1
 
 
 
 
 
          1
 
          2
 
          3
 
          4
 
          5
 
          6
 
          7
                           FDAMA STAKEHOLDERS MEETING
          8
                                 APRIL 28, 1999
          9                  Boston, Massachusetts
 
         10
 
         11     Talking with Stakeholders About FDA Modernization
 
         12
 
         13
 
         14
 
         15
 
         16                         Boston University Medical School
                                    Keefer Auditorium
         17                         715 Albany Street
                                    Boston, Massachusetts
         18                         10:00 a.m. - 4:15 p.m.
 
         19
 
         20
 
         21
 
         22                  LEE A. MARZILLI
                     REGISTERED PROFESSIONAL REPORTER
         23                  18 Boulder Road
                          Lexington, MA  02420
         24                   (781)862-4829
 
 
 
 
 

                                                              2
 
 
 
 
 
          1                     I N D E X
 
          2                                               PAGE
 
          3   OPENING REMARKS BY JOHN MARZILLI:             3
 
          4   REMARKS BY DR. ARAM CHOBANIAN:                8
 
          5   REMARKS BY MICHAEL DONOVAN:                  15
 
          6   PRESENTATION BY MARK ELENGOLD:               16
 
          7   PRESENTATION BY JANICE BOURQUE:              48
 
          8   PRESENTATION BY LISA RAINES:                 64
 
          9   QUESTIONS AND ANSWERS:                       80
 
         10   PRESENTATION BY LISA LOPEZ:                  97
 
         11   PRESENTATION BY CAROLYN JONES:              108
 
         12   QUESTIONS AND ANSWERS:                      127
 
         13
 
         14
 
         15
 
         16
 
         17
 
         18
 
         19
 
         20
 
         21
 
         22
 
         23
 
         24
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              3
 
 
 
 
 
          1                   P R O C E E D I N G S
 
          2            MS. FAIRFIELD:  Good morning.  Why don't we
 
          3       get started.  We're running a little bit behind,
 
          4       and we'll get started and try and keep this on
 
          5       track.  My name is Paula Fairfield.  I'm with the
 
          6       Food and Drug Administration, and I'm just going
 
          7       to give you some housekeeping information.  Rest
 
          8       rooms are just outside the door to the
 
          9       auditorium.  They will be on your right.
 
         10            We're going to have a break after our third
 
         11       speaker this morning from Genzyme Corporation,
 
         12       and the break will be in the Wilkins Boardroom,
 
         13       which is just down the hall on your left.  It's
 
         14       across the hall from the clock on the wall.
 
         15            Lunch is going to be in the vicinity of
 
         16       11:45, and that's going to be on the 14th floor
 
         17       here in the medical center, and there will be
 
         18       signs and people directing you to elevators and
 
         19       around up to the 14th floor.
 
         20            I would like to introduce at this time our
 
         21       District Director at FDA, John Marzilli, from the
 
         22       New England District Office.  John?
 
         23            MR. MARZILLI:  Thank you very much, Paula,
 
         24       and thank you, everyone, for getting here this
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              4
 
 
 
 
 
          1       morning.  I know if any of you came in on the
 
          2       Mass. Pike -- and I came in on the Weston toll
 
          3       link -- then I can assure you that people are
 
          4       crawling along to get here.  Normally I travel to
 
          5       our office up in Stoneham, Massachusetts, and
 
          6       don't experience the delight of Mass. Pike
 
          7       morning traffic coming into downtown Boston, so
 
          8       it was a novel experience for me, and I'm sure
 
          9       I'll do as the director of security here did and
 
         10       get here at 6:00 o'clock and have some coffee so
 
         11       I won't have to be pulling my hair out as I'm
 
         12       driving along the Pike.
 
         13            But I want to thank folks for coming here,
 
         14       and I can assure you, as the day progresses, bit
 
         15       by bit you'll see these seats fill up because we
 
         16       have over a hundred people registered for this
 
         17       meeting, and it shows the tremendous interest in
 
         18       the New England area of people from the biotech
 
         19       industries in getting a chance to meet with us at
 
         20       the Food and Drug Administration.
 
         21            This is truly a historic meeting for the
 
         22       Food and Drug Administration.  We are having this
 
         23       meeting today as an outreach with our
 
         24       stakeholders across the country.  The meeting
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              5
 
 
 
 
 
          1       kicks off here in Boston this morning at 9:30
 
          2       with the first of eight meetings that will be
 
          3       held across the country.  Our meeting will start
 
          4       with the morning session with folks from the
 
          5       District Office and folks from the Center for
 
          6       Biologics.  The day will progress where we'll
 
          7       have speakers from industry addressing us as
 
          8       well, folks that we're near and dear with that
 
          9       we've had working relationships for a long time
 
         10       here in the New England District, and are always
 
         11       first and foremost to come forward and meet with
 
         12       the agency, and we look forward to that
 
         13       opportunity.
 
         14            It's an important aspect of the FDA
 
         15       Modernization Act for us to get together and hear
 
         16       from our stakeholders, hear from the people that
 
         17       we work with on a daily basis, and have a chance
 
         18       to interact and maybe, to paraphrase Ed Cox, to
 
         19       get a chance to say, "So how are we doing?" and
 
         20       see where there's room for improvement and room
 
         21       where we can work together.
 
         22            It's an important opportunity for us as an
 
         23       agency, something that we don't get to do very
 
         24       often and something that this Commissioner has
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              6
 
 
 
 
 
          1       highlighted as her first priority in taking over
 
          2       the reins of the agency that she came on board.
 
          3       So the FDA Modernization Act is Commissioner
 
          4       Henney's, and I can assure you my, first priority
 
          5       as District Director here in the New England
 
          6       District, and it's important for us to take this
 
          7       opportunity to meet with all of you.
 
          8            As I said, there are seven other meetings
 
          9       being conducted across the country.  In Atlanta
 
         10       we'll be having a stakeholders meeting with the
 
         11       Office of Regulatory Affairs.  They will also be
 
         12       meeting in Chicago with the food industry.  They
 
         13       will be meeting in Kansas City with the
 
         14       veterinary drug industry; in the San Diego area,
 
         15       medical devices.  In San Francisco we'll be
 
         16       meeting with the biologics industry as well; and
 
         17       in Philadelphia, we'll be meeting with the Center
 
         18       for Drug Evaluation.
 
         19            And, Paula, have I covered all the
 
         20       meetings?  And if I haven't -- oh, in D.C. we'll
 
         21       be meeting with the world.  Thank you.
 
         22            And I'm sure all of you have clicked onto
 
         23       our Web site and seen where these meetings will
 
         24       be held.  And for those of you that have fellow
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              7
 
 
 
 
 
          1       workers that maybe couldn't make it to this
 
          2       meeting, at the break you may want to call them
 
          3       and tell them they can click onto their computers
 
          4       on www.fda.gov, and click onto our FDAMA Web site
 
          5       and see the Commissioner's broadcast
 
          6       simultaneously on our Web site as well.  So we'll
 
          7       have a satellite broadcast that will be received
 
          8       at eight locations across the country with FDA
 
          9       participants.  There will be other locations that
 
         10       will be receiving the satellite downlink as well,
 
         11       and people can also view it on their Web sites in
 
         12       their offices.
 
         13            This is a first for me as District Director,
 
         14       and it's an exciting opportunity to take part in
 
         15       this activity as it goes across the country and
 
         16       get to meet with folks from the New England area
 
         17       from the industry that we regulate here, and I'm
 
         18       really looking forward to spending the day
 
         19       together with all of you.
 
         20            And I would like to thank Boston University
 
         21       Medical Campus for hosting this meeting with us
 
         22       today.  It was encouraging to work with them, and
 
         23       they have been the greatest of assistance to us
 
         24       in putting this together.  And I'd like to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              8
 
 
 
 
 
          1       welcome Dr. Aram Chobanian, the Provost of the
 
          2       Boston University Medical Campus and the Dean of
 
          3       the School of Medicine.  I'd like to ask him to
 
          4       come up here and welcome us to the site today.
 
          5            DR. CHOBANIAN:  Thank you very much, John.
 
          6       It's a pleasure to have you all here today.  I go
 
          7       back with the FDA for a long time, for twenty-two
 
          8       years served as a consultant to the FDA, chaired
 
          9       the Cardiorenal Advisory Committee, and was on
 
         10       the Orphan Drug Committee for quite a while, so I
 
         11       feel particularly close to the group that we are
 
         12       sponsoring today.
 
         13            Boston University Medical School and Boston
 
         14       University Medical Center is made up of different
 
         15       constituents here.  At the medical campus we have
 
         16       four institutions, three schools and a merged
 
         17       hospital.  The three schools are the School of
 
         18       Medicine, the School of Dentistry, and the School
 
         19       of Public Health.  In addition, as those of you
 
         20       who are living in the Boston area know, we have a
 
         21       hospital that is a merged entity that brought
 
         22       together Boston City Hospital with our University
 
         23       Hospital; and that merger has gone very well, and
 
         24       we really have now a very unified medical
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              9
 
 
 
 
 
          1       campus.
 
          2            There is a lot of research activity here on
 
          3       the campus.  The total sponsored program
 
          4       activity, if you include the school and the
 
          5       hospital, exceeds $150 million this year; and
 
          6       it's a broad range of research projects, some of
 
          7       which are working with your companies, actually.
 
          8       We range from the very fundamental work,
 
          9       molecular genetics, all the way to translational
 
         10       medicine, to studying devices in the animal care
 
         11       facility, and to evaluating clinical
 
         12       instrumentation as well.
 
         13            There are thirteen nationally designated
 
         14       Centers of Excellence, most of which are funded
 
         15       by the NIH, some by other agencies, and those
 
         16       included a wide range of activities.  We have a
 
         17       specialized center of research in hypertension,
 
         18       in coronary heart disease, in Parkinson's disease
 
         19       and Alzheimer's disease, in asthma, in chronic
 
         20       pulmonary disease, in mass spectroscopy, where we
 
         21       competed successfully for the National Mass Spec
 
         22       Center, which collaborates now with people both
 
         23       in academia around the country as well as with
 
         24       industry.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              10
 
 
 
 
 
          1            We have a Navel Blood Research Laboratory
 
          2       that's been very successful, and I know some of
 
          3       the individuals here have worked with Bob Valleri
 
          4       in that kind of setting.  We have a Center of
 
          5       Excellence in Women's Health and so forth.
 
          6            The exciting part of what we're doing right
 
          7       now that I think relates to some of your
 
          8       activities is the BioSquare enterprise, which
 
          9       some of you probably parked really in the middle
 
         10       of that nine-acre complex, and we have a master
 
         11       plan that's been approved that includes six
 
         12       buildings.  The first two buildings you see, the
 
         13       second of the two, the Evans Medical Research
 
         14       Building, will be completed in December or
 
         15       January; and about forty percent of that building
 
         16       is for commercial purposes, for biomedical
 
         17       research for biotech companies.  And we have a
 
         18       third and fourth research building that has been
 
         19       approved by the Master Planning Group.  A garage
 
         20       is going to be started in the summer, and a hotel
 
         21       is currently being planned, and there are some
 
         22       preliminary discussions with companies regarding
 
         23       that.
 
         24            In addition, our hospital here has a very
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              11
 
 
 
 
 
          1       active plan.  Many of the old buildings, Boston
 
          2       City Hospital, will be demolished this year, and
 
          3       a new ambulatory care facility that fits into the
 
          4       style of the other older buildings that are here
 
          5       will be constructed, probably beginning this
 
          6       fall.  So I think we're seeing a major change
 
          7       here in the whole area, and it's going also with
 
          8       the changes in the residential part of this area,
 
          9       which is including now a large number of brown-
 
         10       stone conversions to condominiums.  And I can't
 
         11       believe the prices that these condominiums are
 
         12       now going for.  You could have increased the
 
         13       value fifty-fold.  When I first came here, they
 
         14       were selling for between $5,000 and $10,000, and
 
         15       now they are about a half a million dollars.
 
         16            So thank you all for coming.  We really
 
         17       appreciate the opportunity to host this and hope
 
         18       you have a good day.
 
         19            MR. MARZILLI:  Dr. Chobanian, I'd like to
 
         20       pronounce your name correctly, having my name so
 
         21       often incorrectly pronounced.  Dr. Chobanian, I
 
         22       want to thank you and I want to thank your staff
 
         23       for the wonderful job they have done for all the
 
         24       logistics for this meeting.  It's just been
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              12
 
 
 
 
 
          1       really great.  We really want to thank you and
 
          2       extend our thanks on behalf of the Food and Drug
 
          3       Administration for all the assistance you've
 
          4       given us.  Thank you very much.
 
          5            And now I'd like to introduce Paula
 
          6       Fairfield, our Public Affairs Specialist, and
 
          7       Paula will tell us a bit about the logistics for
 
          8       this morning.
 
          9            MS. FAIRFIELD:  Thank you, John.  We're
 
         10       going to have presentations from the Deputy
 
         11       Director for the Center for Biologics Evaluation
 
         12       and Research, Mark Elengold.  Seated to Mark's
 
         13       left is Steve Masielo, who is the Director of the
 
         14       Office of Compliance at CEBER.
 
         15            I'd like to ask the first three speakers if
 
         16       they'd come up to the stage, please.  We're going
 
         17       to have presentations by Janice Bourque,
 
         18       Executive Director of the Mass. Biotech Council,
 
         19       James Weston, Vice President, Government Affairs
 
         20       and Strategic Policy at Biopure, and Lisa Raines,
 
         21       Senior Vice President from Genzyme Corporation.
 
         22            After their presentations, we'll have a
 
         23       short break.  Then we'll continue with three more
 
         24       presentations.  Alison Taunton-Rigby, President
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              13
 
 
 
 
 
          1       and CEO of the Aquila Biopharmaceuticals, Lisa
 
          2       Lopez, Corporate Vice President and General
 
          3       Counsel of Haemonetics Corporation, and Carolyn
 
          4       Jones representing HIMA.
 
          5            When the presentations are finished, we'll
 
          6       have a period of questions and answers, and then
 
          7       we'll have our lunch break, which will be up on
 
          8       the 14th floor.  At 1:00 o'clock the satellite
 
          9       downlink presentation will begin.
 
         10            If you look in your packets, you'll notice
 
         11       on the left-hand side behind the agenda is a
 
         12       form, FDAMA Stakeholders Meeting.  If you'd fill
 
         13       that out with the questions that you'd like faxed
 
         14       to headquarters, we'll have people that will take
 
         15       them from you and fax them directly.
 
         16            Before the day is over, I'd like you to
 
         17       complete the evaluation for the FDA video
 
         18       teleconference and leave that with one of our
 
         19       people out at the registration desk.
 
         20            On that note, I'll turn the meeting over to
 
         21       Mark Elengold.
 
         22            MR. MARZILLI:  Mark, I just had to make a
 
         23       couple of announcements.
 
         24            MS. FAIRFIELD:  What did I forget?
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              14
 
 
 
 
 
          1            MR. MARZILLI:  No, no, I forgot.  You know,
 
          2       to err is human, since I made the mistake,
 
          3       right?
 
          4            First of all, is Michael Donovan still in
 
          5       the house?  I think he just walked out.  I meant
 
          6       to introduce him earlier but I didn't get a
 
          7       chance earlier, so later I'd like to ask Michael
 
          8       to come down because he was a great help to us in
 
          9       putting all this together.
 
         10            And, lastly, at the rear door there I'd like
 
         11       the two ladies to step forward so I can introduce
 
         12       them.  In case you have any questions during the
 
         13       day and you ask me, I will flag one of them down
 
         14       to get the answer.  And I want to introduce on
 
         15       our left is Karen Archdeacon.  Karen is a
 
         16       Compliance Officer with the District Office.  And
 
         17       on our right is Ellen Madigan.  Ellen is a
 
         18       commissioned officer, and she is a biotech expert
 
         19       in our Investigations Branch.  So I can assure
 
         20       you any questions you have for me, I'll be waving
 
         21       to one of them to come down so I'll be sure to
 
         22       get you all the right answer.
 
         23            MS. FAIRFIELD:  John and I make a good
 
         24       team.  What I forget, he picks up.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              15
 
 
 
 
 
          1            MR. MARZILLI:  Thanks a lot.  And now Mark.
 
          2       And if Michael reappears, I will ask him to come
 
          3       down and introduce himself because he was a great
 
          4       help to us.
 
          5            And here's the introduction.  Let's have a
 
          6       drum roll, ladies and gentlemen, for Michael
 
          7       Donovan.  Mike, come on down.
 
          8            (Applause.)
 
          9            MR. MARZILLI:  I'd like Mike to introduce
 
         10       himself and tell us a little bit about the
 
         11       operation here because he was a great help to us
 
         12       in putting the meeting together.
 
         13            MR. DONOVAN:  Welcome.  My remarks are going
 
         14       to be very brief.  I'm not going to go over what
 
         15       Aram has already described in terms of what's
 
         16       happening around here.  We're delighted to have
 
         17       this group here today.  I work on the BioSquare
 
         18       project with Kathy Doyle who's up there on the
 
         19       right with Thompson, Doyle, Hennessey & Everest.
 
         20       And we're seeing, I think, unprecedented growth
 
         21       going on in this area.  This is a part of Boston
 
         22       that is probably the next frontier, I think, for
 
         23       development in commercial activity.  And today
 
         24       throughout the day I'll be around and Kathy will
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              16
 
 
 
 
 
          1       be around.  You'll probably see some information
 
          2       regarding BioSquare.  If any of you who are from
 
          3       companies or, frankly, for that matter, from the
 
          4       FDA, if you'd like to find out more about what
 
          5       we're doing here, just feel free to talk to me or
 
          6       talk to Kathy, and we'd be glad to answer your
 
          7       questions and give you a tour or presentation
 
          8       later on.  Thank you.  Welcome again.
 
          9            MR. MARZILLI:  And now, since I so rudely
 
         10       interrupted, Mark Elengold.  Mark?
 
         11            MR. ELENGOLD:  Thank you, John.  It's a real
 
         12       pleasure to be here.  I always enjoy getting out
 
         13       of Washington.  I transferred there twenty-seven
 
         14       years ago for a two-year assignment, and I have
 
         15       been trying to get back out to the field ever
 
         16       since, so the closest I get are meetings like
 
         17       this.
 
         18            I really want to thank everybody involved in
 
         19       putting this together:  Dr. Chobanian for making
 
         20       this facility available, the folks at Mass. Medic
 
         21       and the Mass. Biotech Council for their support,
 
         22       particularly to Paula and John, folks back in
 
         23       headquarters who did a lot of the work on it,
 
         24       Lorrie Harrison, some of the other staff in our
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              17
 
 
 
 
 
          1       Office Communications Training Manufacturers
 
          2       Assistance.
 
          3            And the first thing I'd like to do is just
 
          4       introduce some of the other headquarters people
 
          5       that are here so you know who they are and you
 
          6       don't say anything to them that you might be
 
          7       embarrassed about.  John's already introduced
 
          8       Steve Masielo, who is the Director of our Office
 
          9       of Compliance and Biologics Quality.  That is a
 
         10       relatively new office that was formed by joining
 
         11       our staff from the licensing products
 
         12       surveillance people with our compliance folks to
 
         13       make a more unified approach to product quality
 
         14       and show how important that is to the compliance
 
         15       effort.
 
         16            Gail Sherman right here in front, who's with
 
         17       the Division of Manufacturers Assistance and
 
         18       Training, a division that in my former job I
 
         19       created to give more emphasis to the fact that we
 
         20       have to assist manufacturers even if we don't
 
         21       have it in our statutory books that license do.
 
         22       Gail's staff is the one that works in doing
 
         23       outreach programs, and John and I have been
 
         24       discussing various things we can do to work more
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              18
 
 
 
 
 
          1       closely with New England folks.  And so if you
 
          2       have any ideas or needs, the person to talk to is
 
          3       Gail and to John and Paula.  We'll be back, and
 
          4       we will continue our working relationship after
 
          5       this meeting.
 
          6            Also we have Bob Miller from our budget
 
          7       office.  Bob is the one who's responsible for
 
          8       making sure I have the money to pay for plane
 
          9       fares to come up here.  And Bob, if you have
 
         10       anything you want to talk about the FDA budget,
 
         11       he's the guy to talk to.  I was at a conference
 
         12       call the other day and they referred to him as
 
         13       "Bob show-me-the-money Miller."  I've known Bob
 
         14       a long time, and I'd never heard that one
 
         15       before.
 
         16            So that out of the way, let me explain why
 
         17       we're -- how many people were at any of the
 
         18       406(B) meetings last year?  Very few, so I'll go
 
         19       over this.
 
         20            Part of the Food and Drug Modernization Act,
 
         21       a process that in the creation and birthing of
 
         22       was probably rougher than raising my twins for
 
         23       twenty-one years, one of the steps was that we
 
         24       would meet with our stakeholders, the people who
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              19
 
 
 
 
 
          1       are affected by what we do, and consult with them
 
          2       on what the priorities are.  Last year we set up
 
          3       very quickly a series of meetings to do that, and
 
          4       if anyone doubts that they had a profound effect
 
          5       on the way FDA does business, they'd be wrong.
 
          6       We heard the message loud and clear from the
 
          7       device folks that we regulate in CBER, and today
 
          8       we'll be talking about our Device Action Plan,
 
          9       which is a direct outgrowth of what we heard last
 
         10       year at the two 406(B) meetings that we had, and
 
         11       another industry exchange meeting that was held
 
         12       with the Pacific region folks that is directly
 
         13       attributable to that.
 
         14            The way we did this last year was, we had it
 
         15       on different days for different centers, and most
 
         16       of them were in Washington.  We in CBER had a
 
         17       second meeting in addition to the Washington one
 
         18       in Oakland, California.  We believe that the
 
         19       meetings are so important for us to learn that,
 
         20       once again, we're the only center that's having
 
         21       two.  I'm chairing this one here, and Dr. Zinner,
 
         22       our Center Director, is chairing one in
 
         23       San Francisco later today.  The difference is
 
         24       that this year we're doing them simultaneously
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              20
 
 
 
 
 
          1       featuring a video teleconference with Dr. Henney,
 
          2       our new Commissioner.  We say "new," but she's
 
          3       had a stint as the Deputy Commissioner for
 
          4       Operations where she was in charge of the
 
          5       day-to-day operations of FDA, including the
 
          6       operations of the Center, so Dr. Henney is not a
 
          7       newcomer to FDA.
 
          8            Part of that whole process is to have
 
          9       questions answered from around the country, so
 
         10       again I remind you what Paula said about this
 
         11       ivory-colored form.  And, please, if you have any
 
         12       questions you'd like addressed, put them in, give
 
         13       them to the folks in the back, and they'll get
 
         14       them faxed to the teleconference.
 
         15            Any questions that are not addressed during
 
         16       the course of the teleconference, we will have
 
         17       answered.  We'll aggregate them.  They will be
 
         18       answered, and they will be posted on the Web site
 
         19       within a few weeks.  So even if we don't get to
 
         20       your question during the telecast, we will try to
 
         21       address all the questions and concerns.
 
         22            The way we did this last year, and I think
 
         23       we'll do it this year, is I'll do a hopefully
 
         24       brief overview of what CBER is and the directions
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              21
 
 
 
 
 
          1       we're moving in.  Then we'll go to the panelists,
 
          2       and what I'd like to do is have them do their
 
          3       presentations.  I think this group is doing it as
 
          4       one, if I'm correct.  So after they conclude
 
          5       their presentation, my FDA colleagues and I will
 
          6       ask any questions we have on their presentation.
 
          7       Then we will open it up to the floor if anybody
 
          8       on the floor wants to have any comments or put
 
          9       questions to the group.  After the first panel,
 
         10       we'll take a break, and we'll repeat that with
 
         11       the second panel, with the exception that we'll
 
         12       probably go to questions and comments after each
 
         13       speaker.  Then we'll have lunch upstairs.  Then
 
         14       we'll come back for the teleconference.  After
 
         15       the teleconference, if we have not finished any
 
         16       general questions, people who have not
 
         17       registered, speakers who want to talk, we'll do
 
         18       at the end.  Otherwise we'll just wrap up and
 
         19       adjourn.
 
         20            Again I'll ask you to complete the
 
         21       evaluation forms because the statute says we'll
 
         22       do this at least once a year, and anything you
 
         23       can give us feedback on to help us will be
 
         24       appreciated.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              22
 
 
 
 
 
          1            Okay, let's see, I think I've got all of my
 
          2       administrative notes done, and I guess we can
 
          3       start with the slides.  Again I want to thank BU
 
          4       and the audiovisual folks.  This is an amazing
 
          5       facility.
 
          6            This is our mission statement, and those of
 
          7       you who were at this meeting last year, one of
 
          8       the comments we received was that in our mission
 
          9       statement, we didn't properly address the medical
 
         10       devices we regulate.  So we're in the process
 
         11       right now of going through the internal
 
         12       administrative measure of revising our mission
 
         13       statement.  And over on the right side of that
 
         14       slide you see we're adding "and devices."  That
 
         15       shows we have learned, we have listened, and our
 
         16       commitment.
 
         17            These are the spectrum of products we
 
         18       regulate.  We used to do this as a rainbow, but
 
         19       we kept adding products to it and the rainbow
 
         20       wasn't big enough, so we went to the circle,
 
         21       which kind of illustrates that our products are
 
         22       related and do tend to flow from one to the
 
         23       other.  Again you'll notice down at the lower
 
         24       left corner, we've inserted between Tissues and
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              23
 
 
 
 
 
          1       Whole Blood "Medical Devices," again recognition
 
          2       of what we've heard.
 
          3            These are the tools we use to both enter the
 
          4       Olympics and do our job.  They are interlocking
 
          5       systems we have of review, research,
 
          6       surveillance, policy, and compliance.  We have an
 
          7       attitude that compliance is the last resort.  We
 
          8       would rather work through negotiation; but if we
 
          9       reach a point where that's not possible, we have
 
         10       the full tools of both the Food, Drug and
 
         11       Cosmetic Act and the Public Health Service Act to
 
         12       take regulatory action.
 
         13            These are our vision statements.  They are
 
         14       in your handouts, so I'm not going to spend too
 
         15       much time.  It just reflects the history of the
 
         16       biologics regulatory scheme that was started
 
         17       actually before the Food and Drug Act, and the
 
         18       Center for Biologics was originally the Division
 
         19       of Biologic Standards of the National Institutes
 
         20       of Health.  It was transferred to FDA in 1972,
 
         21       and then added the tools of the FD & C Act.  And
 
         22       if you see the last statement is the most
 
         23       important, that our regulatory mission is our
 
         24       guiding principle.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              24
 
 
 
 
 
          1            What are our strategic goals?  Well, the
 
          2       first goal, a high-quality regulatory process
 
          3       which is managed and integrated from discovery
 
          4       through postmarketing.  We want it to be seamless
 
          5       from the day that product is identified in a lab,
 
          6       put in clinical trials, hopefully licensed or
 
          7       approved, depending on the type of product, and
 
          8       then postmarketing surveillance.
 
          9            A high quality research program which
 
         10       contributes directly to the regulatory mission.
 
         11       Over the years that has been misunderstood.  Our
 
         12       research is directly aimed at our core regulatory
 
         13       mission.  To give you an idea of this, very
 
         14       recently a magazine alleged that an illegal
 
         15       vaccine was manufactured with an illegal
 
         16       adjuvant, squalene.  I was able to go to our lab
 
         17       director, and within a week they were able to
 
         18       develop a new method, previously unexisting, to
 
         19       quickly screen for this illegal ingredient down
 
         20       to parts per billion.  And we had to be able to
 
         21       have the research tools available.  I can't even
 
         22       pronounce many of them, but we have multi-toff
 
         23       MNR.  This was using electro-spray ionizing MNR.
 
         24       And they tried four or five methods they came up
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              25
 
 
 
 
 
          1       with in a week.  They totally validated it, and
 
          2       we're now able to run the regulatory samples.
 
          3       Without that research base, we would still be
 
          4       trying to disprove this allegation.  So that's
 
          5       the need for our research program.
 
          6            A high quality diverse work force,
 
          7       interactive information systems, and leveraging
 
          8       resources.  That's where we go out and partner
 
          9       because Bob won't give us enough money to do
 
         10       exactly what we need to do.  Okay, Bob.
 
         11            Okay, what are our priorities?  Well,
 
         12       Dr. Henney will be talking about her priorities
 
         13       during the teleconference, and our priorities are
 
         14       pretty much the same.  Number one, implement FDA
 
         15       reform.  Just last week we published in the
 
         16       Federal Register a required notice under FDAMA
 
         17       adopting specific CDRH guidances, and that was a
 
         18       milestone we were required to do and we met.
 
         19            We have to meet or exceed the PDUFA FY99
 
         20       performance standards.  Just in case anybody
 
         21       doesn't know the acronym, Prescription Drug User
 
         22       Fee Act.
 
         23            Take whatever actions are necessary to
 
         24       assure the safety of and public confidence in the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              26
 
 
 
 
 
          1       nation's blood supply.  Right now, approximately
 
          2       what percentage, Steve?  50 some percent of the
 
          3       blood supply is under consent decree?  60 some,
 
          4       okay.  That shows that a few years ago, we
 
          5       realized the industry was not about to
 
          6       voluntarily comply, so we now have court-imposed
 
          7       sanctions and review of what they are doing.
 
          8       Again, that was a last resort after voluntary
 
          9       measures failed.
 
         10            Facilitate the development and approval of
 
         11       significant vaccine, blood and therapeutic
 
         12       products.  Just again going back to the history
 
         13       of our center, the person who was the first
 
         14       Director after it came in, Hank Myer, and his
 
         15       then Deputy, Paul Parkman, were the actual
 
         16       developers of the German measles, the rubella
 
         17       vaccine.  So we have a proud history of working
 
         18       to actually develop the therapeutics and work
 
         19       with the industry and the National Institutes of
 
         20       Health where we are located to assure that the
 
         21       development process is as quick and seamless.
 
         22            And pursue excellence in research that is
 
         23       directly targeted to the evaluation of
 
         24       regulation, and I've already covered that, I
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              27
 
 
 
 
 
          1       hope.
 
          2            Improve our automated system support.  You
 
          3       can't do anything today without computers.  I
 
          4       don't think any of us would like to go back to
 
          5       the era before e-mail, automated data systems,
 
          6       and tracking of our things.  Well, some of us
 
          7       might want to, but when I get home tonight and I
 
          8       have 140 for being out of the office for 24
 
          9       hours, I don't know.
 
         10            And continue to support efforts for a high
 
         11       quality, diverse work force.
 
         12            This gives you an idea of what we're up
 
         13       against.  If you look over here, the Prescription
 
         14       Drug User Fee Act has really been a two-edge
 
         15       sword for us.  It provided additive resources to
 
         16       the FDA to speed the approval of covered
 
         17       products.  One of the requirements of PDUFA,
 
         18       however, is that we maintain a base level of
 
         19       appropriated resources, that if we don't continue
 
         20       to spend, we don't receive the user fees.  And
 
         21       over the past few years, as our budget overall
 
         22       has been flat-lined -- and a flat-line budget
 
         23       involves a basic decrease because of increased
 
         24       salaries and costs -- the share of what we've had
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              28
 
 
 
 
 
          1       available for the other products we regulate is
 
          2       this little blue dot down there.  So when people
 
          3       ask why we're not doing as much as we could in
 
          4       the medical device area, it's because to keep
 
          5       this area here, we have to spend our appropriated
 
          6       funds and take it from somewhere.  You can also
 
          7       see that this IAG CRADA has been constant or
 
          8       increasing, and that's because we've turned to
 
          9       leveraging and working with outside
 
         10       organizations, getting grants from research
 
         11       institutions, interagency agreements with NIH and
 
         12       NIST to try and fund some of our product
 
         13       characterization and regulatory development by
 
         14       partnering with either early phase industry or
 
         15       the NIH or NIST.
 
         16            Interestingly enough, you can see that our
 
         17       workload has been in the IND, or investigational
 
         18       new drug area.  In our case, it's really
 
         19       investigational biologics.  And you can see that
 
         20       the level, aside from a dip for a few years --
 
         21       and if you plot the stocks of biotech companies,
 
         22       those of you in the industry know that that
 
         23       pretty much tracks declines in the biotech
 
         24       stocks -- has been increasing again.  And,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              29
 
 
 
 
 
          1       importantly, the percentage of biotech is really
 
          2       up there.
 
          3            These are numbers which are interesting.  It
 
          4       shows that while many of the products are coming
 
          5       in as INDs, very few are leading to actual
 
          6       applications.  That's the next phase of product
 
          7       development, and we're gearing up to handle as
 
          8       they move from research into licensure.
 
          9            User fee performance, you can see we're up
 
         10       there at a hundred percent.  We've met all our
 
         11       goals, and we are going to continue to meet
 
         12       them.
 
         13            That's a really horrible slide.  I can't
 
         14       read it from here.  This just shows our review
 
         15       performance in numbers and percentages, and again
 
         16       you have those in your packets.
 
         17            And one of Dr. Henney's key priorities is
 
         18       improving FDA in general, and our goal is to
 
         19       improve CBER's science base.  Again, we have a
 
         20       proud history of research.  Our predecessors have
 
         21       worked with Dr. Salk and Sabin on the original
 
         22       vaccines.  Again, the people who are our
 
         23       management back when I first joined the center
 
         24       developed the rubella vaccine.  And over the past
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              30
 
 
 
 
 
          1       few years our science base has eroded, and we are
 
          2       now in the process of rebuilding it because it is
 
          3       necessary to make good and fast regulatory
 
          4       judgments.
 
          5            And these are the goals we've set for
 
          6       ourselves in science:  To realize the mission of
 
          7       bringing products of new technology to the market
 
          8       rapidly while ensuring their safety and
 
          9       efficacy.  Nobody benefits from rapid approval of
 
         10       an ineffective or unsafe product, not even the
 
         11       sponsor, because the long-term costs of having a
 
         12       bad product out there are not even available to
 
         13       them.
 
         14            And to realize the mission of reducing risks
 
         15       associated with products.  I'm getting ready for
 
         16       a hearing tomorrow in the House, and one of the
 
         17       things we have to stress is:  There is no medical
 
         18       decision that is ever made that is not a
 
         19       risk/benefit judgment.  And it's very important
 
         20       that both the products are approved when that
 
         21       judgment in general is on the benefit side, and
 
         22       the prescribers, or users, have the information
 
         23       they need to make the correct evaluation.
 
         24            And these are the strategies:  Research,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              31
 
 
 
 
 
          1       standards development.  Again, standards
 
          2       development is very heavily interactive with the
 
          3       industry.  Surveillance, outreach, meetings like
 
          4       this, and premarket review.
 
          5            Training scientifically, these seminars, and
 
          6       enhancing our databases.  The meetings and
 
          7       seminars is a key point because traditionally in
 
          8       the federal government, when you start running
 
          9       short on cash, the first thing you do is you
 
         10       reduce travel because travel is extremely
 
         11       expensive and you can't demonstrate a return on
 
         12       investment.  That is one of the things that's
 
         13       eroded our science base.  If our scientists can't
 
         14       get out to meetings, present their results and
 
         15       consult with colleagues, they are not at state of
 
         16       the art.  And so one of our goals is to increase
 
         17       our folks' participation in major scientific
 
         18       meetings.
 
         19            Professional development, many of our
 
         20       physicians have for a long time worked in
 
         21       clinics, mainly free clinics or volunteer
 
         22       clinics, a few hours a week to keep their medical
 
         23       skills and patient treatment ideas up to the
 
         24       standard.  We're enhancing that by getting some
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              32
 
 
 
 
 
          1       of our research types, our microbiologists, our
 
          2       chemists, working in research laboratories in
 
          3       universities part-time, four hours every two
 
          4       weeks, to get some experience on what the real
 
          5       world is in today's day and age.
 
          6            Product testing, we are in the process of
 
          7       developing a new standards group within the
 
          8       center.
 
          9            And infrastructure, for many years our lab
 
         10       equipment was getting very old.  It wasn't up at
 
         11       state of the art.  One of the few benefits of Y2K
 
         12       means that some of that equipment has to be
 
         13       replaced just so it will work next year.
 
         14            And I think I've covered those in previous
 
         15       slides.  The key one I'll just repeat:
 
         16       Anticipate public health needs and support
 
         17       informed decisions.  And that way, when we have
 
         18       our traditional Friday night crisis and my pager
 
         19       goes off at 9:00 o'clock and my wife starts
 
         20       yelling about the FDA, I can pick up the phone
 
         21       and get the people I need who can give the
 
         22       information that is needed to make the right
 
         23       public health choice.
 
         24            And I think I've covered those.  We'll just
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              33
 
 
 
 
 
          1       shoot through those.  You can read them.
 
          2            Major initiatives of action plans:  Two
 
          3       years ago we were faced with the crisis of
 
          4       confidence in the blood supply, and we developed
 
          5       the Blood Action Plan.  And by putting resources
 
          6       and project management to it, we have been able
 
          7       to move a lot of things forward very fast.
 
          8            It has been so successful that we have
 
          9       adopted the action plan approach for several
 
         10       things:  FDAMA/PDUFA II.  We have accountability.
 
         11       We have meetings.  In fact, unfortunately I left
 
         12       yesterday to come here and missed our quarterly
 
         13       Status of Application meetings, where each of our
 
         14       review officers gets up and gives the status of
 
         15       all the applications they are working on; and the
 
         16       senior management can listen, provide input, and
 
         17       make assignments of additional resources or
 
         18       whatever is needed.
 
         19            Strategic Plan, we developed that four years
 
         20       ago to give us a basic ten-year strategy.  It has
 
         21       been very successful in anticipating both our
 
         22       budget problems and what we need to do to focus.
 
         23            Team Biologics, I'm sure there will be some
 
         24       questions about that.  That was a way to bring
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              34
 
 
 
 
 
          1       our inspection compliance activities into line
 
          2       with the rest of the FDA.  Twenty-five years
 
          3       after biologics was absorbed in FDA, we still did
 
          4       business in a major different way.  Our
 
          5       inspection program was conducted out of
 
          6       headquarters, and some believed our GMP attitudes
 
          7       and compliance activities were out of line.
 
          8            We believe that because of the cutting edge
 
          9       of our technology, our scientists really needed
 
         10       to be involved in the inspectional approach.  So
 
         11       ORA and CBER got together, and we developed Team
 
         12       Biologics.  I'll go over it in a couple of
 
         13       minutes.
 
         14            Tissue Regulatory Framework, that's an
 
         15       action plan that's developing strategies to
 
         16       regulate tissues.  Congress has for years been
 
         17       talking about enacting statutes.  They have not
 
         18       yet done so, and we anticipate should it be done,
 
         19       it will be another unfunded mandate, so we have
 
         20       been working on how to come to grips with the
 
         21       tissue issues without any additional funding or
 
         22       resources.
 
         23            The Blood Action Plan I mentioned was the
 
         24       granddaddy of the Xenotransplant Action Plan.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              35
 
 
 
 
 
          1       That came to light with Jeff Getty and his baboon
 
          2       blood marrow implant a few years ago.  We decided
 
          3       we needed to get together and be proactive.
 
          4       There are companies developing human-gene-based
 
          5       pig organs.  Our own research lab discovered
 
          6       porcine endogenous retrovirus, or PER, that's
 
          7       genetic codes from viruses that were embedded in
 
          8       porcine tissue.  And we had some INDs for liver
 
          9       assist devices, and when this was discovered, our
 
         10       lab was able to do the research, find out they
 
         11       were nonreproducing, nonreplicating,
 
         12       noninfectious, and therefore didn't pose a risk.
 
         13       The hold was very minimal, but we were able to
 
         14       investigate it, reach an informed decision,
 
         15       change the informed consent, and move on.  Again,
 
         16       the need for a research program.
 
         17            The Device Action Plan, we'll go into detail
 
         18       on that, and the ICH, so that the industry has a
 
         19       single group of requirements to comply with
 
         20       around the world.
 
         21            Device Action Plan, in part spurred by the
 
         22       device law changes included in FDAMA.  And last
 
         23       year we heard -- I heard it in Oakland, in D.C.,
 
         24       and then again in Irvine.  We had a meeting back
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              36
 
 
 
 
 
          1       in December to discuss this in Bethesda.  And
 
          2       what industry has said we don't provide is
 
          3       consistency, harmonization with CDRH, a
 
          4       transparent process they can understand,
 
          5       facilitated reviews, guidance, and
 
          6       communication.
 
          7            So we have set up four teams as part of the
 
          8       Action Plan:  CBER/CDRH Coordination, Review
 
          9       Performance, Compliance and Team Biologics, which
 
         10       I'm the chair of, and the Outreach/Inreach, which
 
         11       Mary Myers, who is the director of our Office of
 
         12       Communications Training Manufacturers Assistance,
 
         13       is in charge of.  And that is designed to both
 
         14       get our message and hear the messages of our
 
         15       stakeholders in the device area, as well as deal
 
         16       with our own employees who may not understand
 
         17       what's going on.  That's why we added the inreach
 
         18       to the always traditional outreach.
 
         19            Coordination has a bunch of action items.
 
         20       The Intercenter Agreements are now many, many
 
         21       years old.  Aside from my gray hair, my memories
 
         22       of the original Intercenter Agreements and
 
         23       implementing the '76 drug amendments reminds me
 
         24       just how old I am.  We realize that technologies
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              37
 
 
 
 
 
          1       and products have come down the pipeline that
 
          2       weren't even thought of or imagined at the time
 
          3       of those agreements, so we are working with CDRH
 
          4       and, as a matter of fact, CDER, but we're
 
          5       starting with the CBER/CDRH agreement.
 
          6            A Re-engineering Work Group that was so
 
          7       successfully set up by Bruce Burlington, we're
 
          8       working with them to get their lessons learned so
 
          9       that we don't reinvent the wheel.
 
         10            We've published the FR Notice of
 
         11       Concurrence.  I think it was last Friday.
 
         12            FDAMA training at CDRH, our people are
 
         13       attending the training that CDRH reviewers get,
 
         14       and in fact, on some products the CDRH reviewers
 
         15       are attending our training.
 
         16            Device Web page, if you look at our Web
 
         17       site, you now have the devices separately, so you
 
         18       don't have to go hunting through the material,
 
         19       again a direct outgrowth of last year's 406(B)
 
         20       meetings.  And we are preparing guidances on
 
         21       many, many issues relating to medical devices.
 
         22            The CBER/CDRH Coordination Outcomes,
 
         23       Commitment:  The commitment to review devices in
 
         24       a timely manner using the same standards as
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              38
 
 
 
 
 
          1       CDRH.  Coordination with them, cooperation,
 
          2       communication, and again consistency.  I believe
 
          3       those of you who were at the meeting last year
 
          4       can testify that that is exactly what we heard.
 
          5            Review Performance, our review performance
 
          6       in the device area is, quite frankly, very poor.
 
          7       We realize that, and it's a result of funding.
 
          8       The same people who do that have been involved in
 
          9       providing the scientific support of those
 
         10       injunctions on 60 percent of the nation's blood
 
         11       supply.  Compliance issues have to come first,
 
         12       and as you saw in that one slide, we keep
 
         13       reducing the amount available to other products.
 
         14       We have a proposed reorganization in our Office
 
         15       of Blood, and that will hopefully give more
 
         16       attention and control.
 
         17            Set Review Objectives, Implement Managed
 
         18       Review Process.  We developed a managed review
 
         19       process to implement FDAMA and PDUFA.  We are
 
         20       extending that to include the blood process.
 
         21       That is where we mapped out our business rules.
 
         22       They covered three walls.  We're now looking to
 
         23       where we can re-engineer that.  We have something
 
         24       called the 2-B process that we're working on, and
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              39
 
 
 
 
 
          1       that is almost finalized.  When it is, it will be
 
          2       up on our Web site.
 
          3            And Develop Targeted Guidance for specific
 
          4       products in specific areas.
 
          5            Review Performance, again closely managed
 
          6       process, define expectations and priorities, meet
 
          7       time frames and deadlines, and maintain the
 
          8       review quality.  Again, no one benefits from a
 
          9       poor product getting approved.
 
         10            Compliance and Team Biologics, as I said, I
 
         11       chair that group.
 
         12            Review the device inspection policies, make
 
         13       sure they are conforming with the CDRH policies,
 
         14       except where the nature of the risk from the
 
         15       product justifies an exception.  We will not be
 
         16       lowering standards, but we will identify the ones
 
         17       where we can and evaluate that, and where they
 
         18       are different, we're going to clearly explain
 
         19       them, both to our own people and to the industry,
 
         20       as well as why.
 
         21            Training and guidance, we will be training
 
         22       our own people, and we will be doing what we've
 
         23       done traditionally in CBER, and after developing
 
         24       the training program, hold a similar program
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              40
 
 
 
 
 
          1       available to industry so they can hear the same
 
          2       words the investigators hear.
 
          3            Develop sterility and stability, I guess the
 
          4       word got left off there, guidance for the
 
          5       inspectional program, and GMP guidance for CBER
 
          6       IVDs.  That is an issue that came up frequently
 
          7       last year, and we have a group that's composed of
 
          8       CDRH, CBER and ORA, our field people, that will
 
          9       be coming up with an explanation of what the
 
         10       standards are, and if they are different, why.
 
         11            ORA coordination, a transparent inspectional
 
         12       process, just one that when our investigator
 
         13       walks in, whether it's a district investigator or
 
         14       Team Biologics team, you'll know what they are
 
         15       going to be doing.
 
         16            And a consistent compliance approach.  Over
 
         17       the years, we have heard that different districts
 
         18       do things differently.  In fact, I've heard that
 
         19       for close to thirty years now.  The way we're
 
         20       handling that in the biologics area is part of
 
         21       Team Biologics.  We have two compliance officers,
 
         22       one on the East Coast, one on the West Coast, to
 
         23       coordinate our actions.  So we have reduced the
 
         24       number of people to oversee it, and so we get a
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              41
 
 
 
 
 
          1       consistent approach.
 
          2            Outreach/inreach, developing strategies I
 
          3       talked about to explain what we'll be doing
 
          4       there, or actually what we are doing doing here.
 
          5            The 21st Century Biologic Products, when I
 
          6       left the Center for Drugs and came over to
 
          7       Biologics about eleven years ago, I had a long
 
          8       conversation with my mother, who's my
 
          9       reality-based check, and she said, "What's the
 
         10       difference?"  And I tried to explain to her that
 
         11       blood and vaccines and other biotech things like
 
         12       gene therapy, cellular therapy, monoclonal
 
         13       antibodies, and she had no idea what I was
 
         14       talking about.  She has now learned by watching
 
         15       the evening news that every time she hears about
 
         16       one of these new products, she'll ask me, "Is
 
         17       that thing I saw yours?"  I say, "Yes, that's
 
         18       ours."
 
         19            It's clear that the future of biomedical
 
         20       science is in the biologics area.  So what are we
 
         21       going to have to deal with?  New biomedical
 
         22       technologies, the safety of those, ethical
 
         23       issues.  I remember a happy time in my youth at
 
         24       FDA when we used to say ethics weren't really our
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              42
 
 
 
 
 
          1       issue; that was the IRB's and the institutions
 
          2       themselves and the companies.  That's not true
 
          3       anymore.  We really do have to get involved,
 
          4       particularly things affecting the germ line,
 
          5       where the ethical issue is part of the
 
          6       benefit-to-risk equation.  And the harmonization
 
          7       of regulatory standards, both within FDA, but
 
          8       more importantly, around the world.
 
          9            Changing health care environment.  I
 
         10       remember telling people, and telling people on
 
         11       the Hill particularly:  "FDA doesn't get involved
 
         12       in economics.  We deal with safety and
 
         13       effectiveness."  In today's managed care
 
         14       environment, that is part of the risk/benefit
 
         15       equation.  A technology that is incremently
 
         16       better but costs a thousand times more, is it
 
         17       worth it?  And when you get into these
 
         18       discussions, for those of us who started out as
 
         19       FDA investigators, or as they were called when I
 
         20       was, inspectors, life was easy.  You dealt with
 
         21       rat pellets in flour.  You dealt with unsafe,
 
         22       adulterated, or sub- or superpotent drugs.  Now
 
         23       we're involved with incremental change:  Is a
 
         24       product that's a thousand times more expensive,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              43
 
 
 
 
 
          1       that gives a person a one in one thousand chance
 
          2       at a better outcome, worth it?  Well, if you're
 
          3       that one person, you think it is.  And it's a
 
          4       really strange discussion that gets involved with
 
          5       how you make those decisions on whether the
 
          6       approval is worth the increased risk or increased
 
          7       cost.  Again, we try and stay out of it.
 
          8            Bioterrorism, two years ago I knew nothing
 
          9       about bioterrorism.  Now I have a Top Secret
 
         10       clearance and I know more than I ever want to.
 
         11       That is an important part of today's life.  The
 
         12       Department of Health and Human Services has been
 
         13       given a large amount of money to purchase a
 
         14       civilian stockpile of drugs, biologics, and
 
         15       devices for use in terrorism.  We are involved in
 
         16       that and are advising the department,
 
         17       facilitating development in dealing with that,
 
         18       another thing that has been taking up enormous
 
         19       amount of resources, and I'll say this again for
 
         20       Bob's benefit, was not funded in this current
 
         21       year's budget.  Hopefully next year we will get
 
         22       some, but it is a very important thing for the
 
         23       civilian stockpile as well as advising DOD on
 
         24       their actions.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              44
 
 
 
 
 
          1            Y2K Issues.  You can't pick up the paper
 
          2       today without finding out that January 1, the
 
          3       whole world is going to collapse.  I was reading
 
          4       my local paper, and somebody in my neighborhood I
 
          5       know for twenty years has turned into a raging
 
          6       survivalist.  She has more generators, dried
 
          7       foods.  You know, it reminds me, those of us old
 
          8       enough, back in the '60s and the '50s with the
 
          9       fallout shelters.  Now, this is something I've
 
         10       known for twenty years and I think is fairly
 
         11       rational.  And the hype given to this has reduced
 
         12       the confidence of the public.  So we're very
 
         13       involved with working with our industry, working
 
         14       with the department.  We have a Y2K working
 
         15       group.  Those of you in industry will soon be
 
         16       getting a letter from us to submit what you have
 
         17       done with your Y2K preparedness.  We have been
 
         18       working on a shortage plan, which in addition to
 
         19       our normal shortage operations, makes sure that
 
         20       the products that we regulate will be there.
 
         21       Again, another big job that is unfunded, and this
 
         22       one's our bottom line.
 
         23            In closing, I don't want this to be the last
 
         24       time we communicate.  In my last job, I was
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              45
 
 
 
 
 
          1       pretty proud of the information systems that we
 
          2       set up.  I always used to keep this slide for
 
          3       last because most of the people at meetings were
 
          4       Internet-challenged.  But now just about everyone
 
          5       has access, and we have a fairly large Web site.
 
          6       That's the address.  And if you have a question
 
          7       in general, you can e-mail it to that e-mail box,
 
          8       and someone from our Office Communications
 
          9       Training Manufacturers Assistance will either
 
         10       answer it or get it to the person who can answer
 
         11       it.
 
         12            Questions for Stakeholders, this is the
 
         13       purpose of this meeting.  This was in the Federal
 
         14       Register Notice, and this is what we've asked the
 
         15       speakers to address.  And aside from being in the
 
         16       slides, they are on those question sheets as
 
         17       well:
 
         18            "What actions do you propose the Agency
 
         19       take to expand our capability to incorporate
 
         20       state-of-the-art science into its risk/benefit
 
         21       decision making?
 
         22            "What actions do you propose to facilitate
 
         23       the exchange and integration of scientific
 
         24       information to better enable FDA to meet its
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              46
 
 
 
 
 
          1       public health responsibilities throughout the
 
          2       product's life cycle?
 
          3            "What actions do you propose for educating
 
          4       the public about the concept of balancing risks
 
          5       against the benefits in public health decision
 
          6       making?
 
          7            "What actions do you propose to enable FDA
 
          8       and its product centers to focus resources on
 
          9       areas of greatest risk to the public health?"
 
         10            And, "What actions do you propose for
 
         11       enhancing communications processes that allow for
 
         12       ongoing feedback and/or evaluation of our
 
         13       modernization efforts?"
 
         14            And that's it for the slide talk.  I'd be
 
         15       happy to answer any questions or you can save
 
         16       them for after the speakers.  Anyone?  That being
 
         17       said, I thank everybody for their patience in
 
         18       listening to me.
 
         19            (Applause.)
 
         20            And I want to thank the folks back at the
 
         21       office that put that one together.  If any of you
 
         22       are interested in sharing these with
 
         23       colleagues -- I know some companies, I hear from
 
         24       people who have left the FDA, require you guys to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              47
 
 
 
 
 
          1       make out trip reports and things.  These slides
 
          2       have been posted on our Web site since
 
          3       yesterday.  So if you want them in color that you
 
          4       can attach to e-mails and stuff like that, you
 
          5       can just download it.  They are in Powerpoint,
 
          6       and you can get the entire set if you want to do
 
          7       briefings within your own company.
 
          8            The other thing is, as of yesterday, the
 
          9       Device Action Plan, which was signed by
 
         10       Dr. Henney last Friday, is posted there as well.
 
         11       It was only approved last Friday, and we didn't
 
         12       have enough time and we weren't real sure whether
 
         13       we would be able to get it out here.  And if you
 
         14       are in that sector and you want to see the exact
 
         15       plan that follows the tracks of what I had up
 
         16       there but with the specific goals and the due
 
         17       dates, that's there.
 
         18            Okay, our first panel, Janice Bourque,
 
         19       Executive Director Mass. Biotech Council; another
 
         20       friend from last year, Jim Weston from Biopure;
 
         21       and Lisa Raines from Genzyme, a very well-known
 
         22       company here in the Northeast.  And there's Steve
 
         23       and John.  And just go ahead.  Do you want to
 
         24       come up here?
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              48
 
 
 
 
 
          1            MS. BOURQUE:  We're going to use the
 
          2       overhead.
 
          3            Okay, well, thank you for allowing us to
 
          4       speak again today.  As was mentioned, we were in
 
          5       Washington, D.C. last year, so welcome to
 
          6       Boston.  We've also had a recent visit with
 
          7       Dr. Henney.  She came and visited the Mass.
 
          8       Biotech Council and the Device Council as well,
 
          9       so we were pleased to have the opportunity to
 
         10       talk with her about some of our concerns and what
 
         11       some of her concerns are as well.  And we have
 
         12       worked closely with the local FDA office, and
 
         13       I'll point out how well we have worked together
 
         14       on a pilot program that was very successful and
 
         15       has continued and ongoing.
 
         16            Today we have, as I mentioned, three
 
         17       speakers, myself, Jim Weston, and Lisa Raines.
 
         18       And I'm going to talk a little bit about meeting
 
         19       performance time lines, FDA reviewer training,
 
         20       and advisory panels.  Jim Weston is going to talk
 
         21       about risk/benefit and consumer education, and
 
         22       Lisa is going to speak about fast-track generic
 
         23       biologics and pediatric exclusivity extensions
 
         24       with regards to orphan biologics.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              49
 
 
 
 
 
          1            Just so you'll know a little bit about us at
 
          2       the Mass. Biotech Council, we represent about 250
 
          3       companies here in Massachusetts.  They are mainly
 
          4       small to medium size, and they range anywhere
 
          5       from early stage companies of anywhere from two
 
          6       to three people to full-scale commercial
 
          7       manufacturing companies with several thousands.
 
          8            The MBC has been in operation for about
 
          9       fifteen years, and our primary mission is to
 
         10       ensure that all biotech companies, whether they
 
         11       choose to remain small or become fully integrated
 
         12       companies, reach their full potential.
 
         13            Last year the MBC had put together an FDA
 
         14       White Paper in response to FDAMA and actually
 
         15       tried to come up with recommendations on how to
 
         16       actually carry out the implementation and write
 
         17       the regulation and have input into the guidance
 
         18       documents.  It's one thing for Congress to
 
         19       write.  It's another challenge, I think, for the
 
         20       FDA and for industry to work together to ensure
 
         21       that the regulations reflect that legislation and
 
         22       move forward.  So we're very supportive of this
 
         23       mission to ensure that there's prompt approval of
 
         24       new drugs and therapies.  And our primary goal
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              50
 
 
 
 
 
          1       for the FDA, we know, and for the industry is to
 
          2       ensure that these patients have access to these
 
          3       therapies and that we're able to get them to them
 
          4       as quickly as possible.
 
          5            One thing I'll mention today, we do have
 
          6       some copies of these slides.  We will be
 
          7       submitting an actual document to the FDA.  I
 
          8       think we have to about May 14, I think.  And it
 
          9       will be similar to our White Paper.  It will be a
 
         10       second White Paper with the actual text that will
 
         11       go into further detail from these slides, and
 
         12       that will be available.  It will be up on our Web
 
         13       site as well as directly supplied to the FDA and
 
         14       to anyone who would like a copy of that.
 
         15            For the first section on meeting the
 
         16       performance goals, I'd like to speak briefly
 
         17       about our last meeting.  We had come up with
 
         18       recommendations in our White Paper regarding
 
         19       meeting performance goals, and since then a
 
         20       guidance document has been released.  And in this
 
         21       guidance document we noted that we had made some
 
         22       recommendations on dispute resolution, and we had
 
         23       asked that the sponsor be able to provide
 
         24       corrections to the FDA fifteen days from receipt
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              51
 
 
 
 
 
          1       of minutes from the FDA, and that in return the
 
          2       FDA provides response back to the sponsor fifteen
 
          3       days from receipt of the correction from the
 
          4       sponsor.  We think it's very important that we
 
          5       have firm time lines within the guidance
 
          6       documents, and we believe those were not put in
 
          7       there.  And that way the expectations are very
 
          8       clear from both sides just who has been operating
 
          9       within the response time that's necessary.  I
 
         10       think to leave it open, again, leads us to a
 
         11       position where we are now where it's up for
 
         12       discussion, debate, and not necessarily being
 
         13       able to have a sense that we are moving the time
 
         14       line.
 
         15            Secondly, with regards to meeting the
 
         16       performance goals, with regards to fast-track
 
         17       meetings and sponsor-requested fast-track
 
         18       meetings, we wanted those meetings to be
 
         19       scheduled within fourteen days of the request by
 
         20       the sponsor.  And then we also requested that the
 
         21       meeting actually occur within thirty days of
 
         22       receipt of the sponsor's request, and that again
 
         23       was not noted or given firm time lines in the
 
         24       guidance document, and we're hoping that there's
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              52
 
 
 
 
 
          1       still an opportunity to put those expectations in
 
          2       that guidance document.
 
          3            With regards to FDA reviewer training, when
 
          4       Dr. Henney was here, she indicated there were
 
          5       three areas of great concern with her.  One was
 
          6       actually carrying out FDAMA implementation.  The
 
          7       second was on building the science base at the
 
          8       FDA, and the third was addressing real safety
 
          9       issues, and those were three of her primary
 
         10       focuses that she addressed to us.
 
         11            So with regards to building on the science
 
         12       base, which I know some of the questions have
 
         13       been asked, the MBC, as I mentioned earlier, has
 
         14       a model program experience in the success area of
 
         15       manufacturing.  With John's local office, we've
 
         16       been able to develop a preinspection pilot
 
         17       program, and that we actually won in conjunction
 
         18       with the local FDA office Al Gore's Hammer Award
 
         19       for a model program on helping to reinvent
 
         20       government and streamline it.  So we have that
 
         21       expertise.  So what we'd like to recommend is
 
         22       that we could develop a model program for FDA
 
         23       training.
 
         24            Now, we know the reviewers already receive a
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              53
 
 
 
 
 
          1       great degree of training, but we think that
 
          2       together with industry, we might be able to help
 
          3       develop that science base further.  And so what
 
          4       we thought we could do is maybe create a
 
          5       seminar-type format in which cutting edge
 
          6       technology would be presented.  And that could be
 
          7       presented by academia, by industry, leaders in
 
          8       this field of research that's going on who could
 
          9       present this type of cutting edge technology to
 
         10       allow the reviewers to come, ask questions,
 
         11       present the work they are doing.
 
         12            It really creates a certain synergy.  It's
 
         13       not for any one company or researcher to hope to
 
         14       gain an "in" with the FDA.  This is really to
 
         15       talk about the science so the reviewers are right
 
         16       there.  It's a challenge for us as an industry to
 
         17       stay up to date on all of the technology that's
 
         18       being developed, so we can only envision it's a
 
         19       real challenge for the reviewer as well.
 
         20            I have a possible suggestion or solution.
 
         21       We could do it in a neutral location.  We'd love
 
         22       to do it here in Massachusetts.  There is a
 
         23       facility, the Mass. Biologics facility, which now
 
         24       comes under the purview of the University of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              54
 
 
 
 
 
          1       Massachusetts.  There may be another facility as
 
          2       well that I'm not aware of.  But the reason why I
 
          3       suggested this facility is because they already
 
          4       have conducted FDA training there, and it is a
 
          5       CDC alternative site, so we know they probably
 
          6       have the necessary equipment and the presentation
 
          7       rooms in order to do this.
 
          8            And, similarly, seminars could be developed
 
          9       so that it's reciprocal between the FDA and
 
         10       industry.  So if there are ways the industry has
 
         11       shortcomings in terms of its ability to interact
 
         12       or report or have discussions with the FDA, there
 
         13       are things that we continually do, ways that are
 
         14       ineffective, we certainly would welcome the FDA
 
         15       to also give seminars to us in how we can do that
 
         16       better.  So we really see this as an interactive
 
         17       opportunity to develop a model program.  And
 
         18       there may be some things similar.  We certainly
 
         19       don't want to say this is just something
 
         20       associated with Biologics, but maybe this could
 
         21       be expanded to include products.  I mean,
 
         22       whatever opportunities we see there.
 
         23            The last point I'll make has to do with the
 
         24       advisory panels.  In our earlier White Paper, we
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              55
 
 
 
 
 
          1       did ask for harmonization between the two
 
          2       divisions.  Currently CBER has what we believe is
 
          3       a great operating policy, where they actually
 
          4       submit to the sponsor their draft panel
 
          5       documents; and that allows a sponsor then to
 
          6       review and give comments back to the FDA before
 
          7       it goes back to the advisory panel.  That's very
 
          8       important because let's say there was some point
 
          9       that was made incorrectly or confusion over a
 
         10       particular point.  The sponsor has a chance to
 
         11       correct it before it's actually spent a great
 
         12       deal of time at the advisory panel going over
 
         13       something that simply could have been clarified
 
         14       ahead of time, so that when you're at the
 
         15       advisory panel meeting, you're really focusing on
 
         16       what is really crucial and important.
 
         17            Right now CDER does not do that, rarely does
 
         18       that, and we would just really like to see CBER's
 
         19       policy harmonized and carried over into CDER.  We
 
         20       think there's a real opportunity to use the
 
         21       advisory panel in the capacity that they were
 
         22       originally intended.
 
         23            And with that in mind, also I want to talk
 
         24       briefly a little bit about the role at the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              56
 
 
 
 
 
          1       Advisory Panel.  What we see the role of the
 
          2       Advisory Panel -- and I was looking at some of
 
          3       the documentation as to the description of the
 
          4       role of the Advisory Panel. It was really for a
 
          5       third-party evaluation mechanism for advice,
 
          6       particularly regarding scientific controversies
 
          7       or some cutting-edge technology that's really
 
          8       challenging.  It is important that the FDA note
 
          9       the impact these Advisory Panel meetings has on
 
         10       the industry.  They are open public meetings.
 
         11       They are often filled with a variety of
 
         12       individuals, including investors, and they
 
         13       greatly impact our ability to raise research
 
         14       dollars.  And even if you get an approval from
 
         15       the Advisory Panel, we see fluctuations in stock,
 
         16       that even with a positive result, we'll see 20 or
 
         17       30 percent fluctuation on the stock.  So it's
 
         18       important to note that these panels, what they
 
         19       say and do has great impact.
 
         20            But we're very concerned about how the
 
         21       panels are now being used.  We think that perhaps
 
         22       they are used too frequently and they are used
 
         23       just to endorse what the FDA already used, not as
 
         24       third-party evaluators.  And so what we'd like to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              57
 
 
 
 
 
          1       recommend is that if the company has proven
 
          2       safety and efficacy to the extent that the FDA
 
          3       feels is necessary, to maybe not go into an
 
          4       Advisory Panel review process, but go through
 
          5       just a rapid-approval process, and really use the
 
          6       Advisory Panel for controversial issues.
 
          7            Additionally we also, because these are open
 
          8       public forums, we're asking that the FDA consider
 
          9       that these be closed forums, so that the
 
         10       discussion really does not affect the outside
 
         11       investors, the stock market or what not; that
 
         12       really instead of having individuals in the room
 
         13       who really don't necessarily need to be there, if
 
         14       it's going to be a scientific discussion, to
 
         15       really consider having closed Advisory Panel
 
         16       meetings.  Certainly the FDA could have anyone
 
         17       there that they feel is important to be there,
 
         18       but limit who exactly ought to be in that room.
 
         19            Essentially also we'd like to maybe have
 
         20       some conformity or best practices evaluated by
 
         21       the advisory panels.  I think companies have
 
         22       various experiences on what worked well, how some
 
         23       advisory panels really operated, they felt, to
 
         24       both the benefit for the FDA and for the company,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              58
 
 
 
 
 
          1       as well as a third party and others that probably
 
          2       did not operate as well, and that there might be
 
          3       opportunities to develop conformity or best
 
          4       practices to address the Advisory Panel.
 
          5            I'm going to have Jim Weston now come up and
 
          6       talk about consumer education and risk/benefit,
 
          7       and then we'll have Lisa.  Then we'll take
 
          8       questions.
 
          9            MR. WESTON:  Thanks, Janice.  As Mark
 
         10       Elengold mentioned, most products in the American
 
         11       marketplace really, especially medical ones, have
 
         12       two facets.  On one side, we know that they
 
         13       really benefit users and often improve lives.  We
 
         14       also know that they are, however, rarely without
 
         15       at least some risk, and that risk can result in
 
         16       known or unknown side effects.  Consumers must
 
         17       often weigh the benefits and risks before using
 
         18       these products, oftentimes with incomplete
 
         19       information.
 
         20            In order to address this issue, the FDA
 
         21       asked us for responses to the question:  What
 
         22       actions do you propose for educating the public
 
         23       about the concept of balancing risks against
 
         24       benefits in the public health decision making?
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              59
 
 
 
 
 
          1            We know that FDA's mission is to promote the
 
          2       public health by promptly and efficiently
 
          3       reviewing clinical research and taking
 
          4       appropriate action on the marketing of regulated
 
          5       products in a timely manner.  Under FDA's Plan
 
          6       for Statutory Compliance of last November, which
 
          7       addressed the requirements set in Section 406 of
 
          8       the FDAMA Act, several objectives were stated.
 
          9            They included:  Maximizing the availability
 
         10       and clarity of information for consumers and
 
         11       patients regarding new products, implementing
 
         12       inspections and postmarket monitoring, and
 
         13       ensuring FDA's access to scientific and technical
 
         14       expertise.
 
         15            Let's talk a little bit about some of
 
         16       these.  The ability to improve public education
 
         17       and understanding about the concepts of balancing
 
         18       risks against benefits in the public health
 
         19       decision-making process could be enhanced with
 
         20       several new and expanded concepts developed and
 
         21       implemented by FDA, sponsors, patient groups, and
 
         22       other governmental agencies.  First, the concepts
 
         23       of risk/benefit analyses should be expanded in
 
         24       discussions and agreements between the FDA and
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              60
 
 
 
 
 
          1       sponsors throughout the entire development
 
          2       process.  FDAMA provided a guideline for the
 
          3       management of meetings between sponsors and the
 
          4       FDA and the MBC, the Mass. Biotech Council, in
 
          5       its July 18 White Paper provided points to
 
          6       consider relative to the meeting section of that
 
          7       document.  In accordance with some of those
 
          8       proposals which we made and agreed upon, there
 
          9       should be during each critical meeting decisions
 
         10       and agreements made relative to risks as well as
 
         11       benefits.  FDA should discuss the criteria
 
         12       development agreements that will form the basis
 
         13       of an acceptable risk as part of the overall
 
         14       approval and development process.
 
         15            Furthermore, if a product is to be discussed
 
         16       at an Advisory Committee meeting as part of its
 
         17       approval process, a summary of both the FDA and
 
         18       sponsor agreements and opinions regarding the
 
         19       risks/benefits of the drug which have occurred in
 
         20       developing the development process should be
 
         21       presented as well for a balanced review.
 
         22            Secondly, the agency's criteria for
 
         23       presenting well-balanced information to the
 
         24       consumer needs to incorporate all aspects of the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              61
 
 
 
 
 
          1       health care system.  Risk/benefit information is
 
          2       provided in the package inserts which accompany
 
          3       distribution of most prescription products.  It's
 
          4       also associated with ads for prescription
 
          5       products, and a patient package insert is often
 
          6       provided when a prescription product is
 
          7       dispensed.  But because of the complex nature of
 
          8       this information and often the general lack of
 
          9       public knowledge regarding the development
 
         10       process, this information is often not read, is
 
         11       either overlooked or can be misinterpreted if at
 
         12       all read.
 
         13            While other forms of communications are
 
         14       becoming available -- for example, on Web sites --
 
         15       the same information is often provided in just a
 
         16       different manner.  In order to address this
 
         17       concern, we would propose that FDA explore pilot
 
         18       programs with effective education regarding
 
         19       risks/benefits of prescription products, with the
 
         20       primary public contact persons giving out
 
         21       prescription medicines; that is, the prescribing
 
         22       physicians or dispensing pharmacists.  These are
 
         23       the individuals with the background and training
 
         24       to understand the risks/benefits and who can
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              62
 
 
 
 
 
          1       directly assure that patients best understand the
 
          2       risks and benefits of the products.  This type of
 
          3       program would be extremely beneficial,
 
          4       particularly for fast-track products where there
 
          5       are often high risks involved.
 
          6            The FDA does have a Pharmacist Education
 
          7       Outreach Program, and we encourage its
 
          8       expansion.  In today's managed health care
 
          9       system, it's likely that insufficient time is
 
         10       allotted or allowed for this purpose.  Thus a
 
         11       cooperative agreement must be reached between all
 
         12       parties in health care systems, the sponsors, the
 
         13       FDA, the physicians, the pharmacists, and often
 
         14       health care peers, to be able to provide this
 
         15       information in time to give benefit to patients.
 
         16            Collaboration with all stakeholders -- i.e.,
 
         17       the media, the consumers, the patient groups, and
 
         18       other federal agencies -- is encouraged.
 
         19            Third, the timely dissemination of current
 
         20       and cutting-edge "scientifically sound"
 
         21       information regarding potentially new uses and
 
         22       findings of drugs and biologics should be
 
         23       expanded.  This includes the dissemination of
 
         24       information on unapproved new uses and timely
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              63
 
 
 
 
 
          1       information regarding postmarketing surveillance
 
          2       of new and existing products.
 
          3            FDA and sponsors need to work cooperatively
 
          4       to develop the full potential of the Internet as
 
          5       a two-way communication tool as part of this
 
          6       process.  Information regarding new approved and
 
          7       "scientifically sound" information on unapproved
 
          8       uses should be readily available to consumers and
 
          9       health care professionals in an effective
 
         10       manner.  In a similar manner, safety profiles and
 
         11       updated safety information regarding products
 
         12       should also be available freely on the Internet.
 
         13       Information from FDA's Adverse Events Reporting
 
         14       System should also be promptly posted.
 
         15            And, lastly, the FDA in order to communicate
 
         16       effectively with consumers and patients, needs to
 
         17       enhance and expand the agency's collaborations
 
         18       with industry, other governmental agencies,
 
         19       academia, and patient groups.  In this manner,
 
         20       information exchange, scientific expertise, and
 
         21       important interchanges regarding key information,
 
         22       including risk/benefit analyses, can occur.  We
 
         23       strongly encourage FDA to expand its interactions
 
         24       with the NIH, the National Institutes of Health,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              64
 
 
 
 
 
          1       regarding the science-based expertise and patient
 
          2       education process.
 
          3            And Lisa Raines?
 
          4            MS. RAINES:  I didn't make advance
 
          5       arrangements for somebody to do my overheads, so
 
          6       Janice is being very kind to help me out here.
 
          7            In the remaining time, I'm going to address
 
          8       three issues, each of which is fairly complex,
 
          9       and so each of which is going to be addressed in
 
         10       a fairly shorthand manner.  And if there is a
 
         11       minute or two remaining, I may take the
 
         12       opportunity to offer some personal comments on
 
         13       some of the issues that Dr. Elengold raised that
 
         14       we've had some discussions on in the industry.
 
         15            The first issue I'd like to talk about is
 
         16       the new Fast Track Program which we're very
 
         17       excited about, and in fact had the opportunity to
 
         18       discuss with Dr. Henney when she visited Genzyme
 
         19       for close to an hour just a few weeks ago.  And
 
         20       let me begin by saying that the concept of fast
 
         21       track, which was developed in collaboration
 
         22       between FDA, the Congress, and the industry, was
 
         23       to look at best practices that FDA had already
 
         24       adopted through the Accelerated Approval Program,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              65
 
 
 
 
 
          1       or through what we sometimes call "skunk works,"
 
          2       where individual reviewers had taken
 
          3       extraordinary initiative to move products through
 
          4       the pipeline in a rapid and effective way, and to
 
          5       see if we could come up with some way of
 
          6       institutionalizing and broadening the scope of
 
          7       what we viewed as best practices that FDA had
 
          8       already implemented.
 
          9            I think to a significant extent we all
 
         10       recognize that fast track initially builds on the
 
         11       existing accelerated approval regulations.  FDA
 
         12       put out the guidance document required by the
 
         13       statute a few months ago, and by and large, I
 
         14       think it's been very well received by the
 
         15       industry.  It recognizes that fast-track products
 
         16       may either be accelerated approval products based
 
         17       on an approval on either a surrogate end point or
 
         18       a short-term clinical end point, or it may be a
 
         19       regular approval, and you've got the advantage of
 
         20       rule and review in either case.  But I'm going to
 
         21       focus on the accelerated approval side because I
 
         22       think that the regular approval side is the area
 
         23       with which there's broadest experience and
 
         24       broadest knowledge, both on the part of the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              66
 
 
 
 
 
          1       industry and the agency, and at the accelerated
 
          2       approval side where there's still a lot of
 
          3       clarity that we think could be injected in the
 
          4       system.
 
          5            As most of you probably know, in 1992,
 
          6       largely in response to the AIDS crisis, FDA
 
          7       adopted an accelerated approval regulation that
 
          8       recognized that the risk/benefit analysis with
 
          9       respect to a serious or life-threatening disease,
 
         10       for which there was an unmet medical need,
 
         11       required a greater degree of flexibility than
 
         12       another headache remedy.  And so FDA developed a
 
         13       regulation under which they indicated that an
 
         14       accelerated approval could be provided in the
 
         15       absence of proof of effect on morbidity,
 
         16       irreversible morbidity or mortality, if an effect
 
         17       could be shown on a surrogate end point or a
 
         18       short-term clinical end point that was reasonably
 
         19       likely to predict clinical benefit.
 
         20            This provision raises a couple of
 
         21       questions.  Scientists sort of take as a given
 
         22       that a P value of less than .05 proves the
 
         23       validity of an end point in affecting morbidity
 
         24       or mortality; but when you talk about something
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              67
 
 
 
 
 
          1       being reasonably likely, that's clearly less than
 
          2       proving validity.  And so the question is:  How
 
          3       much data do you need to prove that a particular
 
          4       chosen end point is reasonably likely to predict
 
          5       a clinical outcome?  And we're not sure that
 
          6       there is consistency or clarity on this point.
 
          7            If you look at the examples in the past,
 
          8       AIDS, I think, being a brilliant example, the one
 
          9       with which there's most experience and the most
 
         10       products and where the surrogate end point --
 
         11       namely, CD4 cell counts -- has now been validated
 
         12       through showing increased life spans for people
 
         13       who take the products approved under this regime,
 
         14       there was evidence showing that a reduction in
 
         15       the immune system eventually led to people
 
         16       getting sicker and eventually dying.  And so it
 
         17       was hypothesized that if you could increase that
 
         18       cell count and improve the immune system, that
 
         19       you could make people live longer.  But that
 
         20       wasn't proven until long after people had
 
         21       actually gotten these drugs after they were
 
         22       approved, and really over the last year, where
 
         23       major scientific conferences have come to a
 
         24       consensus that the selected end points were
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              68
 
 
 
 
 
          1       validated.  But there was a good scientific basis
 
          2       for expecting that the correlation was so close
 
          3       between morbidity and a decline in the immune
 
          4       system, that an improvement in the immune system
 
          5       would in fact improve life span, and that's now
 
          6       proven to be the case.
 
          7            But as we looked at other non-AIDS products
 
          8       and we look at noncancer products -- and AIDS and
 
          9       cancer are the two principal areas where
 
         10       accelerated approval has been used -- we found
 
         11       great more debate as to how much data you need to
 
         12       show that a particular chosen end point is
 
         13       reasonably likely to predict clinical benefit.
 
         14            Now, remember, in the case of all of these
 
         15       accelerated approval products, there is a phase
 
         16       for postapproval study requirement, which
 
         17       essentially requires that the end point chosen be
 
         18       validated and that ultimate clinical benefit be
 
         19       proven.  So the concept is that ultimately, yes,
 
         20       we do need to prove clinical outcome as approved
 
         21       by the product, but we can approve the product
 
         22       short of that and collect the full validating
 
         23       data on a postapproval basis.  But how much short
 
         24       of that provides adequate confidence for FDA to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              69
 
 
 
 
 
          1       believe there's substantial evidence of safety
 
          2       and efficacy?
 
          3            These are some questions that we would like
 
          4       to ask and we don't have an answer for.  We
 
          5       believe that the industry and the agencies should
 
          6       be collaborating on a discussion of these
 
          7       questions, a discussion that I think has taken
 
          8       place on a very ad hoc basis product by product,
 
          9       but where there aren't general principles.
 
         10            What the AIDS drug manufacturers were able
 
         11       to do, for example, was show an increase in CD4
 
         12       cell counts but not an improvement in mortality.
 
         13       There are now some reviewers in CBER who believe
 
         14       that you must not only show an improvement in the
 
         15       chosen surrogate, but show the improvement all
 
         16       the way up to a normal stage, which was not
 
         17       required in the AIDS cases.
 
         18            Remember also that these are for serious or
 
         19       life-threatening diseases where the drug has the
 
         20       potential to meet an unmet medical need.  So
 
         21       we're not talking about having this greater
 
         22       flexibility except in those cases where there's a
 
         23       compelling case that it's needed.
 
         24            The second question, which is a really
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              70
 
 
 
 
 
          1       difficult one to grapple with, addresses:  What
 
          2       do you do in the case of very, very rare
 
          3       diseases?  My company, Genzyme, sells a product
 
          4       for one of the rarest diseases for which there is
 
          5       an FDA-approved product, serozyme.  There are
 
          6       about a thousand U.S. patients.  Serozyme is the
 
          7       most common of about 40 genetic disorders of the
 
          8       same type.  There is very little data out there
 
          9       regarding the history and pathology of these
 
         10       other disorders.  How is it possible then to
 
         11       develop reasonably reliable surrogate or
 
         12       short-term clinical end points when there's very
 
         13       little historical control data available, and
 
         14       where the patient population is so small that
 
         15       it's almost impossible to get statistically valid
 
         16       results even with a surrogate end point that
 
         17       everybody agrees is appropriate?  You could do a
 
         18       clinical trial that requires every patient in the
 
         19       United States to enroll in the trial for some of
 
         20       these very rare diseases.  How do you get there
 
         21       from here in a way that makes it possible for
 
         22       these products to be developed?
 
         23            I want to just remark that FDA's fast track
 
         24       guidance document does discuss in a footnote the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              71
 
 
 
 
 
          1       use of short-term clinical end points to serve as
 
          2       the basis of an accelerated approval.  There are
 
          3       reviewers in CBER who have said short-term
 
          4       clinical end points can serve as the basis of an
 
          5       accelerated approval.
 
          6            So is this an education issue, or are we
 
          7       misunderstanding the type of short-term end
 
          8       points?  There were some examples given that
 
          9       might serve as the basis of approval.  And to
 
         10       what extent can we look at the previous and, I
 
         11       think, excellent FDA document that deals with the
 
         12       design of clinical trials to look for cross-
 
         13       confirmation of a surrogate end point and a
 
         14       short-term clinical end point that overall
 
         15       increases your confidence level but doesn't quite
 
         16       get you to the level of statistical significance,
 
         17       where there is a very small patient population in
 
         18       particular?  And these are really the two points
 
         19       that I just mentioned, and they are in your
 
         20       handout.
 
         21            I'm going to move now to the issue of
 
         22       generic biologics, and let me begin by saying
 
         23       that we were very pleased with Dr. Henney's
 
         24       response to the Senate indicating that she had no
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              72
 
 
 
 
 
          1       plans to create a generic biologic approval
 
          2       system.  And we were further encouraged when she
 
          3       was up here a few weeks ago and meeting with the
 
          4       MBC where she elaborated on that response and
 
          5       indicated that she believed that Congressional
 
          6       intent would need to be demonstrated before FDA
 
          7       would do that.  And I think that's a wise
 
          8       approach to take.
 
          9            I think aside from the fact that the 1994
 
         10       amendments to the Food, Drug and Cosmetic Act
 
         11       don't address biologics and there's no legal
 
         12       basis for biologics to go through a generic
 
         13       approval process, there are some sound scientific
 
         14       reasons to look at these large complex
 
         15       macromolecules in a different way than the
 
         16       simpler molecules that tend to be the basis of
 
         17       most drug approvals.
 
         18            However, we do have a concern with the fact
 
         19       that some products that most of us non-FDA staff
 
         20       think of as biologics, recombinant proteins,
 
         21       lipoproteins, are sometimes regulated as drugs.
 
         22       Some of these are products that predated the
 
         23       Intercenter Agreement in which CBER and CDER
 
         24       divvied up jurisdiction over these type of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              73
 
 
 
 
 
          1       products.  Some of them have been assigned to one
 
          2       center or the other since then, and we're aware
 
          3       of disputes within the agency over which center
 
          4       would get to regulate a particular recombinant
 
          5       protein.
 
          6            Those kinds of discussions, in our opinion,
 
          7       for scientific public health reasons as well as
 
          8       consistency and fairness reasons, should not
 
          9       create a result in which one product might go
 
         10       generic at some future point and the other
 
         11       wouldn't, merely based on the convenience of the
 
         12       agency.
 
         13            The Intercenter Agreement, which was
 
         14       developed when there was a dispute over a
 
         15       particular product between the two agencies, is
 
         16       based on a very elegant concept, and this is a
 
         17       quote directly from the Intercenter Agreement.
 
         18       I'm sure the CBER people are very familiar with
 
         19       it, and on its face it seems that this concept is
 
         20       very simple:  You basically put the product in
 
         21       whichever center it's appropriate to put it in
 
         22       based on its physical characteristics, source
 
         23       materials, or pharmacologic properties.
 
         24            What we've seen, however, is that when you
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              74
 
 
 
 
 
          1       actually try to apply these principles in
 
          2       combination with the historic jurisdictional
 
          3       interests of both centers, that you get some
 
          4       inconsistent results.  And these are just a few
 
          5       examples that are real-life examples or that are
 
          6       specifically stated in the Intercenter
 
          7       Agreement.
 
          8            For certain kinds of products, how you
 
          9       manufacture a product determines whether it is
 
         10       regulated as a drug or as a biologic.
 
         11       Polynucleotide products, for example, if they are
 
         12       made using recombinant DNA, are regulated as
 
         13       biologics.  The exact same molecule, if it was
 
         14       extracted from tissue or chemically synthesized,
 
         15       would be regulated as a drug.  And yet it may be
 
         16       for the exact same disease.  It may have the same
 
         17       molecular weight.  It may have the same
 
         18       composition.  And the mere manufacturing method
 
         19       determines, is it a drug or is it a biologic?
 
         20            On the other hand, there are other products
 
         21       for which the Intercenter Agreement says
 
         22       manufacturing method is irrelevant.  If your
 
         23       product is a hormone, it gets regulated as a
 
         24       drug, and it doesn't matter if it's a recombinant
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              75
 
 
 
 
 
          1       product or a chemically synthesized product.
 
          2       Similarly, vaccines and allergenic products are
 
          3       regulated as biologics with regard to how they
 
          4       are made.
 
          5            So does manufacturing matter?  The answer
 
          6       is:  It depends on the kind of product.  And I
 
          7       didn't see any clear scientific rationale for
 
          8       differentiating between these two classes of
 
          9       products and the general rule, except that
 
         10       historically CDER has always done hormones and
 
         11       antibiotics, and historically CBER has had
 
         12       authority over blood, and statutory authority at
 
         13       that.  And so we had to carve out exceptions to
 
         14       our general principles to conform with historical
 
         15       jurisdiction, expertise, and other
 
         16       considerations.
 
         17            Again, the source materials matter.  If you
 
         18       take a product from blood, it's regulated by
 
         19       CDER.  If you take it from tissue, which contains
 
         20       a lot of blood and which presumably has pretty
 
         21       much the same product, it's regulated as a drug.
 
         22            Furthermore, if a first-generation product
 
         23       is derived from tissue and regulated as a drug,
 
         24       then the second-generation recombinant product
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              76
 
 
 
 
 
          1       will also get regulated as a drug, even though if
 
          2       that second-generation product was developed
 
          3       first, it would be regulated as a biologic.
 
          4            So as these examples show, and there are
 
          5       many others that will be in the more extensive
 
          6       paper that we've prepared for you and that's just
 
          7       going through all our MBC review process, these
 
          8       general principles don't always have general
 
          9       applicability.  It's not always possible to
 
         10       predict whether a product will be regulated as a
 
         11       drug or as a biologic.  Even where it can be
 
         12       predicted, there can be unfairness.
 
         13            I remember two companies, neither of which
 
         14       was mine, developing products for ALS.  Both were
 
         15       common proteins.  One was regulated as a drug;
 
         16       one was as a biologic.  It turned out both
 
         17       products failed in the clinic.  But to put
 
         18       competitors in different centers with different
 
         19       review groups, with different standards, and with
 
         20       different implications for whether there was
 
         21       going to be a generic version of their product
 
         22       that would be substitutable at the drugstore in
 
         23       the future, creates a competitive issue that
 
         24       competitors are, I think, legitimately concerned
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              77
 
 
 
 
 
          1       about.
 
          2            Here are a couple of further exceptions to
 
          3       the rule.  Erythropoietin is a hormone produced
 
          4       in the kidney.  It's regulated as a biologic.  It
 
          5       did predate the Intercenter Agreement, but Amgen
 
          6       has told me that they went to see Harry Meyer,
 
          7       and Harry said, "Do you want it regulated as a
 
          8       drug or do you want it regulated as a biologic?"
 
          9       And Amgen says, "Well, we like the people in
 
         10       biologics.  They know the science.  We'd like it
 
         11       regulated as a biologic."  And Harry turned to
 
         12       Elaine Esper and said, "Okay, keep those
 
         13       biologic."
 
         14            That is not the way policies should be made,
 
         15       and it has implications that even Amgen didn't
 
         16       anticipate at the time.  Similarly, the fact that
 
         17       Genzyme decided to develop a non-recombinant GCR
 
         18       product means that our recombinant product was
 
         19       regulated as a drug.  Had we gone directly to
 
         20       recombinant, it would have been regulated as a
 
         21       biologic.  That has profound implications for
 
         22       whether companies choose to develop first-
 
         23       generation products and whether the patients have
 
         24       access to those products earlier.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              78
 
 
 
 
 
          1            And, finally, the Intercenter Agreement
 
          2       recognizes, and we agree, that if there's one
 
          3       division in the agency that knows a lot about a
 
          4       particular disease, it probably makes sense for
 
          5       that division to do the review.  But each center
 
          6       has the authority to issue a license of either
 
          7       kind, an NDA or BLA.  I'm not aware of either
 
          8       center having ever issued the type of license
 
          9       that is typically provided by the other center,
 
         10       and that may be something that's worth exploring
 
         11       further.  I'm going to go into that.  That will
 
         12       be a one-minute thing.
 
         13            Given the fact that there's some randomness
 
         14       on whether a biotech product is regulated as a
 
         15       drug or a biologic, we believe that there should
 
         16       be consistency with respect to whether such
 
         17       products are subject to any kind of abbreviated
 
         18       or truncated approval system.  I won't go into
 
         19       further detail on this, but you will see the
 
         20       detail in our paper.  There are good public
 
         21       health reasons to say that minor differences in a
 
         22       molecule should be demonstrated to be clinically
 
         23       irrelevant before assumed to be clinically
 
         24       irrelevant for that purpose.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              79
 
 
 
 
 
          1            If you move on to pediatrics, the pediatric
 
          2       provision of FDAMA provides for a six-month
 
          3       extension of market exclusivity if you do an
 
          4       FDA-requested study and get the results before
 
          5       your exclusivity expires.  This extension only
 
          6       applies to drugs.
 
          7            Now, the only kind of exclusivity that
 
          8       biologics get is orphan drug exclusivity, and we
 
          9       have proposed and we would encourage FDA to
 
         10       support legislation that amends FDAMA so that
 
         11       orphan products, regardless of whether they are
 
         12       drugs or biologics, are equally eligible under
 
         13       the same circumstances for six-month exclusivity
 
         14       extensions.
 
         15            Thank you.
 
         16            (Applause.)
 
         17            MR. ELENGOLD:  Just for the record, in case
 
         18       you didn't notice, we're skipping the break.
 
         19            Let's do questions.
 
         20            MS. FAIRFIELD:  Oh, you want to do
 
         21       questions?  Okay.  After questions and answers,
 
         22       we're really running late, so what we'll do is
 
         23       break for lunch.  And then the last two speakers,
 
         24       Ms. Lopez and Ms. Jones, we'll have present after
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              80
 
 
 
 
 
          1       the satellite downlink.
 
          2            MR. ELENGOLD:  I really am sorry I had to
 
          3       cut you, Lisa, but just for the record, CBER has
 
          4       many -- not many -- yes, many approved new drug
 
          5       applications.  A product that has been in the
 
          6       news quite recently, avicerokylese (sic), is
 
          7       regulated as a new drug application, not a
 
          8       license.  A lot of the plasma expanders are
 
          9       regulated as NDAs.  So we use all of the
 
         10       available tools under the FDAC Act.  We have
 
         11       drugs, we have biologics, we have PMAs, and a
 
         12       510(K)s.  So CBER has used every bit of the
 
         13       flexibility given us by the Act to affect the
 
         14       right products.
 
         15            MS. RAINES:  Has CDER?  I guess I should
 
         16       have been more specific.
 
         17            MR. ELENGOLD:  Let me put it this way.  I
 
         18       worked there twelve years, and I don't remember
 
         19       anything other than new drug applications, the
 
         20       abbreviated new drug applications, Form 5s and
 
         21       Form 6s, which don't exist anymore.
 
         22            MS. RAINES:  I should have been more
 
         23       specific.
 
         24            MR. ELENGOLD:  Okay, I just have a couple of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              81
 
 
 
 
 
          1       questions.  John, do you have any questions?
 
          2            MR. MARZILLI:  I'm all set.
 
          3            MR. ELENGOLD:  Okay, I just have a couple of
 
          4       questions for Janice.  One of the things you had
 
          5       on your list was to use closed advisory
 
          6       committees.  How do you think that impacts on the
 
          7       requirements we're under under the Federal
 
          8       Advisory Committee Act?
 
          9            MS. BOURQUE:  In terms of making it an open
 
         10       public forum?
 
         11            MR. ELENGOLD:  Yes.
 
         12            MS. BOURQUE:  I know that when I reviewed
 
         13       the description of how that was going to be
 
         14       conducted, I think we'll have to think about how
 
         15       we can do this.  It's really challenging, I
 
         16       think, for our industry, where it's open to large
 
         17       groups of individuals that we think don't lend
 
         18       any kind of benefit to the meeting itself, but I
 
         19       know it's challenging.  You want to have an open
 
         20       forum with people; there's nothing hidden.  And
 
         21       at the same time, there are some real challenges
 
         22       as to why are the people there that are there?
 
         23            MR. ELENGOLD:  Yes, I've worked for FDA long
 
         24       enough to remember the point in the early '80s
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              82
 
 
 
 
 
          1       where the advisory committees changed from being
 
          2       virtually empty rooms to lots of guys with at
 
          3       that time briefcase-size cell phones.  You know,
 
          4       I remember that change.  And I know somebody
 
          5       mutters something, and we've actually had to
 
          6       clear rooms because there were so many cell
 
          7       phones ringing.
 
          8            But it is a challenge.  It is a requirement
 
          9       that we're under under the law, and what I did
 
         10       last year, and I'll request it again, where
 
         11       people make suggestions like that, where it
 
         12       appears to go against the legal advice we have
 
         13       been given by our counsel, is say that we'd be
 
         14       happy, if you want to have your counsel prepare,
 
         15       you know, a justification and reason for that,
 
         16       that we can present to our lawyers and committee
 
         17       management people.  That, we can do.  But absent
 
         18       that, I'm afraid, you know, that's one where
 
         19       we're stuck with living with the law.  We're not
 
         20       only the law enforcers.  We're the recipients of
 
         21       law enforcement.
 
         22            MS. BOURQUE:  Right, and I think we'd be
 
         23       willing to pursue that.
 
         24            MR. ELENGOLD:  I personally have been sued
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              83
 
 
 
 
 
          1       by Sid Wolf for closing an advisory committee,
 
          2       so. . .
 
          3            MS. RAINES:  Yes, if I can just add to that,
 
          4       I think you're correct about the Advisory
 
          5       Committee Act requiring open meetings.  However,
 
          6       proprietary information can be discussed in
 
          7       executive session and is discussed by panels in
 
          8       executive session.  And the law provides that our
 
          9       applications are confidential information,
 
         10       including the data therein.  And I think that
 
         11       there is a way.  Maybe you don't even call it an
 
         12       Advisory Panel.  Maybe you call it a meeting of
 
         13       consultants.  But there are mechanisms like
 
         14       the executive session --
 
         15            MR. ELENGOLD:  Meeting of consultants is
 
         16       defined as a Advisory Committee by FACA.  See,
 
         17       that's the problem, but I don't want to get into
 
         18       a lot of it, but I'm just saying, you know, we'd
 
         19       be willing to consider it.  And in fact, last
 
         20       year after one of the things that FARMA brought
 
         21       up at the 406(B) meeting, they did provide us
 
         22       with a legal justification, and we have changed
 
         23       some policies.  So I'm just going to point that
 
         24       out.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              84
 
 
 
 
 
          1            On the training issue, we have been working
 
          2       with large groups over the years.  One of the
 
          3       problems we had is when we cosponsor with a
 
          4       group, generally we're required to make that open
 
          5       to anyone.  And I'm just wondering if you have a
 
          6       problem if we cosponsor something with you, that
 
          7       we would have, you know, everybody flying in from
 
          8       the West Coast as well.
 
          9            MS. BOURQUE:  No.  I mean, no, no.
 
         10            MR. ELENGOLD:  Well, I'll invite you or
 
         11       anybody else that's interested to get in contact
 
         12       with Gail and work that out.
 
         13            And, finally, we'd be willing, under some
 
         14       changes made in the department policy, we can now
 
         15       go into partnership agreements for those kinds of
 
         16       things, even with specific regulating company.
 
         17       And we have exercised that, and we encourage you
 
         18       to do that.
 
         19            Jim, the risk/benefit communications, I have
 
         20       two questions for you on that.
 
         21            MR. WESTON:  Sure.
 
         22            MR. ELENGOLD:  The first one is, we agree
 
         23       that that's a very important thing that FDA
 
         24       should be doing.  The problem is, when we're
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              85
 
 
 
 
 
          1       competing for resources -- and in my old job as
 
          2       Director of the Communications office, I was
 
          3       constantly fighting for resources to do that.
 
          4       Everybody has a simple answer:  "Put it on the
 
          5       Web, put it on the Web, put it on the Web."  And
 
          6       having, you know, one person in our office who's
 
          7       responsible for both our inter- and our
 
          8       intranet -- in fact, we just doubled our staff to
 
          9       two -- does the industry believe that would be a
 
         10       cost that is either acceptable under PDUFA or
 
         11       that a PDUFA amendment or agreement could be made
 
         12       so that PDUFA resources could be used for that?
 
         13       Because as I showed in that slide, the non-PDUFA
 
         14       resources is that little blue box.
 
         15            MR. WESTON:  In response to that, I think
 
         16       that's something we could certainly consider.  I
 
         17       think in the past couple of years, we've all seen
 
         18       the validity of the Internet being a
 
         19       communications tool, and particularly a two-way
 
         20       communications tool, and I think that's something
 
         21       we could take a look at, yes.
 
         22            MR. ELENGOLD:  Okay, so that's that.  And
 
         23       given the priorities that we're all faced with
 
         24       making people in companies as well as the FDA,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              86
 
 
 
 
 
          1       where do you think that putting that effort is in
 
          2       priority to some of the other tasks we have?
 
          3            MR. WESTON:  I think it has a relatively
 
          4       high priority, but I wouldn't necessarily put it
 
          5       above, you know, the approval process.  Obviously
 
          6       that's where you --
 
          7            MR. ELENGOLD:  But you would put it slightly
 
          8       above enforcement actions, right?
 
          9            (Laughter.)
 
         10            MR. WESTON:  I don't think I dare to
 
         11       comment.
 
         12            MR. ELENGOLD:  Okay, that's another thing.
 
         13       You know, since you've made the suggestion,
 
         14       either to the docket or, you know, just in a
 
         15       communication to us you could address, we'd
 
         16       appreciate that.
 
         17            MR. WESTON:  We'd be glad to do that.  It's
 
         18       the type of thing which I think we'd be willing
 
         19       to look at as part of a partnership too.  It's
 
         20       the type of thing where you don't have to
 
         21       necessarily share the entire burden.  It's the
 
         22       type of thing which, with the industry or the
 
         23       industry groups, a partnership could be formed
 
         24       because we both came to see the values of these
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              87
 
 
 
 
 
          1       group.
 
          2            MR. ELENGOLD:  John, do you have any
 
          3       questions?
 
          4            MR. MARZILLI:  No.  I was just going to add,
 
          5       in terms of any of the training and cooperative
 
          6       efforts with Mass. Biotech, surely call the
 
          7       District Office and you can discuss things with
 
          8       us, and coordinate with Gail and the folks in
 
          9       Mark's office as well.  So you know we're always
 
         10       available.
 
         11            MS. BOURQUE:  Great, and, I mean, in terms
 
         12       of what those presentations will look like, what
 
         13       the science ought to be, I think surely that we
 
         14       just need to sit down and say:  What are the
 
         15       areas the reviewers are interested in?  What are
 
         16       the areas the industry thinks we should do some
 
         17       more work on?  And like I said, finding a site,
 
         18       and this is one facility that I think is a
 
         19       natural, but we can explore that further with
 
         20       UMass.  And I think it would be received well
 
         21       from both sides.  It's very exciting for us to be
 
         22       able to do something like that.
 
         23            MR. ELENGOLD:  Steve, do you have anything?
 
         24            MR. MASIELO:  No.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              88
 
 
 
 
 
          1            MR. ELENGOLD:  Okay, does anybody in the
 
          2       audience have any questions for these speakers?
 
          3            One thing, as we go through this, if you
 
          4       either ask a question or later when we get to the
 
          5       open part, if you make a statement, state your
 
          6       name, who you represent, if anybody.  And after
 
          7       you speak, at some point, either on a break or
 
          8       afterward, go over to the Reporter over there and
 
          9       give her a card or identify yourself, because we
 
         10       are transcribing this, and that way it will
 
         11       appear correctly in the record.
 
         12            MR. PIGNATO:  Yes, my name is Bill Pignato.
 
         13       I'm with -- the new name now of my company is
 
         14       Bayer Diagnostics, and we manufacture a wide
 
         15       variety of in vitro diagnostics, some of which
 
         16       have had to go before CBER, and our experience
 
         17       with CBER has always been a lot more frustrating
 
         18       than those of CDRH.  So I'm certainly encouraged
 
         19       by the initiative of the Device Action Plan, and
 
         20       I'd like to offer a couple of suggestions.  And
 
         21       that is, I notice that part of the activity with
 
         22       the Device Action Plan is the development of a
 
         23       number of guidance documents, and I'd like to
 
         24       suggest a different approach in terms of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              89
 
 
 
 
 
          1       development of the guidance documents.  That is,
 
          2       the experience that I have had with CDRH in
 
          3       participating in the development of a couple of
 
          4       their documents, in fact, a modification
 
          5       document, the working document, and that is that
 
          6       forming working groups in the development of
 
          7       these guidance documents as opposed to the
 
          8       traditional approach of issuing the guidance
 
          9       document and asking for comments.
 
         10            I think that those participants, myself and
 
         11       other people that participated in these working
 
         12       groups with FDA, I think that both parties, both
 
         13       FDA and the industry, were both satisfied with
 
         14       the outcomes in the final product; and I would
 
         15       clearly encourage the agency to give that
 
         16       consideration as well.
 
         17            MR. ELENGOLD:  As some here know, we've
 
         18       actually had meetings with the HIMA Board and the
 
         19       Device folks, and I guess Carolyn will get to
 
         20       some of that when she speaks.
 
         21            Anyone else, questions for this panel?  Yes,
 
         22       sir?
 
         23            MR. SCHUBERT:  Thank you.  My name is Dave
 
         24       Schubert.  I'm with Genzyme Corporation.  I'd
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              90
 
 
 
 
 
          1       like you to comment on a question that Lisa asked
 
          2       with respect to the Intercenter training on the
 
          3       fast track and accelerated approval process, and
 
          4       where is CBER on that continuum?
 
          5            MR. ELENGOLD:  Gail?  Yes, we have not
 
          6       started our training on that.  It is going to be
 
          7       a module in the revised reviewer training.  We
 
          8       have coordinated with CDER as much as we could.
 
          9       They are, you know, on their own initiative doing
 
         10       things.  We get the materials.  We try and
 
         11       leverage it.  Quite frankly, with the device
 
         12       interest right now, we have been concentrating
 
         13       our joint reviewer training with CDRH.  But we
 
         14       have talked to Nancy and some of the folks over
 
         15       there, and we would like to leverage it.  But
 
         16       right now, we are in the process of completely
 
         17       redoing our reviewer training, and that's why the
 
         18       suggestion on working with Mass. Biotech is so
 
         19       interesting to us, because it does provide us
 
         20       with a current opportunity.  But that is
 
         21       something that's interesting, and we'll put it in
 
         22       the record and we'll look at it.
 
         23            Carolyn?  You're talking.  You can't ask any
 
         24       questions.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              91
 
 
 
 
 
          1            MS. JONES:  I think it's an interesting
 
          2       concept that Mass. Bio discussed about the
 
          3       reviewer training; but coming from a broader
 
          4       perspective than just a regional trade
 
          5       association, I think it's also important that if
 
          6       you consider that, that there may be issues from
 
          7       biotech companies in California that may not be
 
          8       appropriately totally addressed in anything
 
          9       that's done in a regional setting.  So I would
 
         10       say that if you're going to do anything that
 
         11       involves reviewer training where, you know, that
 
         12       might impact companies that aren't going to be
 
         13       present or in the development of that process,
 
         14       that you consider making it a broad training --
 
         15            MR. ELENGOLD:  That was the purpose of my
 
         16       question.
 
         17            MS. JONES:  Oh, I missed it.
 
         18            MR. ELENGOLD:  Yes, I'm sorry, Carolyn.  I
 
         19       asked that.  I said, would it be expected to be a
 
         20       regional thing?  Because generally when we have
 
         21       partnerships, we put them in the Federal
 
         22       Register, and quite frequently people come from
 
         23       all over, in fact, all over the world, to do
 
         24       that.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              92
 
 
 
 
 
          1            MS. JONES:  One other question for you,
 
          2       Mark.  You talked about budgetary constraints on
 
          3       travel and so on.  How would traveling around the
 
          4       country to training programs like that, how would
 
          5       FDA review staff handle that?
 
          6            MR. ELENGOLD:  Well, we have two options.
 
          7       The most common option is:  We pay for it out of
 
          8       our appropriated funds.  It is possible, if a
 
          9       sponsoring group is a group that is eligible for
 
         10       what we call 348 cash-in-kind reimbursement, that
 
         11       we could allow the group.
 
         12            Now, several of the groups -- we have just
 
         13       been working with the Commissioner's office and
 
         14       the Department and have gotten those types of
 
         15       groups extended.  It pretty much used to be
 
         16       universities and certain groups that had no
 
         17       membership of companies but only individuals.
 
         18       We've gotten that changed a little bit; and in
 
         19       fact to accommodate that, the PDA has changed
 
         20       their charter to eliminate company memberships so
 
         21       they will qualify.  So if an organization like
 
         22       DIA was the sponsor, DIA could provide
 
         23       reimbursement to the government.  The way it
 
         24       works is:  We cut the travel letter.  We turn our
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              93
 
 
 
 
 
          1       voucher into the FDA, and the FDA then sends a
 
          2       bill to the eligible group.
 
          3            And so that would be the mechanism, but, for
 
          4       example, that would not be available to Mass.
 
          5       Biotech.  It would be if DIA or the Parental Drug
 
          6       Association or RAPS, I think RAPS is eligible
 
          7       now, Regulatory Affairs Professionals.
 
          8            So that is one avenue, but again we think
 
          9       the importance is such that we have done a fair
 
         10       amount of allocating travel funds to that.  In
 
         11       fact, one of the things we did in CBER this year
 
         12       is, we imposed a percentage travel cut over last
 
         13       year's, and we have that as a reserve fund so
 
         14       it's available so that we in the Director's
 
         15       office can fund travel to important meetings
 
         16       where our message is getting out, and we're
 
         17       hearing what industry folks in academia
 
         18       and industry are telling us.
 
         19            MS. JONES:  One final question.  Regarding
 
         20       the issue of disseminating information to the
 
         21       public on risks, in your response or in your
 
         22       question, you asked whether PDUFA funds or the
 
         23       priority that MBC would attach to that.  Is that
 
         24       an area where the agency would be willing to use
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              94
 
 
 
 
 
          1       the CRADA concept to allow industry to contribute
 
          2       to it to disseminate the appropriate information
 
          3       if it's not already budgeted for?
 
          4            MR. ELENGOLD:  That's something that I was
 
          5       the pet transfer CRADA person for CBER in my last
 
          6       life, so I guess I have a fair amount of
 
          7       knowledge about that.  It's an issue I hadn't
 
          8       ever really thought about, Carolyn. And again
 
          9       I'll say the same thing I've said, that anybody
 
         10       who would like to propose such a new mechanism,
 
         11       give us the proposal, the legal background from
 
         12       your counsel's viewpoint, and either submit it to
 
         13       the record or just in a communication to us, and
 
         14       we'll consider it and get back to you or answer
 
         15       it for the record, either way.  That's an
 
         16       interesting concept.
 
         17            MR. MARZILLI:  Lisa Lopez, okay, Lisa, the
 
         18       microphone.
 
         19            MS. LOPEZ:  Lisa Lopez, Vice President and
 
         20       General Counsel of Haemonetics Corporation, and I
 
         21       am on the program later this afternoon.  And I
 
         22       apologize, I'm not going to be able to stay.  I
 
         23       have a flight.
 
         24            MR. ELENGOLD:  Okay, I tell you what.  We
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              95
 
 
 
 
 
          1       will let you do your presentation right now.
 
          2            MS. LOPEZ:  Well, I have the remarks that
 
          3       I've left.  I did, however, want to ask a
 
          4       question about something that you've said
 
          5       earlier.  I know that you're on a tight deadline.
 
          6            MR. ELENGOLD:  No, that's okay, that's okay.
 
          7            MS. LOPEZ:  You mentioned, Mark, that two
 
          8       years ago there was a crisis of confidence in the
 
          9       blood supply that gave the FDA a real sense of
 
         10       urgency to jump start very, very quick
 
         11       decisions.  And my question is that certainly
 
         12       many of us in industry perceive that there is a
 
         13       similar seriousness.  I wouldn't characterize it
 
         14       necessarily as a crisis of confidence, but
 
         15       whether it be CJD or EEHP or a proliferation of
 
         16       donor, you know, all of the above, there is the
 
         17       same very strong sense of seriousness attached to
 
         18       issues of blood that we believe give us a great
 
         19       sense of urgency to direct our engineers and our
 
         20       scientists to act quickly, to innovate, to create
 
         21       very, very quickly.  And I'm hoping that you will
 
         22       say that the FDA sees the same kind of sense of
 
         23       urgency to make quick decisions.  I mean, do you
 
         24       think that we're still in that same similar
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              96
 
 
 
 
 
          1       period of time that requires of the agency the
 
          2       same sense of urgency that you referred to a
 
          3       couple of years ago?
 
          4            MR. ELENGOLD:  Well, if you look at
 
          5       Dr. Henney's priorities for the FDA -- I don't
 
          6       have the list in front of me right here but it's
 
          7       in your pact -- I believe the safety and
 
          8       confidence of the public in the blood supply is
 
          9       one of the five.  And therefore we have as our
 
         10       marching orders in implementing the
 
         11       Commissioner's priority anything we can do to
 
         12       increase the safety of and the public confidence
 
         13       in the blood supply.  That is one of the major
 
         14       driving forces for the Device Action Plan because
 
         15       we believe that better tests and better devices
 
         16       for processing blood lead to better safety and
 
         17       more confidence.  So, yes, that is one of our
 
         18       goals, and it is right on the radar screen.
 
         19            MS. LOPEZ:  And my only comment there would
 
         20       be:  We would certainly like to see added to that
 
         21       safety and availability of blood.
 
         22            MR. ELENGOLD:  Yes, well, that's -- you
 
         23       know, I don't go home one night without hearing a
 
         24       donor request on the radio.  And on the NIH
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              97
 
 
 
 
 
          1       campus where our office is, there's also a sign
 
          2       when you pull in of what type of blood the bank
 
          3       needs.  So we're very aware of that, and the
 
          4       availability of blood products is a major concern
 
          5       to us.  There's a chronic GG shortage.  There's,
 
          6       you know, chronic shortages of component blood,
 
          7       and we realize that the equipment used to process
 
          8       it and the devices used to test it are
 
          9       important.
 
         10            Are you sure you don't want to just take
 
         11       five minutes and summarize your --
 
         12            MS. LOPEZ:  I don't know that I'd be able to
 
         13       do so.
 
         14            MR. MARZILLI:  Lisa, are there any comments
 
         15       you want to come up and make?
 
         16            MR. ELENGOLD:  Yes, I feel bad about that.
 
         17       Time is not a problem.  We'll just cut it out of
 
         18       everybody's lunch.  I mean, we're only going up
 
         19       stairs.  It's just that we want to make sure
 
         20       people have enough time to take care of their
 
         21       needs, make their phone calls, return the pages
 
         22       they've got.
 
         23            MS. LOPEZ:  I apologize.  I was directed to
 
         24       actually have prepared written comments.  I don't
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              98
 
 
 
 
 
          1       usually speak this way, but I'll do my best to
 
          2       summarize.  As I mentioned, I do represent
 
          3       Haemonetics Corporation.  We're a medical device
 
          4       company born in Boston over twenty-five years
 
          5       ago.  We're now global with customers throughout
 
          6       the United States, Europe, and Asia, but our
 
          7       headquarters is here, a landmark on Route 128 in
 
          8       Braintree right up the road.
 
          9            Haemonetics has always been associated with
 
         10       invention and innovation, pioneering the
 
         11       collection of specific blood components from
 
         12       healthy donors in the '70s and the '80s,
 
         13       pioneering blood salvage and reinfusion for
 
         14       patients in hospital operating rooms, and most
 
         15       recently we introduced a system for the safe
 
         16       collection of two units of red cells for
 
         17       transfusion from a single donor.  This advance
 
         18       will, in our view, improve both the availability
 
         19       and the safety of transfusion medicine
 
         20       practices.
 
         21            Haemonetics is grateful for this opportunity
 
         22       to talk with CBER's leadership.  We are
 
         23       profoundly encouraged by the responses FDA has
 
         24       made to FDAMA.  We believe that the benefits of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              99
 
 
 
 
 
          1       these fundamental changes and the way that FDA
 
          2       interacts with industry will reap benefits for
 
          3       the agency, for industry, and most important, to
 
          4       all of us in this room today, the public.
 
          5            The questions posed to this meeting center
 
          6       around the challenging environment that we in
 
          7       industry share with the FDA, and that's one of
 
          8       unavoidable risk and imperfect science, one where
 
          9       the pressures of cost containment, competition,
 
         10       and technology are fundamentally altering the
 
         11       architecture of our blood products delivery
 
         12       systems.
 
         13            Now, in addition to sharing environmental
 
         14       challenges, we also share a public that is quick
 
         15       to find fault and slow to forgive; and perhaps
 
         16       because of these mutual challenges, industry and
 
         17       FDA are motivated by many of the same goals:
 
         18       Number one, the desire to make devices as safe as
 
         19       possible for patients, donors, and operators.
 
         20       Number two, the need to make sure that our
 
         21       products meet customers needs and expectations.
 
         22       Number three, genuinely, the desire to make the
 
         23       world a better place.  And that is FDA and
 
         24       industry's mutual goal.  And, number four, the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              100
 
 
 
 
 
          1       need to improve operations by adopting what I
 
          2       think we're all comfortable calling so-called
 
          3       "best practices" to meet, in industry's case,
 
          4       the expectations of our shareholders, and in
 
          5       FDA's case, the expectations of its
 
          6       stakeholders.
 
          7            These shared goals are too often overlooked
 
          8       by the media and external constituencies that we
 
          9       also share, patients and their families, blood
 
         10       oversight bodies and other arms of federal and
 
         11       state governments.  Because we have shared
 
         12       constituencies, we will improve our
 
         13       communications with them if we send a consistent
 
         14       message, one that says we are doing the best that
 
         15       we can.  But we are not perfect.  We must be
 
         16       prepared to say that we're sorry when we make a
 
         17       mistake and avoid setting unrealistic zero-risk
 
         18       expectations for our products and services.
 
         19            Because several of the questions for this
 
         20       meeting involve FDA's responsibilities throughout
 
         21       a product's life cycle, I would like to spend
 
         22       just a few moments and explain the unique
 
         23       environment in which Haemonetics operates in the
 
         24       United States with our licensed blood and plasma
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              101
 
 
 
 
 
          1       customers.  The bullets after Premarket Clearance
 
          2       list the channels of communication with the FDA
 
          3       that already exist for Haemonetics and our
 
          4       customers during a product's life cycle.  The
 
          5       information gathered via these mechanisms provide
 
          6       an important resource for scientific staff
 
          7       involved in risk-based decision making.
 
          8            Parenthetically, we hope that the
 
          9       information is available to the scientists who
 
         10       could benefit from this exposure, and not just
 
         11       limited to the administrative staff charged with
 
         12       reaching a review and the gathering of these
 
         13       statistics.
 
         14            Before leaving this slide, however, I would
 
         15       like to mention the two-tiered premarket approval
 
         16       process that exists for Haemonetics and
 
         17       our licensed blood plasmal customers because it's
 
         18       unique in the U.S. public health regulatory
 
         19       scheme, and I think in most of the world.
 
         20       Although device or drug manufacturers in other
 
         21       medical fields need only obtain premarket
 
         22       clearance to introduce their products in the
 
         23       United States, this scheme applies to Haemonetics
 
         24       only insofar as our sale of instruments to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              102
 
 
 
 
 
          1       unlicensed customers; for example, a hospital
 
          2       customer.  But the use of this same -- same --
 
          3       identical instrument to an unlicensed customer
 
          4       that we sell to a licensed blood or plasma
 
          5       facility is routinely sowed with a second
 
          6       application review, inspection, and approval
 
          7       process.  This means that even after a 510(K)
 
          8       review process, which can take up to several
 
          9       years for a device, and longer for NDA review of
 
         10       a new anticoagulant or a storage solution, there
 
         11       is a further delay for a year or more for
 
         12       implementation of the new technologies by
 
         13       licensed users.  This translates to up to three
 
         14       years between the time the new technology has
 
         15       completed the R and D cycle and the time it may
 
         16       be utilized by users.
 
         17            We spoke of this a moment ago, but in
 
         18       balancing the public policy considerations of
 
         19       regulating blood in the world we share after
 
         20       AIDS, we almost acknowledge that the risk of
 
         21       indecision or and an unduly delayed decision may
 
         22       be just as dangerous to the public health as a
 
         23       poor decision.  And certainly I think all of us
 
         24       in industry would agree with Mark, your remarks,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              103
 
 
 
 
 
          1       that a poor product is not one for which we want
 
          2       to expedite approval.  But given the worldwide
 
          3       need for safer, higher quality, and sufficiently
 
          4       available blood products, industry must be
 
          5       encouraged to direct all of its resources to be
 
          6       more innovative, to be more creative, to be less
 
          7       constrained by conventional approaches to product
 
          8       design.  But for these efforts to result in the
 
          9       kinds of extraordinary public health improvements
 
         10       demanded by the public's sense of urgency about
 
         11       blood safety and availability, they must be
 
         12       coupled with less burdensome paths to regulatory
 
         13       approval.
 
         14            A good example, we believe, was the less
 
         15       burdensome approaches for blood testing which
 
         16       were used very successfully by CBER when it was
 
         17       recognized that the public's urgency for
 
         18       improvements demanded no less.  And, similarly,
 
         19       less burdensome approaches for blood collection
 
         20       equipment users could save FDA what we've spoken
 
         21       about today are admittedly very scarce resources
 
         22       without compromising public health.
 
         23            I think we need to remember that in our
 
         24       case, automated blood collection devices have had
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              104
 
 
 
 
 
          1       a good track record for twenty-five years.  That
 
          2       gives FDA a good basis to make informed
 
          3       decisions.
 
          4            Haemonetics would welcome the opportunity to
 
          5       communicate with FDA scientists in a less formal
 
          6       manner outside the context of application review,
 
          7       inspections, or enforcement actions.  We would be
 
          8       willing to host scientific visitors from the FDA
 
          9       or come to FDA to demonstrate our technologies
 
         10       and to assist in general training and exchange of
 
         11       ideas and expertise.
 
         12            In addition to improving the scientific
 
         13       knowledge base upon which FDA's decisions are
 
         14       made, we believe that this interaction would
 
         15       prevent misunderstandings, reduce the number of
 
         16       cycles during application review, and foster a
 
         17       more constructive climate for problem-solving.  I
 
         18       think these sentiments echo what you've heard
 
         19       from several other speakers.  We are genuinely
 
         20       interested in sharing our technology so that FDA
 
         21       staff, whether they be reviewers or enforcement,
 
         22       have hands-on opportunities to really understand
 
         23       the technology out of the context in which there
 
         24       is some question about enforcement or
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              105
 
 
 
 
 
          1       compliance.
 
          2            FDA's efforts toward harmonization with
 
          3       regulatory authorities in other countries have
 
          4       been encouraging to us, and we hope that they
 
          5       will continue until a -- you know, let's think
 
          6       about this -- single dossier is accepted
 
          7       worldwide.  That would be truly extraordinary,
 
          8       and we think that it is possible to do that.
 
          9            Signs of the internal harmonization that
 
         10       have been referred to this morning between CDRH
 
         11       and CBER, as exhibited by the CBER Device Action
 
         12       Plan and what I picked up on the Internet Monday
 
         13       and the Federal Register, are also very, very
 
         14       encouraging.
 
         15            It's also been gratifying to see the
 
         16       comments from the stakeholders meeting last fall
 
         17       now being introduced into working groups at
 
         18       CBER.  Everyone inevitably will benefit from
 
         19       these plans.
 
         20            We spoke or I spoke earlier about the layers
 
         21       of regulation.  While it may not be possible to
 
         22       eliminate totally the redundancies in premarket
 
         23       clearance for blood technologies and the blood
 
         24       products they manufacture, FDA could make some
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              106
 
 
 
 
 
          1       approval routes less burdensome for itself and
 
          2       industry by reexamining traditional approaches to
 
          3       regulation, with an eye toward integrating some
 
          4       premarket approval processes and streamlining
 
          5       data submission requirements where the risk is
 
          6       low and the track records have been established.
 
          7            Third-party reviews are being used by CDRH,
 
          8       but to the best of our knowledge, have not been
 
          9       tried in the blood devices sector, and we think
 
         10       that they could be.
 
         11            Finally, thank you very much, FDA, for
 
         12       beginning to move away from the zero risk
 
         13       rhetoric.  Particularly for those of us in the
 
         14       blood sector, what I think we remember as a
 
         15       decision paralysis resulting from those years is
 
         16       just beginning to subside, and now it's just
 
         17       decision anxiety for all of us.  We think that's
 
         18       a little bit easier to deal with.  But perhaps
 
         19       now we can move forward to educate the public and
 
         20       other external constituencies about patient
 
         21       decision making and risk acceptance.
 
         22            In this light, prompting media stories about
 
         23       risk, even TV show story lines, as is being
 
         24       planned for the Hepatitis C campaign, would reap
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              107
 
 
 
 
 
          1       benefits.  But these efforts must be ongoing, and
 
          2       maybe with ongoing efforts, we'll get through to
 
          3       the physicians and, an even tougher act, to the
 
          4       lawyers.
 
          5            In conclusion, thanks for this opportunity
 
          6       to speak today and for the improved
 
          7       communications that we've seen on the Internet.
 
          8       Again, I echo the comments of others.  That's a
 
          9       tool that we all utilize daily, and we applaud
 
         10       you for being a leader in that area.
 
         11            Thank you very much.
 
         12            (Applause.)
 
         13            MR. MARZILLI:  Okay, thank you very much,
 
         14       folks.  I've got a caterer who's been hounding my
 
         15       heels, so if you'd please exit, and people will
 
         16       escort you immediately to the 14th floor for
 
         17       where lunch is being served.
 
         18            (Noon recess.)
 
         19            (Satellite Teleconference.)
 
         20            MR. ELENGOLD:  We appreciate everybody
 
         21       coming, and, again, what we had done was figured
 
         22       that we could put any slippage, not that we
 
         23       really anticipated any, in on this end and finish
 
         24       up.  And the last speaker we have, and then we'll
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              108
 
 
 
 
 
          1       open up the floor for questions and comments, is
 
          2       Carolyn Wilson from HIMA.
 
          3            What did I just say?  What did I say?  I'm
 
          4       sorry.  I'm having a real rough day.  Anyway,
 
          5       Carolyn is here for HIMA.  They are at two of our
 
          6       meetings and somebody there.  That shows the way
 
          7       that devices are intrusive into everything we
 
          8       do.
 
          9            Anyway, Carolyn is a former FDA CBER
 
         10       employee, so that's why we're glad she's here.
 
         11            MS. JONES:  Thanks, Mark.  It's often hard
 
         12       to be sort of the last speaker of the day, so I
 
         13       have been sitting there trying to pare down my
 
         14       comments so that I won't hold you here longer
 
         15       than necessary.
 
         16            I want to thank FDA for the opportunity to
 
         17       comment on the progress in implementing FDAMA.
 
         18       And I'm not going to go into the usual spiel
 
         19       about who HIMA is and what we do and all of
 
         20       that.  Needless to say, we represent the medical
 
         21       device industry, a large portion of it, and for a
 
         22       number of our companies, CBER issues are very
 
         23       important.
 
         24            Today FDA is faced with several challenges.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              109
 
 
 
 
 
          1       It is charged with implementing a complex and
 
          2       demanding statute.  It also wields enormous
 
          3       economic power over a substantial portion of the
 
          4       marketplace.  Public expectation of the agency's
 
          5       ability to provide the most technologically
 
          6       advanced products risk-free and immediately can
 
          7       be unrealistic, and the agency is under constant
 
          8       scrutiny by Congress, the public, and we, the
 
          9       stakeholders.
 
         10            And Mark reminded me this morning in his
 
         11       presentation that CBER is faced with an
 
         12       additional challenge because the products that it
 
         13       regulates sort of cross all center bounds.  They
 
         14       regulate products that would be considered drugs
 
         15       as well as devices and traditional biologics.
 
         16            I have some overall general comments that
 
         17       apply not specifically to CBER but just to the
 
         18       agency in general.  We feel that faced with
 
         19       shrinking resources, increased statutory
 
         20       obligations, and public expectations, we
 
         21       recommend that the agency devote its resources to
 
         22       its core statutory obligations.  It needs to
 
         23       focus resources on the highest risk products.  It
 
         24       needs to maximize the tools provided by FDAMA.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              110
 
 
 
 
 
          1       It needs to continue to seek improvements through
 
          2       re-engineering and management initiatives.  It
 
          3       needs to leverage its resources in both the
 
          4       public and private sector.  It needs to cease
 
          5       activities that are not essential to carrying out
 
          6       the law, and to seek additional resources from
 
          7       Congress to address the ever-increasing number of
 
          8       issues it needs to deal with, particularly from
 
          9       our perspective, device reviews.
 
         10            We have some ongoing general concerns, and
 
         11       then I'm going to specifically answer the
 
         12       questions that FDA posed in its March Federal
 
         13       Register notices.
 
         14            While the majority of the devices are
 
         15       regulated by CDRH, there have been a number of
 
         16       devices that are regulated by CBER.  The device
 
         17       provisions of FDAMA apply to those products as
 
         18       well.  Not surprisingly, industry's ongoing
 
         19       concerns with device reviews conducted by CBER
 
         20       don't differ significantly from the concerns we
 
         21       express with the products reviewed by CDRH.
 
         22            Product review times top the list of
 
         23       concerns for manufacturers.  Until very recently,
 
         24       because CBER's focus is not primarily devices,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              111
 
 
 
 
 
          1       little attention had been paid to medical devices
 
          2       industry's concerns about the ever-increasing
 
          3       product backlogs.
 
          4            Changes are in progress.  Mark talked today
 
          5       about the Device Action Plan, and a number of you
 
          6       probably picked up copies of it off the back
 
          7       table.  We are really happy to note that the
 
          8       concerns expressed at earlier stakeholders
 
          9       meetings as well as the December Device Action
 
         10       Plan meeting were taken to heart, and FDA has put
 
         11       this Device Action Plan in place.  We think it's
 
         12       long overdue and needed to address a broad range
 
         13       of device industry concerns, and we look forward
 
         14       to reading it and providing comments to the
 
         15       agency, and probably meeting with them to discuss
 
         16       our particular concerns with the plan.
 
         17            One of the things before we knew that the
 
         18       plan was going to be issued, we had a concern
 
         19       about the input provided into developing a plan.
 
         20       We wanted to remind CBER of a necessity to
 
         21       communicate, collaborate, and consult with the
 
         22       stakeholders in the development of the plan and
 
         23       with the plan's implementation.  We feel it's a
 
         24       challenge for CBER to involve industry as a
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              112
 
 
 
 
 
          1       partner in the development and implementation,
 
          2       and part of that challenge will be for CBER to
 
          3       think beyond its traditional ways of doing things
 
          4       and allow the stakeholders, both in industry and
 
          5       the blood banking community, to help CBER set
 
          6       realistic science-based goals for its
 
          7       device-related functions.
 
          8            One of the questions put by one of my
 
          9       co-workers had to do with product development
 
         10       times, and I'm not going to go through the
 
         11       aspects of the FDAMA regulations that address
 
         12       product development times, but needless to say,
 
         13       product development times are an important issue
 
         14       for the device industry.  As review times go down
 
         15       at CDRH, the product development times go up.  We
 
         16       don't want to see the same thing happen at CBER.
 
         17            We have put together what we call a Least
 
         18       Burdensome Industry Task Force and sent some
 
         19       proposals to CDRH on how we feel that least
 
         20       burdensome issues should be addressed, and we
 
         21       urge the agency to consider these proposals, but
 
         22       we also urge CBER to be involved in that
 
         23       process.  CBER needs to insure that its reviewers
 
         24       are adequately trained to make appropriate use of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              113
 
 
 
 
 
          1       the least burdensome concept.
 
          2            One of the things that we found in trying to
 
          3       gather information from our industry constituents
 
          4       is that a complaint has been that CBER asks for
 
          5       extensive studies when other less burdensome
 
          6       studies could demonstrate the same safety and
 
          7       effectiveness.  This often discourages
 
          8       manufacturers, who will often develop and market
 
          9       products that could improve the safety of the
 
         10       nation's blood supply, to market these products
 
         11       outside of the U.S.
 
         12            Again, we recommend that CBER participate in
 
         13       any meetings that the Device Center has with the
 
         14       industry to work out issues related to least
 
         15       burdensome.
 
         16            Although long product review times remain
 
         17       the issue of primary concern, manufacturers also
 
         18       note an apparent disconnect between what
 
         19       manufacturers submit or what they think CBER
 
         20       wants in the product submissions and what CBER
 
         21       actually wants in the submissions.  And I'm going
 
         22       to explain a little bit by saying, the example we
 
         23       have been given in-house is that after waiting
 
         24       about six months to receive the first round of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              114
 
 
 
 
 
          1       questions on a submission, on average, it will
 
          2       take a manufacturer three to six months to
 
          3       respond to CBER's queries.
 
          4            In our discussions, we found that CBER
 
          5       believes the problem was based on poor product
 
          6       submissions, and that's not borne out by the fact
 
          7       that CBER has refused to file any of these things
 
          8       or anything of that nature.  So we sort of think
 
          9       it's based in the idea that maybe there's a lack
 
         10       of guidance out there on CBER's expectations of
 
         11       industry.  And so we need to, as industry, to
 
         12       work with CBER to develop guidance so it's very
 
         13       clear on both our parts what's going to be
 
         14       expected and what's going to be the outcome.  If
 
         15       CBER is looking for A and we give them B, of
 
         16       course we're not giving them what they need, so
 
         17       we need to be on the same page.
 
         18            Any good plan, one of the things that we
 
         19       talked about in our industry groups, needs some
 
         20       way to measure progress.  Traditionally industry
 
         21       has measured FDA progress from origin product
 
         22       review time.  Complete timely data on CBER review
 
         23       times is generally not available.  CBER should
 
         24       publish its review time metrics on a regular
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              115
 
 
 
 
 
          1       basis to provide the agency and the industry a
 
          2       yardstick to gauge the progress made.  And I was
 
          3       listening to Mark's presentation this morning,
 
          4       and he was talking about how you routinely have
 
          5       those meetings internally to see where the
 
          6       reviews are in-house and, you know, give
 
          7       suggestions to the various divisions on how to
 
          8       improve that process.  We'd like to have some
 
          9       access to those review times quarterly, every six
 
         10       months, but some kind of metric so that we know
 
         11       how we're doing and how you're doing.
 
         12            Now, with respect to the specific questions
 
         13       that CBER asked, we will be submitting comments
 
         14       to the docket, a combined set of responses,
 
         15       because we don't think the answers to these
 
         16       questions significantly differ whether you're
 
         17       talking to a CBER audience or whether you're
 
         18       talking to a CDRH audience, so there will be
 
         19       comments submitted to the docket.
 
         20            On the issue of the capacity or capability
 
         21       to incorporate state-of-the-art science into its
 
         22       risk-based decision making, we think one of the
 
         23       issues this question raises as a general matter
 
         24       is the need for FDA to be vigilant in insuring
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              116
 
 
 
 
 
          1       that it is incorporating the appropriate level of
 
          2       science in its decision-making processes.  For
 
          3       instance, the regulatory requirements for a PMA
 
          4       approval incorporate a reasonable assurance of
 
          5       safety and effectiveness standard, not an
 
          6       absolute assurance of safety and effectiveness.
 
          7       FDA must insure that whatever quantum of science
 
          8       it applies to its decision making, it must be
 
          9       within the regulatory construct of the law.
 
         10       Scientifically based conclusions must represent a
 
         11       balance between risks to the public and benefits
 
         12       to the public.
 
         13            In addition, as a government agency there
 
         14       will always be a financial constraint on FDA's
 
         15       ability to hire experts.  The agency will seldom
 
         16       be able to compete with the resources of academia
 
         17       or industry.  However, the key to incorporating
 
         18       state-of-the-art science into FDA's
 
         19       decision-making process lies in the ability of
 
         20       its reviewers to understand data, interpret
 
         21       results, and ask appropriate questions.  FDA
 
         22       should focus on developing and cultivating these
 
         23       skills in its reviewers.
 
         24            Some of the recommendations we're going to
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              117
 
 
 
 
 
          1       make were addressed in Dr. Henney's presentation,
 
          2       and I was encouraged by that.  The specific
 
          3       recommendations we have in those areas consist
 
          4       of:  FDA should leverage the industry resources,
 
          5       company tutorials, vendor days, cosponsored
 
          6       educational workshops, et cetera.  HIMA proposes
 
          7       that FDA take advantage of industry resources to
 
          8       expand its own scientific knowledge.
 
          9            Dr. Henney addressed the issue of vendor
 
         10       days.  Most of the vendor days that we've helped
 
         11       work on have been directed toward CDRH.  We would
 
         12       like to see a vendor day that's directed toward
 
         13       CBER, and we would be willing to work with the
 
         14       CBER in the same way we've worked with CDRH to
 
         15       come and set up a vendor day so that your review
 
         16       staff can actually see the technology that they
 
         17       review.  It's important to understand that FDA's
 
         18       review is a paper review; and in a non-
 
         19       confrontational environment of a vendor day when
 
         20       you get to talk to the company, you're not
 
         21       reviewing product, it's a relaxed environment, I
 
         22       think the CBER staff would benefit greatly from
 
         23       that interaction.
 
         24            We recommend the cosponsored educational
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              118
 
 
 
 
 
          1       workshops be another vehicle for dissemination of
 
          2       information, and we at HIMA are working with the
 
          3       agency to develop CRADAs to fund such workshops.
 
          4            We also agree with Dr. Henney that outside
 
          5       experts, government agencies, academia, the
 
          6       private sector, and even the scientific advisory
 
          7       committees, could be used to help build your
 
          8       science base.  You know, again, due to the
 
          9       budgetary constrictions, you are not going to be
 
         10       able to compete with industry to obtain the
 
         11       disciplines that you need to do your product
 
         12       reviews.  FDA needs to strengthen its use and
 
         13       relationships with its sister organizations, such
 
         14       as the NIH, NSF, and the other organizations that
 
         15       have a scientific base or laboratories and so on
 
         16       to help it through this process.
 
         17            We should also find ways of using
 
         18       consultants and contracting outside the agency to
 
         19       bring in the scientific expertise.
 
         20            We also looked at your conflict of interest
 
         21       policy.  We think the current conflict of
 
         22       interest policy prevents FDA from gaining the
 
         23       input from the private sector or using those
 
         24       resources in a way, and we think that FDA should
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              119
 
 
 
 
 
          1       sort of consider reevaluating the conflict of
 
          2       interest policy to provide a little greater
 
          3       flexibility in your use of outside entities to
 
          4       help you build that science base.
 
          5            We also agree that continuing education is
 
          6       important for your medical staff, for your
 
          7       scientific reviewers; that FDA should at least
 
          8       encourage, if not require, scientists to keep
 
          9       current in the field by taking advantage of
 
         10       seminars or other educational opportunities.
 
         11            One of the other things that we think in
 
         12       industry that we can do is to make use of the
 
         13       collaborative meetings, to make that a learning
 
         14       tool as well, to bring the important people, the
 
         15       experts, the statisticians to these meetings so
 
         16       that these meetings can be productive and provide
 
         17       additional information on the way technology is
 
         18       moving with regard to a particular company
 
         19       submission.  Oftentimes I'm hearing from the FDA,
 
         20       and even from industry, that these meetings
 
         21       aren't always as productive as they could be.  I
 
         22       think industry needs to take part of the gauntlet
 
         23       here and provide and bring the appropriate people
 
         24       to those meetings, too, so that FDA can learn and
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              120
 
 
 
 
 
          1       have a correct interaction in those up-front
 
          2       meetings.
 
          3            Another opportunity for FDA to gain the
 
          4       scientific knowledge that it needs is standards
 
          5       development activities.  Many scientific experts,
 
          6       including some of FDA's own experts, are involved
 
          7       in developing standards, and it's a really good
 
          8       opportunity for groups to get together their FDA
 
          9       base, their academic base, or their industry base
 
         10       to debate issues in the development of
 
         11       standards.  And I think that brings out a lot of
 
         12       information on the technologies that are being
 
         13       addressed, that FDA also has another opportunity
 
         14       for a learning experience there.  We would
 
         15       recommend both industry and FDA continue to
 
         16       participate in standards development
 
         17       opportunities.
 
         18            As for question two, what actions do we
 
         19       propose to continue the exchange of information
 
         20       throughout a product's life cycle?  This question
 
         21       first asks for ways to improve FDA's access to
 
         22       scientific information.  We think the access to
 
         23       scientific information, that issue was addressed
 
         24       in that first question, and we've already listed
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              121
 
 
 
 
 
          1       out a number of ways you can approach that.
 
          2            I was glad to hear Dr. Henney mention the
 
          3       use of FDA staff, college and training
 
          4       institutions, as an additional mechanism for
 
          5       keeping abreast of what's going on.  We recommend
 
          6       that the agency adopt, if it hasn't already done
 
          7       so, something that's used in the industry which
 
          8       is called "train the trainer."  Industry, too,
 
          9       has financial constraints often, and they send
 
         10       people to training seminars and standards
 
         11       development activities, and that individual has
 
         12       the responsibility to go back and train the folks
 
         13       who weren't able to attend the meeting, to relay
 
         14       the information that was obtained.  FDA needs to
 
         15       make use of that if there are still constraints
 
         16       on traveling to meetings and to different
 
         17       functions.
 
         18            Also, information on product life cycles,
 
         19       manufacturers and companies have annual reports.
 
         20       That's a way of continually tracking information
 
         21       on products and so on.  There are more specific
 
         22       recommendations in our written comments.  I don't
 
         23       want to keep you here any longer than necessary.
 
         24            The issue of educating the public on the
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              122
 
 
 
 
 
          1       concept of risk, consumers are increasingly
 
          2       becoming better educated about their own health
 
          3       and their personal medical problems.  The
 
          4       availability of the Internet resources can result
 
          5       in patients having sometimes more information
 
          6       than their physicians about a particular device
 
          7       or drug or whatever.  This creates a demand in
 
          8       the marketplace for additional information by
 
          9       both consumers and physicians, a demand that will
 
         10       largely be met by the marketplace and not a
 
         11       government agency like FDA.
 
         12            There's no magic bullet that will fully
 
         13       educate the public about how to balance risks and
 
         14       benefits.  For CBER, this is particularly
 
         15       difficult because some consumers believe that
 
         16       products, including the nation's blood supply,
 
         17       should be completely risk-free.  FDA can play a
 
         18       useful role in educating the public generally
 
         19       about the risks and benefits of the product it
 
         20       regulates and about continuing efforts to reduce
 
         21       those risks.  FDA can also work with the medical
 
         22       community to discuss ways of adequately informing
 
         23       patients about the risks and benefits of the
 
         24       products that they proscribe.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              123
 
 
 
 
 
          1            Another opportunity for FDA, and I guess
 
          2       industry as well, to provide information to
 
          3       patients about the risks are the use of the
 
          4       various Web sites, and that also is
 
          5       resource-intensive, but, again, that's not a
 
          6       burden FDA must bear alone.  Companies also have
 
          7       a responsibility to put important information on
 
          8       their Web sites, or at least FDA could possibly
 
          9       link to some of the company Web sites so that
 
         10       they don't have to provide the information.
 
         11            How to focus resources on the areas of
 
         12       greatest risk to public health?  CBER should
 
         13       continue to implement the tools of FDAMA and to
 
         14       adopt, where appropriate, CDRH's re-engineering
 
         15       tools.  We think this will free up some of your
 
         16       resources.  This includes taking a critical look
 
         17       at ways to expand the list of recognized
 
         18       standards and increase their use by industry, to
 
         19       make optimal use of early collaboration meetings,
 
         20       and to harmonize the regulatory requirements.  In
 
         21       perusing your Device Action Plan, these are some
 
         22       of the same things that the plan addresses, and
 
         23       we're glad to see that.
 
         24            As far as training, industry training,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              124
 
 
 
 
 
          1       education and communication, in order to maximize
 
          2       the tools at FDAMA and to create the most
 
          3       efficient system possible, FDA staff must be
 
          4       adequately trained in their application.  It's
 
          5       not enough for Linda to sit in a stakeholders
 
          6       meeting and outline what's contained in FDAMA.
 
          7       Your front-line reviewers, your inspectional
 
          8       staff, the district offices, need to be
 
          9       thoroughly versed in what's contained in FDAMA
 
         10       and how it should be applied.  The industry must
 
         11       also be educated on the tools available as well
 
         12       as the agency expectations.
 
         13            We also look at focusing resources.  We've
 
         14       all got to in belt-tightening situations
 
         15       eliminate unnecessary or redundant functions.
 
         16       FDA should closely examine all of its functions
 
         17       and determine which are not essential to carrying
 
         18       out its core statutory obligations.  FDA should
 
         19       look to rid itself of all but absolutely
 
         20       necessary functions mandated by law.
 
         21            On the inspectional side, HIMA has
 
         22       participated in several initiatives to improve
 
         23       FDA's device functions.  Those comments or
 
         24       testimony with regard to those initiatives are
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              125
 
 
 
 
 
          1       included in our written comments, and we think
 
          2       that CBER should review those comments and look
 
          3       to see what aspects of those initiatives can be
 
          4       adopted by CBER to enhance its inspectional
 
          5       program as well.
 
          6            On Question 5, enhancing the communication
 
          7       process and allowing ongoing feedback, the
 
          8       statute uses the term "consultation" in
 
          9       connection with FDA's 406(B) obligation.  This
 
         10       means more than just listening or reading
 
         11       comments.  If Congress had intended the FDA to
 
         12       only seek public comments, it would have said
 
         13       so.  Webster defines "consultation" as "Meeting
 
         14       to discuss, decide, or plan."  Discussions,
 
         15       decision making, and planning all involve
 
         16       brainstorming and a give-and-take kind of
 
         17       activity.  We urge the agency to engage in
 
         18       consultation with its stakeholders that may be
 
         19       more meaningful and productive than the type of
 
         20       consultation exemplified by most of the meetings
 
         21       that we've had with the agency.
 
         22            The other thing that the agency can do is
 
         23       that -- I know HIMA has commented extensively on
 
         24       the regulations, notices, and guidance documents
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              126
 
 
 
 
 
          1       developed by CDRH to implement FDAMA.  It's
 
          2       unclear on our part what input CBER has actually
 
          3       had in the development of a number of these
 
          4       documents, and we'd like to know what your input
 
          5       has been.  But the problem is, in some cases it
 
          6       appears that our comments go unacknowledged.
 
          7       While we do not expect that all of our comments
 
          8       would be adopted, we do believe, especially on
 
          9       key issues, the process would benefit from a true
 
         10       dialogue with industry and other interested
 
         11       parties.  A true dialogue is especially important
 
         12       when there are documents, from CBER's
 
         13       perspective, that they may be reluctant to
 
         14       adopt.  It is important for industry to
 
         15       understand the basis for CBER's reluctance to
 
         16       adopt specific documents.
 
         17            And, again, that goes back to the point:  If
 
         18       we had a true consultation, a true dialogue, each
 
         19       of us would know up-front why there's a
 
         20       reluctance.  But because of the process that's
 
         21       used currently, we don't.
 
         22            The one thing that we've done at HIMA -- and
 
         23       at some point, Mark, when we have future
 
         24       discussions on CBER's Device Action Plan, we'd
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              127
 
 
 
 
 
          1       like to be able to share this information -- we
 
          2       sent out a questionnaire to our member companies
 
          3       on their experiences with FDAMA, and we're in the
 
          4       process of collecting those surveys and collating
 
          5       the data.  And, again, we will share the results
 
          6       of this questionnaire with the agency, and
 
          7       particularly we want to share the specific
 
          8       questions related to CBER with the CBER folks.
 
          9            In conclusion, we want to thank the agency
 
         10       for this opportunity to provide our ideas and our
 
         11       comments.  We look forward to working with CBER
 
         12       to implement the appropriate provisions of FDAMA,
 
         13       to utilize the relevant CDRH re-engineering
 
         14       initiatives, to develop and implement the Device
 
         15       Action Plan that appropriately focuses CBER's
 
         16       device-related functions, so that together we can
 
         17       eliminate the product review backlog and
 
         18       significantly reduce product review times.
 
         19            MR. ELENGOLD:  Thank you.  I've got a couple
 
         20       questions.
 
         21            MS. JONES:  Sure.
 
         22            MR. ELENGOLD:  I've got a couple questions.
 
         23       One of the ways that CDRH -- and I'll be fast,
 
         24       too, because I know everybody wants to catch a
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              128
 
 
 
 
 
          1       plane -- that one of the things CDRH did was
 
          2       down-classify devices.  We've looked pretty hard
 
          3       at our inventory of regulated devices, and many
 
          4       of them are treating either people with fatal
 
          5       nontreatable diseases, like in cell separation,
 
          6       or in safety of the blood supply.  Could you give
 
          7       me an example that HIMA might think might be a
 
          8       CBER-regulated device that would be eligible for
 
          9       down-classification, what we say in our
 
         10       vernacular as the "tongue depressor bedpan"?  I
 
         11       remember when the device amendments were
 
         12       implemented in '76, a lot of things that were
 
         13       relatively simple were classified too high; and
 
         14       in down-classifying them, that's one of the ways
 
         15       CDRH lessened their review workload.  But we've
 
         16       had extensive internal discussions over the
 
         17       years, and we, frankly, can see one or two things
 
         18       that might be down-classifiable; but I'm sure
 
         19       that HIMA has had the same discussion.  Do you
 
         20       have any ideas on that?
 
         21            MS. JONES:  Honestly, we haven't had the
 
         22       discussion about the list of products that could
 
         23       be down-classified.  That is a discussion that we
 
         24       can have with our CBER steering committee.  We do
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              129
 
 
 
 
 
          1       feel -- I guess in Lisa Lopez's presentation, she
 
          2       talked about some of the products that you've had
 
          3       extensive experience with in triaging your
 
          4       reviews that may not get to the level of actual
 
          5       down-classification, but the amount of time and
 
          6       effort spent in the review of the products that
 
          7       you have had extensive experience may be
 
          8       lessened.
 
          9            We realize CBER's discomfort with
 
         10       down-classification of instrumentation associated
 
         11       with some of the IVDs and so on; whereas CDRH has
 
         12       down-classified or exempted, really, the
 
         13       instrumentation.  And in discussions with
 
         14       Dr. Epstein and his staff, we realized their
 
         15       discomfort with that, and --
 
         16            MR. ELENGOLD:  You have to keep in mind that
 
         17       I've spent the past ten years dealing with four
 
         18       different oversight committees on the safety of
 
         19       the blood supply.  The Secretary of the
 
         20       Department of Health and Human Services has
 
         21       publicly stated that the safety of the blood
 
         22       supply is one of her priorities, and Dr. Henney
 
         23       gave it to you as three or four, depending on how
 
         24       you count today.  And something as simple as
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              130
 
 
 
 
 
          1       recently a filter that's been in use for many
 
          2       years, an acceptable manufacturing change was
 
          3       made that led to severe adverse reactions across
 
          4       the country.  So we've got to keep in mind --
 
          5            MS. JONES:  But you reviewed that product,
 
          6       didn't you?
 
          7            MR. ELENGOLD:  Yes.
 
          8            MS. JONES:  And it didn't stop that?
 
          9            MR. ELENGOLD:  Yes, that's right, that's
 
         10       right.  And that's the problem.  So maybe we need
 
         11       more controls and extensive clinical trials
 
         12       before allowing manufacturing changes.  I'm just
 
         13       giving you the questions that we get on those
 
         14       issues.
 
         15            MS. JONES:  I understand, I understand,
 
         16       but --
 
         17            MR. ELENGOLD:  And we have to strike a
 
         18       balance.
 
         19            MS. JONES:  We do have to strike a balance,
 
         20       and we understand that you're not going to catch
 
         21       everything, even in an extensive premarket
 
         22       review.
 
         23            MR. ELENGOLD:  That's right, but the reality
 
         24       is, the public has demanded through their elected
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              131
 
 
 
 
 
          1       representatives that we devote additional
 
          2       resources and additional controls.  And that's
 
          3       something that FDA has to face in its life.
 
          4            Let me go on.  You've said we've changed our
 
          5       conflict of interest.  That's a major concern to
 
          6       us.  One of my previous jobs was dealing with
 
          7       what we like to call the "generic events."
 
          8            Now, the problem as I see it and the one
 
          9       I've dealt with is:  We go to seek an outside
 
         10       expert that's been to a hypothetical school like
 
         11       Boston University to come into our Advisory
 
         12       Committee as an expert, and we find out that the
 
         13       main expert in the field at BU has been a
 
         14       consultant to another company, and the conflict
 
         15       of interest prohibits us from doing that.  Does
 
         16       HIMA believe that its members are willing to
 
         17       waive that type of conflict of interest?
 
         18            MS. JONES:  I think on certain levels, yes.
 
         19       The discussions we've had in developing our
 
         20       answers to the questions posed by FDA, the
 
         21       companies indicated that they would be, and that
 
         22       in certain instances, the public disclosure of
 
         23       that information that you have had some dealing
 
         24       with the company, and so on, is what we thought
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              132
 
 
 
 
 
          1       was more important than waiving, you know, the
 
          2       company rights there.  And as long as the
 
          3       conflict or the involvement with the company was
 
          4       adequately disclosed and everybody was singing
 
          5       from the same song sheet, that it would be
 
          6       appropriate.
 
          7            MR. ELENGOLD:  Well, perhaps we can work on
 
          8       a pilot on that, and when your members are
 
          9       bringing products to our Advisory Committees,
 
         10       they could suggest experts along with their
 
         11       agreement to waive any conflict, because
 
         12       everybody knows who's working on the alternative
 
         13       products, and I encourage HIMA to back up that
 
         14       with some examples and some working with us
 
         15       because, you know, we don't invent the ethics
 
         16       laws or the conflict of interest requirements.
 
         17       For the main, they are either imposed upon us or
 
         18       demanded by companies to protect their own
 
         19       rights, and that's just another thing that I'd
 
         20       like to see.
 
         21            Training you brought up, training the
 
         22       trainer.  I went to train-the-trainer school in
 
         23       1971 or '72 back before we had project hiring and
 
         24       a lot of the people here today were hired.  We
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              133
 
 
 
 
 
          1       have embraced that concept.  The problem that we
 
          2       face is that every training that we do, including
 
          3       that type of thing, takes away from review and
 
          4       investigational time.  And that's one of the
 
          5       reasons we are really interested in partnering
 
          6       because having our people do the training takes
 
          7       away even more time, and that's one of our
 
          8       concerns with that.  We have looked at that.
 
          9            And, finally, you made the comment twice
 
         10       that you think we should stop doing things we
 
         11       don't need to do.  My experience over the years
 
         12       is:  Anything someone thinks we shouldn't be
 
         13       doing is something that somebody else is
 
         14       demanding we're doing it.  And the tautology of
 
         15       that is, you know, we don't need Consumer Affairs
 
         16       people, we don't need Web engineers.  And yet all
 
         17       this morning and all last year we heard:  "Put it
 
         18       on the Web, expand the Web, increase the Web."
 
         19       So I would just like, you know, as an example one
 
         20       function that we have in CBER that HIMA thinks we
 
         21       could eliminate.
 
         22            MS. JONES:  Mark, I did preface my comments
 
         23       by saying that the answers to the question may
 
         24       not specifically relate to CBER, that they are
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              134
 
 
 
 
 
          1       answers that we think go across FDA quite
 
          2       broadly.  We're asking your agency to be quite
 
          3       introspective and to look at things that it
 
          4       thinks, you know, that you're doing.  I didn't
 
          5       come prepared today to list out the things that
 
          6       we think are totally unnecessary.  I mean, I'm
 
          7       sure that if I got an industry group together,
 
          8       they could probably give me a list.  But we're
 
          9       asking the agency to do a self-check and look at
 
         10       those things that you think really don't add a
 
         11       great deal of benefit to the process or those
 
         12       things that are redundant of other things that
 
         13       could be collapsed into one.
 
         14            MR. ELENGOLD:  Well, again, I'd really
 
         15       appreciate either a submission or an off-line
 
         16       conversation.
 
         17            MS. JONES:  Okay.
 
         18            MR. ELENGOLD:  Because the budget situation
 
         19       has really forced us into doing that.  I didn't
 
         20       show one of the slides that I usually do show
 
         21       that shows we're spending 40 percent less than
 
         22       our laboratory function in actual dollars, not
 
         23       adjusted dollars, than we were four years ago.
 
         24       We have eliminated a lot of our management
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              135
 
 
 
 
 
          1       overhead.  We've cut travel just this year 25 to
 
          2       30 percent.  We're really interested, you know,
 
          3       and again, you know, in what functions industry
 
          4       thinks we can stop doing because we'd like to see
 
          5       if we can stop doing them.  But the rhetoric of
 
          6       just, you know, "There are things you can stop
 
          7       doing," we think we've stopped, at least in CBER.
 
          8       And I think Dr. Henney's proposed reorganization
 
          9       of the Commissioner's office, which is
 
         10       eliminating overhead and redundant things there,
 
         11       has also gone a long way to doing that.  So I'd
 
         12       really be interested.
 
         13            MS. JONES:  I think part of the problem,
 
         14       Mark, as you've seen at earlier stakeholders
 
         15       meetings, is the issue of transparency that you
 
         16       stressed in your presentation.  Maybe it's
 
         17       evident to the agency some of the things that
 
         18       you've stopped doing, but because of the lack of
 
         19       transparency, it's not evident to us some of the
 
         20       things you've stopped doing.
 
         21            MR. ELENGOLD:  Okay, thanks.
 
         22            John, do you have anything?
 
         23            MR. MARZILLI:  As we're getting a mike down
 
         24       to David, I'd just like to make a couple of
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              136
 
 
 
 
 
          1       comments.  One of the things that I think CBER
 
          2       should be applauded on in terms of increasing the
 
          3       science base of the agency and really focusing
 
          4       our resources, and you did mention it earlier,
 
          5       Mark, and that is Team Biologics.  I think for
 
          6       the first time in a long time this agency has had
 
          7       a highly focused, well-trained work force to go
 
          8       out there nationwide and to do the fieldwork for
 
          9       CBER, and I know you've played an active role in
 
         10       that, and it's an important aspect.
 
         11            For those of you that have had members of
 
         12       Team Biologics come out, we've really been able
 
         13       to focus our training opportunities on a devoted
 
         14       cadre that are devoted to these products.  And
 
         15       Mark has taken a leadership role in that from the
 
         16       Center for Biologics; and as a District Director,
 
         17       I've seen that it's been a tremendous resource
 
         18       boost to me in terms of trying to get my work
 
         19       done in the field organization.  I want to
 
         20       compliment you on that.
 
         21            MR. ELENGOLD:  Thanks.  I was quoted in one
 
         22       of the meetings as saying, "Team Biologics is
 
         23       either way above high technology regulation of
 
         24       the future or something we're going to look back
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              137
 
 
 
 
 
          1       on as a massive failure," and so far, I've been
 
          2       really happy that I think it is the wave of the
 
          3       future for high-tech regulation.
 
          4            MR. MARZILLI:  And the other thing I'd like
 
          5       to add, the technology that we've seen here today
 
          6       in terms of satellite training, and Al Levitt
 
          7       sitting over there is my training officer for the
 
          8       New England District.  We have at least two
 
          9       satellite broadcasts a week related to training
 
         10       opportunities within FDA, either seminars that
 
         11       are given by the various centers or other areas
 
         12       of interest to our folks that are usually
 
         13       broadcast in each of the twenty district offices
 
         14       and five regional offices across the country.
 
         15       Locally we record them on videotape and get them
 
         16       out to our district offices, so there is a
 
         17       multiplier effect, and I think we're doing a lot
 
         18       of innovative things.  And I'm excited about this
 
         19       Webcast that we saw today.  That's the first time
 
         20       I've seen that, and I think that would be an
 
         21       excellent training opportunity for us in the
 
         22       field to get the message out.
 
         23            And most recently our blood bank inspection
 
         24       cadre has an interactive CD-ROM training program
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              138
 
 
 
 
 
          1       with a little Hector-Hector guy over there that
 
          2       tells you whether or not you did your blood bank
 
          3       inspection right.  And there's a lot of high-tech
 
          4       training, and CBER has taken a leadership role in
 
          5       developing that with the field organization, and
 
          6       I really wanted to compliment you guys on it.
 
          7            MR. ELENGOLD:  What we did, in fact, to do
 
          8       that was we leveraged -- the CDRH folks have this
 
          9       Tech Center where you saw that satellite
 
         10       broadcast from today, and that is a
 
         11       state-of-the-art network grade facility.  And
 
         12       rather than try to develop any of our own, we
 
         13       decided to leverage that, and rather than spend a
 
         14       lot of money on satellite technology, we paid
 
         15       Bell Atlantic to put a fiber line in that runs
 
         16       from the Tech Center to all four of our
 
         17       buildings.  And again, at least two, three times
 
         18       a week we use our system to have them down-link
 
         19       to us educational opportunities, NIH grand
 
         20       rounds, association things; and our people can
 
         21       get their continuing medical or pharmacy
 
         22       education by just going down to a conference
 
         23       room.
 
         24            MR. MARZILLI:  Okay, David Fleming from
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              139
 
 
 
 
 
          1       Genzyme had a comment.
 
          2            MR. FLEMING:  Mark, let me try to pose one
 
          3       possible issue of one area where possibly CBER
 
          4       and industry can work together, and I guess
 
          5       that's the first point.  I think industry, I'm
 
          6       hearing today, wants some more open collaborative
 
          7       dialogue and better communication with CBER, and
 
          8       I think it's improving, but we want to improve it
 
          9       more.  And one example is just, again, the long
 
         10       review times.  I think we might have different
 
         11       perspectives as to what the issues are.  And I
 
         12       think industry sometimes believes that there's a
 
         13       disconnect, there continues to be a disconnect,
 
         14       in that we see it on the submission side between
 
         15       what we feel CBER wants in a submission and what
 
         16       CBER feels that it wants.  And what happens is,
 
         17       you end up having six months while CBER is
 
         18       reviewing, and then it comes back to the
 
         19       manufacturer, but it's three to six months to get
 
         20       back because there are unanticipated issues.  So
 
         21       I think -- Bill Pignato mentioned it earlier -- I
 
         22       think there's a great interest in working
 
         23       collaboratively on guidance and on guidance
 
         24       documents, and not for industry to go away and do
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              140
 
 
 
 
 
          1       it, not for CBER to go away and do it, but for
 
          2       both to sit down in some manner that's acceptable
 
          3       and to work these out so that there is a clear
 
          4       commonality that goes into the submission process
 
          5       so that we bring down the review time, bring down
 
          6       the number of rounds, and really get down to
 
          7       where not only is the product going through
 
          8       faster, but you are able to use your resources
 
          9       more effectively.
 
         10            MR. ELENGOLD:  Yes, I agree with that.  You
 
         11       know, extra rounds of review do cost us money
 
         12       too, and we don't see any great benefit from
 
         13       those.  And had I been answering this about a
 
         14       week ago, I would have said I would suggest you
 
         15       put a proposal together and submit it to Becky
 
         16       Devine, our Associate Director for Policy, on a
 
         17       proposed pilot to do that.  Unfortunately, Becky
 
         18       has decided to leave the government in June; so
 
         19       in the interim, until someone takes her place,
 
         20       I'll suggest you put a pilot suggestion together,
 
         21       pick a topic, and send it to me, and I'll get it
 
         22       worked on.
 
         23            One other thing that Carolyn Jones brought
 
         24       up, the review metrics issue.  We acknowledge
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              141
 
 
 
 
 
          1       that that's something industry has asked for.
 
          2       We, frankly, do not have a mechanism in place to
 
          3       do the kind of a review metric analysis that I
 
          4       remember doing in the new drug report from twenty
 
          5       years ago and we do in our review performance.
 
          6       We put together a pilot and we're refining it to
 
          7       get the system to work right, and I did present
 
          8       some of those figures out at the HIMA meeting
 
          9       back -- was that a month or so ago?  I can't
 
         10       remember.  And those are posted on the Web, and
 
         11       they give you the last year's performance, and we
 
         12       will be posting those at least on a quarterly
 
         13       basis.  We heard that last year.  We're working
 
         14       on it, and we will start doing that.  You saw
 
         15       those when I did those.
 
         16            And Steve just wanted to say something just
 
         17       before we get to the next question.
 
         18            MR. MASIELO:  I just wanted to mention that,
 
         19       you know, when you talked about scaling back the
 
         20       regulation of various products, something as
 
         21       simple as a pipet tip came into the forefront not
 
         22       too long ago.
 
         23            MR. ELENGOLD:  On a Friday night.
 
         24            MR. MASIELO:  On a Friday night, yes, where,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              142
 
 
 
 
 
          1       you know, a manufacturer's pipet tips weren't
 
          2       picking up enough sample, and that had an impact
 
          3       across the blood industry with some really severe
 
          4       potential consequences.  So, you know, even
 
          5       though on its face it might appear like a simple
 
          6       device, it has major impact.
 
          7            MR. ELENGOLD:  Nothing but a piece of blown
 
          8       glass, but it was sampling too small an amount.
 
          9            MR. MASIELO:  Another thing I wanted to say,
 
         10       we've heard a lot today about making more
 
         11       information available through the Web and all
 
         12       kinds of sources.  One of the things that I'm
 
         13       looking at is making sure information that's made
 
         14       available through the recall process is useful
 
         15       information.  There's a lot of information that
 
         16       gets out there, and you have to question:  Well,
 
         17       just how useful is this to the public?  What is
 
         18       the need to know this doing for them?  And so
 
         19       we're looking closely at that kind of information
 
         20       to make sure that the stuff that gets out there
 
         21       has some meaning to people and it's not just more
 
         22       info. they've got to sift through to get
 
         23       something useful.  So that's something we're
 
         24       looking closely at.  I just wanted to mention
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              143
 
 
 
 
 
          1       that.
 
          2            MS. DeMARINIS:  Hi, Anna DeMarinis from
 
          3       bioMerieux and a former CBER person, so please
 
          4       take what I say with a grain of levity.  I have
 
          5       two issues on which I want to take issue with
 
          6       you, Mark, two comments that you made.  One was,
 
          7       you sort of gently chided Carolyn on her remark
 
          8       that "What would you have us cut out for us to be
 
          9       able to better utilize our existing resources?"
 
         10       And I think Carolyn's response to look within
 
         11       yourself first is a very important one.  You
 
         12       said, "What would you have us do?  Get rid of
 
         13       consumer affairs, public affairs?"  And I know
 
         14       some of those people, and I know that they are
 
         15       very scientifically and technically capable.  And
 
         16       I would submit those individuals could be
 
         17       cross-trained to conduct inspections, to be
 
         18       reviewing applications when there's a backlog.
 
         19       Within your organization there are quite a few
 
         20       very talented people that may not be utilized at
 
         21       the present time as effectively as they could be,
 
         22       so I would certainly support Carolyn's suggestion
 
         23       that we would be very happy as an industry group
 
         24       to give you some instructions, some very
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              144
 
 
 
 
 
          1       constructive and positive suggestions on how you
 
          2       could reorient --
 
          3            MR. ELENGOLD:  Well, that wasn't my point.
 
          4       I mean, folks in ACMA, I mean, Mike Hooten who
 
          5       just retired last month, had done the plague
 
          6       inspection just about every year, even though he
 
          7       was mainly answering Congressionals, and Mary
 
          8       Myers, who's now the office director, was doing
 
          9       prelicense blood bank inspections up to three
 
         10       years ago.  I even did one.  They even let me do
 
         11       one.
 
         12            The point is:  If they do that, then they
 
         13       are not doing the consumer affairs work.  I'm not
 
         14       saying that the people couldn't be reprogrammed,
 
         15       but if we stop doing the Web work, the consumer
 
         16       affairs work, you heard the people this morning
 
         17       say:  It's FDA's job to post more information.
 
         18       It isn't the matter that we can't reprogram the
 
         19       people.  It's that whatever they stop doing, one
 
         20       of our stakeholders will object to.  That was the
 
         21       point to that.
 
         22            MS. DeMARINIS:  And I think that's a very
 
         23       valid point.
 
         24            MR. ELENGOLD:  You know, personally I'd
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              145
 
 
 
 
 
          1       rather be a full-time compliance officer and
 
          2       write warning letters, something I'm very capable
 
          3       of doing; but most of the time they have me in
 
          4       meetings on budget, you know, so. . .
 
          5            So that was the point.  It wasn't that the
 
          6       people aren't multi-talented.  It was that
 
          7       anything anybody has ever suggested to us that we
 
          8       stop doing or have stopped doing, we are
 
          9       immediately chided by somebody else:  Why did you
 
         10       stop doing that?
 
         11            MS. DeMARINIS:  And I think that that
 
         12       further supports the whole notion that we need to
 
         13       meet with all stakeholders regularly and
 
         14       frequently to hash out these issues, because we
 
         15       in industry, we do have to do more with less
 
         16       sometimes.  It's a reality of life, so we have to
 
         17       work on it.
 
         18            The other comment that I wanted to make was
 
         19       in response to your comment that if we're sending
 
         20       someone to training, they are not reviewing an
 
         21       application.  And I was a former teacher, so
 
         22       again, to me, the whole notion of training being
 
         23       an unnecessary or a frivolous activity is very
 
         24       unsatisfactory because I think if individuals are
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              146
 
 
 
 
 
          1       properly trained, then they do their work much
 
          2       better.
 
          3            I would throw back the comment to you:
 
          4       Research is another activity that if individuals
 
          5       are doing research, they are not reviewing
 
          6       applications; and yet research, as you shown in
 
          7       your own slides, is a very important training
 
          8       function.  So, again, I would submit again that a
 
          9       number of these kinds of issues that tend to fall
 
         10       on the fringes need to be kept in the mix and
 
         11       used as effectively as possible.
 
         12            MR. ELENGOLD:  I hope no one took that as
 
         13       belittling training.  At the period when I became
 
         14       responsible for the training operation, I don't
 
         15       know, what was that Gail, about four years ago?
 
         16       No, no, I've been in this job two years.  What?
 
         17       What?  Was it only two and a half?  Man!  The
 
         18       reorganization for training into my organization,
 
         19       the staffing has increased about 30 percent.  The
 
         20       budget has probably tripled.  We have gone to the
 
         21       on-line learning.  We have gone to orientations
 
         22       by videotape.
 
         23            I think we need much more training.  I just
 
         24       meant to say that by having trained the trainer
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              147
 
 
 
 
 
          1       and -- you know, the joke I hear constantly at --
 
          2       we have been doing internal stakeholders
 
          3       meetings.  We call them "voice your opinion
 
          4       meetings," and it's basically an opportunity for
 
          5       the staff at CBER one office at a time to get up
 
          6       and yell at me.  And the one thing I keep hearing
 
          7       is:  "The reward for good work is more work."
 
          8       And the problem that we're faced with is, if we
 
          9       put our best people in more training -- I mean,
 
         10       we have been trying to set up this vaccine
 
         11       training course, to give you an idea, with ORA's
 
         12       Team Biologics transfers to the inspections on
 
         13       October 1.  And one week is a Ver PAC meeting;
 
         14       one week is a religious holiday; one week is a
 
         15       professional association meeting.  And that was
 
         16       the point, that we can only spread our people --
 
         17       and we'd really, rather than train the trainer,
 
         18       to have our line people do it, one option we have
 
         19       to explore is, rather than using line people and
 
         20       training the trainer, is to get full-time
 
         21       training people that can do the technical
 
         22       training.  And that's all.  I did not mean to
 
         23       belittle the need for training.  I am perhaps one
 
         24       of the most overtrained employees in the federal
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              148
 
 
 
 
 
          1       government sometimes.
 
          2            MS. DeMARINIS:  If you hire full-time
 
          3       trainers, how do you keep the trainers -- you say
 
          4       that you'd only send the trainers to the
 
          5       seminars?
 
          6            MR. ELENGOLD:  No, no.  No, I mean full-time
 
          7       training people so they can work with the actual
 
          8       product experts and not have to do their own
 
          9       overheads.  As I said, we have been doing that
 
         10       more and more, because the training, anybody's
 
         11       who's ever done training, is really the smallest
 
         12       part of your time.  It's the logistics, the prep.
 
         13       work, the follow-up work.  So that was all I
 
         14       meant by that.  I'm sorry, I did not mean to
 
         15       belittle training.  I am probably the greatest
 
         16       supporter that we have of it.
 
         17            Anyone else?
 
         18            MR. RIDER:  Yes, I'd like to thank all of
 
         19       you for bringing the stakeholders here.  As one
 
         20       who represents a stakeholder group, I enjoyed
 
         21       hearing the "early and often" comment on the
 
         22       video in relation to communication.  I think that
 
         23       adverse reactions are bad publicity.  Loss of
 
         24       market share on products, all of that results
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              149
 
 
 
 
 
          1       from the lack of early and often communication
 
          2       with stakeholders.
 
          3            I'd also like to encourage, as one that's
 
          4       interested in blood safety, working for a group
 
          5       that has a direct stake in that issue, the
 
          6       involvement of ethicists in relation to the risk,
 
          7       potential risk, and how not only the physical
 
          8       impacts of adverse reactions but psychological,
 
          9       mental health reactions.  I deal full time with
 
         10       the impact that that has on families all over
 
         11       this country, and, of course, that impacts on our
 
         12       industry and our bottom line in terms of
 
         13       productivity, because when you decimate family
 
         14       systems' mental health, you have unfortunate
 
         15       spin-off consequences to the economy.  But in
 
         16       relation to that, I would say that you have good
 
         17       scientific data base that you can tap into in
 
         18       many professional nonprofit associations for
 
         19       scientific review, such as Physicians for Social
 
         20       Responsibility, who have the empirical training
 
         21       and knowledge and also an ethical basis for which
 
         22       to do some peer review.
 
         23            Thank you.
 
         24            MR. ELENGOLD:  Will you identify yourself
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              150
 
 
 
 
 
          1       for the record, please?
 
          2            MR. RIDER:  I am John Rider.  I work for the
 
          3       Committee of 10,000.  I am an advocate nationally
 
          4       for that organization.
 
          5            MR. ELENGOLD:  Thank you.  Anyone else?
 
          6       Well, then I will do my thank-yous and then turn
 
          7       it over to John.  I just want to thank everyone
 
          8       for coming, first off, and participating.  The
 
          9       only way we're going to get where we all want to
 
         10       go is by working together.  You know, reasonable
 
         11       people can disagree, and the basis of progress is
 
         12       getting together and reaching compromises and
 
         13       doing what we need to do.
 
         14            I particularly want to thank Paula
 
         15       Fairfield, John, the folks here at BU who have
 
         16       just been wonderful, the AD folks.  I do this
 
         17       probably at least once every ten days or so, and
 
         18       this is the most professional, best organized
 
         19       group I've dealt with in probably fifteen, twenty
 
         20       years, and I do appreciate that.
 
         21            I want to thank the folks back in Rockville
 
         22       who did the work, the folks who came up here,
 
         23       Gail and all of her people, Lorrie Harrison, who
 
         24       some of you spoke to in registering for this,
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              151
 
 
 
 
 
          1       Steve, John, the folks from Winchester, and Bob
 
          2       Miller who have been the butt of several of my
 
          3       jokes just because when I need money, he's the
 
          4       one I give the bank.
 
          5            I appreciate it, and this is not the end of
 
          6       this process.  We will be continuing it.
 
          7            One other thing I'll mention is if you look
 
          8       at our Web site, one of the things that I set up
 
          9       that I'm fairly proud of is our automated e-mail
 
         10       system.  You can subscribe to those automatically
 
         11       and then get notices of all our guidance
 
         12       documents, meetings, workshops, new initiatives,
 
         13       things we're posting, and I would urge everyone
 
         14       to look and consider signing up for that.
 
         15            It's easy to find me.  If anybody wants to
 
         16       contact me, my number is (301)827-0372, and I'm
 
         17       never there because I'm always in budget
 
         18       meetings, so the best way to do it is to send me
 
         19       an e-mail.  It's Elengold @CBER.FDA.Gov.  I
 
         20       usually try to answer things within a day or two,
 
         21       or get it to the right place, so if you don't
 
         22       know where to start, you're always free to send
 
         23       it to me.
 
         24            And, John, thank you very much.
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              152
 
 
 
 
 
          1            MR. MARZILLI:  Okay, Mark, thank you as
 
          2       well.  And I do want to salute the BU staff.  I
 
          3       think they did an excellent job.  And once again
 
          4       I want to say a special thank-you to Paula
 
          5       Fairfield who has handled this from the very
 
          6       beginning.  Paula, my appreciation for the hard
 
          7       work that you've done in putting this whole thing
 
          8       together.
 
          9            Again, we passed out some brochures.  They
 
         10       are available in the back of the room.  If you
 
         11       want to reach the District Office, we talked
 
         12       about consumer complaints, we have a 1-800 number
 
         13       for consumer complaints, et cetera.
 
         14            Again I want to thank our representatives
 
         15       from CBER who came down today.  And in the times
 
         16       of diminishing resources, I want everyone to know
 
         17       that they got up at the crack of dawn and took a
 
         18       flight in and came here from the airport and will
 
         19       be leaving promptly.  So we want to --
 
         20            MR. ELENGOLD:  We came in last night.  I
 
         21       don't want to go on any false pretenses.  We got
 
         22       in at what, 8:00 o'clock last night?
 
         23            MR. MARZILLI:  Okay, okay.  But I do want to
 
         24       thank you all for coming in and making it into
 
 
 
 
                    FDAMA STAKEHOLDERS MEETING, 4/28/99

                                                              153
 
 
 
 
 
          1       the meeting and spending the time with us.
 
          2            MR. ELENGOLD:  We have done it in one day.
 
          3       Boston is pushing it.
 
          4            MR. MARZILLI:  And, folks, your parking
 
          5       stickers should be validated with the word "FDA,"
 
          6       and thank you once again for coming and thank you
 
          7       for spending some time with us.
 
          8            (Applause.)
 
          9                         *  *  *
 
         10
 
         11
 
         12
 
         13
 
         14
 
         15
 
         16
 
         17
 
         18
 
         19
 
         20
 
         21
 
         22
 
         23
 
         24
 
 
 
 
 

 
 
 
 
 
 
          1                 C E R T I F I C A T E
 
          2
 
          3
 
          4                 I, Lee A. Marzilli, Registered
 
          5       Professional Reporter, do hereby certify that the
 
          6       foregoing transcript, Pages 1 through 153
 
          7       inclusive, was recorded by me stenographically
 
          8       and thereafter by me reduced to typewriting and
 
          9       is a true and accurate record of the proceedings
 
         10       to the best of my skill and ability.
 
         11            Dated this 3rd day of May, 1999, at
 
         12       Lexington, Massachusetts.
 
         13
 
         14
 
         15
 
         16
                                 __________________________________
         17                      LEE A. MARZILLI
                                 REGISTERED PROFESSIONAL REPORTER
         18                      CERTIFIED REALTIME REPORTER
 
         19
 
         20
 
         21
 
         22
 
         23
 
         24