9              MR. BARNETT:  Okay, thank you, Bob.

          10    Anyone want a clarification on that?  If

          11    that's the case, is there anyone here who

          12    would like to come up to the mic say a few

          13    words?  Sure, come on.  Please identify

          14    yourself.

          15              MR. LASERSOHN:  Jack Lasersohn from

          16    the National Venture Capital Association.  I

          17    would like to endorse in part, and disagree

          18    to some extent, with the first two industry

          19    representatives.  On the one hand, while we

          20    absolutely believe it is appropriate to focus

          21    on quantitative goals; for example, cycle

          22    times and review times, it is very important




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             81


           1    to remember, too, that you should not merely

           2    focus on goals simply because they are

           3    measurable.  And I think one of the issues

           4    that we have a real concern about is the

           5    exclusive focus on quantitative goals simply

           6    because they are measurable.

           7              The biggest concern for the

           8    venture-backed medical industry, that segment

           9    of the industry, is really not how fast a

          10    review is completed at the end of a cycle,

          11    but rather how long the entire approval cycle

          12    takes.  And by that I mean not merely the FDA

          13    review at the end, but the entire PMA

          14    process.

          15              Shaving 10 or 20 days off of the

          16    end of a five-year PMA process that has cost

          17    on average $40 million or $50 million is a

          18    commendable goal.  It's certainly not

          19    something I would object to, but I have to

          20    say that in the context of the companies that

          21    we represent who are really almost always

          22    looking to produce very innovative, unusual,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             82


           1    almost revolutionary devices, that goal

           2    really only affects perhaps 1 or 2 percent of

           3    the total cycle time, which can typically be

           4    in a PMA, which is unfortunately what most of

           5    our companies end up doing are very fat

           6    510(k)s, it can be four to five years.  So I

           7    think that we are going to be asking in this

           8    MDUFMA 2 review to begin to try to focus on

           9    qualitative goals of improvement that can

          10    improve the entire cycle.

          11              The other thing that I would say,

          12    and in this regard I strongly endorse the

          13    views of AdvaMed -- the data that was put up.

          14    It is very important to be careful to not

          15    have a result that produces wrong decisions

          16    more quickly.  And that to a great extent is

          17    what we hear from the representatives of our

          18    industry.  That is, we can get decisions on

          19    PMAs and in various cycles at 90 days or at

          20    75 days, but they are the wrong decisions,

          21    and we then have to go back and spend endless

          22    cycles trying to fix these decisions.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             83


           1              So making bad decisions or punting

           2    that as asking for more information, more

           3    quickly does not -- while it does technically

           4    reach the goals of the cycle times -- has not

           5    improved the overall cycle of getting these

           6    devices to the market more quickly.

           7              Thank you.

           8              MR. BARNETT:  Thank you.

           9              MS. KAHAN:  Can I ask a clarifying

          10    question?  Can you describe what you're

          11    talking about in terms of these qualitative

          12    goals?  Are they things that you think FDA

          13    needs to be doing, the industry --

          14              MR. LASERSOHN:  Well, it's always

          15    both, right; it's always collaborative.  For

          16    example, we find really when we look at where

          17    the biggest delays and the biggest problems

          18    are in the entire approval cycle, we find

          19    it's very often at the front-end of the

          20    cycle, not at the back-end of the cycle; for

          21    example, in an endless negotiation over

          22    endpoints in clinical trials and clinical




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             84


           1    trial design.  Now, we do recognize that that

           2    is because we are almost always showing up at

           3    the FDA with something that they have never

           4    seen before.  That's the nature of the

           5    venture capital industry, to be revolutionary

           6    rather than evolutionary.  But there has to

           7    be a better way to manage this other than a

           8    one- or two-year education process.

           9              We recognize the need for an

          10    education process, defining the goals of an

          11    acute AMI trial, for example -- for an

          12    interventional device for acute AMI if the

          13    FDA has never seen it before and the

          14    physician community doesn't really understand

          15    it yet, can clearly take time.

          16              On the other hand, it shouldn't

          17    take one or two years.  We need to figure out

          18    a faster way to accelerate the collaboration.

          19    And that's what we are going to be -- as one

          20    example -- and that's one of the things we

          21    will be focusing on.

          22              MS. KAHAN:  Thank you.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             85


           1              MR. BARNETT:  Thank you.  Anyone

           2    else in the panel?  Anyone else in the

           3    audience want to come up and say a few words?

           4    Yes, please.

           5              MR. McKEEN:  My name is Mac McKeen.

           6    I'm with St. Jude Medical.  And I'd like to

           7    echo and reiterate Ms. Valenti's call for the

           8    release of the PMA change guidance document.

           9    Such a guidance is key for manufacturers to

          10    consider when both sustaining the performance

          11    of currently marketed devices as well as

          12    iterating and developing new versions of

          13    these marketed devices.

          14              I say that in a real context in

          15    that there was a draft guidance out there

          16    that AdvaMed had actually worked with FDA in

          17    developing, and it served as a very good

          18    guide.  Granted it was draft and not

          19    official.  I think it was pretty widespread

          20    throughout the industry -- providing a

          21    framework of what were the boundaries, when

          22    to submit, when to do an annual report, and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             86


           1    how to document such product iterations.

           2              In addition, such a guidance would

           3    also serve FDA's post-market program by

           4    helping to clarify annual reporting criteria.

           5    It's not one of life's big mysteries, but

           6    making that more transparent and clear as to

           7    what goes in an annual report versus document

           8    file, or a supplement for a PMA product I

           9    think will be helpful for both parties and

          10    clearly to the product lifecycle for FDA.

          11              So I'd mention that the original

          12    version was essentially complete, at least in

          13    my use and practice of that device -- clearly

          14    now, over time, it may have evolved, and it

          15    can have some new items included.  But

          16    clearly, the 510(k) product has had a

          17    guidance in place for years and it's been a

          18    very effective tool, so I think we need to

          19    build on that.

          20              MR. BARNETT:  Thank you.  Anyone

          21    else?  All right.  If that's the case, let's

          22    go on -- yes?




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             87


           1              MR. ST. PIERRE:  Since we're ahead

           2    of time -- I'm just going to ask one

           3    question.  The earlier presentations, the two

           4    presentations from Mark and Marlene, talked

           5    about the fact that FDA is meeting the

           6    performance goals, but maybe the performance

           7    goals aren't enough.  And managing the

           8    premarket program or the programs within a

           9    center require managing and lot of different

          10    principles.  So if you're looking just at the

          11    goals of review times, that's not nearly the

          12    entire picture.

          13              So can you put a weight on how

          14    important some of the other aspects are, so

          15    if you look at like guidance document

          16    develop -- like in our office, we

          17    probably -- from the last two years to the

          18    previous two years, we've tripled the

          19    guidance document output.

          20              How much weight should that take

          21    from the cycle goals or the decision goals?

          22    We've given, as Dan mentioned in his opening




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             88


           1    remarks, you know, 500 meetings.  So we've

           2    increased the number of meetings, and I

           3    realize they're getting harder to schedule,

           4    but they've actually gone up.  So that's an

           5    important aspect of the program that factors

           6    in, too.

           7              And I know the Agency's been giving

           8    lots of presentations, more educational

           9    presentations and things of that nature.  And

          10    at least in the IVD industry, I'm sure that

          11    the rest of the medical device industry isn't

          12    any different.  There's a lot more innovation

          13    that seems to be going on, and it's moving

          14    very quickly.

          15              And a lot of those newer

          16    technologies seem to be going out quicker.

          17    We're doing lots more de novo applications

          18    and getting newer technologies out what I

          19    think are pretty quickly.  So how much can we

          20    wait all those different things to see, am I

          21    managing correctly, to just to give -- you

          22    know, to split the resources all that way,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             89


           1    because I could take them all off the other

           2    things and just put them on just reviewing

           3    the submissions that come in, so that's a

           4    short-term gain, but probably a long-term

           5    loss.  So can you help the Agency try to

           6    wait --

           7              MR. LEAHY:  I don't know if I can

           8    put specific percentages or weights

           9    associated with each of those different

          10    initiatives.  I think they certainly are all

          11    important, and I think the next panel is

          12    actually qualitative performance.  I mean,

          13    this one was focused on the premarket

          14    performance goals.

          15              I think certainly, the meetings

          16    before submission takes place are important.

          17    To get it right, the guidance documents are

          18    very, very helpful.  And I think those are

          19    things that'll be brought up in the next

          20    session as far as qualitative issues.

          21              One of the things I will say is, I

          22    don't think it has to be an either/or




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             90


           1    approach.  I think when you have an

           2    $80 million infusion from the industry, when

           3    you have Congressional appropriations,

           4    maintaining the status quo or simply

           5    enhancing it a little bit is something that

           6    should be achieved and is being achieved, but

           7    I don't think those other things have to be

           8    taken off the table.

           9              So I don't view it as an either/or

          10    approach.  I think you're moving in the right

          11    direction on all fronts, and I would hate to

          12    have it be viewed as an either/or.  I think

          13    they are complementary, and I think that's

          14    indicative of the way you structured this

          15    program, where in this session it's the

          16    premarket performance goals, the next

          17    session, it's a qualitative goal.

          18              So I think you're moving in the

          19    right direction.  I think we just need to

          20    enhance all areas moving forward, because

          21    again, this is a substantial investment on

          22    behalf of the industry.  And for that




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             91


           1    investment, we really need to see returns.

           2    You know, we are seeing returns, but we need

           3    that to continue to improve.

           4              MR. BARNETT:  Anyone else want to

           5    respond to Don's question?  Yes.

           6              MS. VALENTI:  I would echo a lot of

           7    what Mark said in regards to the fact that

           8    you really can't say it's an either/or, it's

           9    a combination.  And like the gentleman said

          10    in terms of the whole cycle, we do need to

          11    look at the whole cycle in making sure that

          12    we're managing appropriately in regards to

          13    that.

          14              And we don't want to just look at

          15    the end.  You know, we want to look at the

          16    entire cycle, and I know we have some

          17    comments in regards to the qualitative goals

          18    that were set also.  But I think in terms of

          19    when we do talk about the review times, it's

          20    important to look at how it's being managed

          21    in terms of the cycle times versus the

          22    decision times or the overall time.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             92


           1              And I think we've had numerous

           2    conversations, not only myself, but others,

           3    in terms of with branch chiefs, and they've

           4    indicated that even if they're not sure

           5    whether or not they can make a decision

           6    within 180 days, they issue a non-approvable

           7    letter because they're managing to that cycle

           8    time.  So even if they're on the fence or not

           9    even the -- they're pretty sure you can do

          10    it, but they're not 100 percent sure, they're

          11    indicating that they're issuing

          12    non-approvable letters.

          13              So I think there is a lot of

          14    flexibility even with what we have today in

          15    the funds that you have today, to be managing

          16    it a little bit differently, to be able to

          17    manage the entire life cycle.

          18              MR. BARNETT:  Thank you.  Anyone

          19    else?  We have two here.  Bob.

          20              MR. BRITAIN:  Well, I hope this

          21    will be helpful.  I think that a guideline is

          22    a heck of an investment.  It's worth doing,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             93


           1    and it's worth doing well.  At what cost, I

           2    don't know, but if you don't have an

           3    established guideline, the reviewers are

           4    going to have their own.  They're going to

           5    have the things that they tick off.  So

           6    invest your resources in 510(k) guidance and

           7    PMA guidance, and how you deal with that in

           8    pitting that against the actual reviews, I'm

           9    not sure, but guidance is a worthwhile

          10    investment.

          11              MR. BARNETT:  Thank you.  Go ahead.

          12                   (Phone Interruption)

          13              MR. LASERSOHN:  Sorry.

          14                   (Laughter)

          15              MR. LASERSOHN:  That's inevitable.

          16    Two points:  I absolutely agree that the

          17    quantitative goals are very important.  On

          18    the other hand, I would point out again,

          19    citing AdvaMed's presentation, that it is

          20    possible to meet quantitative goals very

          21    often by changing the rules or by asking

          22    questions along the way.  So for example, if




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             94


           1    in fact a non-approvable letter rate goes up

           2    while the cycle time goes down, that is not a

           3    good outcome.  So I would suggest, for

           4    example, that if in fact we are going to have

           5    quantitative goals, that situations like that

           6    have to be considered, and one obvious

           7    solution is that the cycle time goals will be

           8    penalized to the extent that there are

           9    increases in non-approvable letters.

          10              So I would say that's point number

          11    one.  With respect to guidance documents and

          12    other things, I do have a different position

          13    than the rest of the industry, because again,

          14    we are representing the segment of the

          15    industry that is almost always doing

          16    something new, by definition.  And the

          17    guidance documents almost never help us, they

          18    almost always hurt us, because there's an

          19    attempt to squeeze a particular completely

          20    novel technology that nobody has ever seen

          21    before into an existing guidance document.

          22              And what we find is the first two




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             95


           1    meetings that we have with the FDA over a

           2    period of three or four months is

           3    demonstrating that in fact this doesn't fit

           4    into a particular guidance; you cannot apply

           5    a particular guidance because it's completely

           6    different.

           7              So I think guidance can be very

           8    helpful for those things for which it is

           9    appropriate, you know, the 14th drug-eluting

          10    stent -- it's a pathway that's

          11    well-understood.  There should clearly be a

          12    guidance on how to get a drug-eluting stent

          13    approved.  But the first drug-eluting stent

          14    is much more problematic.

          15              MR. BARNETT:  Thank you.  Anyone

          16    else?  Yes, two more.

          17              MR. McKEEN:  Mac McKeen again, with

          18    St. Jude.  I just would like to recommend

          19    that FDA work within an existing guidance.  I

          20    mean, there's been call for new guidance this

          21    year in terms of the review process, and this

          22    FDA clock.  In fact, that's one of the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             96


           1    guidances, is how we calculate the FDA clock;

           2    the stops and starts.  And I think in the

           3    end, that's what could put pressure or roll

           4    up into that metric of when this thing gets

           5    approved.

           6              What I would suggest is that the

           7    Agency give reviewers of PMA and PMA

           8    supplements more discretion, and perhaps even

           9    incentive, to engage in interactive reviews

          10    rather than deficiency letters, because

          11    deficiency letters stop the clock, and then,

          12    tagger it, and then the industry has to get

          13    back to restart the clock.

          14              And certainly there is occasion

          15    where that's necessary if there's a gap or a

          16    hole in the content of the submission.  But

          17    in many cases -- or in some cases, I should

          18    say -- pretty straightforward questions may

          19    be contained elsewhere in the submissions or

          20    easily answered through an interactive e-mail

          21    or a phone conversation.

          22              In business, that's how we get




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             97


           1    things done.  We don't stop the car and get

           2    out to fix it.  We keep having meetings and

           3    working together collaboratively to keep this

           4    whole process moving forward.  So again, not

           5    new or novel by any means, but I think it's a

           6    part of the FDA review process that can be

           7    easily expanded within the current guidance.

           8              MR. BARNETT:  Thank you.  There was

           9    another one there.  Yes, please.

          10              MR. ST. PIERRE:  Well, I hope

          11    that's actually happening now.  And actually,

          12    I agree with those other speakers, too,

          13    decision goals are much important than cycle

          14    goals.  So let's focus on that.

          15              MR. BARNETT:  Since you haven't

          16    spoken before, identify yourself.

          17              MR. HAHN:  Dennis Hahn, Ethicon

          18    Endo Surgery.  I'd love to give you a number

          19    in terms of the number of guidance documents,

          20    but again, it's a qualitative goal; it's

          21    difficult to give.  The concern that I have

          22    is that all of our MDUFMA goals are based on




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             98


           1    the back-end of the process.  User fees are

           2    based on -- once all of the data has been

           3    collected, it's based on the review cycle,

           4    and all the performance goals are based upon

           5    that.

           6              One of the things that we're

           7    missing, and Linda, to your point earlier, as

           8    we look forward to MDUFMA 2, we really need

           9    to focus both quantitative and qualitative

          10    goals on the front end of the process, and

          11    that is things like the IDE review process,

          12    and even more importantly -- and I have only

          13    an NF 2, but really pre-IDE meetings, both

          14    the quality and the ability to schedule.

          15              What I have been seeing in my NF 2

          16    is that pre-IDE meetings are being pushed to

          17    the very limit because of the focus on cycle

          18    time in terms of PMA review and so trying to

          19    schedule a pre-IDE meeting is very difficult,

          20    it takes the full 60 days at best, to try to

          21    get all of the players together; both from

          22    the Agency and from industry.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                             99


           1              So my focus for at least MDUFMA 2

           2    is to look at some of the leading indicators,

           3    which is really the early phase in the IDE

           4    phase.

           5              MR. BARNETT:  Thank you.  Anyone

           6    else.  Well, Don, you started a good

           7    conversation there.  Thank you.

           8              MR. ST. PIERRE:  I'm not on the

           9    next panel.

          10                   (Laughter)

          11              MR. BARNETT:  Well, several people

          12    have talked about qualitative performance

          13    goals, and now we've got a session on that,

          14    so thank you, guys.

          15              And let me call up the next two FDA

          16    subject matter experts, both from the Office

          17    of Compliance, Tim Ulatowski and Mike

          18    Marcarelli.

          19              Our first speaker is Pat Shrader,

          20    with AdvaMed.

          21              MS. SHRADER:  Good morning.  My

          22    name is Pat Shrader.  I'm vice president of




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            100


           1    corporate regulatory for Becton Dickenson,

           2    and I am speaking today on behalf of AdvaMed.

           3    My topic is qualitative goals, and I

           4    certainly appreciate the nice lead-in from

           5    both Don St. Pierre and other members of the

           6    audience who have already spoken about this,

           7    and have emphasized the importance of some of

           8    these qualitative goals in making sure that

           9    the intent of MDUFMA is really met.

          10              First, I would like to add my

          11    compliments to the compliments of some of the

          12    earlier speakers to FDA for being able to

          13    meet many of the explicit performance goals

          14    for MDUFMA.  I think FDA has made a lot of

          15    progress in this area.  It's been a lot of

          16    hard work on both sides, but it's been some

          17    very important work.

          18              We talked last year about

          19    qualitative goals, and particularly

          20    scheduling of meetings, modular PMA reviews,

          21    bundling and pre-approval GMP audits, and

          22    we've seen improvements in some areas, and in




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            101


           1    other areas, we see additional opportunity

           2    for improvement.

           3              And let me point out that one of

           4    the downsides of speaking about qualitative

           5    goals is that these things aren't measured,

           6    and we don't have good metrics around them,

           7    so much of what I will be sharing with you is

           8    anecdotal information.

           9              But those of you who deal with

          10    things like customer complaints or

          11    constituent complaints on a day-to-day basis

          12    realize that you can get a pretty good feel

          13    for how things are really working based on

          14    the amount of background noise around

          15    something.

          16              I did want to point out, if you

          17    look at CDRH's 2006 priorities, you will see

          18    that the performance record in fiscal year

          19    '05 has been good, and also that there has

          20    been focus on more than just the performance.

          21    It's been on a change in the culture, and I

          22    think this is particularly important to tie




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            102


           1    in to the qualitative goals; that the

           2    coordination of all the activities that lead

           3    to the quickest possible time to market for

           4    products, and the accountability on both

           5    sides, both industry and FDA, is something

           6    that we need to pay attention to.  And I

           7    think we also appreciate the fact that FDA

           8    has identified continued improvement as one

           9    of their goals.

          10              So "Scheduling of Meetings," you

          11    have already heard a few words about that in

          12    the goals letter that was done at the time of

          13    MDUFMA in 2002.  FDA and the industry stated

          14    that both agreed that the use of informal and

          15    formal meetings is critical not just to

          16    ensure high application quality, but also to

          17    ensure speedy reviews.

          18              Yet AdvaMed members are currently

          19    indicating that scheduling of meetings is

          20    becoming more and more a concern, and I think

          21    it goes without saying that improvements in

          22    scheduling are going to be important to




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            103


           1    assure that the overall intent and the

           2    specific performance goals are met.

           3              So I would encourage us on both

           4    sides to try to develop some meaningful

           5    metrics around scheduling of meetings, how

           6    long does it actually take to get meetings

           7    scheduled, and how does that play into the

           8    full review cycle?

           9              PMA Modular Reviews.  The Industry

          10    has always been very supportive of modular

          11    review.  It has a lot of benefits in that as

          12    you finish up a particular area,

          13    pre-clinical studies, for example, you can go

          14    ahead and put the submission in, get

          15    questions on the table, get those questions

          16    answered, and optimistically not have to go

          17    back and re-review that.

          18              It also provides an opportunity for

          19    FDA to get some of the work done ahead of

          20    time and really to be able to focus on the

          21    clinical data as the last piece of

          22    information that goes into the review cycle.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            104


           1    FDA's perspective on modular PMAs has been

           2    mixed, some people seem to favor them, other

           3    people are concerned about the additional

           4    resources that are required, but certainly

           5    from an industry perspective, we would

           6    encourage you to continue this program.  And

           7    more importantly, we think there should be

           8    specific performance goals for modular PMAs,

           9    and would be interested in seeing this as an

          10    element for MDUFMA reauthorization.

          11              And in terms of setting metrics for

          12    that module should be closed and in a timely

          13    fashion, and in order to do so, questions

          14    would have to come back from FDA to the

          15    company in a very timely fashion, and we are

          16    suggesting that 75 days for questions, and 90

          17    days to review a completed module, should be

          18    appropriate.

          19              I don't believe that we talked

          20    about bundling last year, but bundling was a

          21    real concern that the industry brought up

          22    back again in 2002.  On both the device and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            105


           1    the diagnostic side, there were concerns that

           2    FDA would try to find a way to split a

           3    product or a product line into too many

           4    separate applications in order to collect the

           5    fee.  And in reality, that's not what has

           6    happened.

           7              On the medical device side,

           8    bundling, I think, has been very effective.

           9    On the in-vitro diagnostic side, it may

          10    require some reconsideration.  FDA did put

          11    out a guidance on bundling.  A specific

          12    example provided by one AdvaMed member is

          13    that that guidance specifies that for

          14    anti-microbial susceptibility tests, one

          15    submission is required per drug, and can

          16    cover both gram positive and gram negative

          17    organisms.

          18              In fact, that has not always been

          19    the case, the actual decision is made on a

          20    case-by-case basis, and the result of this is

          21    that the fees for some in-vitro diagnostic

          22    products are disproportionately large.  Just




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            106


           1    to provide one example for one particular

           2    product platform, 56 submissions were

           3    required that actually covered only 22

           4    products.  So in that case, the effective

           5    510(k) fee was $8000 per product.

           6              And ending on a positive note, last

           7    year, we mentioned the need for coordination

           8    in the timing of pre-approval inspections,

           9    because various AdvaMed members were noting

          10    that these were holding up the final PMA

          11    approval.  And we also noted that this was

          12    not only responsibility on the part of FDA,

          13    but also that it was important for sponsors

          14    of PMAs to be sure that this was incorporated

          15    in their project planning, and that in fact

          16    they would be prepared for their pre-approval

          17    inspections at the appropriate time.

          18              The good news this year is that the

          19    noise level around this issue seems to have

          20    gone down substantially, indicating that in

          21    more and more instances, FDA is able to

          22    appropriately schedule the pre-approval




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            107


           1    inspections so that they don't in fact hold

           2    up the final decision.

           3              So in summary, what I'd like to say

           4    is that we have certainly seen some

           5    significant areas of improvement in

           6    qualitative goals.  There are still some

           7    opportunities that remain in a variety of

           8    areas.  I think both FDA and the industry

           9    agree that these are important, and these are

          10    areas in which we should try to establish

          11    some baseline metrics, and wherever possible,

          12    some goals for a MDUFMA reauthorization.

          13              Thank you.

          14              MR. BARNETT:  Thank you, Pat.  Is

          15    there anyone on the panel who wants

          16    clarification.  Yes, Joanne?

          17              MS. LESS:  Pat, sorry, I don't have

          18    much of a voice.  One of the previous

          19    speakers mentioned the difficulty in

          20    scheduling pre-IDE meetings.

          21              MS. SHRADER:  Yes.

          22              MS. LESS:  And in your slide, you




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            108


           1    just referred to meetings in general, so are

           2    you seeing it across all the three program

           3    areas, or still predominately in IDE area?

           4              MS. SHRADER:  I think it crosses

           5    this all three program areas.  My own

           6    experience has been with informal meetings,

           7    and scheduling is becoming difficult.

           8              MS. LESS:  Okay, thank you.

           9              MR. BARNETT:  Tim?

          10              MR. ULATOWSKI:  Yes, Pat, perhaps

          11    you want to respond, or it may generate other

          12    responses after you, because I think you are

          13    the only scheduled speaker, but anyway, a

          14    couple of things:  What are your views in

          15    regard to pre-IDE meetings and IDE meetings,

          16    participation of compliance folk to discuss

          17    GMPs and BIMO aspects during the course of

          18    the early days of investigations?

          19              MS. SHRADER:  Well, I think

          20    certainly getting input on any expectations

          21    around inspections, whether they be BIMO or

          22    GMP inspections, is important.  So I think




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            109


           1    that having participants from FDA who can

           2    address those areas and give some insight

           3    into what they maybe looking for and what

           4    their concerns might be would be appropriate.

           5              MR. ULATOWSKI:  You mentioned the

           6    "not ready for inspection" aspect.

           7              MS. SHRADER:  Yes.

           8              MR. ULATOWSKI:  What has the

           9    industry done, to your knowledge, to make

          10    improvements in regard to this aspect?

          11              MS. SHRADER:  Well, I think that

          12    the trade associations have certainly carried

          13    the message home to all of their members that

          14    this is a collaborative effort, and for

          15    industry to make this process work as well as

          16    it should, that it's very important that we

          17    be very mindful of timing and scheduling, be

          18    mindful of the workload that FDA has and make

          19    sure that we are in there prepared and

          20    talking to the appropriate people at the

          21    appropriate time.  So I think the

          22    associations have done a good job of letting




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            110


           1    their members know.

           2              MR. ULATOWSKI:  Let me just ask a

           3    third question:  People are keeping track of

           4    my questions here.  What are your views

           5    regarding what I will call early intervention

           6    inspections; for example, on BIMO, as a means

           7    to reduce total process time for PMAs?

           8              MS. SHRADER:  I'm not clear what

           9    you mean by "early intervention."

          10              MR. ULATOWSKI:  Meaning inspections

          11    during the early course of investigations to

          12    perhaps reduce the back-end load on the BIMO

          13    inspections, when things are coming to a head

          14    at the end.

          15              MS. SHRADER:  Well, I would have to

          16    give that a little additional thought.  One

          17    concern that I would express is that I don't

          18    think that the BIMO inspections can be

          19    terribly early in the process, because

          20    experience with clinical investigation

          21    suggests that you select your investigators,

          22    get all your agreements in place, you go in




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            111


           1    and train the investigators.

           2              But depending on the device, there

           3    may be a learning curve, and as a result,

           4    companies do try to monitor their studies

           5    carefully, and in fact, may intervene early

           6    themselves to try to either make changes in

           7    techniques, changes in devices, or changes in

           8    training for investigators.  So I think

           9    earlier rather than later is a positive, but

          10    I would caution against trying to get

          11    involved too early in the course of a

          12    clinical investigation.

          13              MR. ULATOWSKI:  Thank you.

          14              MR. BARNETT:  Anyone else on the

          15    panel who wants to add anything?  How about

          16    in the audience?  Yes, we have a lot of them,

          17    okay.

          18              MS. VALENTI:  To the last point, I

          19    would reiterate what Pat indicated in regards

          20    to the clinicals:  That we do have to

          21    intervene early on in the process sometimes

          22    in order to correct those.  So I think it is




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            112


           1    more appropriate for the sponsor to do that

           2    rather than using the resources of FDA to do

           3    that.

           4              So moving it not necessarily at the

           5    end, but closer to the end would probably be

           6    more appropriate.  But your question in

           7    regards to having the Office of Compliance at

           8    the meetings early upfront during the IDE

           9    process I think is very critical, especially

          10    for combination products.  And where we are

          11    looking at which of the GMPs and QSR should

          12    apply for that product, I think in that case,

          13    it would be very critical.

          14              MR. BARNETT:  Thank you.  Before we

          15    go to the next one, let me ask our

          16    transcriber, if someone has spoken before, is

          17    it still necessary to identify themselves?

          18    Where are you, transcriber?

          19              COURT REPORTER:  No, unless I can't

          20    remember their names.

          21              MR. BARNETT:  So it's only when

          22    they haven't spoken before.  Thank you.  All




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            113


           1    right, who is next?

           2              MR. DURGIN:  Bob Durgin with

           3    Biomet.  I just want to speak about one of

           4    the things that I think we have seen work

           5    well from our experience, and that is the

           6    Office of Compliance's review of

           7    manufacturing modules of PMAs.  I want to

           8    compliment the Office of Compliance for their

           9    internal metrics.

          10              I know there are no performance

          11    goals in this area, but we have seen very

          12    good performance on those internal metrics.

          13    There has been good accessibility of the

          14    staff, informal discussions during the review

          15    process.  And we have also seen very timely

          16    scheduling of a pre-PMA inspection.

          17              I guess the one area where I think

          18    there is still some room for improvement is

          19    similar to what we see in the other

          20    performance goals, that there be focus on the

          21    total decision time as opposed to meeting

          22    just the individual cycles for reviews.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            114


           1              I think we have seen in one of our

           2    PMAs a number of letters where the

           3    internal -- I think it's 30-day goal -- has

           4    been met, but ultimately there were more

           5    cycles than I think was necessary in the

           6    process.  But overall, I think it really has

           7    been an area that's worked well and there has

           8    been significant improvement.

           9              MR. BARNETT:  Thank you.  Anyone

          10    else?  We had several hands earlier.  Please?

          11              MR. LASERSOHN:  First of all, I

          12    apologize for stepping up here each time.  I

          13    didn't realize that we could present at the

          14    end of each session, so I going to do it this

          15    way.  First, a caution, as I said before:

          16    Trying to apply quantitative metrics to

          17    qualitative performance goals is very

          18    problematic, and the natural tendency is

          19    always to measure something -- it would not

          20    matter what it is -- whether that is really,

          21    what matters or not.

          22              And for those of you who do




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            115


           1    clinical trials, you know that that's always

           2    a problem, measuring things, or you tend to

           3    measure what you want to measure or what's

           4    easy to measure, and sometimes the stuff

           5    that's much more difficult to measure is the

           6    stuff that really matters.

           7              So I will get to that point in a

           8    second.  But speaking of quantitative goals

           9    with respect to qualitative, as the last

          10    speaker indicated, the total cycle time for

          11    regulatory approval is what matters to our

          12    members.

          13              And clearly one of the things that

          14    we can do is begin to measure that, so that

          15    instead of thinking about merely the cycle at

          16    the end of a four- or five-year approval

          17    process, we really need to start to keep

          18    track of the total time for an approval of a

          19    product, starting from the very first

          20    communication, for example, by a sponsor with

          21    the FDA with respect to a particular

          22    approval.  We have to begin to measure that.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            116


           1    And I think that we would find that beginning

           2    to focus on that, just to at least measure

           3    it, would be very, very productive.

           4              With respect to the qualitative

           5    types of improvements that we can make for

           6    qualitative outcomes, I think we have to look

           7    at broader regulatory changes rather than

           8    trying to quantify performance measurements.

           9    So for example, we will be proposing in this

          10    next cycle that the entire risk-based

          11    assessment process be given much much greater

          12    priority, and that a risk-based approval

          13    process really be defined as a separate

          14    process.

          15              A sponsor should be able to put

          16    things to request that approval cycles be in

          17    a different category, even if they are PMA or

          18    510(k) or de novo 510(k), that we can create

          19    a new category, a new pathway on a risk-based

          20    basis.

          21              Similarly, we believe that it's

          22    necessary to begin to think about a separate




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            117


           1    process for novel devices.  That is, if one

           2    of our companies walks in with something that

           3    we know you have never seen before, it really

           4    makes no sense to attempt to fit it in into

           5    an existing PMA or 510(k) process, and there

           6    should be a mechanism for requesting -- not

           7    an expedited process; that's not at all what

           8    we are talking about, but a process that

           9    recognizes the novelty of a particular

          10    device, and as a result, is going to bring

          11    different resources of the FDA to bear and

          12    make additional resources of the FDA

          13    available to avoid the problem of negotiating

          14    endpoints for a year or two in an IDE trial

          15    because the reviewer has simply never seen

          16    such a thing before and is going through a

          17    long learning curve.

          18              So we are going to be emphasizing

          19    qualitative changes in process, or new

          20    qualitative processes in order to address

          21    these qualitative performance requirements.

          22              MR. BARNETT:  Thank you.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            118


           1              MR. ULATOWSKI:  I have one

           2    question.

           3              MR. BARNETT:  Yes, please.

           4              MS. KAHAN:  Could you clarify what

           5    you mean about that first category of risk

           6    based -- I'm sorry, risk-based products --

           7    and we usually think of it as risk benefit.

           8    Are you talking about qualitative --

           9              MR. LASERSOHN:  Well, of course,

          10    risk benefit is a safety question, and there

          11    is an explicit de novo 510(k) process which

          12    is a risk-based process, but it technically

          13    applies only to products that don't fall into

          14    other categories.

          15              What we are going to request, for

          16    example, is that on products that we believe

          17    are demonstrably safe, that we can put them

          18    into a different review category and treat

          19    them in a different way so that there is an

          20    explicit understanding, not so much at the

          21    top of CDRH, which frankly we think works

          22    very, very well, but at the staff level of




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            119


           1    CDRH, that they must consider risk

           2    adjustments to, for example, the endpoints of

           3    clinical trials.

           4              This is, I would say, of all of the

           5    things that we encounter, the risk-benefit

           6    discussion around the question of what kinds

           7    of assurance of efficacy do we need, what

           8    kinds of evidence do we need, has been one of

           9    the most difficult problems we've faced with

          10    the FDA in the past five years.

          11              That is, there should be an

          12    adjustment -- since the statute requires for

          13    a reasonable assurance of efficacy -- there

          14    should be an adjustment of the efficacy

          15    evidence requirements based on the relative

          16    safety or lack of safety or risk of the

          17    device.

          18              And while the top of the CDRH

          19    clearly understands that, that is really not

          20    understood at the staff levels, so we think a

          21    process that would elevate, for example, that

          22    aspect of a particular approval would help




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            120


           1    the staff to apply the correct metrics.  So

           2    that's the kind of suggestion that we would

           3    be making.

           4              MR. BARNETT:  Someone else up here

           5    had a question?  It's answered, okay.  Anyone

           6    else in the audience want to speak?  Yes,

           7    sir, come on up.

           8              MR. TOTAH:  Good morning, Alan

           9    Totah with Cyberonics.  Just one point I

          10    think I would like to make to the panel, have

          11    you consider: when companies develop not only

          12    new, unique technology, but if they are

          13    developing new indications that the Center

          14    has never had to deal with before, we would

          15    ask that where the reviewing branch or

          16    division does not have that expertise, and I

          17    know we have to separate your jobs a little

          18    from our jobs, but in reality most of us in

          19    the regulatory profession, we are all doing,

          20    roughly, the same thing.

          21              If the company has an expertise,

          22    which they obviously do since they have gone




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            121


           1    through a trial to develop the data, we would

           2    ask that they should consider meeting with

           3    the company if the company is willing, so

           4    that we can provide some in-depth knowledge

           5    about the new indication, the expertise to

           6    help the process of determining safety and

           7    effectiveness  a quicker process.

           8              We often know that within each

           9    division, they may not have all the

          10    expertise, and they will go to another

          11    division to get that expertise, but in some

          12    cases that doesn't even exist.  And for some

          13    unique products or indications, the expertise

          14    may reside fundamentally within that company.

          15              And I know, speaking for my

          16    company, and I'm sure many other companies

          17    here, we're very willing to meet with FDA

          18    early in the review process to help provide

          19    education, answer questions, to help the

          20    review process move more quickly.  So that's

          21    my only comment.  Thank you.

          22              MR. BARNETT:  Thank you, anyone




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            122


           1    would want to respond to that?  Okay, anyone

           2    else in the audience?  Going, going and gone

           3    for lunch.

           4              It's time to eat now; you have

           5    gotten in your handouts some local places

           6    where you can eat.  There is also a dining

           7    room in the hotel.

           8              I have 11:30 a.m., why don't we

           9    plan on being back here at 12:30 p.m.

          10              Thanks.

          11                   (Whereupon, at approximately

          12                   11:30 a.m. a luncheon recess was

          13                   taken.)

          14

          15

          16

          17

          18

          19

          20

          21

          22




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            123


           1            A F T E R N O O N     S E S S I O N

           2                                            (12:41 p.m.)

           3              MR. BARNETT:  We're ready now to

           4    begin the fourth of our six sessions, this

           5    one on the third-party inspection program.

           6    Our FDA representative joining our standing

           7    panel is Steve Niedelman, with the Office of

           8    Regulatory Affairs of FDA.  And our first

           9    speaker under this topic is a return -- oh,

          10    you can.  Look who's here!  Yeah, please,

          11    sure.

          12              SPEAKER:  Thank you.

          13              MR. SCHULTZ:  Good afternoon.  I

          14    got to listen to part of the discussion this

          15    morning, and I just want to tell you that I'm

          16    incredibly impressed with all the great ideas

          17    that were expressed here this morning.

          18              I found myself agreeing with the

          19    majority -- I can't say everything -- but the

          20    majority of what I heard in terms of all the

          21    various areas that we need to work together

          22    to try to find some improvements, whether it




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            124


           1    be looking at innovative products that we

           2    don't fully understand, whether it be looking

           3    at the review process and making sure that

           4    we're focusing on what it is that really

           5    needs to be done, and whether it be looking

           6    at resource issues that clearly, clearly are

           7    part and parcel of making sure that we're

           8    able to accomplish all of these lofty goals.

           9              So I just wanted to say hi, I got

          10    to do it on a little tape, but I just wanted

          11    to say hi in person and to thank each and

          12    every person that came to this meeting, and

          13    to tell you that we are certainly looking

          14    forward to working with you to try to realize

          15    a lot of what you are discussing here today.

          16    Thank you very much.

          17              MR. BARNETT:  Thank you, Dan.  And

          18    now for our first scheduled speaker for this

          19    session, we have a return of Bob Britain from

          20    NEMA.

          21              MR. BRITAIN:  I'm sure you can hear

          22    me; I just can't hear myself over this air




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            125


           1    conditioning unit up here.  I think most of

           2    you know the original intent for seeking

           3    legislation to allow for third-party

           4    inspections was to be a win-win situation for

           5    both FDA and industry.

           6              Now FDA would receive inspection

           7    reports of participating manufacturers every

           8    two years, whereas at least several years

           9    ago, FDA inspection frequency was as high as

          10    every six years, so this would have been a

          11    big boost to FDA.

          12              Manufacturers, on the other hand,

          13    would submit to more frequent inspections,

          14    with the thought that the FDA inspections

          15    could be meshed with EU notified body audits,

          16    making the whole process more efficient.  We

          17    will not know for sure whether this goal is

          18    achievable until the process is up and

          19    running, which it isn't yet.  Since a large

          20    number of medical device manufacturers have

          21    global businesses, it makes sense to push the

          22    third-party inspection concept globally or




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            126


           1    even regionally.

           2              And to do this successfully,

           3    however, you need to have a successful track

           4    record, and this is where FDA comes in, as

           5    many countries with developing programs look

           6    to FDA as the gold standard.  And this is why

           7    it is so important that the third party or

           8    accredited persons program works

           9    successfully.  If it doesn't, we will have

          10    much difficulty selling this abroad.

          11              A few concerns.  There are many

          12    issues that need to be addressed and solved

          13    before this program will be successful.  The

          14    process for accrediting accredited persons

          15    and their organizations has been slow and

          16    arduous and expensive for both FDA and the

          17    accredited person organizations.  It is

          18    simply not simple to qualify auditors or

          19    these organizations.

          20              Scheduling prequalification audits

          21    is difficult.  FDA's availability rarely

          22    coincides with the manufacturers' audit




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            127


           1    schedule.  So far, only five of fifteen

           2    organizations in MDUFMA are accredited to

           3    perform inspections.  And since it has been

           4    several years since MDUFMA was enacted, I

           5    don't know how many of the auditors have to

           6    be actually retrained.  I'm not sure about

           7    that.

           8              Besides the problems in getting the

           9    accredited persons and their organizations in

          10    place, the current program is cumbersome and

          11    far from user-friendly.  Entering the program

          12    and staying in the program for manufacturers

          13    has yet to be tested.  On paper, it has its

          14    drawbacks.  Having to change accredited

          15    persons after so many inspections may be a

          16    burden for some manufacturers.  These reasons

          17    alone may limit the participation by

          18    manufacturers in the program.

          19              Even if some manufacturers make it

          20    through the hoops and hurdles, participation

          21    will be small in the beginning.  You have to

          22    expect that.  It took several years to be




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            128


           1    considered the third -- we saw this with the

           2    510(k) third-party review program, because it

           3    took several years to be considered a

           4    worthwhile program for FDA.

           5              The bright side is that many of us

           6    in the industry are optimistic about the

           7    accredited persons program; we want to make

           8    it work.  But it will be a matter of trust

           9    and willingness on FDA's part to work with

          10    the industry to make the program, number one,

          11    least burdensome and efficient, and to be

          12    done at reasonable cost.  And so we have

          13    hopes.  We need to make it work; we need to

          14    take it global.  That's the only thing that's

          15    going to save this industry from hundreds of

          16    inspections.  Thank you.

          17              MR. BARNETT:  Thank you, Bob.

          18    Anyone on the panel want to respond to that?

          19              MR. NIEDELMAN:  The only thing I

          20    would like to just suggest, and Bob knows

          21    some of this:  We do have five accredited

          22    persons that are currently available, and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            129


           1    those who are Class II and III manufacturers

           2    should shortly be receiving a letter that I

           3    just signed a few days ago indicating that

           4    these five are available, but there is new

           5    guidance out there since the middle of

           6    September on how to use the AP Program.  And

           7    we certainly encourage firms to offer their

           8    facilities as audit sites so we can get more

           9    of these APs through the system as rapidly as

          10    possible.  It is not easy, as Bob said, to

          11    schedule a lot of these audits.

          12              MR. BARNETT:  Thank you, Steve.

          13    Anyone in the audience want to respond?

          14    Let's go to our next speaker, Diane

          15    Wurzburger, from AdvaMed.

          16              MS. WURZBURGER:  Good afternoon.

          17    Diane Wurzburger, Director of Government

          18    Affairs from Siemens Medical Solutions,

          19    representing AdvaMed this afternoon.  Thank

          20    you for having the opportunity to speak.

          21              First, I would like to say that

          22    AdvaMed concurs with Bob Britain's points




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            130


           1    just now, what NEMA said.  I think the

           2    experience has been pretty consistent in our

           3    industry with this program.

           4              But I would like to add emphasis to

           5    a few of the points that are important to our

           6    members.  While the program has been received

           7    initially by industry with great expectation,

           8    of course, to improve the efficiencies with

           9    respect to our inspection programs, we're

          10    still facing several practical challenges, as

          11    Bob noted.

          12              First of course is with those

          13    manufacturers who have volunteered thus far,

          14    they are faced with the difficulty of

          15    scheduling the prequalification inspections.

          16    And additionally, the entry requirements of

          17    the programs themselves are very cumbersome

          18    and complex.  Both of these issues have

          19    frustrated industry, who have -- again, the

          20    primary interest of participating in this

          21    program to make more efficient their

          22    inspectional program.  So we hope that FDA




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            131


           1    will consider those concerns and review those

           2    for us.

           3              We would like to recognize,

           4    however, the effort FDA has taken with

           5    respect to implementation of the program.  As

           6    Bob noted, similar to the third-party review

           7    program, every new system implementation

           8    takes time and has some bumps on the road,

           9    and we hope that we can work together to

          10    resolve those issues and move forward with

          11    the program.

          12              Thank you.

          13              MR. BARNETT:  Thank you, Diane.

          14    Anyone want to respond to that?  Anyone in

          15    the audience want to respond or have a

          16    comment?  If not, we'll go to our next

          17    speaker, Lindsey Wade, from the National

          18    Research Center for Women and Families.

          19              MS. WADE:  Hi.  My name is Lindsey

          20    Wade, and I'm a policy associate at the

          21    National Research Center for Women and

          22    Families.  We're a non-profit, non-partisan




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            132


           1    advocacy center that works to improve the

           2    health and well-being of women and children

           3    in the United States.  I'm here today mostly

           4    to remind the FDA that the concerns shared by

           5    public health advocates, consumer advocates,

           6    and patient advocates about third-party

           7    review in 2002 still exist.

           8              At the National Research Center for

           9    Women and Families, it's our position that

          10    third-party inspections weaken safety

          11    precautions.  To put it more bluntly, the

          12    accredited persons program creates an

          13    inherent conflict of interest that is

          14    unacceptable.  The third-party inspectors

          15    have little incentive to find problems,

          16    because there is no firewall between the

          17    inspector and the company that hires them.

          18              Manufacturers can attempt to

          19    influence the accredited persons with high

          20    payments and promises of increased future

          21    business.  The accredited persons can curry

          22    favor by consulting rather than strictly




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            133


           1    auditing manufacturers and overlooking

           2    problems they identify.  The client-employer

           3    relationship is very different from the

           4    inspector-inspectee relationship that should

           5    exist in this situation.

           6              Accredited persons even promote

           7    their ability to improve their client's

           8    business, virtually eliminating the

           9    possibility that they are unbiased auditors.

          10    For example, one AP claims that "Our founders

          11    sought out and recruited more of the best

          12    auditors in our business because they know

          13    that it is auditors that make the difference

          14    to you.  You will find that our auditors are

          15    fair and consistent; they are

          16    service-oriented and look for ways to add

          17    value to your company."

          18              "Our auditors won't tell you how to

          19    run your business, they will help you

          20    understand the requirements and the various

          21    ways you can fulfill them.  We will partner

          22    with you in order to improve your systems and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            134


           1    therefore your bottom line."

           2              And from our perspective, the APs

           3    aren't supposed to be partners, they are

           4    supposed to be inspectors and auditors.

           5              Further evidence of the conflict of

           6    interest that exists between the

           7    manufacturers and the accredited persons is

           8    the fact that manufacturers provide

           9    accredited persons with testimonials and

          10    offer to serve as references to increase

          11    their AP's future business.  And I just would

          12    like to briefly read excerpts from some

          13    testimonials.

          14              This one is from an American device

          15    company to an American accredited persons

          16    company.  It starts off with: "I feel like we

          17    are in a partnership, and I see tangible

          18    value to our relationship.  We have had

          19    assessors at both companies on an annual

          20    basis for many years who worked for our

          21    former registrar.  We had no idea what we

          22    were missing."




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            135


           1              "All your assessors are very

           2    thorough and professional and take their

           3    responsibility seriously.  I felt like they

           4    were there not only to assess our companies

           5    but to help us become better.  They obviously

           6    cannot consult, but they can and did offer

           7    comments in how others had addressed similar

           8    issues.  In short, we can't be happier.

           9    Please pass along my sincere thanks and

          10    congratulations to your entire organization,

          11    and feel free to share my comments with

          12    others as you feel appropriate."

          13              Similarly, another letter commends

          14    the AP for an excellent job, and says:

          15    "Please do not hesitate to use me as a

          16    reference."

          17              It's entirely out of character for

          18    an inspectee to offer such services to an

          19    unbiased inspector.  And there is no question

          20    that this sort of communication reduces that

          21    accredited person's ability to be unbiased.

          22    Just to clarify this with an analogy,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            136


           1    consider local county public health

           2    departments and the inspections of

           3    restaurants.

           4              Local city and county departments

           5    of health are responsible for ensuring that

           6    restaurants comply with local ordinances in

           7    order to ensure that the restaurants comply

           8    with requirements for sanitary food prep

           9    areas and other issues.  Without these

          10    inspectors making inspections on a regular

          11    basis to all the restaurants that we go to,

          12    we would have no assurance that we're eating

          13    food that is safe to eat.

          14              If those restaurants were able to

          15    hire a private inspector to guide them and

          16    partner with them, the public might not ever

          17    know about problems that exist in the past or

          18    currently with health hazards at that

          19    restaurant.  With the system with public

          20    health employees reviewing restaurants to

          21    make sure that there is safe food

          22    preparation, there is a public record of that




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            137


           1    restaurant's behavior, whether it is good or

           2    bad.

           3              We understand that the Center for

           4    Devices and Radiological Health is

           5    underfunded and understaffed.  However, we

           6    would prefer fewer reliable inspections to

           7    yearly biased reports from third-party

           8    investigators.

           9              Thank you for the opportunity to

          10    speak today.

          11              MR. BARNETT:  Thank you, Ms. Wade.

          12    Any comments or reactions from the panel?

          13    And if that's the case, that's the last of

          14    our three.

          15              So let me open the floor to

          16    comments or reactions to any of the things

          17    that you heard during this panel.  Anyone

          18    want to say anything about this, about

          19    third-party inspections?  Comments that we

          20    haven't heard before?  Okay, if that's the

          21    case, we're ready then for the next session.

          22              Steve, thank you.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            138


           1              MR. NIEDELMAN:  Thank you.

           2              MR. BARNETT:  We'll call up Ginette

           3    Michaud from the Office of Device Evaluation

           4    at CDRH, and we're going to be talking now

           5    about reprocessing of single-use devices.

           6    And our first speaker is Naomi Halpern from

           7    the Association of Medical Device

           8    Reprocessors.  Naomi?

           9              MS. HALPERN:  I'm sorry.  Hi, I'm

          10    sorry to keep you waiting.  I'm Naomi

          11    Halpern.  I'm an attorney specializing in

          12    providing advice to companies and individuals

          13    with respect to the regulation of medical

          14    devices and pharmaceuticals by the United

          15    States Food and Drug Administration.  My

          16    firm, Olsson Frank and Weeda, is regulatory

          17    counsel to the Association of Medical Device

          18    Reprocessors, or AMDR.

          19              AMDR is the trade association

          20    representing the legal, legislative and

          21    regulatory interests of third-party

          22    reprocessors of medical devices labeled for




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            139


           1    single use.  AMDR's members represent

           2    approximately 95 percent of the commercial

           3    reprocessing industry.

           4              It's worth reiterating what we've

           5    said in the past, which is that prior to the

           6    enactment of MDUFMA; reprocessors were

           7    already subject to the same regulatory

           8    requirements as original equipment

           9    manufacturers.  The safety record of

          10    reprocessing has always been and continues to

          11    be excellent.  Today, more than 30 million

          12    devices have been reprocessed and used in

          13    this country without any evidence of

          14    increased risk to patients.

          15              The fact that certain devices

          16    labeled by their original manufacturers as

          17    being for single use that can safely be

          18    reprocessed is widely recognized by the

          19    clinical community, which has repeatedly

          20    expressed overwhelming support for and

          21    confidence in the safety of the reprocessed

          22    devices.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            140


           1              Reprocessors use state-of-the-art

           2    validated procedures to clean, sterilize, and

           3    restore their devices, and every device is

           4    tested or inspected before being returned to

           5    service.

           6              America's finest medical facilities

           7    use reprocessed devices, including 13 of the

           8    14 hospitals ranked by U.S. News and World

           9    Report in 2004 as America's top hospitals.

          10    These institutions include Massachusetts

          11    General, Brigham and Women's Hospital, The

          12    Mayo Clinic, The Cleveland Clinic, and Johns

          13    Hopkins University.  It defies belief to

          14    argue, as some have and continue to do, that

          15    these fine institutions would put their

          16    patients at risk in order to save money.

          17              To the contrary, these facilities

          18    use reprocessed devices because they have

          19    studied the issue thoroughly and they have

          20    determined that reprocessing is safe.

          21              In light of the strict regulation

          22    that was in place at the time that MDUFMA was




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            141


           1    enacted, and in light of the safety record of

           2    reprocessing, it is difficult to find any

           3    public health rationale for MDUFMA's

           4    reprocessing provisions.

           5              Rather, it seems entirely clear

           6    that economics were the driving force behind

           7    these provisions, which were the product of

           8    OEM's continuing frustration with the

           9    economic threat posed by reprocessing.

          10    Nevertheless, MDUFMA does contain some

          11    important messages about reprocessing.

          12              First, Congress clearly stated that

          13    there are cost savings associated with using

          14    reprocessed devices.  Therefore, Congress

          15    said, we want to ensure continued access to

          16    safe and effective reprocessed devices.

          17              Second, Congress intended that

          18    MDUFMA be implemented in the least burdensome

          19    manner consistent with FDAMA.  AMDR has seen

          20    its role over the past year as being in part

          21    to keep reminding regulators of these

          22    objectives as the Agency goes about




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            142


           1    implementing the statute.

           2              So where are we now?  FDA continues

           3    to implement MDUFMA, and reprocessors are

           4    complying with the requirements.

           5              First, I would like to talk about

           6    the MDUFMA-imposed requirement that

           7    reprocessors make supplemental validation

           8    submissions for some of their previously

           9    cleared devices.  Despite feeling that the

          10    requirement may not have been implemented in

          11    the least burdensome manner, as required by

          12    FDAMA, our members have complied with this

          13    new requirement, and FDA has completed its

          14    review of most of these submissions.

          15              Much more than the typical 510(k)

          16    submission, the process of submitting

          17    validation data has been an exercise in

          18    working with the Agency to determine what a

          19    submission was going to have to contain and

          20    what it was going to have to look like.  The

          21    process of clarifying and responding to

          22    questions about submissions occurred in the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            143


           1    context of a very tight deadline for

           2    concluding the process.  An enormous amount

           3    of work was required to gather the

           4    FDA-required information.

           5              At the end of the day, many of the

           6    submissions were cleared by the Agency.  For

           7    the submissions that were not cleared, AMDR's

           8    members ceased shipping the devices that were

           9    covered by those submissions.  But AMDR's

          10    members estimate that more than 95 percent of

          11    their products lines were made legally

          12    marketable.

          13              We are aware that OEMs have

          14    continued to assert that the issuance of "Not

          15    Substantially Equivalent," NSE letters, to

          16    the reprocessors just confirms their

          17    oft-stated allegation that it is not possible

          18    to establish that the reprocessing of some of

          19    these devices is safe and results in

          20    effective devices.

          21              I want to remind you that all of

          22    these devices were previously cleared by the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            144


           1    Agency.  Safety was not the issue.  And in

           2    fact, the Agency has publicly clarified that

           3    the fact that a particular submission was not

           4    cleared before the deadline does not mean

           5    that the devices were unsafe in FDA's

           6    opinion.

           7              The issuance of an NSE letter means

           8    only that to date, the data and information

           9    submitted were not sufficient to support a

          10    finding of substantial equivalence, and

          11    therefore, to be cleared by FDA.  Indeed in

          12    some cases, the NSE letters reflected nothing

          13    more than the lack of sufficient time to

          14    develop and submit the information due to the

          15    Agency's imposition of a non-statutory

          16    deadline.

          17              In other cases, NSE letters were

          18    issued because the reprocessor did not make a

          19    submission or withdrew an initial submission

          20    after making a business decision that the

          21    economics of the market did not justify the

          22    expenditure of the substantial resources that




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            145


           1    would be required by the SVS process.

           2              In short, as a factual matter, an

           3    NSE letter does not establish that the device

           4    covered by the letter is not safe or

           5    effective, and there is clearly no

           6    justification for the assertion that an NSE

           7    letter is evidence that the submitter is not

           8    capable of producing a safe or effective

           9    device.

          10              Over the last year, AMDR's members

          11    have continued to work cooperatively with the

          12    Agency, and many of the submissions that were

          13    initially designated NSE have now been

          14    cleared.  In the past year, of course,

          15    certain OEMs have continued their efforts to

          16    persuade Congress to revisit the marking

          17    provision of Section 301 of MDUFMA, and

          18    specifically to apply that provision only to

          19    reprocessors.

          20              It's worth remembering that when

          21    Congress was in the process of drafting

          22    MDUFMA, FDA took the position that marking of




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            146


           1    devices would have value, and in fact, it

           2    would be helpful from a regulatory point of

           3    view if all devices were marked.  At the

           4    time, OEM industry representatives were

           5    willing to commit to doing that.

           6              MR. BARNETT:  Two more minutes.

           7              MS. HALPERN:  Congress, when

           8    enacting the provision, specifically

           9    emphasized that the section applies to all

          10    devices, not just single-use devices.  OEMs

          11    afterwards recognized that complying with the

          12    provisions would be burdensome, and for that

          13    reason, OEMs returned to Congress to ask them

          14    to amend Section 301 to apply only to

          15    reprocessors.  Congress yielded to this

          16    pressure, and the Act was so amended.

          17              AMDR's members will comply with and

          18    flourish under the additional regulatory

          19    burdens.  In the last year, we have seen

          20    further efforts from the OEMs to use the

          21    regulatory process to further their economic

          22    agenda.  Specifically, there have been




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            147


           1    several petitions from trade associations

           2    asking FDA to add more devices to the lists

           3    of reprocessed devices that require the

           4    submission of validation data.

           5              In general, we believe that these

           6    requests have failed to include any credible

           7    public health rationale.  In the last few

           8    months, FDA has, in response to these

           9    petitions, added heart positioning devices

          10    and endoscopic and microscopic devices to the

          11    list of devices that require 510(k)s with

          12    validation data.  AMDR's members do not

          13    oppose the requirement for 510(k)s for heart

          14    positioning devices.

          15              But AMDR believes that in fact, all

          16    heart positioning devices should be subject

          17    to 510(k) requirements.  The exemption for

          18    heart positioners appears to be based on the

          19    fact that they are covered by the same

          20    classification regulation as forceps,

          21    retractors and other relatively simple

          22    devices.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            148


           1              However, the heart positioners and

           2    stabilizers of today are much more

           3    complicated devices that allow a surgeon

           4    actually to lift and turn the heart.  The

           5    failure of such a device during surgery,

           6    whether it is reprocessed or not, could

           7    easily cause serious injury to a patient, and

           8    the AMDR urges FDA to consider up-classifying

           9    all of these devices and requiring 510(k)s

          10    for all of them.

          11              Apart from heart positioners, AMDR

          12    strongly urges FDA to preserve the 510(k)

          13    exemption for all currently exempt

          14    reprocessed single-use devices, and to

          15    decline to require SVSes for additional

          16    devices.  Finally, this year, we have seen an

          17    upswing in activity on the state level to

          18    enact legislation to burden reprocessing.

          19              Typically, the OEMs involved in

          20    pushing these efforts suggest to legislators

          21    that despite the stellar safety history of

          22    reprocessing, these bills are necessary




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            149


           1    because safety of reprocessing cannot be

           2    established.  Although they have not to our

           3    knowledge provided legislators with actual

           4    examples of patient harm, they have

           5    distributed photographs that purport to

           6    establish that reprocessed devices may not in

           7    fact be clean.  In fact, they may show you

           8    these photographs today.

           9              However, to date, these OEMs have

          10    to our knowledge been unable or unwilling to

          11    authenticate these photographs, and the

          12    bottom line is that there is no credible

          13    evidence that devices reprocessed in

          14    compliance with FDA requirements present any

          15    risk to patients beyond the risk that is

          16    associated with reprocessed devices.  Let me

          17    skip through most of this and just finish up.

          18              I do want to say that one aspect of

          19    the state level activity is informed consent

          20    provisions.  The purpose of informed consent

          21    is to advice patients when a procedure

          22    involves increased risk.  However,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            150


           1    reprocessed devices are as safe and effective

           2    as the original equipment, and are in fact

           3    arguably more stringently regulated.

           4    Therefore, there is no legal, medical, or

           5    ethical basis for imposing informed consent.

           6              That said, AMDR does not oppose

           7    state-level informed consent legislation that

           8    honestly seeks to increase patient awareness

           9    of medical device safety.  Such a bill would

          10    apply equally to OEMs, many of whom have

          11    recently experienced serious safety problems

          12    associated with their own devices.

          13              Just a few weeks ago, FDA announced

          14    that it had seized devices manufactured by

          15    one major OEM because FDA inspections had

          16    revealed that the firm is continually out of

          17    compliance with GMPs.  A few months ago,

          18    another OEM acknowledged that it knew, that

          19    it had not told doctors or patients for three

          20    years about a flaw in its device.

          21              Let me just say that reprocessing

          22    saves hospitals substantial amounts of money.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            151


           1    It's good for patients, it's good for

           2    hospitals, it's good for the environment.

           3    The good news for hospitals is that despite

           4    the additional regulatory burdens that have

           5    been increasingly placed on the industry,

           6    reprocessing is continuing to flourish and

           7    also to drive prices down of original

           8    equipment itself.

           9              In short, reprocessing plays a

          10    vital role in our health care system because

          11    it is one of the few ways that hospitals can

          12    achieve substantial cost savings while

          13    maintaining the absolute highest standard of

          14    patient care.  The implementation of MDUFMA

          15    has presented some new hurdles this year,

          16    hurdles that the industry does not believe

          17    are warranted, but they are hurdles that the

          18    industry is meeting and will continue meeting

          19    in the coming year.  Thank you.

          20              MR. BARNETT:  Thank you, Naomi.

          21    Anyone on the panel want to respond or ask a

          22    question?  Anyone in the audience?  Okay, if




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            152


           1    that's the case, let's go into our next

           2    speaker from AdvaMed, Tony Blank.

           3              MR. BLANK:  Good afternoon.  I have

           4    two promises:  One, I'll make sure I finish

           5    on time; second, I have no gross pictures.

           6    Just one response to the comments before with

           7    regards to the provision of validation data,

           8    is where data that under the quality system

           9    regulation one would expect any medical

          10    device manufacturer to have in their files

          11    and at their fingertips and ready to be

          12    bundled into submission.

          13              So when I put together the outline

          14    for this, I thought a little bit about the

          15    attempts my little brother has given to me to

          16    teach me the game of golf.  He has told me

          17    that I have made significant progress,

          18    although I still have some lingering

          19    challenges, and one of the things I need to

          20    work on is my follow-through.

          21              So progress that has been made.

          22    There was a Congressional mandate in MDUFMA,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            153


           1    lots of changes came as a result of that; for

           2    example, there were revisions to the MedWatch

           3    form to capture the reprocess status of a

           4    device if there was an event associated with

           5    it.  FDA has issued numerous guidance

           6    documents to provide direction to industry on

           7    reprocessing.

           8              They have done a marvelous job, I

           9    would say, and should be congratulated for

          10    the vast rapid review of the supplemental

          11    validation data submissions.  There have been

          12    some exemption terminations which we as

          13    AdvaMed believe are warranted and valid for

          14    very valid reasons.

          15              And with the recent MDUFSA

          16    legislation, there was a narrowing of the

          17    Section 301 provisions to reprocess

          18    single-use devices.

          19              So sort of significant progress has

          20    continued in terms of the continued review

          21    and termination of exemptions when warranted;

          22    for example, stone dislodgers, orthodontic




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            154


           1    brackets.  There have been continued reviews

           2    and calls for supplemental validation data,

           3    again, I believe when warranted, specifically

           4    endoscopic accessories and heart stabilizers.

           5              There are some lingering

           6    challenges, however.  There is, as you can

           7    imagine, continued pressure on FDA from a

           8    variety of stakeholders:  The OEMs, the

           9    hospitals, the reprocessors.  There is a

          10    tremendous amount of education that must

          11    continue, I think, that needs to be balanced

          12    and fair.  For example, if a single-use

          13    device fails after it has been reprocessed,

          14    there can be no underlying problem with the

          15    original device.

          16              So if the product was designed,

          17    manufactured, labeled as a single-use device,

          18    and it made it through the single-use and it

          19    was subsequently reprocessed and that device

          20    failed, there was nothing wrong with the

          21    single-use device.  Any failure, by

          22    definition, is associated with the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            155


           1    reprocessing.  Period.

           2              If a reprocessed single-use device

           3    fails or there is an event, the report must

           4    always go to the reprocessor.  Another

           5    significant challenge that lingers is proper

           6    AMDR reporting.  As I said, there has been a

           7    change to the MedWatch form.  However, we

           8    have to admit and recognize, I believe, that

           9    there is an inherent disincentive for the

          10    user facilities to acknowledge, when

          11    reporting events, that the event was

          12    associated with the device that had in fact

          13    been reprocessed.

          14              And frankly -- which gave birth to

          15    the Section 301 provisions at the

          16    beginning -- there is an inherent lack of

          17    awareness by physicians and by health care

          18    practitioners generally and by patients as to

          19    whether or not the device that is used on

          20    them has in fact been reprocessed.

          21              So working on the follow-through,

          22    we think it's important, and in fact it is




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            156


           1    critical, that we continue to follow-through

           2    as Congress has intended.  There is a quote

           3    from the House report; here is a quote from

           4    the Senate report, from the recent

           5    legislation, and I won't read it to you.

           6              However, at the very beginning, the

           7    Senate is very explicit:  "Reprocessed

           8    single-use devices are not generally marked

           9    to identify the reprocessors.  Adverse events

          10    associated with the reprocessed device may

          11    therefore be misattributed to the original

          12    manufacturer, not to the reprocessor."  The

          13    reason these provisions to Section 301 have

          14    been introduced is to lead to the marking of

          15    reprocessed single-use devices.

          16              The Senate has stated that the

          17    reason for this provision is to ensure that

          18    the practitioners and the hospital

          19    administrators know that the device that they

          20    are using has in fact been reprocessed, and

          21    it cannot work as intended unless health care

          22    providers, original manufacturers, device




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            157


           1    reprocessors and FDA can readily and

           2    accurately identify when an SUD has been

           3    reprocessed.  This is also taken straight out

           4    of the Senate report language.

           5              The Senate recognized that there

           6    has been, associated with the failure to

           7    accurately identify reprocessed devices,

           8    inadequate reporting, which fundamentally

           9    challenges the underlying cornerstone of

          10    FDA's post-market surveillance system.

          11              Congress believes, believed, and

          12    continues to believe there is no reason for

          13    FDA to delay implementation of this

          14    provision, and the committee expects

          15    reprocessors to implement its requirements as

          16    soon as possible.

          17              So in sum, great progress, not sure

          18    my brother would say that about my golf game.

          19    However, challenges do remain, but patient

          20    safety, regardless of any pressure from

          21    anybody else, must always be tantamount and

          22    first.  And that's it.  Thanks.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            158


           1              MR. BARNETT:  Thank you, Tony.

           2    Does the panel have any response or questions

           3    for Tony?  Anyone in the room want to say

           4    anything?  If that's the case, let's go to

           5    our final speaker, Mark Leahey, from MDMA.

           6              MR. LEAHEY:  Thanks Mark, and I

           7    promise this is the last time I will be

           8    getting up today.  I want to, I think, go a

           9    little beyond what Tony mentioned.  I think

          10    he highlighted a lot of the important steps

          11    that had been taken to ensure patient safety

          12    in this area.  But I want to specifically

          13    focus on FDA's recently published draft

          14    guidance for industry and staff, entitled

          15    "Compliance with Section 301 of the Medical

          16    Device User Fee and Modernization Act of

          17    2002," as amended prominent and conspicuous

          18    marks manufacturers' single use devices.

          19              Now, before I go further, I think

          20    that this is a critical moment here, probably

          21    the first in the three years that I have been

          22    participating in these stakeholder meetings,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            159


           1    that I 100 percent agree and am aligned with

           2    FDA's position on this.

           3              MDMA agrees with FDA's

           4    interpretation of Section 502(u) of the Food

           5    and Drug Cosmetic Act as amended by MDUFMA,

           6    which requires manufacturers of reprocessed

           7    SUDs to mark the reprocessed device

           8    prominently and conspicuously, with the name

           9    of the reprocessor, a generally recognized

          10    abbreviation of such name, or unique and

          11    generally recognized symbol identifying the

          12    reprocessor.

          13              Section (v)(2) of the FDA guidance

          14    document outlines the effective date for

          15    implementing the reprocessor labeling

          16    requirements of Section 502(u).  According to

          17    the guidance document, if the original

          18    equipment manufacturer first marks the device

          19    with its name or symbol before

          20    August 1, 2006, the reprocessor must mark the

          21    reprocessed device by August 1, 2006.

          22              If the OEM first marks the device




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            160


           1    after August 1, 2006, the reprocessor must

           2    immediately mark the device.  MDMA agrees

           3    that the approach described in the FDA

           4    guidance document clearly reflects the

           5    language of the statute, and ensures the

           6    legislation's goal of protecting patient

           7    health is fulfilled as expeditiously as

           8    possible.

           9              Congress has repeatedly recognized

          10    that unmarked reprocessed SUDs may pose

          11    significant patient safety risk.  When the

          12    reprocessor of an SUD is not identified, the

          13    FDA is prevented from adequately identifying

          14    and controlling the risk posed by

          15    reprocessing.  FDA's NDR regulations are the

          16    cornerstone of FDA's post-marketing

          17    surveillance system for medical devices, as

          18    Tony mentioned.  These regulations require

          19    manufacturers to report patient injuries and

          20    product malfunctions to FDA.

          21              This information enables both the

          22    manufacturer and FDA to identify the safety




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            161


           1    and/or effectiveness problems, and to take

           2    any needed corrective action.  Sometimes

           3    these protective actions include recalls or

           4    other notifications to the field to prevent

           5    unnecessary patient injuries.  This system

           6    cannot work unless the health care providers,

           7    the OEM and the FDA can readily identify when

           8    and whom a SUD has been reprocessed.

           9              Unless reprocessor devices are

          10    clearly marked as such and the reprocessors

          11    clearly identified, the OEM will likely be

          12    erroneously identified as a source of a

          13    reprocessed device.  This may significantly

          14    hinder or preclude FDA's ability to identify

          15    and address safety and efficacy failures

          16    associated with reprocessed SUDs.  In light

          17    of these serious public health concerns,

          18    Congress required reprocessors to mark their

          19    reprocessed SUDs by August 1, 2006, within

          20    one year after the implementation of the Act.

          21              Further, Congress indicated that

          22    the reprocessors should mark their devices as




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            162


           1    soon as possible.  Congress suggested that it

           2    should not take reprocessors a year to mark

           3    their reprocessed devices, and discouraged

           4    reprocessors from taking the entire year to

           5    comply.

           6              Specifically, in the MDUFSA report,

           7    the committee stated, "Although Section

           8    502(u) will first become effective twelve

           9    months after the legislation is enacted, the

          10    committee believes that it is clear how this

          11    section applies to the vast majority of

          12    reprocessed devices.  And the committee

          13    expects reprocessors to implement these

          14    requirements as soon as possible for the

          15    devices they reprocess, in the best interests

          16    of post-market surveillance and the public

          17    health."

          18              In other words, reprocessors were

          19    on notice as of August 1, 2005, that devices

          20    currently on the market and for products

          21    under development that the marking of devices

          22    is a component of their required product




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            163


           1    manufacturing, labeling development and

           2    intake procedures to identify when a

           3    previously used device is marked.

           4    Reprocessors were given a full 12 months to

           5    do so.  The vast majority of devices that are

           6    reprocessed require 510(k) pre-market

           7    notification clearance prior to marketing.

           8              This requires reprocessors to

           9    develop and implement reprocessing

          10    procedures, develop and print product labels,

          11    labeling and packaging, and to ensure that

          12    their manufacturing practices are in full

          13    compliance with FDA's QSR before the

          14    reprocessed device is ever marketed.

          15              Marking the device with a

          16    reprocessor's name or symbol, in addition to

          17    other product labels and labeling that must

          18    be developed, is a relatively minor aspect of

          19    this process, and certainly does not require

          20    an additional year to implement after

          21    receiving clearance for marketing.

          22              There is no justifiable reason for




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            164


           1    permitting a reprocessor a year of anonymity

           2    to hide from regulatory requirements

           3    specifically designed to protect patient

           4    safety.  Under these circumstances, if the

           5    concept of allowing reprocessors an

           6    additional year to mark their reprocessed

           7    devices has been a part of the discussions

           8    between industry, patient advocacy

           9    organizations, FDA and Congress in the

          10    developing of MDUFMA amendments, industry and

          11    the patient advocacy organizations would have

          12    strongly objected and urged Congress not to

          13    adopt this approach.

          14              Therefore, I want to again

          15    encourage and commend the FDA for the initial

          16    draft guidance.  And in closing, I want to

          17    say again it's an area where MDMA certainly

          18    supports FDA's position on this, and I think

          19    it's certainly in the best interests of

          20    patient safety.

          21              Thank you.

          22              MR. BARNETT:  Thank you, Mark.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            165


           1    Anyone on the panel want to respond or ask

           2    questions?  If that's the case, before we

           3    close this panel, is there anyone in the

           4    audience that wants to say anything, or react

           5    about this particular issue of reprocessing

           6    single-use devices?

           7              Okay, that being the case, we're

           8    ready for a break.  It's listed on the

           9    schedule as 15 minutes.  I have 1:25, so why

          10    don't we say about 20 minutes to 2:00.

          11                   (Recess)

          12              MR. BARNETT:  We're ready to go

          13    into our sixth session, on other provisions,

          14    and we have our standing FDA panel here:

          15    Linda, Joanne, Diane and Bob.  And we have

          16    added to that Pat Love, who's here with the

          17    Office of Combination Products in FDA, and

          18    she's here in place of Mark Kramer, who

          19    couldn't come, and Steve Sykes, who's with

          20    the Office of Surveillance and Biometrics in

          21    CDRH.

          22              And our first speaker, a constant




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            166


           1    lead-off speaker, Bob Britain from NEMA.

           2              MR. BRITAIN:  Pat, I'm not going to

           3    say anything bad.

           4              MS. LOVE:  You're allowed.

           5              MR. BRITAIN:  Just a very brief few

           6    words about combination products.  I think

           7    you all know what combination products are.

           8    This isn't a new issue; it's been at FDA for

           9    many, many years:  Drugs and devices.

          10    Medical imaging devices and contrast agents

          11    are used together.  Contrast agents improve

          12    or enhance the image of x-ray, of magnetic

          13    resonance, of ultrasound.  And it's been a

          14    problem in the past, because obviously,

          15    combination products means two different

          16    agencies that you're working with.

          17              And the problem is the focus.  You

          18    need a focus at FDA, so when we had the

          19    opportunity to work with FDA and the Capitol

          20    Hill staff, everyone was pretty excited about

          21    the possibility of putting an Office of

          22    Combination Products together.  And we worked




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            167


           1    very hard to push this through because it's

           2    pretty hard to get legislation that sets up

           3    offices.  It's not easy.

           4              So we had very high expectations

           5    when MDUFMA was passed and signed into law.

           6    It gave the Secretary the authority to set up

           7    this Office of Combination Products.  And we

           8    obviously had high hopes that it would

           9    improve the approval process of contrast

          10    agents with their use with MRI, et cetera,

          11    ultrasound.  And after many meetings with the

          12    Office of Combination Products -- and I must

          13    say the Office of Combination Products has

          14    met with us on many occasions -- it's working

          15    with us to try and see this through.

          16              But we were finally advised that we

          17    were a concomitant product instead of a

          18    combination product, which kind of took the

          19    wind out of our sails, because we probably

          20    wouldn't accrue the same benefits and

          21    efficiencies that we would have been if we

          22    were a combination product.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            168


           1              The interesting thing is, when we

           2    were working on the legislation, everybody

           3    thought this was a combination product, the

           4    medical imaging and contrast agent.

           5    Everybody.  The Hill staff, industry.

           6              So my only reason for being here

           7    and spending a couple of minutes with you is

           8    not to offer any solutions, because we intend

           9    to keep working with the Office of

          10    Combination Products.  They seem to be happy

          11    to continue to work with us even though we're

          12    not a combination product.  And so my only

          13    reason to be here and tell you about this is

          14    that it's a solution that MDUFMA did not

          15    bring to us that we worked very hard to get.

          16    And Pat, we will continue to work through

          17    this.  We don't know what the final solution

          18    will be, but I think we'll get there.

          19              MR. BARNETT:  Thank you, Bob.

          20    Anyone want to respond to that?

          21              MS. LOVE:  I just like to ask a

          22    question, please, Bob.  Certainly the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            169


           1    definition of combination products, those

           2    that are separately provided under 3.2(e)(3),

           3    talks a bit about mutually conforming

           4    labeling and how things are specifically

           5    identified.  And as you alluded to, imaging

           6    agents are not necessarily labeled in that

           7    way.  It's possible, but most of them aren't

           8    at this point.

           9              Do you have some general thoughts

          10    or recommendations?  I know you said you

          11    didn't have a definite recommendation under

          12    MDUFMA, but do you think that issues such as

          13    this that might relate to classes of products

          14    that are often used together, either

          15    off-label or maybe there are co-development

          16    questions -- do you feel that this is

          17    something that should in some way be

          18    addressed in MDUFMA, or are these things that

          19    should be addressed as in the course of

          20    providing the guidance, some of the issues

          21    about the quality aspect of things that were

          22    mentioned earlier?




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            170


           1              Is this a guidance approach issue?

           2    Is this something that you see in

           3    clarification of mutually conforming labeling

           4    issues?  Where might this fall as a class

           5    concept?  Sorry to put you on the spot.

           6              MR. BRITAIN:  I don't know.  I

           7    should have said the reason this is so

           8    important -- to find a solution.  I don't

           9    know where it is in guidance or pushing

          10    contrast agent manufacturers harder and

          11    faster to get these things approved -- but

          12    the problem is the using community, the

          13    radiologists, et cetera, that use MRI and CT

          14    and ultrasound use contrast agents that are

          15    not labeled to be used with MRI or CT, and so

          16    the manufacturers of the equipment cannot

          17    label or train the users because this is

          18    off-label use.

          19              And so this is why it's so

          20    important to find a resolution, because the

          21    real world is -- they are being used together

          22    unapproved.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            171


           1              Pat, I'm sorry, I just don't have a

           2    solution for you.

           3              MR. BARNETT:  Anyone else on the

           4    panel want to respond or comment?  Someone in

           5    the audience?  If that's the case, let's call

           6    our next speaker, who's Jack Lasersohn from

           7    the National Venture Capital Association.

           8              MR. LASERSOHN:  Thank you very much

           9    for inviting us to attend.  I'm Jack

          10    Lasersohn, and I'm a general partner at the

          11    Vertical Group, which is a major medical

          12    device venture capital firm.  I'm past

          13    chairman of the medical industry group at the

          14    National Venture Capital Association, which

          15    is the national trade association of the

          16    venture capital community.  Now, in this

          17    talk, since this is the first time that we

          18    have really presented in front of the FDA

          19    stakeholder meeting, we really wanted to just

          20    introduce who we are to a large extent to the

          21    FDA, and put some context around why we have

          22    a somewhat different view of some of these




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            172


           1    issues than perhaps the rest of the industry.

           2    That's what this talk will focus on.

           3              By way of background, the National

           4    Venture Capital Association is 500-member

           5    venture capital firms.  We have approximately

           6    $100 billion under management at any given

           7    time.

           8              We're investing about $20 billion a

           9    year in high technology start-ups, primarily

          10    in the United States.  Most of you probably

          11    think of us as people who do the internet and

          12    semi-conductors and computers.  And that is

          13    true, that is still about 60 to 70 percent of

          14    the venture capital money flows.  But in

          15    addition, we have financed, for example, the

          16    entire biotechnology industry, and

          17    historically probably about 50 percent of all

          18    medical device firms today.  We're founded

          19    with venture capital money.

          20              About 100 million Americans have

          21    benefited from the investment the venture

          22    community has made in medicine over the last




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            173


           1    25 years.  Twenty-five million, we believe,

           2    conservatively, have had their lives extended

           3    or quality of life improved every year

           4    through the use at this moment of technology

           5    originally developed by companies funded with

           6    venture capital.  These are some of the areas

           7    that we have made very significant

           8    investments in.  Heart disease has been a

           9    leading area.

          10              We did create, we founded the first

          11    angioplasty companies in the 1980s, founded

          12    the minimally invasive heart bypass, all of

          13    the electroablation companies, first

          14    implantable cardiac defibrillators, automatic

          15    external defibrillators, and then

          16    biotechnology, many, many drugs, including

          17    ReoPro, Integrilin, tPA.  In imaging, we

          18    founded the first superconducting MRI

          19    systems, the first ultrasound systems, the

          20    first Doppler ultrasound systems, as well as

          21    many other drugs for cancer.

          22              So our activities are very broad




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            174


           1    within the health care space.  As I said,

           2    medical devices in biotechnology make up

           3    about 25 to 30 percent of all venture capital

           4    activities right now, medical devices about

           5    10 percent.  And that's out of an annual

           6    money flow of about $20 billion a year.  So

           7    about $2 billion to $3 billion a year right

           8    now from the venture industries going into

           9    medical device technology.

          10              These are the first financing, so

          11    these are classic start-up financings in the

          12    life sciences area, including biotechnology.

          13    They are pretty steady, at about 200 per

          14    year.  These are first financing, so start-up

          15    companies in that segment.  These are the

          16    number of first financings in medical

          17    devices -- '05 second quarter is an

          18    aberration.  It's historically been about 100

          19    companies a year, so very, very active.

          20    These are again start-up companies, first

          21    financings for start-up companies in medical

          22    devices.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            175


           1              The investment that we're making

           2    has continued to grow, it did peak in 2000

           3    and 2001.  But even in 2002 and today, it's

           4    much, much higher than it was historically,

           5    and we project that it will continue to

           6    increase.  The number of companies is very

           7    steady.  Again, this is total financing for

           8    companies, not just start-up companies.

           9    Second round financings, financings as they

          10    get more mature, but 4- to 700 per year is

          11    very typical of the number of companies in

          12    the medical and life sciences area that's

          13    been financed exclusively essentially by the

          14    venture capital community.

          15              And within that, the medical device

          16    sector continues to be very strong, about $2

          17    billion a year in all medical device

          18    companies for venture capital, anywhere from

          19    $400 to $500 million per quarter.  One of the

          20    points I would like to make that's very

          21    important is that the funding requirements

          22    for medical devices has just increased




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            176


           1    dramatically, partly because of the

           2    complexity of the technology, but also

           3    because of the regulatory hurdles.

           4              We started the first angioplasty

           5    company in 1980.  It cost $3 million to get

           6    it to profitability, and then it was sold to

           7    Eli Lilly.  A very, very similar technology,

           8    in fact simpler technology balloon,

           9    kyphoplasty, we started in 1994, took

          10    $75 million to get to the same point.  That

          11    number continues to grow dramatically.

          12              One of the key points I think we

          13    need to make is that we're investing in

          14    revolutionary medical technology by

          15    definition.

          16              We will not fund VC technology as

          17    much as it might be very important to evolve

          18    technology along the line.  Big companies do

          19    that incredibly well, much better than we

          20    can.  So we're investing almost exclusively

          21    in revolutionary technology, so the first

          22    angioplasty company, the first MRI, the first




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            177


           1    pulse oximetry, first ablation, ICDs,

           2    neurostimulation, triple As.  These were all

           3    started by the venture capital community.

           4              As a result of the novelty, we face

           5    peculiar problems, different problems.

           6    Often, the staff of the FDA has never seen

           7    the type of device that we're talking about.

           8    So we have an enormous learning curve hurdle

           9    to get over with the FDA.  There's always a

          10    lack of precedence and pathways, and in some

          11    cases, there are precedents that actually

          12    hurt us.

          13              I mentioned before that sometimes

          14    having guidances can be difficult because we

          15    have to get ourselves out of a particular

          16    guidance pathway because what we're doing

          17    really doesn't fit.

          18              And we always face a tremendous

          19    problem in clinical trial design and

          20    interpretation because of the novelty factor.

          21    So this brings a -- we really do have a

          22    different emphasis -- not better, just




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            178


           1    different -- than the rest of the industry.

           2    And our focus is going to be on solving these

           3    problems.  To give you some idea of just the

           4    kinds of things that we're doing right now, I

           5    took a survey of the venture community.

           6              And this is a snapshot in time

           7    today of sort of what the venture community

           8    is working on, you will see that many of

           9    these things -- not all of them, but many are

          10    things the FDA has never seen before.

          11              So the very first spinal nucleus

          12    replacements are going to be produced by the

          13    venture community.  They are going to be

          14    showing up at the FDA.  They are showing up

          15    at the FDA right now and will be very

          16    challenging.  All of these are different in

          17    kind than the types of products that you are

          18    used to seeing.  We agree with everything

          19    that has been said before about the need for

          20    transparency and consistency and

          21    predictability.

          22              We are very much in favor of fees.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            179


           1    We have no problem paying fees if they are

           2    based on performance.  Our companies do have

           3    money.  Even though they are start-ups, they

           4    are well-funded.  They will pay for fees if

           5    that will shorten the regulatory or improve

           6    the regulatory outcomes.  We do believe that

           7    the whole concept of least burdensome is very

           8    important, and our intention is in fact to,

           9    as part of the MDUFMA process, to revisit

          10    this.

          11              MR. BARNETT:  Two more minutes,

          12    please.

          13              MR. LASERSOHN:  Thank you.  At the

          14    statutory level.  We've tested this concept,

          15    we think it really can work, and we're going

          16    to be asking to think more about how to bring

          17    the least burdensome process forward.

          18    Obviously, we agree with meeting management.

          19    All of the things that have been said before

          20    about quantitative results are certainly

          21    supported by us.  I have also said that we

          22    are in favor of new processes, particularly




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            180


           1    for novel products.

           2              I don't mean expedited processes, I

           3    just mean processes that are able to draw in

           4    different resources that have a different

           5    pathway, not in terms of safety and

           6    effectiveness, but in terms of the types of

           7    pathways through the FDA.

           8              We do think that HDEs are an area

           9    that we should return to focus on.  A draft

          10    guidance has essentially shut down the HDE

          11    process at the moment, requiring that sub

          12    populate -- that you can essentially not have

          13    off-label use is a matter of physical

          14    reality.

          15              We think that that is not a good

          16    decision by the FDA.  We would like to

          17    revisit that.  We think that creates an

          18    opportunity for another pathway for truly

          19    novel devices that really may not be able to

          20    be approved through existing regulatory

          21    pathways.

          22              We support the critical path




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            181


           1    initiatives.  We want to collaborate with the

           2    FDA in trying to define that.  And our

           3    intention going forward is to be as actively

           4    engaged with FDA as possible and defining

           5    some of these new ideas.  Thank you.

           6              MR. BARNETT:  Thank you.  Anyone on

           7    the panel want clarification, have a

           8    question?  Yes.

           9              MS. LESS:  I just want to ask you,

          10    what did you mean by continuous medical

          11    application?  Is that what you were talking

          12    about earlier, risk-based approach?

          13              MR. LASERSOHN:  I don't know if I

          14    used the word "continuous."  If I did --

          15              MS. LESS:  It was on the slide.

          16              MR. LASERSOHN:  Continuous was

          17    probably a typo.  The risk-based approach, if

          18    that's what you're asking about, is again to

          19    try to have a process that

          20    defines -- particularly for the staff, not so

          21    much for the higher level -- at CDRH, which I

          22    think understands this concept well.  That




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            182


           1    defines for the staff ab initio at the

           2    beginning of the process; that is, in pre-IDE

           3    discussions, that decisions about the pathway

           4    should be made consciously with a particular

           5    level of risk in mind.

           6              That is, if a device comes in that

           7    really has proven to be, through feasibility

           8    studies, for example, very likely to be very

           9    low-risk, the level of evidence of

          10    effectiveness should be adjusted accordingly.

          11    And we have found -- and this is just one

          12    narrow point, but we have found that this is

          13    a -- that process, that discussion has taken

          14    very often months or years to cycle with

          15    acceptable results at the end, but has taken

          16    a long time to get to the proper result.

          17              MR. BARNETT:  Any other questions

          18    from panel?  If not, thank you.  And let's go

          19    to our next speaker, Diana Zuckerman, of the

          20    National Research Center for Women and

          21    Families.

          22              MS. ZUCKERMANN:  While we're




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            183


           1    waiting for the slides, I can say thank you

           2    very much for the opportunity to be here.

           3    I'm Dr. Diana Zuckermann.  I'm president of

           4    the National Research Center for Women and

           5    Families.  And here is my slide.  Our center

           6    is a non-profit research center, and we use

           7    research information to work for programs and

           8    policies that improve the health and safety

           9    of women, children and families.

          10              Just for a little background, my

          11    background is as an epidemiologist, and I've

          12    worked on Capitol Hill doing oversight on FDA

          13    issues, so these are issues of particular

          14    interest to me.  And although there are not

          15    too many consumer-oriented non-profits here

          16    today, there are a lot of consumer-oriented

          17    non-profit organizations that we work with on

          18    these issues.  And although they were not

          19    able to be here today, we have been working

          20    in coalition with them, and they do care a

          21    lot about this particular legislation, even

          22    though they weren't able to be here today.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            184


           1              These are the healthy people that

           2    we do research on.  These are the people in

           3    clinical trials in the PMAs.  And so these

           4    are the people that are very often studied

           5    for hip replacements, or sometimes heart

           6    valves and so on.

           7              These are what I like to think of

           8    as my baby boomer friends.  And those of us

           9    who are baby boomers know that there are lot

          10    of spare parts that a lot of us are using.

          11    And we're pretty healthy.  And we use them

          12    and we're very happy to have these medical

          13    devices.

          14              However, these medical devices

          15    don't always last that long, and so one of

          16    the concerns that we have about MDUFMA is to

          17    make sure that resources are allocated in a

          18    way that helps make sure that products are

          19    safe for long-term use and that we know what

          20    the long-term risks are.  Because one of

          21    these days, those of us who look like this

          22    now, 10 or 20 years later or a little bit




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            185


           1    more, are going to be the frail elderly.  And

           2    if those devices, if those hip replacements

           3    or breast implants or whatever they are start

           4    to fail, those people might be in a situation

           5    where they're not healthy enough to have them

           6    surgically removed and replaced at that time.

           7              So that's one of the reasons why we

           8    think that the long-term safety of many

           9    medical devices are really very crucial.

          10    Even if they last a long time and are very

          11    good in the short run, we need to be aware of

          12    what's going to happen in the long run, and

          13    people need to know so that they can plan

          14    accordingly.

          15              So for example, if somebody knows

          16    that a hip replacement is likely to fail

          17    after some number of years, they might want

          18    to have that hip replaced while they're still

          19    healthy enough to have the surgery instead of

          20    waiting to a point where they're too frail

          21    and not able to do that.

          22              In the guidance for industry, the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            186


           1    FDA had issued this guidance, as you know, in

           2    September, regarding race and ethnicity data,

           3    and the focus I'd like to talk about today is

           4    the differences between who uses devices and

           5    who it's studied on.  The guidance for

           6    industry specified that race should be

           7    categorized the same way that it is for other

           8    HHS agencies.

           9              The FDA does not have regulations

          10    or guidance that require adequate

          11    participation levels, however, of either

          12    racial and ethnic groups or age groups, or

          13    sometimes even women and men.

          14              So we have a situation where

          15    people -- according to the guidance, there is

          16    some suggestion of how people be categorized.

          17    But there can be zero people in some of those

          18    categories.  And I have seen that -- in

          19    looking at data for PMAs, I have seen

          20    situations where there were zero

          21    African-Americans, or perhaps one or two,

          22    zero Asian-Americans, or perhaps one or two.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            187


           1              Now, the differences in drugs and

           2    devices is that for NDAs, the sponsors must

           3    present a summary of safety and effectiveness

           4    data by demographic subgroup.

           5              And the IND holders must submit

           6    annual reports with information about the

           7    age, gender and race of subjects enrolled in

           8    clinical studies.  But there are no similar

           9    requirements for medical devices.  And we

          10    think that's something that it's time to

          11    really start looking at and using the

          12    resources from MDUFMA as well as

          13    appropriations to make sure that that's done.

          14              Let's look at the NIH policy.  The

          15    NIH policy requires the inclusion of women

          16    and minorities in all research involving

          17    human subjects.

          18              And the exception to the policy is

          19    in situations where it would not work to

          20    protect the health of the human subjects

          21    because it would be unsafe, or if such

          22    research is not needed.  And we think this is




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            188


           1    an excellent model for CDRH.

           2              I'm going to talk a little bit

           3    about cosmetic surgery.  I think it's a

           4    really good example, because we're talking

           5    about devices and I'm talking about cosmetic

           6    surgery involving devices such as -- wrinkle

           7    fillers and breast implants are two good

           8    examples where the product is not

           9    life-saving.

          10              So we're not dealing with something

          11    that has to be rushed to market because

          12    people's lives are at stake.  And so for that

          13    reason, we have to be particularly concerned

          14    about the safety, short-term and long-term,

          15    and the safety for all Americans, not just

          16    white people who are already young and

          17    healthy.  In 2000, people of color accounted

          18    for 14 percent of all cosmetic surgery

          19    procedures in the country according to the

          20    plastic surgeons.  And in 2005, people of

          21    color accounted for 20 percent of all

          22    cosmetic surgery procedures, so it's on the




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            189


           1    increase.

           2              Unfortunately, many of these

           3    wrinkle fillers and other cosmetic devices

           4    are being approved without any useful

           5    information about people of color.  As I

           6    said, the products are not life-saving, and

           7    it is also important to note that these

           8    products are often used off-label.  So even

           9    if they are safe for some groups or for some

          10    procedures, they may be used for other groups

          11    and other procedures.

          12              We know that racial and ethnic

          13    groups do respond differently to medical

          14    treatments and devices, and of course FDA has

          15    recently approved a prescription drug

          16    specifically for African-Americans.

          17              But let's look at how implants and

          18    implanted medical devices might have a

          19    different response.  We know that

          20    African-Americans are more likely to have

          21    keloid scarring.  We know that in response to

          22    laser treatments, there is hypo-pigmentation




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            190


           1    risk.  And we also know that

           2    African-Americans are more susceptible to

           3    autoimmune disease.

           4              Keloid scarring can occur after an

           5    incision, and it's is more likely for

           6    African-Americans and Asian-Americans.  And

           7    here is two examples of keloid scarring:  The

           8    woman has a scar on her ear from having her

           9    ear pierced, and it's a huge, like ball on

          10    the bottom of her ear.  It looks like an

          11    earring, but it's actually her scar.

          12              And the scar on that ankle is also

          13    from a cut.

          14              Here are some granulomas in the

          15    mouth region -- it's not so clear, but you

          16    can see this was a cosmetic injection, an

          17    approved medical device, and there was a

          18    reaction with these rather large granulomous

          19    lumps over the lip.

          20              This one was in the forehead where

          21    there was necrosis and the skin died and left

          22    that not very attractive appearance.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            191


           1              And as I mentioned, autoimmune

           2    disease is of particular concern because

           3    African-Americans are more at risk for

           4    autoimmune disease, and implanted medical

           5    devices, some may increase the risk of

           6    autoimmune disease.

           7              So for breast implants, there were

           8    only a few, less than a dozen,

           9    African-Americans and Asian-Americans in the

          10    recent PMA for breast implants, even though

          11    reconstruction with breast implants is

          12    popular among African-American women and

          13    augmentation with breast implants is very

          14    popular among Asian-American women.

          15              This is a sample photo for the

          16    implant makers of what breasts are supposed

          17    to look like after augmentation.  And this is

          18    what's called capsular contracture, where the

          19    scar tissue hardens around the implant and

          20    causes a distortion in the shape and can be

          21    extremely hard and painful.  Since we know

          22    that there are racial differences in keloid




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            192


           1    scarring, we do have to worry about scar

           2    tissue development with implants.

           3              MR. BARNETT:  Two more minutes

           4    please.

           5              MS. ZUCKERMAN:  This is a necrosis

           6    after an implant.  I just wanted to give an

           7    example of Sculptra, a product that was

           8    recently approved as a medical device for

           9    HIV-AIDS patients but is now being widely

          10    advertised for the horror and tragedy of

          11    SmileLines for young women.  So we need to

          12    make sure that these products are safe for

          13    everyone.  And we need to make sure that the

          14    post-market surveillance is also enough to

          15    ensure the long-term safety for everyone.

          16    And we know from experience and from the

          17    report that FDA did that pre-market

          18    agreements that require post-market

          19    surveillance are not necessarily being

          20    followed.

          21              So we want to make sure it's safe

          22    for everyone, again:  Asian-Americans,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            193


           1    Hispanics, everybody.  Elderly people.  I

           2    want to remind you that the National Academy

           3    of Science's report found some problems with

           4    medical devices surveillance for children.

           5    And we want to make sure that these products

           6    are safe for our kids.

           7              The NAS recommended among other

           8    things post-market studies be a condition of

           9    approval, and that those post-market studies

          10    follow children for a long enough time to

          11    make sure that the product accounts for

          12    children's growth and development, and to

          13    make sure that there are annual reports on

          14    that to make sure that when medical devices

          15    are used for children, whether on-label or

          16    off-label, that they're safe.

          17              I want to end with a quote from

          18    Dr. Jane Henney, former FDA commissioner:

          19    "It's only through the participation of the

          20    many populations that will ultimately receive

          21    a new product that we can ensure that the

          22    medical products we approve are appropriate,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            194


           1    safe and effective for all Americans and not

           2    just a narrow cut of our country's

           3    population."

           4              Thanks very much.

           5              MR. BARNETT:  Thank you.  Anyone on

           6    the panel want to ask for clarification?  If

           7    not, I'd like to call a speaker who

           8    registered today.  She is Claudia Miller from

           9    the University of Texas.  Is she here?  Okay,

          10    come on up.

          11              MS. MILLER:  I'm a researcher, so I

          12    guess I have a letter, handouts.  I apologize

          13    for that.

          14              MR. BARNETT:  Okay.

          15              MS. MILLER:  And I'll give you a

          16    copy of my testimony as well.

          17              Thank you for this opportunity to

          18    talk about my views regarding improvements

          19    that are needed to actually increase

          20    safeguards for medical devices.  I'm a

          21    professor of environmental and occupational

          22    medicine and a board-certified internist,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            195


           1    allergist and immunologist at the University

           2    of Texas Health Science Center in San

           3    Antonio.

           4              For more than a decade, my research

           5    has been focusing on people who report

           6    developing chronic multisystem illnesses,

           7    headaches, memory and concentration

           8    difficulties, depression, fatigue, chronic GI

           9    problems, fibromyalgia following an

          10    identifiable exposure; for example, implants

          11    in the body or to pesticides and solvents

          12    used during remodeling, or chemicals used

          13    during the first Gulf War.

          14              I've served as a consultant to the

          15    Department of Veterans' Affairs on the Gulf

          16    War veterans' illnesses, the EPA on sick

          17    buildings, including its own headquarters

          18    building here in Washington, the National

          19    Institute of Dental and Craniofacial Research

          20    on temporomandibular joint implants, the

          21    National Institute of Environmental Health

          22    Sciences, the National Toxicology Program of




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            196


           1    the governments of Canada, Germany, Sweden

           2    and others.

           3              What unites these seemingly diverse

           4    groups, patients with implants, Gulf War

           5    veterans and sick building occupants, is the

           6    fact that following a well-defined exposure

           7    event, a subset of individuals appears to

           8    lose their prior innate tolerance, their

           9    natural tolerance, for a wide variety of

          10    structurally unrelated chemicals.  I compare

          11    to the way that diabetics lose their

          12    tolerance for sugar; they lose their innate

          13    tolerance for exposures.

          14              Thereafter, everyday exposures,

          15    including commonly eaten foods, medications,

          16    alcoholic beverages, caffeine and chemical

          17    inhalants such as fragrances, diesel exhaust

          18    and tobacco smoke -- exposures that had never

          19    bothered these people before and don't bother

          20    most of us, but now they're triggering myriad

          21    often disabling symptoms in these

          22    individuals.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            197


           1              In environmental medicine, this

           2    two-step disease process has come to be known

           3    as Toxicant-Induced Loss Of Tolerance, or

           4    TILT.  It does not appear to matter whether

           5    the exposure that initiated this process was

           6    exogenous, like a chemical exposure to

           7    pesticides, solvents; or endogenous such as

           8    an implant.  The body's response is

           9    remarkable similar.

          10              We've studied and reported on 87

          11    people with surgical implants and I've given

          12    you those papers.  Three quarters of these

          13    individuals had received breast implants.

          14    Among the latter, 69 percent reported rupture

          15    of an implant and 78 percent had one or more

          16    implants removed.  But these also include

          17    other types of implanted devices, including

          18    TMJ implants.  Of those women who had

          19    undergone explantation for breast implants,

          20    almost half reported their health status as

          21    greatly improved or somewhat improved.

          22              Although we have not said all kinds




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            198


           1    of implants, it appears that certain kinds

           2    are more likely to cause this loss of

           3    tolerance.  Silicon gel breast implants, for

           4    one, appear to cause these problems because

           5    they tend to leak and rupture.  TMJ implants

           6    made of Teflon tend to cause similar problems

           7    because the friction of the jaw joint, high

           8    pressures cause the Teflon to flake off

           9    basically inside the body.

          10              And the fact that these are

          11    long-term permanent implants often used by

          12    relatively young patients means that

          13    long-term research is especially important

          14    before approval and post-market surveillance.

          15              It's essential that MDUFMA ensure

          16    adequate resources for long-term premarket

          17    clinical trials and well-conducted

          18    post-market surveillance.  Using a validated

          19    screening questionnaire which I've provided

          20    to you, the quick environmental exposure and

          21    sensitivity inventory, which is of very high

          22    sensitivity and specificity and it's a




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            199


           1    validating instrument to measure this problem

           2    of chemical intolerance.

           3              We found that the symptom severity

           4    scores of implant recipients rival those of

           5    environmentally exposed groups we were

           6    studying, including Gulf War vets -- ill Gulf

           7    War vets, I should add.

           8              Compared to controls, implant

           9    recipients also reported many more and more

          10    severe adverse responses to everyday

          11    environmental chemical exposures.  Further,

          12    implant recipients reported far more severe

          13    reactions to a wide variety of foods,

          14    medications, alcoholic beverages, caffeine

          15    and other common exposures than did controls.

          16    This is a new paradigm; we're not talking

          17    about usually classified autoimmune diseases,

          18    as have been studied in certain studies.

          19    These are a much broader classification of

          20    diseases, and this appears to be a new

          21    paradigm for environmentally induced disease

          22    that differs from classical toxicology and




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            200


           1    allergy in important ways.

           2              Toxicant-Induced Loss of Tolerance,

           3    or TILT, for short, explains why infected

           4    individuals may remain sick years after their

           5    initial exposure.  This is as a result of

           6    subsequent triggering by everyday exposures

           7    that they now have lost tolerance to.

           8              Why do symptoms wax and wane in

           9    such a bewildering fashion?  Because

          10    triggering exposures change over time in the

          11    effects of these exposures, the symptoms

          12    resulting from their exposures as they go

          13    through the day overlap in time.  Ironically,

          14    affected individuals and their physicians may

          15    be completely unaware of their intolerances

          16    resulting from TILT because of a phenomenon

          17    called masking.  If people are reacting

          18    adversely to multiple chemicals, foods,

          19    drugs, and so on, and they are exposed to

          20    these substances one after another during the

          21    day, the symptoms resulting from these

          22    exposures overlap in time.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            201


           1              Again, that's called masking.  As a

           2    consequence, there is so much background

           3    noise that patients can't identify, nor can

           4    their physicians, any specific triggers for

           5    their symptoms.  They just feel bad most of

           6    the time, with chronic fatigue or flu-like

           7    symptoms that won't go away.

           8              Recent Canadian studies done at the

           9    University of Toronto indicate that genetic

          10    polymorphisms may underlie who is more

          11    vulnerable to developing Toxicant-Induced

          12    Loss Of Tolerance.  At the same time, no one

          13    is able to predict, and this is very

          14    important, which individuals will be

          15    affected.

          16              In September, I chaired a meeting

          17    on TILT sponsored by two NIH institutes:

          18    NIEHS and National Institute of Alcohol Abuse

          19    and Alcoholism.  There is a report on that

          20    meeting from a journal I've given you.

          21              Invited scientists explored

          22    clinical observations, animal models,




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            202


           1    neuroimaging and genetic approaches for

           2    understanding this emerging new disease

           3    paradigm.  The implications for you are

           4    clear.  To safeguard health, you must

           5    determine which types of implants are more

           6    likely to cause loss of tolerance, and the

           7    time frame for problems.

           8              If certain materials are more

           9    likely to cause serious health risks, they

          10    should not be approved unless benefits

          11    outweigh the risks.  The FDA must assure that

          12    there are adequate warnings on the label so

          13    that patients can avoid the health risks and

          14    respond quickly to remove the implants that

          15    are starting to cause symptoms.

          16    Unfortunately, that may be too late in some

          17    cases.  And since removal of cosmetic

          18    implanted devices such as breast implants are

          19    not covered by health insurance, it is

          20    especially crucial that they be held to a

          21    high safety standard.

          22              Unfortunately, women who become ill




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            203


           1    from their implants may not be able to afford

           2    surgical removal.  Our research indicates

           3    that a substantial proportion of implanted

           4    women with TILT become so debilitated that

           5    they are no longer able to earn a living, and

           6    therefore unable to afford surgical removal

           7    for many years unless they become eligible

           8    for Medicare or Medicaid.

           9              Some become so ill over time that

          10    they are not able to tolerate hospitals or

          11    surgery, even if they could otherwise afford

          12    to have their implants removed.

          13              Today's meeting is focused

          14    principally on the device industry's

          15    perspective, but as a clinician, I'm here to

          16    encourage you to ensure long-term safety

          17    standards and to take into account this more

          18    susceptible subset of the population that may

          19    have exposures to various devices.

          20              We cannot predict ahead of time who

          21    is going to have adverse effects until we

          22    have more science.  Thank you.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            204


           1              MR. BARNETT:  Thank you.  Anyone on

           2    the panel want clarification on that?  Okay,

           3    now since this is the close of the last of

           4    our six sessions, let me open the floor now

           5    to questions from anyone about any of the

           6    things you heard today; that is, any of the

           7    six sessions.  The only ground rule for this

           8    one is that your comment apply to MDUFMA.  So

           9    let me do that.  Anybody?  You all talked

          10    out?  Okay, if that's the case, then let me

          11    ask Linda if she wants to make a few closing

          12    comments before we say goodbye.

          13              MS. KAHAN:  I just want to

          14    reiterate Dan's appreciation for everybody

          15    coming.  I think that we did hear a lot of

          16    good ideas, many of which focused on issues

          17    that we ourselves of course have been

          18    thinking about and that many of you have

          19    brought to our attention before, and that

          20    we're working on thinking about the right way

          21    to go ahead, at the same time we're working

          22    on meeting the current MDUFMA goals.




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382





                                                            205


           1              We look forward to working with all

           2    of you over the next year so that we can

           3    again get a program in place that's even

           4    better than what we've got, so that we can

           5    get safe and effective products to the

           6    American public as quickly as possible.

           7              Thank you very much for helping us.

           8              MR. BARNETT:  Thank you all.

           9                   (Whereupon, at approximately 2:24

          10                   p.m., the PROCEEDINGS were

          11                   adjourned.)

          12                       *  *  *  *  *

          13

          14

          15

          16

          17

          18

          19

          20

          21

          22




                                BETA COURT REPORTING
                                www.betareporting.com
                    202-464-2400                     800-522-2382