1

        2

        3                   FDAMA STAKEHOLDER MEETING

        4

        5                           ---oOo---

        6

        7

        8                         April 28, 1999

        9
                      SOUTH SAN FRANCISCO CONFERENCE CENTER
       10                  255 South Airport Boulevard
                         South San Francisco, California
       11

       12

       13

       14

       15              REPORTER'S TRANSCRIPT OF PROCEEDINGS

       16

       17

       18

       19

       20

       21    REPORTED BY:  CLARE MACY, CSR 5256     (01-76508)

       22

       23

       24

       25

                                                                   1



        1                           I N D E X

        2

        3    INTRODUCTION      Pat Ziobro                       3
                               San Francisco District Director
        4

        5    OPENING REMARKS     Kathryn C. Zoon, Ph.D.         6
                                 Director, Center for Biologics
        6                           Evaluation and Research

        7              INTERACTIVE SATELLITE TELECONFERENCE
                                  (Not reported)
        8
             STAKEHOLDER PRESENTATIONS
        9
                      ROBERT GARNICK, Ph.D.                       21
       10             Vice President, Regulatory Affairs
                      Genentech, Inc.
       11
                      CINDY MORROW                                33
       12             Senior Regulatory Specialist
                      Becton-Dickinson
       13
                      PAUL HOLLAND, M.D.                          42
       14             Medical Director/CBO
                      Sacramento Medical Foundation
       15                  Blood Centers

       16    OPEN DISCUSSION                                      54

       17                            --oOo--

       18

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        1    April 28, 1999      P R O C E E D I N G S      9:34 a.m.

        2                            --oOo--

        3               MS. ZIOBRO:  Good morning, everyone.

        4               I think we're going to have quite a bunch

        5    more people joining us as we get into this morning's

        6    program.

        7               I'd like to introduce myself.  My name is Pat

        8    Ziobro, and I'm the district director of the

        9    San Francisco District in Alameda.  And we're really

       10    pleased this morning to be able to cohost one of the

       11    live sessions with Kathy Zoon from CBER.  I'd like to

       12    tell you a little bit about the game plan this morning.

       13    Our satellite downlink will begin promptly at 10 o'clock

       14    with Dr. Jane Henney, our new commissioner, discussing

       15    her vision and priorities and the accomplishments we've

       16    made in support of FDAMA.  Following Dr. Henney, we'll

       17    hear some remarks from Linda Suydam, who is also in the

       18    office of the commissioner, who will give us additional

       19    remarks about where the agency is headed, obstacles we

       20    have.  And we will be seeking questions, input and so

       21    forth during the teleconference as well.

       22               There will be an opportunity to fax and phone

       23    in your questions, and I'd like to ask if you have any

       24    of those, that you put them on this gray-colored sheet

       25    that's in your packet and step outside.  Immediately

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        1    outside the door here we have a fax and phone line that

        2    we can send those questions in directly.

        3               This will be an interactive session, and it's

        4    going on all around the country.  In addition to this

        5    facility here, we have another CBER group on the East

        6    Coast in Boston; we have a device group down in

        7    San Diego; veterinary medicine in Kansas City; a foods

        8    group in Washington; and an ORA group in Washington as

        9    well; CBER in Philadelphia.  So we have other live

       10    sessions in addition to groups that are just hosting the

       11    video satellite this morning.

       12               Because we have sessions going on all over

       13    the country, you understand that it is possible your

       14    question may not be answered live while we're on this

       15    morning.  But I assure you all those questions are going

       16    to be kept and answered someplace in those minutes that

       17    will issue.  The report will probably be on the

       18    Internet.  Kathy?

       19               DR. ZOON:  Yes.

       20               MS. ZIOBRO:  As they have in the past, we

       21    have a reporter here who is going to record all the

       22    comments and all the live testimony that we're going to

       23    have today during the teleconference as well as in this

       24    afternoon's session.

       25               At the end of the day, I would appreciate if

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        1    you would take the blue sheet of paper in your packet

        2    and give us some feedback as to what your thoughts were

        3    about today's session.  Today is unique in that we are

        4    having this all over the country rather than the

        5    separate sessions that we held last summer for each of

        6    our stakeholder groups.

        7               The video conference will go until about

        8    noon.  We'll take a short break and resume after that

        9    break with our session here with Kathy and your

       10    particular interests in the CBER program areas.  And

       11    then I think we'll take a lunch break and come back

       12    between 2:00 and 3:00.  Is that correct?

       13               MR. STRICKLAND:  Yes.  We will have a panel

       14    from 12 to 1 o'clock, and then from 1 clock to 2 o'clock

       15    will be lunch, and we'll come back at 2 o'clock and

       16    adjourn between 3:00 and 3:30.

       17               MS. ZIOBRO:  Okay.  I'm sure you've all found

       18    the rest rooms around the corner as well.

       19               Help yourself, get up during the video

       20    conference, to some refreshments in the back of the

       21    room.

       22               And again, this is our opportunity to listen

       23    to your concerns.  We don't have a whole lot to say.  We

       24    want to listen.  Again, I extend a welcome to all of

       25    you, and I know this is going to be an exciting day.

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        1    It's new for us as well.

        2               DR. ZOON:  Thank you, Pat.

        3               First I'd like to welcome everyone.  This is

        4    a wonderful opportunity to come out to the West Coast to

        5    meet with many of our colleagues and to hear how we're

        6    doing and what you think we could be doing better, and

        7    constructive advice is always welcome, and also to talk

        8    with you a little bit about our priorities.

        9               But before going onto that, I want to

       10    personally thank Pat Ziobro, the district director, and

       11    her staff, Kathryn Macropol, Mary Ellen Taylor, and also

       12    Mark Roh for helping us put this on out in

       13    San Francisco, and Dennis Strickland, who is here,

       14    again, is my deputy director of Office of Communications

       15    and Manufacturing Assistance.

       16               Also here from CBER, Dr. Jerry Donlon, who is

       17    deputy director of the Office of Compliance and

       18    Biologics Quality, and Dr. Lillian Yen, who is the

       19    special advisor on medical devices for biologics, are

       20    here.  And they will be taking over for me at 1 o'clock

       21    because I have to go back for a hearing tomorrow

       22    morning.  So I need to leave at 1:00 to make my plane to

       23    get back for that.

       24               But I really appreciate your coming, and

       25    Jerry and Lillian will be here subsequently to listen

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        1    and answer any questions you have.  So thank you.

        2               I would like to give you a brief overview if

        3    I can now using some overheads, and I'll speak until

        4    10:00.  Wherever I am, I will stop.  So just to warn you

        5    if it sounds like I'm stopping in the middle of

        6    something, I probably will be.

        7               Part of the outreach that we would like to --

        8    you can leave the lights on.

        9               MR. STRICKLAND:  Okay.

       10               DR. ZOON:  That's not necessary to shut them

       11    off.

       12               I would like to just remind everyone about

       13    CBER's mission.  And that is the mission of CBER is to

       14    protect and enhance the public health through the

       15    regulation of biological products and related products

       16    including blood vaccines, biological therapeutics -- and

       17    I have changed the mission statement.  We might have it

       18    approved by our organization as a whole to include

       19    devices based on comments we had gotten at our last 406B

       20    meeting.

       21               According to the statutory authorities, the

       22    regulation of these products is founded on science and

       23    law to insure purity, potency, efficacy and safety and

       24    availability.

       25               I think what we regulate at CBER is no

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        1    stranger to many of you in the audience.  We have a

        2    spectrum of products here including blood, blood

        3    derivatives, tissues, devices, diagnostics,

        4    xenotransplantation and many biotech products.

        5               The regulation of these products is based on

        6    what we call our biologic Olympic rings, and it's

        7    review, research, surveillance, policy and compliance.

        8               CBER has prepared a vision statement, and

        9    this is very much -- is very consistent with what

       10    Dr. Henney will be talking to us today about with

       11    respect to focusing on the science base.  And that is

       12    that CBER advances the public health and merits the

       13    public trust through high quality science-based

       14    regulation to insure that safe and effective products

       15    reach the public as rapidly as possible.  CBER

       16    demonstrates international leadership in regulation

       17    through development of innovative regulatory strategies

       18    and standards, a managed regulatory process, coordinated

       19    research and the use of partnerships.  And partnerships

       20    can be with academia, other government agencies, as well

       21    as the industry.  And many of these partnerships have

       22    already been established, and we would like to continue.

       23               I'd like to just share briefly our priorities

       24    for FY99 as they stand and we have been implementing.

       25    One is to implement the FDA Modernization Act, and we've

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        1    been working very diligently on that, and you will hear

        2    more regarding that from Dr. Henney.

        3               One of the major initiatives that CBER led

        4    this year was the fast track program, which is a program

        5    for products for severe and life-threatening illnesses.

        6    And a guidance document was issued last November which

        7    gives comprehensive instructions on that program.  And I

        8    would refer you to that if you are interested.

        9               The next priority was to meet and exceed our

       10    PDUFA goals for FY99.  And I'm happy to report to you

       11    CBER has met all its goals thus far for both FY98, and

       12    we are meeting all our milestones for FY99.  So I think

       13    we're very proud of that and hope that not only the

       14    numbers but the spirit of FDA reform is being exhibited

       15    in our performance, and we are trying to pay very close

       16    attention that we are doing that.

       17               Take whatever actions are necessary to assure

       18    the safety and the public confidence in the nation's

       19    blood supply.

       20               A major activity for CBER that was started in

       21    the summer of '97 was our blood action plan.  This

       22    particular plan covers a variety of issues from

       23    reinventing our processes, to improving our performance,

       24    to getting regulations out.  And we have been very

       25    successful in this program and have a number of other

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        1    milestones that we will be meeting for this upcoming

        2    year.

        3               To facilitate the development and approval of

        4    significant vaccine, blood and therapeutic products

        5    through review, policy formulation, regulation

        6    development, et cetera, and to pursue excellence in

        7    research that's directly targeted to our regulatory

        8    mission.

        9               These I believe are fundamentally important.

       10    They are in the spirit of FDAMA.  I think that we really

       11    are looking at trying to see innovative ways not only to

       12    reduce the review time for applications for marketing

       13    but also looking at the total development time it takes

       14    from when an IND is submitted to when the product is

       15    actually approved, because that's really where the

       16    rubber meets the road.

       17               Some of our other priorities are to focus on

       18    our information systems, and this includes not only

       19    within the center but for our review.  We have this as

       20    one of our prescription drug producers goals.  It's part

       21    of that program.  We have engaged in working on guidance

       22    documents that provide support for the industry and

       23    others who use these information systems to give you the

       24    standards and how we are going to proceed.  We've also

       25    spent a great deal of time developing our infrastructure

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        1    at the center improving the capabilities of our

        2    equipment so that we will be in a position to receive

        3    electronic submissions, both for INDs and BLAs by the

        4    year 2000 and continue our effort to have a high quality

        5    diverse work force.

        6               Well, some of our challenges at CBER are

        7    shown in this slide.  Our operating budget, while it

        8    looks reasonably steady, has had some major challenges

        9    especially in the products that are non-PDUFA.  That's

       10    the purple.  And we have had a 40 percent decline in our

       11    operating budget over the past five years.  And this has

       12    taken a fairly heavy toll on some of our non-PDUFA

       13    programs.

       14               This year we were able to use some of the

       15    PDUFA reserve one time to promote and actually give a

       16    jump start to the PDUFA II program to insure we could

       17    meet the milestones.  But I think this will not occur

       18    next year, and we need to really be careful to maintain

       19    a certain balance on our programs, and I think right now

       20    our biggest concern is in the non-PDUFA supported area.

       21               If we look at our workload, the workload at

       22    CBER has been, if not steady, but a slight increase

       23    especially in our investigational new drug applications,

       24    IDEs and master files.  This year we had 538 new INDs,

       25    IDEs and master files submitted.  60 percent of this

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        1    were in biotech products.  So I think that's an

        2    interesting number.  So that two-thirds of what CBER

        3    does actually in the investigational area is related to

        4    biotech.

        5               The number of licenses we had last year has

        6    been -- applications received has gone up slightly

        7    although the numbers for the biotech applications are

        8    about the same.  So for FY 98 we had 77 applications

        9    received.

       10               Just to show you our performance with respect

       11    to PDUFA, this gives you full cohort years that we have

       12    complete data on.  98 and 99 are still in progress.  But

       13    as you can see, CBER has met or exceeded all our

       14    performance goals.

       15               In looking at the future and where are we

       16    going, one of the key areas for us to focus on, I

       17    believe, to meet the challenges of the new biomedical

       18    products coming out into the public as a result of large

       19    investments in biomedical research really require an

       20    enhancement across FDA, including CBER, of the science

       21    base.  And this is particularly important to facilitate

       22    sound, timely regulatory decisions.

       23               I think when you don't have the proper

       24    scientific underpinning, one tends to be more

       25    conservative and more timid in your decision making

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        1    because you're afraid of making an error.  And I think

        2    the opportunity to enhance the science, make good

        3    scientific judgments, is absolutely necessary for many

        4    of us to realize the fruits of the products of new

        5    technology.

        6               So what are some of the things that we want

        7    to do for our science base?

        8               One is to really focus this on bringing the

        9    new products and improvements to products to the market

       10    as rapidly as possible while assuring their safety and

       11    efficacy.  And second is to make sure that we reduce the

       12    risks of the products that are on the market while

       13    enabling access.  Some of the strategies we're looking

       14    at to do that include enhancing research, standards

       15    development, surveillance, outreach and premarket

       16    review.

       17               Many people ask, "Well, does FDA really do

       18    research?  And why do they do research?"  Well, there

       19    are some fundamental reasons.  One is to facilitate the

       20    approval of safe and effective products.  Two is to

       21    support decisions to withdraw products that are found to

       22    be unsafe.  And to anticipate public health needs and

       23    really provide the support for that decision making and

       24    prevention of a public health crisis.  It also

       25    encourages the adoption of standards and also

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        1    contributes to the development of new products.  And

        2    probably not insignificantly, it aids in the recruitment

        3    and retention of scientists at the agency.

        4               Some of the major initiatives that we're

        5    currently engaged in at CBER include, as I said, the

        6    implementation of FDAMA.  We have a strategic plan that

        7    we're in the process of implementing.  Team Biologics,

        8    of which you heard, that we have an active team with

        9    CBER and ORA and field in doing a team approach with

       10    product and GMP experts and cross-training.  And I think

       11    that's proceeding quite well.  We're almost finished

       12    rolling it out.  Coming this October, vaccines and other

       13    products will be transitioned into Team Biologics, and

       14    most of the other products have already been

       15    transitioned.

       16               We have a tissue action plan, which I won't

       17    have time to talk about today, but that's proceeding

       18    well.

       19               A blood action plan, which I had alluded to

       20    previously.

       21               And a xenotransplantation action plan to deal

       22    with this new technology for potentially using animals

       23    as a source of organs and tissues but mindful of the

       24    infectious disease risk.

       25               And one of the big areas I'd just like to

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        1    mention this morning is device action plan.  Last year

        2    at the 406B meeting, we had heard your concerns with

        3    respect to CBER and its performance regarding the device

        4    review and management.  We heard you.  We put together a

        5    device action plan.  I'm proud to announce today as of

        6    two days ago it has been signed off by myself, Liz

        7    Jacobson, Dennis Baker, the new head of -- the new ACRA,

        8    Associate Commissioner of Regulatory Affairs, and

        9    Dr. Henney.  That action plan is now up on the Web.  And

       10    Dr. Lillian Yen, who is here today, and Dr. Donlon will

       11    be happy if this afternoon you have additional questions

       12    regarding this plan to be available and discuss it with

       13    you.

       14               Some of the concerns we had heard that we

       15    were trying to respond to were the consistency with

       16    CDRH, harmonization on some of the standards both with

       17    the review and the oversight -- compliance oversight and

       18    inspections, facilitation of reviews, guidance and

       19    communications.

       20               In the interest of time, because we only have

       21    a couple of minutes before Dr. Henney comes on, I would

       22    just like to say that this particular plan really

       23    focuses on four areas:  The CBER-CDRH coordination;

       24    review performance; compliance including Team Biologics,

       25    and having uniform standards; and outreach and inreach

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        1    both to the outside communities we serve as well as

        2    within our own organization to get the very best ideas

        3    to work on needs of particular issues.

        4               The coordination with CDRH includes adoption

        5    of certain guidances that CDRH has already submitted, in

        6    which one applied to CBER that should publish shortly

        7    we're going to be reviewing the innercenter agreement

        8    and working on that.  And we're also working very hard

        9    on a number of areas in terms of re-engineering our

       10    processes as well as having joint training with CDRH and

       11    having a web page devoted to the CBER devices.  We are

       12    also actively engaged in guidance documents as they may

       13    be unique to the (unintelligible).

       14               In closing, I wanted to just say that we very

       15    much value the information and the feedback that we get

       16    from these 406B meetings.  It's very important for us to

       17    hear from you.  This is your opportunity particularly

       18    today to talk about your experiences, your issues, your

       19    concerns and also to give your ideas on how we can do

       20    our jobs better, which we will take under serious

       21    advisement and discussion.

       22               And I think the device action plan is our

       23    response to the commitments that we have to seeing that

       24    when legitimate issues are brought to us with ideas, we

       25    try to incorporate your ideas into what we have

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        1    developed to be responsive.

        2               So thank you very much.  I appreciate the

        3    opportunity to be here.

        4               (Clapping)

        5               DR. ZOON:  Now I hope they start on time.

        6               Are there any questions?

        7               I'm sure I can answer everything, no.  Yes?

        8               MS. MAURER:  My name is Kerry Maurer of Gene

        9    Labs Technologies.  My question refers to the fast track

       10    program, which I think first off I commend the agency

       11    for adopting this type of program, and I use the

       12    guideline many times, and I think it's comprehensive.

       13    However, I think it's assumed that if the drug is

       14    granted fast track that -- or during scientific

       15    development or prior to NDA filing that the standard NDA

       16    supported studies, (unintelligible) can somehow be waive

       17    or postponed into a post-NDA commitment

       18    (unintelligible).  Is the agency using that vehicle?

       19    Activity?  Is that something that's really happening, or

       20    is that sort of a feeling you get when you get a fast

       21    track for your --

       22               DR. ZOON:  I'd have to know the specifics.  I

       23    think depending on the plan you have and how you come

       24    into the agency and how you discuss what you think your

       25    development plan is, that's something to put on the

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        1    table when you come in to develop that.

        2               I encourage many folks when we deal with them

        3    that if they actually have a five-year plan that they're

        4    discussing with one or more of their products that they

        5    actually come in and talk to us about it.  One, it helps

        6    us to understand what your issues are and what

        7    flexibilities you actually have with the particular

        8    product, because some of these are very

        9    product-specific, and you have to deal with them.  In

       10    addition, it helps us to understand that there are going

       11    to be areas as you go forward and not only for fast

       12    track but in your whole development profile what we may

       13    need to be looking at down the road because sometimes if

       14    standards have not been developed or biomarkers are in

       15    the process of being developed, sometimes we can give

       16    you advice on that area.  Or if there's a big need that

       17    we're seeing in certain areas for the development of

       18    biomarkers or discussions on others, that puts it on our

       19    radar screen so that we can then work with NIH or other

       20    interested parties in making that a more public meeting

       21    or developing guidance documents, et cetera.

       22               So that would be very helpful if you can come

       23    in early to give us your development plan, and then we

       24    can work through the specifics.

       25               MS. MAURER:  But if it's a situation where

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        1    you're receiving a fast track designation prior to --

        2    just prior to your NDA filing, say a year or so ahead of

        3    time, where you've been working with an accelerated

        4    critical development, say under subpart E, or you hadn't

        5    worked (unintelligible) for example, is the agency

        6    looking towards postponing some of these standards

        7    (unintelligible) very long-term expensive studies such

        8    as carcinogenicity studies?

        9               DR. ZOON:  Again, I think we're looking at it

       10    in a flexible way because some of them it depends on the

       11    nature of the product and what the properties of that

       12    product are as whether you can or cannot look at it

       13    postapproval, which is what I think you're trying to

       14    say.

       15               So some of these things I think really

       16    depends on what the data you have now are, what some of

       17    these issues are with respect to the product in having

       18    to manage that.  So I can't answer specifically because

       19    there's a lot that would come into that.

       20               MR. STRICKLAND:  Dr. Zoon, we have 30

       21    seconds.

       22               Let me ask one important thing.  We have a

       23    transcriber here.  So this is part of a public record.

       24    And anyone who has questions, please use the mike.  And

       25    also, can you spell your name for the transcriber in the

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        1    corner so she can get the appropriate spelling of your

        2    name for the record?  And the same will be true of the

        3    presenters, if you can give copies of your presentation

        4    to me or to the transcriber.  Thank you.

        5               (Interactive satellite teleconference)

        6               DR. ZOON:  I would like to open the

        7    stakeholder presentation session.  One, if you have any

        8    comments that either you didn't get to fax to Dr. Henney

        9    or you have other information -- if you have any other

       10    information or comments you'd like to submit, Dennis

       11    Strickland will be taking those.  Dennis, please stand

       12    up.  Dennis will be taking your comments, and we'll add

       13    them to the comments that were received at headquarters.

       14               So overall, I think the presentation was --

       15    my own personal view -- very good.  I hope it was

       16    interesting and informative to everyone and also a good

       17    opportunity to hear from Dr. Henney and Ms. Suydam.  So

       18    hopefully, we'll look forward to your feedback on how

       19    effective you think that type of communication is.

       20               We have several people that are listed to

       21    speak here -- I guess it's this afternoon now, and first

       22    is Dr. Rob Garnick.  He is the vice president of

       23    Regulatory Affairs at Genentech.  Rob?

       24               MS. ZIOBRO:  We'd like to ask if you have a

       25    copy of your comments and remarks, that you give them to

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        1    Dennis or to our transcriber so that we'll have them for

        2    the record.

        3               DR. GARNICK:  Thank you very much.  And I'd

        4    actually like to take the opportunity to thank the FDA,

        5    Dr. Henney, Dr. Suydam and you, Kathy, for the

        6    opportunity to have this meeting here.  And it's really

        7    a wonderful opportunity for the stakeholders to provide

        8    information and prospective thoughts to the agency about

        9    how we as the regulated industry understand the

       10    provisions for FDAMA, the work you've been doing with

       11    PDUFA, and to provide some thoughts about how we could

       12    actually do a better job working together.

       13               If I could have the first slide, please.

       14               Some of the prospective thoughts that we have

       15    actually been considering and providing the agency with,

       16    some prospective and positive feedback is the thought of

       17    providing and creating technical advisory boards.  This

       18    will consist of mixed boards containing mixtures of

       19    thought leaders from industry, academia and FDA who

       20    would recommend to the agency when important national

       21    issues need to be discussed in a very open and positive

       22    forum.  I'm mindful of some of the very positive things

       23    that we've had from the biotechnology perspective in the

       24    past, the performance of genetic stability as well as a

       25    very important one on well-characterized proteins that

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        1    has led to a lot of forward and positive issues that

        2    actually have occurred under FDAMA, in particular with

        3    respect to fast track.  These are really important

        4    areas, and at the time I am mindful of the fact that we

        5    have had mixed groups.  But to codify this and put this

        6    into routine operation, I think it would be a very

        7    positive and forward-thinking approach for the agency.

        8               This would create, I think, very importantly

        9    a climate where important issues that are on the

       10    forefront of concern from the agency, the public and FDA

       11    would be brought forward and discussed, and a very clear

       12    risk-based decision making approach can be used.

       13               One of the issues that I think is very

       14    contemporary right now is the issue of generic

       15    biologics.  This might be a good opportunity to consider

       16    the use of such a technical advisory board.

       17               Next slide, please.

       18               To answer the question that was asked on

       19    reciprocating exchange and integration of scientific

       20    information and agency scientists, I think one of the

       21    important areas that we might be able to contribute is

       22    the advice to hire and maintain experienced and

       23    pragmatic staff.  And from this standpoint, as we know,

       24    many of the regulatory agencies around the world insist

       25    upon their staff having had actual industry experience.

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        1    And I can't say enough about the fact that experience in

        2    making risk/benefit decisions is a crucial area for us

        3    and that the agency really needs to think very clearly

        4    and carefully about the ability to hire experienced and

        5    pragmatic staff.

        6               There's also the opportunity to provide for

        7    agency scientists' engagement in laboratory research.  I

        8    think this is a very critical area.  To be able to use

        9    the proper judgment to review the very complicated

       10    submissions that are being proposed today from the novel

       11    sciences that are being developed in the biotechnology

       12    area, it's critical that scientists have both the

       13    experience and understanding in order to make those

       14    judgments.  We propose that sabbatical programs be

       15    created and that corporate internships be considered

       16    where FDA scientists could spend time actually in the

       17    regulated industry to be able to learn the state of the

       18    art that is being considered at those times.

       19               We'd like to propose that scientists from the

       20    industry present state of the art symposia to FDA

       21    scientists and that potentially we use the technical

       22    advisory board as a forum to discuss new information,

       23    advise FDA and hold appropriate symposia.

       24               Next slide, please.

       25               With respect to educating the public on risks

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        1    and benefits, I think it's important to better educate

        2    the public on the basis for the approval of new

        3    medicines.  As we've heard in the video conference by

        4    Dr. Henney and others, the public unfortunately does not

        5    understand the complexity of the drug development and

        6    approval process.  And this leads to a lot of confusion

        7    and difficulties with respect to reporting adverse

        8    reactions and other problems, and for the FDA to take a

        9    proactive stance in terms of educating the public would

       10    be a very positive and forward-thinking approach.

       11               This would provide the public with better

       12    information about the pharmaceuticals that they have

       13    been prescribed and also for them to understand the

       14    risks that are associated with the use of those

       15    pharmaceuticals.

       16               And one thought would be to look at using the

       17    publicly supported forum like National Public Radio or

       18    television for patient education to have actual FDA

       19    fireside chats.  I'm actually mindful of this

       20    presentation that we just heard and that having that on

       21    a national public television, I think would go a long

       22    way to having the public better understand the

       23    complexity of drug development and use of

       24    pharmaceuticals as well as how best to report adverse

       25    reactions when they're observed.

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        1               Next slide, please.

        2               A very important issue I think as you pointed

        3    out is limited resources.  The agency clearly is

        4    limited.  PDUFA has gone a long way to improve the

        5    situation.  But as we all know, it is still far from

        6    perfect.  I think some of the ways in which the agency

        7    could use its limited resources in the most productive

        8    way would be to partner more actively with product

        9    sponsors, to use the advisory committees that are

       10    proposed, to establish priorities potentially for fast

       11    track products because we are mindful that, as we heard,

       12    under FDAMA fast track is a wonderful and powerful

       13    addition to our (unintelligible).  However, it comes

       14    with a cost, in that not all fast track products have as

       15    high a priority as others.  It is a difficult decision

       16    to make with limited priorities.  I'm mindful of

       17    Dr. Henney's words that priorities priorities priorities

       18    are the most important thing before us.

       19               It's also important, I think, to have FDA

       20    influence the sponsors with respect to what will

       21    actually help the reviewers to make their decisions the

       22    most appropriate way.  FDA could actually sponsor a

       23    workshop that would focus on what reviewers want in

       24    terms of making their life easier.

       25               And a final point is the inspection program.

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        1    I think inspections -- and having been in the regulated

        2    industry now for 22 years and having gone through

        3    literally hundreds of inspections, I would have to say

        4    that the inspection program, while very valuable, may be

        5    more important to be applied selectively rather than in

        6    a uniform way.  The industry does go through -- spends

        7    enormous amounts of time on inspections, and not all of

        8    the industry are those that need to be inspected more

        9    frequently.  And that the agency might want to consider

       10    an inspection policy where companies with excellent

       11    compliance and GMP history are perhaps not as heavily

       12    inspected as those who are nowhere near as compliant or

       13    have poor GMP experiences.

       14               Next slide, please.

       15               With respect to stakeholder communications, I

       16    think this has been an excellent venue, and I would like

       17    to encourage you to continue to seek the stakeholder

       18    input, that more and more frequent and early discussions

       19    such as these will benefit both the agencies as well as

       20    the industry, that we'd like to continue to develop and

       21    draft guidance and keep industry informed.  And I would

       22    also like to reiterate that having the industry

       23    participate in the development of these draft guidance

       24    documents would, I believe, facilitate the development

       25    of these guidances and their acceptance throughout the

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        1    industry.

        2               I think to implement modernization

        3    effectively and consistently, it's important to

        4    harmonize the guidance and process across the centers.

        5    At this time, while there is a tremendous value in

        6    development of this guidance, it is clearly not

        7    harmonized across the various centers of FDA, and this

        8    would be very helpful to the industry, particularly

        9    those who may deal with biologic drugs as well as

       10    devices.

       11               To harmonize globally, I think the ICH

       12    process is a critical area.  FDA has actually led the

       13    way in ICH, and this requires a lot of time and effort

       14    and dedication.  And to continue to provide the

       15    horsepower necessary to facilitate the ICH process will

       16    make I think the entire situation very productive and

       17    positive.

       18               Finally, there is the situation of

       19    pharmacopeia in that the regulated industry does follow

       20    the pharmacopeia and is highly involved with them, and

       21    they do provide very excellent guidance.  I would like

       22    to encourage the agency and all the centers to work

       23    closely with pharmacopeia in defined areas where mutual

       24    partnership and value can be obtained.

       25               In conclusion, I would like to say that I

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        1    think the agency has done a wonderful job implementing

        2    FDAMA.  I think it has been a hard and difficult road to

        3    follow.  But your clear wisdom and guidance and

        4    leadership in the area is appreciated by the industry.

        5               Thank you.

        6               DR. ZOON:  Thank you.  Thank you very much.

        7               (Clapping)

        8               DR. ZOON:  Yes.  If I could -- would you take

        9    a few questions for clarification?  One of the things I

       10    would like to ask, when you talk about input into

       11    guidances, because of the federal advisory committee on

       12    some parts of this is a bit limiting both with the

       13    boards and with the ability to really formulate some of

       14    these things in an interactive process.  And I was

       15    wondering -- I love the concept of these.  Do you have

       16    some suggestions on how you think we could from the

       17    perspective, could it be workshops, in ways that we

       18    could do the interactions on the scientific issues that

       19    would lead into the documents?

       20               And secondly, in looking at the technical

       21    boards, how do you perceive those to come about in some

       22    of the dilemmas we have with respect to other provisions

       23    that we need to comply with?

       24               DR. GARNICK:  It's a good question, and I

       25    probably don't have all the answers for it.  But I

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        1    remember the well-characterized protein symposia that

        2    FDA began a few years ago and the value of that in which

        3    you actually had representatives from industry as well

        4    as FDA begin to think through and plan that type of

        5    meeting.  That was a one-of, and it was very valuable.

        6    And I think the ramifications of what were done at that

        7    meeting we're still developing today.

        8               But to codify this type of approach, the

        9    development of boards -- and I think you can have boards

       10    in the area of clinical studies, free clinical studies,

       11    and manufacturing and controls and potentially

       12    post-marketing safety.  You could develop boards like

       13    this that would be standing.  The membership could be

       14    chosen by FDA.  For example, they would be publicized.

       15    People would know who are the members.  They would

       16    probably have some rotation basis.  But the challenge to

       17    them would be those picked by the agency so that when

       18    timely and important issues begin to emerge, and we all

       19    see them emerging, that you could be able to get the

       20    horsepower of those groups together to decide what the

       21    situation really is or isn't, whether a national

       22    symposia such as a well-characterized protein, what

       23    needs to be held in those areas and to provide you with

       24    the guidance in terms of where to go from there.  And I

       25    think that would help quite a bit.

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        1               With respect to the requirements that you

        2    have with disclosure and things like that, I think we

        3    would have to work to find -- to work our way around

        4    that, but it clearly is possible to be done.

        5               DR. ZOON:  Thank you.  Jerry?

        6               DR. DONLON:  I just have a few simple

        7    questions.  One thing in the area of enhancing the

        8    science base for the agency or for (unintelligible) --

        9    are there specific disciplinary areas or scientific

       10    areas that you recommend we pay attention to or root for

       11    or enhance?

       12               DR. GARNICK:  Actually, I think that from my

       13    own experience the agency does find people with good

       14    educational backgrounds.  But it's the experience base

       15    that sometimes is lacking.  There are a lot of excellent

       16    universities, but they don't teach you what actually

       17    happens in real life.  And it's people -- I would

       18    encourage you to find and hire people who have had

       19    experience and who know -- or are more pragmatic in

       20    their approach and judgment.  And some of the areas in

       21    which you might be looking in I think in terms of

       22    chemistry, chemistry, biochemistry, clinical trial

       23    design, pharmaco (unintelligible).  These would be

       24    important areas to focus on.

       25               DR. DONLON:  Would some of the emerging

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        1    technologies in pharmacogenetics, things of that nature,

        2    should we be looking to enhance our abilities in those

        3    areas as well?

        4               DR. GARNICK:  Absolutely.  I think there's

        5    quite a lot of work going on now in the areas of cell

        6    and gene therapies.  And this is clearly an emerging

        7    technology which there are very many new things that

        8    need to be discovered and dealt with.  And there are a

        9    lot of interesting and complicated regulatory aspects to

       10    them.

       11               So looking for people in those areas I think

       12    would also be very valuable.

       13               DR. DONLON:  Brief question:  You mentioned

       14    inspection program, the need to perhaps modernize the

       15    inspection program in a way.  There is an initiative

       16    clearly with the foods and the seafood issues by looking

       17    at the pass -- applying passive analysis and critical

       18    control points type of programs, and devices is looking

       19    at piloting that into the device area.  What's your

       20    sense as far as industry's reception to that type of an

       21    approach more broadly in the biotech industry?

       22               DR. GARNICK:  With respect to the biotech

       23    industry, I think to put it in perspective, this is a

       24    new industry that people who are involved I think are

       25    extremely serious and dedicated to the development of

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        1    new products and (unintelligible) mode.  They are

        2    particularly mindful, I believe, of FDA guidance and

        3    interactions, and they probably are the most

        4    inspection-conscious members of the industry.  That may

        5    or may not be true in all cases.  But in general, they

        6    are probably very highly inspectional -- inspection

        7    concerned and experienced.  And they're probably not the

        8    problem.  The problem may well be elsewhere.  And to

        9    spend enormous amounts of precious FDA resources,

       10    particularly with respect to the new BLA process and

       11    under fast track where inspectional issues as well as

       12    issues with response to the submission are actually

       13    being reviewed, it's probably not the best use of FDA's

       14    time.  I would concentrate my efforts where the problems

       15    really lie, and I think you know from your compliance

       16    and GMP experience exactly where they are.

       17               DR. DONLON:  One other observation.  You

       18    mentioned we should have a closer working relationship

       19    with the pharmacopeia.  I just want to point out that

       20    Dr. Kenney is past president of the U.S. Pharmocopeia.

       21               DR. GARNICK:  Yes, I am quite aware of that.

       22    I think she has gone a wonderful job in that area.  I

       23    would really encourage the pharmacopeias and the FDA to

       24    find a harmonized ground in which real value could be

       25    added to the industry.

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        1               MS. ZIOBRO:  Thank you.  I'd like to ask our

        2    next speaker to come up, Cindy Morrow, who is the senior

        3    regulatory specialist at Becton Dickinson.

        4               MS. MORROW:  Hello.  My name is Cindy Morrow,

        5    and I'm an employee of Becton Dickinson Biosciences in

        6    San Jose.  I wish to thank the Center for Biologic

        7    Evaluation and Research for providing this opportunity

        8    to share our suggestions for FDA's efforts to improve

        9    its implementation of the law.  I'd also like to thank

       10    my mentor and boss, Anna Longwell, who helped me

       11    actually prepare these comments.

       12               First, I would like to address some ideas of

       13    how FDA might expand its capability to incorporate

       14    state-of-the-art science into its decisions.

       15               CBER is noted for its commitment to biologic

       16    science.  From the origins at Treasury through its long

       17    (and continuing) association with NIH, CBER has been

       18    committed to understanding and contributing to advances

       19    in pharmacology and molecular and cell biology.

       20    However, now CBER must also review devices, ancillary

       21    products and combination products, which require

       22    additional expertise in such varied disciplines as

       23    computer science, polymer and surface chemistry, and

       24    many other technologies.  We suggest that CBER work more

       25    closely with the other FDA centers to acquire this

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        1    expertise.

        2               Please take advantage of the resources you

        3    already have within FDA, but perhaps use them

        4    differently.  Also, get more advisory committee members

        5    with expertise in the physical sciences and computers.

        6    You could also ask manufacturers to provide more

        7    information about the basic science and technology

        8    involved in the development of their products well in

        9    advance of product review.

       10               A vendor day is a technique employed by other

       11    centers to gain knowledge and allow interaction with

       12    industry.  This idea could be expanded to a more

       13    science-fair-like event, to include discussions on areas

       14    of mutual interest for industry, regulators, and the

       15    public and provide opportunities for hands-on

       16    demonstrations of technology, including instrumentation,

       17    hardware, software and product information.

       18               It's important that FDA management provide

       19    the time and resources to allow all levels of FDA

       20    employees to participate in learning opportunities in

       21    order to encourage and maintain the good people that you

       22    already have employed at FDA.  In your hiring, seek out

       23    individuals who have both scientific expertise and

       24    experience in the practical application of medical

       25    products.  Look for opportunities for reviewers and

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        1    investigators to participate in externship programs

        2    where they can gain experience with medical products and

        3    the practice of medicine.

        4               Next I would like to address how FDA might

        5    incorporate state-of-the-art science into its risk-based

        6    decision making especially in the area of new product

        7    reviews.

        8               We all acknowledge that the rate of

        9    scientific discovery and development is accelerating.

       10    Under today's product development systems for biologics,

       11    or for devices reviewed by biologics, any truly novel

       12    product reaching the U.S. market will be at least one

       13    generation (or more) removed from state-of-the-art.

       14    However, this situation can be beneficial.

       15               An extensive program of design and testing is

       16    not only a regulatory expectation but has become an

       17    industry (and indeed a public) expectation for any truly

       18    novel health care product entering our market.

       19               One result of this careful and organized

       20    approach to product development and evaluation, combined

       21    with the almost daily changes in technology and science,

       22    is that no product will be state-of-the-art when it

       23    reaches the reviewer's hands.  If the FDA insists on

       24    "state of the art," companies are continually thrown

       25    into a round of revisions and validations for each

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        1    significant improvement.  And products that will have

        2    significant health benefits for patients and their

        3    providers will not reach the market in an appropriately

        4    timely fashion.

        5               FDA should not feel that it alone has to

        6    provide incentive to manufacturers for continual product

        7    improvement.  For high-technology industries making

        8    regulated product, there is ample incentive to continue

        9    state-of-the-art product development.  Our competitors

       10    provide this incentive.  For most of us, the motto is

       11    "improve or die."

       12               In review, FDA should principally base its

       13    expectations for product performance on what is

       14    currently available for use in the U.S. market, not on

       15    what is being explored at the NIH or other world-class

       16    research institutions.  Risk/benefit assessments for

       17    marketing permits should not be conducted on what could

       18    be developed, but on what is currently available.

       19               For issues concerning product safety, FDA

       20    should base its review on the very latest information,

       21    as long as that information is based on labeled claims

       22    for the products, statistically valid scientifically

       23    sound studies, and is not anecdotal information, whether

       24    obtained from peer-reviewed scientific journals or other

       25    sources.

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        1               One use of state-of-the-art science which in

        2    the assessment of risk for which FDA deserves

        3    commendation is their consideration of new surrogate

        4    endpoints for clinical studies and new in vitro

        5    analogues for lengthy animal studies.  These advances in

        6    science serve to shorten testing time and allow

        7    innovative products to reach the market sooner, thus

        8    shortening the product life cycle while still protecting

        9    the public health.  We expect FDA will continue to

       10    encourage advances in these areas.  By encouraging more

       11    scientific ways of establishing product performance, FDA

       12    will also assure that the product reaching the market is

       13    as close to state-of-the-art as it can reasonably be

       14    expected.

       15               When there are scientific disagreements, we

       16    recommend that FDA have available mechanisms to take the

       17    issue to an outside scientific review process, short of

       18    convening an advisory committee.  However, yesterday, I

       19    ran across a new CDRH draft guidance on resolving

       20    scientific disputes concerning the regulation of medical

       21    devices that I'm looking forward to reviewing.  I just

       22    had a chance to print it out.  It showed up on the

       23    Internet yesterday.

       24               Next, educating the public about risk/benefit

       25    analysis.  Risk/benefit analysis is not well understood

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        1    by the general public.  We see this frequently, when the

        2    news of a single disaster with a product outweighs the

        3    years of positive health effect obtained by use of the

        4    same product.  News stories about disasters command

        5    attention, while statistics do not get the same

        6    coverage.

        7               If the FDA wishes to provide outreach to the

        8    general public about risk analysis, we suggest an

        9    approach that might utilize the Internet to capitalize

       10    on some more familiar risk/benefit choices that people

       11    have to make every day.  It might be possible to utilize

       12    FDA's Office of Special Health Issues home page to

       13    develop an outreach program that explains risk/benefit

       14    analysis in simple terms.

       15               The approach might provide examples of what

       16    people have to consider when evaluating their own

       17    medical treatment options with the help of their

       18    physician.  For example, what questions they need to ask

       19    their doctor and risks and benefits associated with each

       20    treatment option.  This might be done for key diseases

       21    with three or four alternate therapies to help explain

       22    the concept of risk evaluation.  Then, once the basic

       23    idea is established, you could explain how the same

       24    techniques are employed by FDA on a more global scale to

       25    review therapeutic or diagnostic products aimed at the

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        1    same disease categories.

        2               Also, it would be helpful if you could

        3    convince nonprofit organizations interested in public

        4    health issues to provide a link to this same web page.

        5    It would afford greater public access to alternative

        6    points of view.

        7               Next, improving FDA's focus.  In this era of

        8    restricted funds, more cooperation between centers and

        9    between government agencies seems indicated.

       10               If FDA wishes to concentrate more resources

       11    on areas of greatest risk to public health, we suggest

       12    close cooperation with the Centers for Disease Control,

       13    which has long been developing information on public

       14    health, and on our most serious public health problems.

       15    Once areas of greatest public health risk are agreed

       16    upon by FDA, they should be published, and a mechanism

       17    for updating these findings should be established.  FDA

       18    might then consider expanding the Accelerating Approval

       19    process to include products which are employed to treat,

       20    diagnose or prevent these identified public health

       21    problems.

       22               Additionally, CBER should work with industry

       23    to actively identify and downclassify lower risk devices

       24    that have a good record for safety.

       25               Also, CBER should work with the CDRH to

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        1    standardize and clarify the "least burdensome"

        2    provisions of FDAMA relating to device review and

        3    clearance to market.

        4               Cooperation between centers is now being

        5    attempted more frequently, and we applaud FDA,

        6    especially CBER, for their efforts in this area.  We

        7    believe that more could be done to tap inter-agency and

        8    intra-center expertise in the areas of device review,

        9    web page design, and communication about processes in

       10    general.

       11               Finally, enhancing public feedback for FDA

       12    communication efforts.  We believe that CBER should make

       13    better use of its website to obtain feedback.  Also, we

       14    believe that the website could be updated more

       15    frequently and be more transparent in its use.  For

       16    devices in particular, it would be helpful to provide

       17    linkages to relevant guidance developed by CDRH.  Just

       18    yesterday, I found a Federal Register notice listing

       19    guidance documents that were issued by CDRH that apply

       20    to medical devices regulated by CBER.  That was

       21    published on Monday on the website.  So you mentioned

       22    that.  That's very helpful, especially if this

       23    information can then be incorporated into your website

       24    with links.

       25               To obtain public feedback on particular

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        1    topics, it might be possible to post questionnaires to

        2    the website with "fill out the blank" type forms that

        3    could be returned via electronic mail.  However, we have

        4    found at Becton Dickinson that many people are unwilling

        5    to give completely honest feedback especially internally

        6    unless they are assured of anonymity.  Therefore, it

        7    might be a good idea for the FDA to contract with a

        8    third party and have them analyze the report on feedback

        9    to questionnaires.

       10               We believe that local grassroots groups such

       11    as the OCRA group in L.A., the Orange County Regulatory

       12    Affairs, discussion group; the PAIR group in the Oakland

       13    district, Partners on Industry and Regulators; and IVD

       14    Roundtable, for example, in the Baltimore area should be

       15    supported and that more districts should be encouraged

       16    to form outreach groups with local industry.  These

       17    provide for valuable interaction and feedback from

       18    members of regulated industry to regulators, and vice

       19    versa.

       20               One area in which more feedback could be

       21    solicited is in the development of internal procedures

       22    and processes to implement FDAMA at CBER.  We hope that

       23    CBER will allow greater and earlier stakeholder

       24    participation in the development of FDAMA implementation

       25    procedures.

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        1               Thank you.

        2               DR. ZOON:  Thank you very much.  I appreciate

        3    all those comments.  Any clarifications?  I think it's

        4    clear.

        5               (Clapping)

        6               DR. ZOON:  I'd like to ask Paul Holland, the

        7    last scheduled speaker, to please come up.  Paul is from

        8    Sacramento Medical Foundation Blood Centers.

        9               DR. HOLLAND:  Thank you, Kathy.  I'd like to

       10    thank the FDA for holding these sessions.  I think they

       11    are useful.  I appreciate the ones you have had in the

       12    past and that you've provided us feedback from those.  I

       13    think that was very helpful to us all.  I'm disappointed

       14    and dismayed that more people from blood banking and

       15    transfusion medicine, my field, are not here to comment

       16    or at least attend.  It's a great opportunity to provide

       17    your input.

       18               In providing my comments today, I hope you'll

       19    take them as constructive comments, that they are from

       20    our own center, my staff, and not from anyone else.  I

       21    tried to organize them in response to the questions, and

       22    so I'll go through them.

       23               The first one is what actions do you propose

       24    the agency take to expand FDA's capability to

       25    incorporate state-of-the-art science into its risk-based

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        1    decision making?

        2               Implement your own quality assurance

        3    guidelines -- these were issued in July of '97 -- and

        4    put them into your labs and processes at the FDA.  They

        5    apply to us, and I think they should apply to you, too.

        6               Certainly if you adopt a systems approach to

        7    FDA's own quality system and operational areas, such as

        8    the ISO 9000 model, incorporating principles of

        9    continuous process improvement, tracking and trending,

       10    et cetera, I think that will help you.

       11               We certainly support your goals of

       12    maintaining firsthand scientific expertise on relevant

       13    technology and diseases.  But you need to supplement

       14    with experts or by partnering from various fields to

       15    expedite evaluations of new applications of old products

       16    and the requirements for, in my case, donor blood

       17    testing.

       18               You can certainly access outside scientists

       19    and medical experts.  As was said in other ways, I think

       20    you might have a scientific advisory committee.  You

       21    have a blood products advisory committee, but today this

       22    has few scientific blood banking transfusion experts on

       23    it.

       24               I think you need to perform risk assessment

       25    based on true hazards or harmful incidents, not just

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        1    every GMP violation.  The FDA has made extra work that

        2    has nothing to do with minimizing harmful risks.

        3               You need to identify errors that present

        4    known harmful risks and require only those to be FDA

        5    reportable.  For example, these would be FDA reportable:

        6    A true infectious diseases reactive unit that was

        7    issued; a contaminated unit that was issued; untested

        8    unit issued; ABO/Rh mislabeling.  You really need to

        9    minimize FDA reporting to critical issues.

       10               Use scientific evidence (by expert consensus)

       11    to establish new regulations.

       12               Please do not implement precautionary

       13    measures without known fact or cause/effect impact that

       14    will decrease the donor or donation rates, and by how

       15    much.  Eliminating eligible donors on speculation or

       16    just theoretical possibilities can result in lack of an

       17    adequate blood supply, and this could actually result in

       18    real patient death, very directly.

       19               The next question was what actions do you

       20    propose to facilitate the exchange and integration of

       21    scientific information to better enable FDA to meet its

       22    public health responsibilities throughout a product's

       23    life cycle?

       24               A specific example:  Reconsider the need to

       25    continue the requirement for submitting products for

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        1    platelet quality control.  Are any discrepancies and

        2    perceived failures in counts at CBER due to equipment

        3    differences, modes of use?  Has this been scientifically

        4    investigated?  If the facility producing these platelets

        5    has adequate data to show the required criteria have

        6    been met, why continue this requirement on only this one

        7    product?  What is the real public health risk?  Is there

        8    one?  The requirement is costly; it uses up a valuable

        9    component that patients cannot receive.  And we really

       10    wonder how meaningful this process is.

       11               We think you should establish a hotline, fax

       12    line, Internet page, whatever, for the regulated

       13    industries to obtain quick answers to questions from an

       14    identified pool of FDA subject matter experts.  This

       15    would really enable greater collaboration with FDA in

       16    bringing new products to market to benefit patients.

       17    For example, my area again, licensed pediatric platelet

       18    dose, a blood product, to streamlining submissions and

       19    clarification of new processes coming, like the BLA

       20    (Blood License Application).  We need to work with you

       21    on such issues as a comparability protocol, monographs

       22    for standardized blood products, and pilot programs for

       23    licensed blood products (like irradiated blood pilot)

       24    that you produce.

       25               Again, echoing comments of other speakers,

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        1    establish public forums and workshops at national

        2    meetings with scientific information presented.  The FDA

        3    must take quicker actions and finalize documents more

        4    quickly.  Some items, like the product license

        5    applications, are approved after the blood center has

        6    moved on to new methodologies.  We are no longer using

        7    the methodology anymore, and we finally get them

        8    approved.

        9               We think you should do away with PLAs all

       10    together, product license applications.  If a center

       11    validates and meets the criteria of regulations, why not

       12    allow the product to move in interstate commerce in that

       13    basis.

       14               We would appreciate if you would finalize

       15    some of your draft guidelines a little more quickly.  As

       16    an example, the draft computer guideline is years old,

       17    and it still hasn't been finalized.

       18               Question No. 3 was what actions do you

       19    propose for educating the public about the concept of

       20    balancing risks against benefits in public health

       21    decision making?

       22               I think you need to provide analogies with

       23    real-life risks that are undertaken daily.  That is, how

       24    does the risk compare to driving a car, flying in a

       25    commercial airliner, riding a bike, walking up stairs?

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        1    This approach would really, I think, assist the public

        2    in gaining a perspective on risk-related issues that are

        3    often very emotionally charged.

        4               Question 4:  What actions do you propose to

        5    enable FDA and its product centers to focus resources on

        6    areas of greatest risk to the public health?

        7               As I said, that's another answer, is really

        8    streamline your product licensing for standard blood and

        9    blood products to a monograph system of basic

       10    specifications.

       11               Echoing, again, the comment I made before,

       12    eliminate the need to submit actual platelet products to

       13    be sent to CBER for quality.

       14               On site inspections and overall enforcement

       15    via reporting of errors and accidents and recalls focus

       16    on minute details, not usually the overall system, or

       17    real risk to transfusion recipients.  A systems approach

       18    to both would allow delineation of isolated events, from

       19    true system-wide issues that need to be addressed in a

       20    much larger context.

       21               We wish you would require that error and

       22    accident reporting and recalls only apply to issues that

       23    pose real risk (by some predefined criteria) to the

       24    public.  Some of the errors and accidents we have to

       25    report are GMP related only, and almost all donor

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        1    accidents from post-donation information are low risk or

        2    have such low potential such as potential malarial

        3    exposure travel, subsequent illness.  You and we need to

        4    focus on higher risk issues for the biggest benefit of

        5    the public and really require only reporting if the data

        6    are used for some follow-up purpose.  Just to gain this

        7    data without using them doesn't help any of us.  What do

        8    you do with this data other than making internal

        9    reports?  What is it used for?  How is it used?  I think

       10    we need to have you and us have use of that.

       11               We suggest to set a timetable for updating

       12    all blood and blood product regulations and fold them

       13    all together in one set, incorporate all the previous

       14    FDA memos that are endorsed into regulations.

       15               Make the regulations in the CFR available on

       16    the Internet with a search capability by topic and

       17    cross-referencing to related topics.

       18               We really appreciate your efforts, but we

       19    need you to continue to work on decreasing and

       20    eliminating the paperwork burden for reporting and

       21    licensing.  The annual report is one example of

       22    additional new reporting requirements that have a

       23    significant increase in data handling and reporting to

       24    CBER.  The new BLA and form 356h will require more data

       25    and information to be submitted for product licensing

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        1    than the previous process required.

        2               You need to revise the recall regulations to

        3    provide more specific criteria based on real risk, for

        4    required notifications and recall, and follow-up on the

        5    disposition of products.  This action would decrease the

        6    amount of activity now required for many low risk

        7    recalls, which most of which are just GMP breach only.

        8               We would appreciate if you would plan the

        9    public meetings on new regulations, new guidance

       10    documents, new proposed programs to be bi-coastal or via

       11    satellite downlink (unintelligible) such as today.  Due

       12    to the distance and travel expenses, we cannot send a

       13    representative to a one-day meeting in the middle of a

       14    week on the opposite coast.

       15               FDA assessments of fiscal impact and are

       16    often totally unrealistic in proposed documents and, we

       17    believe, largely unfounded.  We need to have you base

       18    these on real data, please.

       19               As a plea, we'd like you to address, up

       20    front, the reimbursement issues of blood centers and

       21    hospitals for FDA mandates or recommendations for

       22    testing, or product manufacturing, or strongly support

       23    new research testing, such as H.I.V. antigen,

       24    Nucleo-acid testing, (unintelligible) blood products.

       25    We need you to help us, and you need to notify and

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        1    encourage HCFA about adequately reimbursing us for added

        2    costs of FDA mandates and recommendations.  We too have

        3    budget limitations, and we cannot do more with less as

        4    you've heard.

        5               Most blood centers and hospitals are not

        6    for-profit.  The decisions for new requirements must

        7    include how they are going to be paid for.

        8               We'd appreciate if you would eliminate

        9    unnecessary activities such as recalls that will not

       10    provide a beneficial outcome or prevent harm.  Many

       11    recalls and component retrievals are useless in really

       12    reducing risk.

       13               As was mentioned by one of the speakers,

       14    there is a coalition for regulatory reform, CFRR.  The

       15    blood banking community tries to get its comments and

       16    concerns in to them and from them to you.  But often,

       17    they don't seem to have much weight.  We are often told

       18    that CBER wants to hear individually from centers and

       19    from individual people, not the CFRR.  We rely on the

       20    CFRR to represent us since most of us cannot send

       21    representatives to meetings that CFRR would attend.

       22               Question No. 5, what actions do you propose

       23    for enhancing communication processes that allow for

       24    ongoing feedback and/or evaluation of our modernization

       25    efforts?

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        1               I think some written surveys to stakeholders

        2    seeking input on top of some questions would be

        3    worthwhile.

        4               We need you to provide feedback from these

        5    surveys or meetings by the Internet, written reports,

        6    whatever.

        7               Setting up an Internet page for a

        8    dialogue/feedback on topics or on defined questions that

        9    change on some regular basis would be of help.

       10               Set up a mechanism for error and accident

       11    reporting via Internet with encryption preferable.

       12               The new FDA annual report notification of

       13    changes process has added pounds of paper work for blood

       14    centers.  What good is this doing to protect the blood

       15    supply or for the center?  FDA inspectors can inspect

       16    for any and all changes they want during reinspections.

       17    What is the value of submitting all this input to help

       18    you?  Parenthetically, we can't really digest it all.

       19               Having inspectors review product validation

       20    on site.  Can the FDA really manage all the reports it

       21    gets and in a timely manner?

       22               In general, the comments I'm trying to make

       23    are that we really need help from you.  We need to help

       24    you.  No doubt about it.  And one of the areas is that

       25    when we ask for advice or questions, we would like a

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        1    concrete and specific answer, preferably in writing.  So

        2    often we get an answer, "that's under review," or "that

        3    document will be out soon" or "we're here to help you."

        4    Without something in writing in a specific response, we

        5    are not helped a great deal.  And it should be based on

        6    the current regulations.  And hopefully, it should be a

        7    quick response.

        8               All of your biologic regulations need to be

        9    updated.  Many are archaic.  Put them all in one

       10    section.  Resolve discrepancies between the CFR and FDA

       11    memos and guidelines.  We need you to take the words

       12    "just do it" just as we have to based on scientific

       13    information from expert consensus.  And if there is no

       14    consensus, then I'm not sure we should have such

       15    regulations.

       16               Our final plea is basically to consider risk

       17    in general.  I thought one of the most valuable things I

       18    learned today was a comment by Dr. Henney.  She said

       19    "Safety does not mean there is no risk."  And we are

       20    working harder and harder and spending more and more

       21    resources on making the blood supply safer and safer,

       22    when we might think that our tax dollars might be better

       23    spent on societal issues such as smoking, drugs, guns,

       24    poor education, lack of medical access, underage

       25    drinking.  These are really more worthy topics than

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        1    trying to further minimize the small risk we have from

        2    the blood supply, which is extremely safe today.

        3               In closing, once again, thank you for the

        4    opportunity to make these comments.  If you have any

        5    further feedback, please, I am happy to answer them, or

        6    my staff, especially Sally Morgan-Gannon and Sallie

        7    Holliman, who helped me write this statement.

        8               Thank you.

        9               DR. ZOON:  Thank you, Paul.  One question

       10    that I'd like to ask you is do you think the blood -- in

       11    hearing your comments, many of the objectives that we

       12    have put forward in the blood action plan, there is a

       13    lot of overlap.  And my sense is in your review of that,

       14    do you think that captures a lot of what you're trying

       15    to do?  Because that's where we are right now.

       16               DR. HOLLAND:  I think it does, but I think we

       17    have to get on with it.  We have to get to it and do it.

       18    And some of these suggestions we both agree on; we just

       19    need to do them, because it will eliminate your

       20    unnecessary work, allow you to have better use of your

       21    limited resources, as would be true for us, too.

       22               DR. ZOON:  Thank you.  Do you have any

       23    comments?

       24               DR. DONLON:  Just one observation.  You were

       25    commenting on the quality assurance practices.  The

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        1    agency is initiating an evaluation of a proposal

        2    basically to accredit the laboratories in the agency, to

        3    accredit them to the ISO 25 or ISO 17025 version of

        4    that, so we are moving in that direction.  And our

        5    center certainly, I think, has taken the lead in that

        6    regard.  So we are recognizing that we know it's

        7    appropriate for industry, certainly appropriate for our

        8    laboratories.

        9               DR. HOLLAND:  Great.  I applaud that.  Thank

       10    you.

       11               DR. ZOON:  I might also add we had an

       12    external review of our entire science program at CBER

       13    last year, and one of the recommendations that we have

       14    started implementing from that external review was to

       15    increase the quality assurance program at the center and

       16    with respect to private testing.

       17               So those recommendations have been made and

       18    instructions to each of the offices to -- as resources

       19    permit, to start implementing that recommendation.  I

       20    think the findings of the plan is being drafted as we

       21    speak.

       22               So I think that's very timely and very much

       23    on target with the external review.  So thank you for

       24    those comments.

       25               DR. HOLLAND:  Thank you.

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        1               (Clapping)

        2               MS. ZIOBRO:  I'd like to ask now, do we have

        3    any comments from the rest of our audience here?

        4               Margie, would you please come up to the

        5    microphone, state your name, who you're with, and spell

        6    your name.

        7               MS. VASILEVSKY:  Okay.  My name is Margie

        8    Vasilevsky.  That's spelled V-A-S-I-L-E-V-S-K-Y.  And

        9    I'm with Bayer Corporation.  I'm a QA manager, and I'm

       10    also on the (unintelligible) steering committee

       11    representing biologics.  On this issue I am representing

       12    the West Coast chapter of ISPE.

       13               And the issue is that we would like to

       14    participate in a rewrite of the 1987 process validation

       15    guidelines.  We have an advisory board, industry

       16    executives, and they overwhelmingly said that their

       17    biggest concern is out of control cost as it relates to

       18    validation.  And we looked into this, and it seems to be

       19    the consensus of the industry that there's been an

       20    incorrect emphasis on validation, non-value added versus

       21    value-added activity.  We would like to see it go back

       22    to scientific principles that really insure product

       23    quality.  For example, 80 percent of our time, generally

       24    speaking, is spent on IOQ.  It should be the other way

       25    around.  We should be spending 80 percent of the time on

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        1    PQ and on process validation.

        2               So that is -- I just had that one issue.

        3               DR. ZOON:  Thank you.

        4               MS. ZIOBRO:  Anyone else?

        5               Kathy may be able to make her plane now.

        6               DR. ZOON:  Thank you very much.

        7               I just want to say it is a pleasure to be

        8    here.  Sometimes when you're sitting here and listening

        9    to the comments makes you feel a little bit bad, but I

       10    know they're given in the right spirit.  And we take

       11    them that way.  So I thank you for that.

       12               And if we all can sit and discuss it in a

       13    good old-fashioned honest way, I think we will make

       14    progress.  And we do appreciate that.

       15               I would like to thank everybody who spoke up

       16    today as well as those of you who have been considering

       17    jotting something down to please do so.  I really

       18    encourage you to because that's the only way we'll

       19    really know where your concerns are.  We will do our

       20    best within our resources to be responsive.

       21               I do have to say, especially in the blood

       22    area, that has been a problem that we're facing in our

       23    resource areas.  So we really -- to the level that you

       24    can help us, give us your priorities as what needs to be

       25    done first, that's always very helpful.  We ask the same

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        1    question to the device industry as well, because of the

        2    limited resources we have, what is most important to do,

        3    so that we can make sure that we're targeting the right

        4    things in the right order at the right time.

        5               So to all of you who have come, I want to

        6    personally thank you.  I appreciate it.  And you don't

        7    need to just wait one time a year to give us your

        8    feedback.  I think we're willing to accept feedback any

        9    time during the year.  And our Office of Communication

       10    and Manufacturing Assistance with Dennis Strickland, who

       11    is here, can give you information to get word back to

       12    the agency and CBER on any issues that you might need.

       13               I would also like to thank our host,

       14    San Francisco District.  Thank you so much.  And we

       15    really appreciate it, Pat.  And for all your

       16    hospitality.

       17               MS. ZIOBRO:  And as you suggested,

       18    Dr. Holland, we would really like to continue having

       19    bi-coastal meetings such as this because that's where

       20    the bulk of the industry is.  So we appreciate that.

       21               I'd like to remind you all to fill out your

       22    evaluation of the teleconference because what we hear

       23    from you today will govern whether we have more of

       24    these.  And I think we all agree it was a real

       25    beneficial experience for all of us.

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        1               Is there a need for anybody to return after

        2    lunch?  I see us at a point where we've run out of

        3    comments.  If you feel you would like to come back for a

        4    discussion, we can do that.  Is there anybody who feels

        5    they would like to come back and have discussion?  Okay.

        6    Because we want to do what you want to do.

        7               All right.  I think that will be the end of

        8    it.  Again, thank you for joining us.  We'll see you

        9    again soon, I hope.

       10               (Proceedings adjourned at 12:56 p.m.)

       11                            --oOo--

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        1

        2                    CERTIFICATE OF REPORTER

        3

        4               I, CLARE MACY, a Certified Shorthand

        5    Reporter, hereby certify that the foregoing proceedings

        6    were taken in shorthand by me, at the time and place

        7    therein stated, and that the said proceedings were

        8    thereafter reduced to typewriting, by computer, under my

        9    direction and supervision;

       10               I further certify that I am not of counsel or

       11    attorney for either or any of the parties nor in any way

       12    interested in the event of this cause, and that I am not

       13    related to any of the parties thereto.

       14

       15               DATED: _____________________, 1999.

       16

       17

       18

       19

       20                         _____________________________

       21                         CLARE MACY, CSR #5256

       22

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