1


           1
           2
           3
           4            FDA/CENTER FOR VETERINARY MEDICINE
           5                    STAKEHOLDER MEETING
           6
           7
           8
           9                      April 28, 1998
          10
          11
          12
          13
          14             Johnson County Community College
          15                   Overland Park, Kansas
          16
          17
          18
          19
          20
          21
          22
          23
          24
          25



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           1                MR. ROGERS:  To start our afternoon 
           2    session Dr. Sundlof, the Director for the Center 
           3    for Veterinary Medicine, is going to give us an 
           4    update.  His colleague, Dr. Tollefson will sit in 
           5    for him and tell us what has happened since our 
           6    last stakeholder meeting in August.  And now to 
           7    launch us for this afternoon's session, 
           8    Dr. Sundlof.
           9                     DR. SUNDLOF:  Thank you, Mike.  
          10    And I do apologize for being late this morning, but 
          11    I think it was very ably handled.
          12                     We will go ahead and talk just a 
          13    little bit about some of the things -- some of the 
          14    problems that we face at the CVM.
          15                     Although we're trying very hard to 
          16    meet people's expectations, sometimes it's a little
          17    bit difficult.
          18                     Here's kind of the problem.  We 
          19    showed a similar slide at the last stakeholders' 
          20    meeting, and at least to date nothing much has 
          21    changed.  In the last five years, as Dr. Henney 
          22    mentioned, the FDA in general has had an eroding 
          23    base budget, even though the numbers have stayed 
          24    the same or even increased in some areas at least a 
          25    little bit, certainly in the area of user fees 



                                                                3


           1    there's been a change in the resources available to 
           2    the agency.  That's not the case at CVM.
           3                     We have had some increases in food 
           4    safety issues, but that's very targeted and 
           5    focused.  So we do have decreasing resources in the 
           6    face of expanding responsibilities.  And there are 
           7    a number of those.
           8                     Just to list some of the areas 
           9    where we're at, we've had no program increases in 
          10    nonfood safety initiative programs in the '90s. 
          11    There's been no increase for inflation, pay raises 
          12    or cost of living from '92 to '99.  We've had no 
          13    pay increases in cost of living.  That comes out of 
          14    our operation budget.  So we have less money to 
          15    hire new people in such activities as standards and 
          16    new development, regulation-writing, et cetera.  
          17    We've had to absorb reductions to cover tobacco, 
          18    and food safety initiatives in 1998.  And the way 
          19    that worked was we asked in our budget for certain 
          20    amount of money; and in the case of tobacco it was 
          21    about $34 million to put tobacco programs together 
          22    that we were appropriated $16 million but told to 
          23    spend $3 million dollars.  So that additional $17 
          24    million -- or whatever it comes out to be -- $20 
          25    million, $18 million came out of all of the 



                                                                4


           1    programs within FDA.
           2                     As a result of the present 
           3    streamlining initiative, the national performance 
           4    review we've had to downsize and streamline some of 
           5    our processes.  And in addition, we've had to take 
           6    on some new legislative initiatives which we fully 
           7    support and we're very glad that we did have 
           8    success in getting legislation.  But along with 
           9    that legislation is a demand that we do a lot of 
          10    work to implement the right regulations and et 
          11    cetera, and that takes away from some of our more 
          12    core functions. 
          13                     Here's what we've asked for in the 
          14    year 2000.  As Dr. Henney said in her program, this 
          15    is the biggest increase that the FDA has ever asked 
          16    for, and if we're successful, we will be very 
          17    grateful.  This will help to restore some of the 
          18    erosion that has occurred in the '90s.  If we are 
          19    successful in what we've asked for -- and the 
          20    President has already supported this -- there will 
          21    be an additional 36 positions in the Office of New 
          22    Animal Drug Evaluation to help us with some of the 
          23    backlog and in the regulation-writing process.
          24                     We also will ask for about $4 
          25    million in operating costs for the agency, which 



                                                                5


           1    would give us a total of a little bit over $7 
           2    million, and that doesn't include the increases to 
           3    the field.  That would be substantial in CVM's  
           4    base budget.
           5                     Here's what we identified in the 
           6    year 2000 as some of the gaps.  And if you look at 
           7    this chart, the entire bar is where we think we 
           8    ought to be.  This is what we would need to do our 
           9    job as we think expectations are out there.  A lot 
          10    of this is based on our last stakeholders meeting 
          11    where people told us where we should be spending 
          12    our resources, the things that we're supposed to be 
          13    doing.
          14                     You can see that the green area is 
          15    what we're presently able to do.  If we get our 
          16    year 2000 increase, that's what the red bar is.  So 
          17    even with an increase in people and money, it 
          18    doesn't make a lot of impact on our overall ability 
          19    to reach our goal of a hundred percent.
          20                     Premarket Approval.  Again that's 
          21    an area where we want to focus a lot of our 
          22    resources.
          23                     Product Quality Assurance.  That's 
          24    making sure that we are inspecting, making sure 
          25    that we're out there in the plants and doing our 



                                                                6


           1    job in a timely manner so that we're making it once 
           2    every two years.
           3                     Our research will actually 
           4    decrease a little bit in 2000.  But research is in 
           5    fairly good shape presently and that's largely due 
           6    to the Food Safety Initiative.
           7                     Outreach, our ability to 
           8    communicate with our stakeholders, is important, 
           9    and we will not be doing as much next year as we 
          10    were doing this year.
          11                     Enforcement.  Again, an area that 
          12    is suffering because of the erosion of our base. 
          13                     Injury Reporting.  Although in 
          14    2000 we are asking for $800,000 to do a better job 
          15    of injury reporting or event reporting, some of 
          16    these areas where you see we're actually going 
          17    down, it was planned that we would ask for 
          18    increases in those areas in the year 2001.  So if 
          19    we are successful this year, in our budget for 2001 
          20    we'll try and make up for some of those losses this 
          21    year.  
          22                     Well, in -- based on the chart 
          23    that I just showed you, those are just the things 
          24    that are -- those are the products that FDA/CVM 
          25    produces.



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           1                     The whole budget was targeted at 
           2    productivity, but it didn't really take into 
           3    account many of the things that Dr. Henney has just 
           4    talked about, and especially improving the science 
           5    base of the organization.  And so we're going to 
           6    have to address that also in our year 2000 budget.
           7                     I'll talk a little bit about why I 
           8    think improving the science base is very 
           9    important.  I fully support what Dr. Henney's 
          10    vision is for improving the science base.
          11                     This is kind of a schematic that I 
          12    came up with, and that's about as complex as can I 
          13    get it, drawing a triangle.  This is supposed to be 
          14    a pyramid in which the base of the pyramid is the 
          15    science, and the science is the support of most of 
          16    our regulatory activities, all of the standard- 
          17    setting, et cetera, et cetera.  When you have a 
          18    fairly minimal science base, you have a very large 
          19    regulatory oversight.  
          20                     The caption says, "In the Face of 
          21    Uncertainty FDA Will Over-Regulate Every Time."  
          22    And that's fairly true.  I found that to be very 
          23    consistent that with imperfect knowledge where 
          24    there is uncertainty, the FDA and other regulatory 
          25    agencies -- especially public health agencies -- 



                                                                8


           1    will always take a conservative approach, because 
           2    they are accountable.  Those agencies are 
           3    accountable.  But the better the information, the 
           4    more surgical, the more precise those regulations 
           5    can be so that they are less burdensome to the 
           6    industry.
           7                     We look at the science base.  
           8    Again, the white part of that schematic represents 
           9    the science base with the regulatory oversight 
          10    being the top part.  Where we'd like to get to is 
          11    to have a relatively small oversight that draws 
          12    from a very large scientific base.
          13                     I put surveillance on the bottom 
          14    because I think surveillance is critically 
          15    important to our ability to write correct 
          16    regulations and have feedback as to if the things 
          17    that we've done in terms of standard-setting, 
          18    regulations are providing the results that we 
          19    anticipate.  
          20                     Surveillance is very important 
          21    from the standpoint of things that we don't know. 
          22    We really look at surveillance as an activity where 
          23    we're casting a broad net out there and we're 
          24    trying to find out information, burdening our 
          25    regulated products that we may not have any idea 



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           1    exists out there.
           2                     We require fairly indepth clinical 
           3    studies before we approve a drug, but things happen 
           4    that were never anticipated.  This happens in 
           5    veterinary products; it also happens widely in 
           6    human products.  Without a good surveillance 
           7    program out there -- and I think some of the 
           8    questions that you just heard in the telecast 
           9    really supported that -- how can we get information 
          10    back to the FDA that we're having problems with 
          11    certain products?  Having a good surveillance 
          12    program out there that's sensitive and picking up 
          13    critical information that we can feed back into the 
          14    regulatory process is very important because we 
          15    just don't know everything.  
          16                     In the face of ignorance we will 
          17    tend to underregulate, and that's not good either.
          18                     Research is a second component.  
          19    Research will provide answers to questions that we 
          20    know to ask.  If we know that we need more 
          21    information in a specific area, we can use research 
          22    to provide us with those answers.  This doesn't 
          23    mean that all of the research and all of the 
          24    surveillance is the responsibility of FDA.  In 
          25    fact, most of the research -- actually only a very 



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           1    small part of the research that we use in our 
           2    decision-making process and standard-setting 
           3    process comes directly from FDA research.  We draw 
           4    from the full scientific body of knowledge out 
           5    there.
           6                     Similarly, although a lot of our 
           7    activities, because they are product-related in 
           8    terms of surveillance, are related to FDA-based 
           9    surveillance, there are other surveillance systems 
          10    out there, too, such as Centers for Disease 
          11    Control, MedWatch and other things that are funded 
          12    by FDA will add to that surveillance information 
          13    that we need.
          14                     Then the most important thing that 
          15    I think we do as a regulatory agency is set 
          16    standards that are reasonable, that are protective 
          17    of the public, that are not overly burdensome on 
          18    the regulated industry.  Standard-setting is a very 
          19    public process.  We set standards that we think 
          20    conform with what society expects from us.  That's 
          21    why it is an open process.  But once we set those 
          22    standards, then it's up to us to help the 
          23    industries meet those standards.  So we want to set 
          24    standards that are focused, that are not overly 
          25    burdensome, but that are protective of the public 



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           1    health and then help the industries meet those 
           2    standards.
           3                     The last two things on the top of 
           4    that that aren't labeled up there:  Enforcement and 
           5    Approval.  Those are the two regulatory actions 
           6    that we generally take -- as FDA is we approve 
           7    products and we take regulatory action against 
           8    products that don't come into compliance with the 
           9    standards.
          10                     So now this is a chart that you 
          11    already saw where we just talked about improving 
          12    our capacity to do the things to make the outputs
          13    that we have generally.  What are we going to need 
          14    in the year 2001 in order to not only improve our 
          15    ability to meet our statutory requirements but also
          16    to improve the science base.  We're in the process 
          17    of working on that budget right now.  But certainly 
          18    trying to keep people current, making sure that the 
          19    scientists and the FDA are on par, have parity with 
          20    the scientists in the industries that we regulate, 
          21    et cetera.
          22                     I think I'll just stop right 
          23    there.  Thank you.
          24                     MR. ROGERS:  Thank you, Steve.
          25                     A couple of ground rules for our 



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           1    stakeholders session this afternoon.  I'm going to 
           2    ask each of the speakers to please identify 
           3    yourselves before you start speaking, for the 
           4    benefit of our transcriber.  You will each have two 
           5    minutes -- I'm sorry -- ten minutes; except the 
           6    National Pork Producers, Paul and Beth, will have 
           7    five minutes each.  But two minutes.
           8                     I am going to introduce my black 
           9    belt karate member of our compliance group, Noel 
          10    Ferguson.  He is black belt, and I brought him 
          11    along to be sure that we adhere to the time limits 
          12    of ten minutes.
          13                     All right.  Our FDA panel is not 
          14    to engage in debate but to clarify questions as 
          15    appropriate.
          16                     You might also notice that at 
          17    about 4:30 we will be inviting statements, 
          18    questions from the audience.  The microphones are 
          19    on the side of the aisles and are provided for that 
          20    purpose.
          21                     So with no further ado, Panel No. 
          22    1, starting with Dr. Swanson.
          23                     DR. SWANSON:  Dr. Richard Swanson.  
          24    I'm president of the American Veterinary Medical 
          25    Association.



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           1                     Good afternoon to all of you.  
           2    It's good to see you.  And thanks for eventually 
           3    showing up, Steve.  
           4                     As president of the American 
           5    Veterinary Medicine Association I am pleased to 
           6    participate in the stakeholders meeting.  These 
           7    issues are near and dear to the AVMA's heart, as 
           8    drug availability is directly related to the 
           9    veterinarian's ability relieve the pain and 
          10    suffering of animals.
          11                     The objective of the AVMA is to 
          12    advance the science and art of veterinary medicine, 
          13    including the relationship to public health, 
          14    biological science and agriculture.  The 
          15    Association provides a forum for the discussion of 
          16    issues of importance to the veterinary profession 
          17    and for the development of official positions.  The 
          18    Association is the authorized voice of the 
          19    profession in presenting the views to government, 
          20    academia, agriculture, pet owners, the media, and 
          21    other concerned public.
          22                     The FDA seeks input on the animal 
          23    Drug Availability Act and how to strengthen the 
          24    Agency's science base and improve the communication 
          25    processes.  With regard to the ADAA, areas of 



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           1    progress have included the definition of "adequate 
           2    and well-controlled study," approval of one 
           3    veterinary Feed Directive product, though no 
           4    regulations, feed mill licensure, approval of 
           5    combination products and the CVM's minor use  minor 
           6    species proposal.  The determination of 
           7    "substantial evidence" of efficacy is a big piece 
           8    of the ADAA that is still being tracked; that is, 
           9    determining when greater one adequate and 
          10    well-controlled study is needed or when field 
          11    studies are needed to establish efficacy.  It is 
          12    through this piece that the AVMA and others seek a 
          13    speedier drug approval process.
          14                     With respect to the FDA's desire 
          15    to strengthen the science base and improve its 
          16    communication processes, let me offer the AVMA's 
          17    replies to Questions 1, 2, and 5.
          18                     Question No. 1 asks what actions 
          19    the agency might take to expand FDA's capability to 
          20    include state-of-the-art science into its 
          21    risk-based decision-making.  The AVMA applauds 
          22    science and risk-based decision-making, and it is 
          23    apparent that the CVM's concern with the approval 
          24    requirements for antimicrobials for food-producing 
          25    animals is an obvious opportunity for CVM to apply 



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           1    these principles.
           2                     The agency has made it clear that 
           3    the approval of some new antimicrobials of high 
           4    public health concern for use in food-producing 
           5    animals will not proceed without the incorporation 
           6    of a framework to address the microbial safety 
           7    aspect of these products and a potential impact on 
           8    human health.
           9                     The AVMA is committed to working 
          10    closely, in cooperation, with the FDA/CVM on the 
          11    proposed framework.  Nevertheless, the AVMA urges 
          12    two principles:  First, that the agency consider 
          13    regulating microbial safety under the rules for 
          14    food contaminants instead of those for food 
          15    additives.  Food contaminants are substances that 
          16    are unavoidably present and whose presence is 
          17    tolerated, while food additives are those 
          18    substances deliberately incorporated into foods.  
          19    Each of these categories clearly engender different 
          20    requirements. 
          21                     Second, the AVMA advises that the 
          22    agency conduct a risk assessment to characterize 
          23    the actual human health impact of the use of 
          24    antimicrobials in food-producing animals and derive 
          25    the other benefits that a risk assessment offers.



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           1                     Risk assessment is well recognized 
           2    as a tool that supports decisions.  The discipline 
           3    uses scientific data to evaluate risk and was 
           4    introduced in the 1970s to evaluate the human 
           5    cancer risk.  Risk assessment provides what has 
           6    been called by Anna Lammerding of Health Canada, "a 
           7    common, unified work space for people of different 
           8    backgrounds to contribute to a better understanding 
           9    of the whole system."  Risk assessments show where 
          10    there are data gaps, serve as a storage vehicle for 
          11    valuable knowledge as it is accumulated, and 
          12    describe a chain of cause-and-effect events where 
          13    proposed changes can be evaluated.
          14                     We recognize that this is an      
          15    onerous task and realize that many data gaps will 
          16    be revealed.  But this tool puts us all on the same 
          17    page looking at the entire process.
          18                     Research needs to be elucidated 
          19    and can be prioritized, and as data is collected it 
          20    can be plugged into the many holes.  Over time we 
          21    will have a more coherent understanding of the 
          22    human health impact of anti-microbial use in 
          23    food-producing animals.  Forgive my oversimplified 
          24    comparison to 3,000 pieces of a jigsaw puzzle 
          25    spread out over a large table whereby a number of 



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           1    different people identify pieces and assemble these 
           2    pieces into distinct parts.  Together these parts 
           3    are assembled to make the whole and complete
           4    picture, visible to us all.  I believe that example 
           5    illustrates in an admittedly simple way that the 
           6    benefits to all of us of conducting a risk 
           7    assessment.  I believe the subject of 
           8    anti-microbial resistance and potential human 
           9    health impact is too important for us not to 
          10    prepare a risk assessment.
          11                     The second question seeks to 
          12    determine the ways the agency can facilitate the 
          13    exchange and integration of scientific information 
          14    to better enable FDA to meet its public health 
          15    responsibilities throughout a product's life cycle.
          16                     Antimicrobial use in 
          17    food-producing animals is, again, a fitting 
          18    example.  The AVMA sees the value in the 
          19    establishment of a panel of experts, as described 
          20    in the Institute of Medicine/National Research 
          21    Council report "The Use of Drugs in Food Animals:  
          22    Benefits and Risks."  In the report, the Committee 
          23    on Drug Use in Food Animals recommended that 
          24    further development and use of antibiotics in both 
          25    human medicine and food animal practices have 



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           1    oversight by an interdisciplinary panel of experts 
           2    composed of representatives of the veterinary and 
           3    animal health industry, the human medicine 
           4    community, consumer advocacy, the animal production 
           5    industry, research, epidemiology and the regulatory 
           6    agencies.  The mission of this panel would be to 
           7    review on a scheduled basis data that address the 
           8    concerns of antibiotic resistance development in 
           9    animals and humans and to advise regulatory 
          10    agencies in the development and use of antibiotics 
          11    in agriculture and human medicine.
          12                     We would also suggest that FDA 
          13    foster a more cooperative relationship with the 
          14    USDA Agricultural Research Service and the 
          15    Cooperative State Research, Education and Extension 
          16    Service for scientific expertise and the USDA Food 
          17    Safety and Inspection Service in the conduct of the 
          18    microbial risk assessments.
          19                     Question No. 5 asks how to enhance 
          20    the communication process.  Allow us to be 
          21    participants.  We look forward to the active 
          22    involvement in planning the CVM's upcoming 
          23    workshops that pertain to the requirements posed in 
          24    the framework document, for example.
          25                     Let me also take this opportunity 



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           1    to compliment the CVM on some of their existing 
           2    means of communication; for example, on their 
           3    outstanding representation at the AVMA council and 
           4    committee meetings.  This vehicle of communication 
           5    is effective and greatly appreciated by the AVMA. 
           6                     I'm also pleased that the CVM 
           7    actively submits articles and information for 
           8    inclusion in the journal of the American Veterinary 
           9    Medical Association.  The journal reaches 63,000 
          10    veterinarians, a very large portion -- in fact, 
          11    almost all -- of our profession.
          12                     We also find the FDA Veterinarian, 
          13    CVM Updates and CVM web site to be helpful.
          14                     In closing, the American 
          15    Veterinary Medical Association wishes to thank the 
          16    Center for Veterinary Medicine for this opportunity 
          17    to comment and looks forward to ongoing cooperation 
          18    with the Center.  We thank the Center for 
          19    recognizing the role of the veterinarian as an 
          20    informed professional in the safe and effective 
          21    administration of drugs to animals.  Such 
          22    recognition is apparent in CVM's  assignment of 
          23    prescription or Veterinary Fed Directive status to 
          24    drugs, creation of regulations for extralabel drug 
          25    use, application of professional flexible labeling 



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           1    and the most recent acknowledgment of the AVMA 
           2    judicious antimicrobial use principles.  We pledge 
           3    continued responsible drug use in the care of 
           4    animals and active participation in the many 
           5    deliberations that lie ahead.  
           6                     Thank you very much.
           7                     (Applause.)
           8                     MR. ROGERS:  Any questions from 
           9    the FDA?  
          10                     (No response.)
          11                     MR. ROGERS:  Dr. Carnevale.
          12                     DR. CARNEVALE:  Thank you, Mike. 
          13                     I can personally vouch for Steve.  
          14    He had a good excuse.  I think we got on and off 
          15    that plane more times in one morning than I think 
          16    I've ever done in the last year.
          17                     In any case, thanks for inviting 
          18    us here to the stakeholders meeting.  I am 
          19    Dr. Richard Carnevale of the Animal Health 
          20    Institute, Vice President for Scientific Regulatory 
          21    and International Affairs and on behalf of the 
          22    Animal Health Institute and the Coalition for 
          23    Animal Health I appreciate the opportunity to 
          24    discuss the challenges that face the Center for 
          25    Veterinary Medicine.



                                                               21


           1                     As you know, AHI represents the 
           2    companies that research and develop the drugs and 
           3    vaccines that protect the health of both food and 
           4    companion animals.  Today I plan to discuss the 
           5    overall effectiveness and operation of the drug 
           6    approval process, both as it pertains to the FDA 
           7    Modernization Act and the current efforts by CVM to 
           8    alter the existing process for review of 
           9    antibacterials.  I will not address my comments to 
          10    the Animal Drug Availability Act.  Joel 
          11    Brandenberger and Dave Bossman will specifically 
          12    address issues on ADAA later in the program.
          13                     As you are aware, AHI and the 
          14    members of the Coalition for Animal Health have 
          15    voiced strong concerns about CVM's proposed new 
          16    safety requirements for animal antibacterials 
          17    without having adequately assessed the actual risks 
          18    to public health.  Dr. Swanson just addressed 
          19    similar comments in his presentation. 
          20                     These concerns were addressed 
          21    directly in comments to the Veterinary Advisory 
          22    Committee and amplified in the AHI comments filed 
          23    on the proposed framework document in early April.  
          24    It continues to cause us concern that while the 
          25    Office of Epizootics and the World Health 



                                                               22


           1    Organization, among other scientific bodies, have 
           2    continued to suggest that documented risk 
           3    assessment is the appropriate tool to develop and 
           4    refine policy for animal/human safety, however, we 
           5    fear that CVM may have established a zero risk 
           6    policy for this issue.  
           7                     Throughout the debate on 
           8    antibiotic resistance, AHI has vocally supported 
           9    the collection of national data to provide a 
          10    meaningful overview of the prevalence of resistant 
          11    food-borne pathogens.  Specifically we believe that 
          12    the National Antimicrobial Resistance Monitoring 
          13    System should be expanded to provide a more robust 
          14    picture of change in susceptibility.  We look 
          15    forward to the opportunity to work directly with 
          16    USDA and FDA to improve and expand the NARMS 
          17    system.  We believe that CVM shares our goals in 
          18    this area, and we also believe that within AHI and 
          19    the Coalition we  have expertise that will be 
          20    valuable if utilized in a positive manner.  We hope 
          21    CVM will take the opportunity to involve industry 
          22    in workshops and symposia on this and other key 
          23    elements of the effort to better understand the 
          24    potential for resistance development.
          25                     In fact, we are working to develop 



                                                               23


           1    a workshop with CVM on the concept of resistance 
           2    thresholds that is broadly laid out and discussed 
           3    in the framework document.  Again, while this is a 
           4    positive step, CVM must make every effort to make 
           5    sure that workshops and other efforts to get public 
           6    input allow balanced participation and open input.  
           7    We fear this was not the case in the VMAC hearing, 
           8    the only previous opportunity for scientific review 
           9    and public comment.  In that case the format 
          10    narrowed the range of questions that VMAC Committee 
          11    members were allowed to pursue, and the public 
          12    comments in many instances seems to have been 
          13    overlooked.  We certainly hope that CVM will 
          14    carefully review these and subsequent comments to 
          15    the framework document when preparing revisions. 
          16                     All of the members of the 
          17    Coalition for Animal Health have been active 
          18    participants in the AVMA's association efforts to 
          19    develop judicious use guidelines.  We believe those 
          20    efforts to combat the development of resistance are 
          21    a key part of meaningful strategies to protect 
          22    animal and human health.  
          23                     We were somewhat disappointed when 
          24    the judicious use guidelines did not figure 
          25    prominently in the proposed framework or in the CVM 



                                                               24


           1    presentation at VMAC.  We would encourage CVM to 
           2    make judicious use guidelines the cornerstone of 
           3    the framework.  
           4                     The member companies of AHI 
           5    believe that the approval process for animal drugs 
           6    should be based on science and the actual 
           7    assessment of risk and not on assumed risk.  
           8    Furthermore, the approval process should be certain 
           9    and predictable.  In many ways the current approval 
          10    process at CVM fails to meet these standards.  In 
          11    October 1998, AHI filed a Citizens Petition with 
          12    the Food and Drug Administration asking that CVM 
          13    refrain from imposing additional requirements on 
          14    individual applicants until the legal and 
          15    scientific justifications for these requirements 
          16    were clarified.  We believe that the approval 
          17    process continues to be disrupted by the 
          18    uncertainty of these product-specific 
          19    requirements.  AHI looks forward to CVM's review 
          20    and response to its petition.  
          21                     AHI and the Coalition for Animal 
          22    Health have always been committed to working 
          23    constructively with CVM and attempting to address 
          24    issues of concern in a positive and proactive 
          25    manner.  The record of cooperation with CVM 



                                                               25


           1    established during development and passage of the 
           2    Animal Drug Availability Act is a testament to that 
           3    commitment.  We believe that the spirit of 
           4    cooperation can and should be brought to the table 
           5    as the issue of antibiotic resistance is addressed.
           6                     With my remaining time, let me 
           7    turn my comments to the Food and Drug Modernization 
           8    Act.  We would like to focus on five areas of that 
           9    legislation in regard to their impact on animal 
          10    drugs, impact and implementation.  
          11                     Section 116, Manufacturing 
          12    Changes.  We welcome the fact that congress and FDA 
          13    are moving to implement a more streamlined 
          14    procedure for making changes in the manufacturing 
          15    process and/or specifications of new human and 
          16    animal drugs, particularly for those changes 
          17    considered minor.  However, we want to point out 
          18    the long before FDMA, AHI and CVM had worked out a 
          19    procedure for the agency review of Category I 
          20    manufacturing changes called the Alternate 
          21    Administrative Procedure.  This allowed firms to 
          22    submit many changes considered minor as biennial 
          23    reports to the Agency, both expanding the current 
          24    list of changes that don't need prior approval and 
          25    also reducing the paperwork burden for documenting  



                                                               26


           1    such changes.  AHI co-sponsored a workshop with CVM 
           2    to introduce the procedure for the AAP.  We viewed 
           3    this as a highly productive exercise with many of 
           4    our member firms participating in the program.  
           5    With passage of FDMA, our initial reading was that 
           6    the law should not change the basic tenets of the 
           7    AAP,  but more recent feedback from the agency 
           8    indicates that may not be the case.  In particular 
           9    Section 116 requires annual reporting while the AAP 
          10    permits biennial.
          11                     The major concern with our members 
          12    at this stage is that we're unable to get any 
          13    specific guidance from CVM on this issue.  We hope 
          14    that the benefits gained from the AAP are not lost 
          15    because of the knew legislation.
          16                     Section 130, Reports of 
          17    Post-Market Approval.  This is a new provision of 
          18    the law which requires reports of post-marketing 
          19    studies on new drugs and presumably new animal 
          20    drugs.  AHI has several questions with regard to 
          21    the provision.  What was the intent of this section 
          22    and how is it applicable to animal drugs?  What 
          23    types of studies will it apply to?  Could it 
          24    potentially apply to antibiotic resistance 
          25    monitoring, which may not be a study, per se, but 



                                                               27


           1    the ongoing collection of data?  We are also 
           2    concerned with the public release of such studies.  
           3    The law only indicates the identification of the 
           4    sponsor and the status of the study will be 
           5    released.  Could that potentially be interpreted to 
           6    allow release to the public?
           7                     Finally will there be a lead 
           8    office for reporting the information to the public 
           9    or to Congress, or will each Center be 
          10    responsible? 
          11                     Section 402, Expanded Access to 
          12    Investigational Therapies and Devices.  An 
          13    important section or part of the law allows greater 
          14    access to lifesaving therapies that may not be 
          15    available commercially but are under investigation. 
          16    This is clearly aimed at human therapeutics, but 
          17    could it be applicable under similar circumstances 
          18    to animal drugs?  CVM has a compassionate use 
          19    policy that permits the use of certain unapproved 
          20    drugs for treating animal diseases where there may 
          21    be no approved drug.  However, this policy is tied 
          22    to the INAD in that the veterinarian wishing to use 
          23    the drug must be engaged in an active 
          24    investigation.  Furthermore, it's uncertain whether 
          25    or not the company would be able to recover costs 



                                                               28


           1    for providing the drug and must maintain specific 
           2    records of the distribution and use.  
           3                     Companies frequently get requests 
           4    for investigational drugs that have data -- at 
           5    least partial data -- showing them to be safe and 
           6    effective, but they're just not yet approved.  They 
           7    have a difficult time honoring those legitimate 
           8    requests unless they're able to assume the costs 
           9    and all the recordkeeping and other 
          10    responsibilities that go into it.
          11                     We'd encourage the Center to 
          12    consider to apply the intention of this section of 
          13    FDMA to animal drugs.  
          14                     Approval of Supplemental 
          15    Applications for Approved Products under Section 
          16    403.  This section covers new criteria for 
          17    supplemental applications.  AHI would like to know 
          18    when guidance on implementing this provision would 
          19    be available for animal drug manufacturers.  We 
          20    know that FDAMA encourages the companies to submit 
          21    supplemental applications based wholly or in part 
          22    on published literature or data already submitted 
          23    to prevent duplication of research.  This does seem 
          24    at odds with the proposed regulation published last 
          25    year on the new definition of "substantial evidence 



                                                               29


           1    of effectiveness" under the Animal Drug 
           2    Availability Act.  In that proposal, the agency 
           3    appeared to be discouraging the use of public 
           4    literature as a demonstration of substantial 
           5    evidence as well as the previously submitted data 
           6    considered less than contemporary.  We wonder how 
           7    the ADAA and the intent of FDMA will be reconciled 
           8    on this matter.
           9                     At that point I can conclude my 
          10    comments.  Thank you.
          11                     (Applause.)
          12                     DR. WAGES:  My name is Dennis 
          13    Wages, and I'm a veterinarian representing the 
          14    American Association of Avian Pathologists, which 
          15    is primarily composed of poultry veterinarians, 
          16    allied industries, commercial production, research 
          17    and academia.  Veterinarians in AAAP are involved 
          18    in the production of over seven billion broilers, 
          19    300 million turkeys and 325 million table egg 
          20    layers, producing over eighty million eggs 
          21    annually.  
          22                     One of the intents of the FDA 
          23    Modernization Act is to make available new animal 
          24    drugs for use in livestock.  However circumstances 
          25    surrounding the recently discussed framework 



                                                               30


           1    document produced by FDA/CVM seems to have 
           2    disrupted the approval process and the potential 
           3    for new animal drug development.  It's my 
           4    understanding that until the framework document is 
           5    finalized, new animal drug approvals are on hold.  
           6    Likewise, the major pharmaceutical players in our 
           7    industry have put the discovery of such new animal 
           8    drugs with potential use in poultry not only on the 
           9    back burner, but the discovery process for food 
          10    animal drugs as a whole has ceased.
          11                     Even though the intent of the 
          12    framework document was to increase the availability 
          13    of drugs used in veterinary medicine and provide a 
          14    comfort zone of use of antibacterials to all those 
          15    involved, in reality it has brought it to an end.
          16                     I would encourage CVM to encourage 
          17    the drug approval process while the framework 
          18    document is being fine-tuned, because there are 
          19    more questions than answers regarding the document.  
          20    Discovery of new and innovative therapeutic 
          21    regimens are vital to the food animal industry as 
          22    the arsenal of therapeutic agents declines.  
          23                     From the FDAMA communications 
          24    listed on the CVM web page it's stated and we've 
          25    heard today that Dr. Henney places a high premium 



                                                               31


           1    and priority on making sure that science anchors 
           2    FDA's decision-making process.  The poultry 
           3    industry is concerned where the science and the 
           4    risk assessments are associated with some of the 
           5    current thinking regarding antibacterial uses.  Is 
           6    it not possible for an impartial or at least a 
           7    diverse panel to be identified by CVM to peer 
           8    and/or scientifically review studies and articles 
           9    that are released to not only CVM but professional 
          10    and private sectors to comment on the implications 
          11    of such articles.
          12                     For example, the study from 
          13    Minnesota regarding Campylobacter resistance in 
          14    ready-to-eat poultry raises some serious questions.  
          15    It's my understanding that the majority of the 
          16    Minneapolis-St. Paul chickens originates from one 
          17    company which, during the study, had not used any 
          18    flouroquinolones.  Also during that same time 
          19    period, the National Chicken Council says that only 
          20    1.1 percent of the chickens in the United States 
          21    were even treated with flouroquinolones.  It starts 
          22    in my mind a question, is there the potential for 
          23    this antibiotic to actually cause the resistance 
          24    that was noted?  Although we don't have the true 
          25    answers, it raises concerns about potential       



                                                               32


           1    cross-contamination at the retail level, as 
           2    production companies have little control over their 
           3    product after it leaves the processing facility, 
           4    and other questions about ready-to-eat poultry.
           5                     The poultry industry has for many 
           6    years cautioned that much cross-contamination 
           7    occurs in repackaging of ready-to-cook chicken and 
           8    that proper preparation is necessary.  Sometimes 
           9    these common-sense procedures are never emphasized 
          10    in the prevention of exposure to food-borne 
          11    pathogens at the CVM level.  We believe that CVM 
          12    needs to take advantage at an educational level.  
          13    If we are going to place science in our decision 
          14    process, then let's do it based on scientific 
          15    experts from both sides of the question, both pro 
          16    and con, and not base our decisions on politics and 
          17    consumers -- excuse me, consumer groups, CDC or 
          18    actions from our European neighbors. 
          19                     It seems initiatives and 
          20    directions are implemented when science does not 
          21    appear to support the decisions; not in all cases 
          22    but in some of the more controversial ones.  A 
          23    diverse panel of scientific experts identified by 
          24    FDA/CVM could be valuable in determining the 
          25    scientific merit of reports that have a potential 



                                                               33


           1    for controversy.  Get all the facts from all the 
           2    people and then make decisions.  Likewise, the same 
           3    experts could be involved in aiding the Agency 
           4    into what scientific methods and applications are 
           5    needed that would hopefully result in data being 
           6    generated that all sides could derive value from.
           7                     There's no question that there are 
           8    two sides to every story.  However, concerning the 
           9    antibiotic use controversy, there are pieces of the 
          10    scientific information that certain groups seem to 
          11    overlook, depending on their own agenda, and no one 
          12    more group is any more at fault than any other.  I 
          13    would encourage CVM to continue to look at all 
          14    sides of the issues and determine the true risks 
          15    and outcomes of such issues.
          16                     For example, antibiotic use leads 
          17    to resistance.  It's a known fact that the 
          18    antibiotic resistant bacteria concerning certain 
          19    microbials are found in certain animals and that 
          20    food-borne illness becomes more complex and many 
          21    factors need to fall into place.  We need to 
          22    understand and to know that if, in fact, the 
          23    treatment of poultry and/or any other animals 
          24    actually does lead to antimicrobial resistance and 
          25    truly an untreatable or at least food-borne illness 



                                                               34


           1    that refractory to treatment in humans.  If there 
           2    are food-borne illnesses that are, in fact, 
           3    refractory to treatment, is this caused by the use 
           4    of antimicrobials in poultry flocks?  I guess 
           5    that's the $64,000 question that I think people, 
           6    especially science, needs to answer.
           7                     I would encourage the Agency to 
           8    focus on the probability of the occurrence of such 
           9    antibiotic use when it's controversial and the 
          10    probability of such use and not the possibility of 
          11    such use.
          12                     Risk assessment is the buzz word 
          13    in the world of regulatory affairs and we feel that 
          14    it's the appropriate scientific route of choice for
          15    some of these issues that face us.  Retrospective 
          16    studies with adequate numbers of groups represented 
          17    to epidemiologically demonstrate that there is, 
          18    indeed, a cause-and-effect relationship of the use 
          19    of these antibacterials in veterinary medicine with 
          20    the result being a food-borne illness refractory to 
          21    treatment.  
          22                     There are many statistic- 
          23    gathering mechanisms in process concerning 
          24    antimicrobial resistance that needs to be 
          25    correlated, evaluated and disseminated to 



                                                               35


           1    stakeholders.  NARMS, Food-Net, Food Safety 
           2    Initiative, post-approval monitoring programs are 
           3    all in various stages of data collection.  This 
           4    information needs to be carefully evaluated and 
           5    disseminated and to avoid misinterpretation of the 
           6    data.
           7                     What information is public versus 
           8    what is proprietary and where is this information 
           9    to be consistently found?  This is information 
          10    that's being generated that can put all the pieces 
          11    of the puzzle together, but also pieces of that 
          12    information can be used to carry on certain 
          13    agendas.
          14                     We don't have all the answers, but 
          15    hope that the future direction of FDA/CVM be driven 
          16    by the emphasis placed on addressing these issues 
          17    scientifically and not do what may be politically 
          18    correct.  
          19                     I don't envy the pressure that CVM
          20    has put on them from all sides.  Strengthening the 
          21    agency science base through well-defined studies 
          22    that are going to tell us what we need to
          23    know is paramount.  I think we need to outline 
          24    objectives, design a plan of action that answers 
          25    the key questions to our objectives.



                                                               36


           1                     Let us ask ourselves:  What 
           2    information do we have that's available to us right 
           3    now that provides us insight and what gaps are 
           4    there present in the information, and then what do 
           5    we need to do to formalize an evaluation process   
           6    that will be meaningful and address the Agency's 
           7    objectives and concerns?  
           8                     Outside objective evaluation of 
           9    the plan of action and studies to be implemented 
          10    are key to the success of the Agency's goal to 
          11    strengthen its science base.  As you are doing 
          12    today, allowing all stakeholders to be involved as 
          13    to the future of assessing public health risks is a 
          14    vital part of it.  
          15                     The future of antimicrobial use in 
          16    all medical professions and the future availability 
          17    of drugs depends on the Agency's process as to its 
          18    future direction.  Of course actions will always 
          19    speak louder than words.
          20                     Thank you for allowing me to 
          21    address these concerns of the poultry industry and 
          22    the poultry veterinary concerns to you today.  I 
          23    feel that FDA/CVM will direct themselves in a 
          24    manner that will provide the comfort zone for all 
          25    stakeholders involved in these hot and very 



                                                               37


           1    controversial issues.  Thank you.
           2                     (Applause ) 
           3                     MR. WADDELL:  I'm John Waddell.  
           4    I'm a practitioner from Nebraska.  I'm here 
           5    representing the American Association of Swine 
           6    Practitioners.
           7                     The AASP is a professional 
           8    organization of over 1300 veterinarians in the 
           9    United States.  Our members are integrally involved 
          10    in all aspects of swine health and production.  The 
          11    AASP has a vested interest in assisting the FDA, 
          12    and specifically the CVM, in implementation of the 
          13    FDA Modernization Act.  
          14                     Modernization is a continual 
          15    process for any organization.  Without some plan to 
          16    improve, any organization, including the FDA, may 
          17    find itself providing no real value to its 
          18    customers or stakeholders.  The development of 
          19    creative strategies as part of this improvement 
          20    process but true and measurable success depends on 
          21    the implementation of these strategies; therefore, 
          22    the implementation of ideas and strategies 
          23    discussed today will speak much louder than any 
          24    words that will be spoken here.
          25                     One of the stated objectives under 



                                                               38


           1    FDA's Modernization Act is to strengthen its 
           2    science base.  We applaud the CVM in its desire to 
           3    use science in its decision-making.
           4                     The application of science can be 
           5    a powerful tool.  This raises the key issue of what 
           6    level and kind of science is needed.  The intuitive 
           7    answer is that we need good science; however CVM 
           8    needs to identify the attributes of good science, 
           9    which include methodology and verification.  Good 
          10    science is not intuition and perception.
          11                     It is often tempting to forego 
          12    science in the face of expediency and emotionalism.  
          13    When science is not available, the challenge is not 
          14    merely strengthening the science but also involves 
          15    the balance between politics and science.  
          16    Regulatory decision-making needs to balance 
          17    political agendas and science.  The line between 
          18    the two often becomes obscured and distorted.  
          19    Unfortunately, in the absence of science, political
          20    expediency rules the day.  We must not let that 
          21    happen.  
          22                     We urge the FDA/CVM to remain 
          23    committed to using science in the risk-based 
          24    decision-making process.  Before the FDA finalizes 
          25    any decision, perhaps the following question should 



                                                               39


           1    be asked:  Will the decision significantly lower 
           2    the risk to public health?
           3                     Most AASP members practice in a 
           4    world of applied science.  Science dictates what 
           5    medication and what treatment regimen to use.  It 
           6    dictates the avoidance of violative residues.  It 
           7    is this adherence to science that ensures we are 
           8    producing a healthy and safe food product while 
           9    securing the livelihood of our clients.
          10                     Can you imagine what would happen 
          11    if veterinarians disregarded our scientific 
          12    knowledge?  What will FDA's decisions be like if 
          13    they disregard scientific knowledge?  
          14                     For veterinarians our measure of
          15    success in the field are well-defined.  
          16    Unfortunately, the measure of success for 
          17    regulatory decision-making is not always so 
          18    clear-cut.  However, this does not diminish the 
          19    need to discover and identify the attributes of 
          20    strong science as the CVM incorporates the 
          21    state-of-the-art science in its decision-making 
          22    process.  
          23                     How can CVM strengthen its 
          24    science?  The first step is to define a process 
          25    that can objectively review and select appropriate



                                                               40


           1    studies and investigations that are pertinent to 
           2    the decision at hand.  The agency should not 
           3    utilize a subjective process of intuition and 
           4    perception that biases the decision-making 
           5    process.  Any selective use of data to accomplish a 
           6    political agenda does little to protect the public 
           7    health, nor does it build the credibility of the 
           8    Agency.
           9                     Strong science must be considered 
          10    when drawing data from many disciplines and 
          11    sources.  The application of experimental research 
          12    can be extremely limited and biased.  For example, 
          13    so-called bench research can prove that some event 
          14    is possible.  The question then becomes:  Is this 
          15    significant in terms of applied science?  In light 
          16    of such research, I return to the original question 
          17    posed to decision-makers earlier:   Will this 
          18    decision significantly lower the risk to public 
          19    health?
          20                     Strong science dictates that each 
          21    scientific discipline be placed in perspective with 
          22    relation to its value to the decision process.  For 
          23    example, we are faced with the issue of 
          24    antimicrobial resistance.  This issue is 
          25    overshadowing everything else that CVM is currently 



                                                               41


           1    doing.  Epidemiology is a discipline that seems to 
           2    be occupying much of the discussion on the issue.  
           3    As an investigational science, epidemiology relies 
           4    on observing populations and then making inferences 
           5    about those observations.  The subjective nature of 
           6    inferences can allow errors that bias the 
           7    interpretation of data, thus weakening the science.
           8                     Biological systems are inherently 
           9    variable.  Attempts to misrepresent a state of 
          10    nature may provide sensational news stories and 
          11    good editorial fodder, but they do little to 
          12    strengthen the science.  Superbugs may be today's 
          13    headlines, but such sensationalism has no place in 
          14    an attempt to strengthen the science in 
          15    decision-making.
          16                     Strong science embraces the 
          17    concept of consistency in a number of different 
          18    circumstances.  Any attempt to oversimplify a 
          19    cause-and-effect mechanism and the interventions 
          20    required to mitigate a risk may produce unintended 
          21    consequences.  The failure to account for 
          22    variability in veterinary medicine and the 
          23    production of food animals will do little to 
          24    protect the public health, but it may unwittingly 
          25    devastate an agricultural industry.  



                                                               42


           1                     CVM must recognize the limitations 
           2    of the science that is available for their 
           3    decision-making.  The agency must be prepared to 
           4    deal with variability and uncertainty.  It must not 
           5    use the lack of data as an excuse to employ 
           6    unscientific reasoning such as the precautionary 
           7    principle.  The precautionary principle is based 
           8    primarily on perception and intuition, not 
           9    characteristics of strong science.
          10                     The logical place to start in the 
          11    agency's quest for effective risk-based 
          12    decision-making would seem to be the use of 
          13    scientific risk assessment.  The attainment of some 
          14    understanding of the presenting level of risk,      
          15    whether qualitative or quantitative, is essential.  
          16    Without this in place, the Agency cannot begin to 
          17    come to grips with the level of science or data 
          18    needed for the process.  
          19                     A great deal of the value of 
          20    determining acceptable risk and understanding a 
          21    level of risk is the role that they can play in 
          22    assuring the CVM's limited resources will be 
          23    allocated to achieve the greatest impact.  
          24                     The concept of risk assessment is 
          25    also consistent with the efforts of other 



                                                               43


           1    governmental agencies.  By clearly understanding 
           2    the areas of greatest risk and employing a more 
           3    comprehensive and systematic approach, the CVM can 
           4    utilize a cooperative approach to improving food 
           5    safety.  The U.S. Department of Agriculture, 
           6    through the Food Safety and Inspection Service, 
           7    represents an important resource to mitigate the 
           8    risk of food-borne disease at the point of 
           9    slaughter.
          10                     CVM's demonstration of its 
          11    willingness to adopt a formal risk assessment 
          12    approach and strengthen the science will enhance 
          13    the Agency's credibility and its efforts to
          14    communicate with its stakeholders.
          15                     A key factor in improving 
          16    communication is trust.  Unfortunately, there 
          17    appears to be very little trust present between the 
          18    CVM and its stakeholders.  This lack of trust 
          19    should not be misconstrued as malicious intent by 
          20    any party.  It is, however, symptomatic of the 
          21    uncertainty and lack of transparency in the 
          22    decision-making process.
          23                     Consistent and sustained 
          24    communication efforts are required by all 
          25    involved.  Stakeholders cannot be embraced by CVM 



                                                               44


           1    during its modernization efforts and then held at 
           2    arm's length with disdain during the decision- 
           3    making process.  Likewise, CVM cannot be portrayed 
           4    as the enemy with no redeeming value for animal 
           5    agriculture or public health. 
           6                     When faced with uncertainty from a 
           7    lack of science, CVM should look to its 
           8    stakeholders for assistance.  The timing of such a 
           9    request is vital.  If the decision-making process 
          10    has proceeded too far, the assistance will have 
          11    little value or real impact on the process.  When 
          12    the process has gone too far, stakeholders have to 
          13    wonder whether their input was desired at all or 
          14    whether it was merely window-dressing needed to
          15    satisfy a statutory requirement.  The result is  
          16    the loss of credibility in these situations.  FDA 
          17    needs to bring the stakeholders into the process at 
          18    the earliest moment.  
          19                     Stakeholders have an obligation to 
          20    respond with credible data where available.  When 
          21    data is not available, stakeholders should provide 
          22    expert assistance in setting the research agenda 
          23    and perhaps in conducting pertinent research.  A 
          24    fostering of communications, collaboration and 
          25    cooperation must take place if CVM wishes to be 



                                                               45


           1    efficient and effective at meeting its 
           2    responsibilities.  
           3                     I thank you for this continuing 
           4    opportunity to offer comment.  As I stated before, 
           5    the development of creative strategies is part of 
           6    modernization, but true and measurable success 
           7    depends on the implementation of these strategies.  
           8    Any resulting action from today's discussion will 
           9    speak much louder than any words spoken here.
          10                     (Applause.)
          11                     MR. ROGERS:  Pork Producers will 
          12    have five minutes each.  
          13                     MR. SUNDBERG:  Good afternoon.  
          14    I'm Paul Sundberg.  I'm the Assistant Vice 
          15    President of Veterinary Issues from the National 
          16    Pork Producer Council.
          17                     I want to begin by thanking the 
          18    agency for the opportunity to offer comments this 
          19    afternoon on behalf of approximately 85,000 
          20    producer members in 44 affiliated state 
          21    associations.
          22                     The National Pork Producers 
          23    Council is committed to the evaluation of 
          24    scientific data to assess many of the issues that
          25    affect our industry.  We have a series of pork 



                                                               46


           1    producer committees that do this with the advice  
           2    of a variety of scientific experts.  They then take 
           3    their evaluation and look at various management 
           4    alternatives and develop communication strategies 
           5    when appropriate.
           6                     I'd like to offer some comments on 
           7    the Agency's strategic directions as well as the 
           8    specific questions posed in the Federal Register 
           9    notice of this meeting. 
          10                     The first two strategic directions 
          11    and the first question in the Federal Register 
          12    bring together the concept of scientific analysis 
          13    and risk-based decision-making.  Our comments at 
          14    the last VMAC meeting demonstrate our support of 
          15    the use of science to assess risk.  It's clear the 
          16    continuing challenge is to evaluate the accuracy 
          17    and appropriateness of the science.
          18                     There seems to be at least two 
          19    primary research areas that have occupied much of 
          20    the debate about the risk of antimicrobial use in 
          21    agriculture and how it affects public health.  
          22    Therefore, two examples are bacteriology and 
          23    epidemiology, and these two are really two 
          24    different examples of approaches to a science-based 
          25    mechanism.  



                                                               47


           1                     The first, bacteriology, has 
           2    focused on the laboratory discovery of the genetic 
           3    basis for resistance, its mechanism of action and 
           4    its transmission from one individual bacterium to 
           5    another.  We have improved our scientific 
           6    techniques from describing R factors to an 
           7    investigation of integrons and transposons.  In the 
           8    years to come we will find even more innovative 
           9    ways that bacteria adapt to their environment.  
          10    This doesn't imply these are new bacterial 
          11    mechanisms, only that our discovery or 
          12    understanding of them is new.  
          13                     Laboratory experiments are limited 
          14    by the laboratory conditions under which they're 
          15    conducted.  There's a danger of taking the results 
          16    or the findings of the experiment as a template of 
          17    what happens outside of the lab.  The field does 
          18    not have the ability to control laboratory 
          19    environment.
          20                     Epidemiology has been defined as 
          21    the study of patterns of disease that exist under 
          22    those field conditions; the frequency, distribution 
          23    and determinants of health and disease of 
          24    populations.  The unit of interest is the 
          25    population and not the individual.  It's useful to 



                                                               48


           1    provide some data that suggests associations among 
           2    health determinants but usually not a 
           3    cause-and-effect relationship.
           4                     As with other sciences, all of 
           5    these data are only valid if it has the power to be 
           6    supported by statistical analysis, if the study was 
           7    designed properly and if it makes intuitive sense.  
           8    Epidemiological studies that fail in any of these, 
           9    as with the other bench sciences, may divert our 
          10    attention, efforts and resources.
          11                     As Dr. Waddell said, unfortunately 
          12    peer review publication does not always insure 
          13    equality.  For the Agency to stand on a risk-based 
          14    decision-making policy it has to use the best 
          15    information available from the bench sciences and 
          16    the field sciences to do a risk measurement or 
          17    assessment.  Using just one discipline will 
          18    dangerously narrow and invalidate any assessment of 
          19    risk and probably will be misleading.  This is true 
          20    whether you're using only bacteriology, 
          21    epidemiology or any other scientific discipline.  A 
          22    systems approach is needed for risk assessment to 
          23    be scientifically valid -- similar to that of the 
          24    Agency's strategic directions that calls for a 
          25    systems approach to Agency regulation and looking 



                                                               49


           1    for problem solutions rather than piecemeal review 
           2    and enforcement.  Only then can it reasonably 
           3    assume what policies are going to have an effect on 
           4    the risk. 
           5                     The first question asks what 
           6    actions the agency can take to expand its 
           7    incorporation of state-of-the-art science into its 
           8    risk-based decision-making.  The Agency should 
           9    develop the model so that it can assure itself that 
          10    its decision-making is, in fact, risk-based, using 
          11    the expertise available within and without the 
          12    agency to define and develop risk-based risk 
          13    assessment approach.  This will ensure the 
          14    inclusion of the state-of-the-art science because 
          15    the risk assessment model has be to continually 
          16    refined as more information comes available.  Once 
          17    the model for risk assessment is developed through 
          18    a transparent, scientifically defensible process, 
          19    the agency, in conjunction with its stakeholders, 
          20    can move on to the risk management and risk 
          21    communication portion of the total risk analysis.
          22                     The basic message is to follow the 
          23    risk analysis process and not implement risk 
          24    management policies before doing an assessment of 
          25    the risk.  The risk communication strategy appears 



                                                               50


           1    to be the point of Question 3, the actions needed 
           2    for educating the public.  This is exactly why the 
           3    agency must have already completed the defensible, 
           4    credible assessment of risk, to communicate those
           5    strategies to the public.  Without that credible 
           6    assessment, its message of the balance between 
           7    risks and benefits may not be believable or even 
           8    well founded.  Completing an assessment of risk and 
           9    the transparent transfer of risk management policy 
          10    will give the stakeholders the tools that will 
          11    enable them to carry the FDA's message to the 
          12    public.  
          13                     We stand ready to help the agency 
          14    in this task.  The nation's pork producers are 
          15    willing to spend their own checkoff money on this 
          16    because they recognize the important role of 
          17    science in this issue.
          18                     I'd like to introduce Barb 
          19    Determan.  She's a pork producer from Iowa, also 
          20    from the National Pork Producers Council.  
          21                     And I'd also like to thank the CVM 
          22    to allow us to split up our time. 
          23                     MS. DETERMAN:  As Paul said, I'm a 
          24    producer from Early, Iowa.  Myself and my husband, 
          25    Steve, and our three children have a family farming 



                                                               51


           1    operation in northwest Iowa.  Our farrow-to-finish 
           2    operation produces about 2000 head of hogs a year.  
           3    I am a volunteer for the National Pork Producer 
           4    Council.  I donate my time to represent producers 
           5    from across the nation.
           6                     I appreciate the opportunity to 
           7    talk with you this afternoon about the agency's 
           8    reliance on science to meet its obligations.  I 
           9    would like to give you my perception after I've had 
          10    a chance to meet with the CVM on two occasions on 
          11    its decision-making process.  Thank you for those 
          12    two opportunities as well as this one today.
          13                     Meetings like this are very 
          14    important in helping to foster open communication 
          15    and exchange of ideas between the CVM and its 
          16    constituents.  We also need to explore new ways 
          17    that this can go farther.  The CVM has people with 
          18    the decision-making power.  Those decisions will 
          19    affect the way that the nation's pork producers, my 
          20    husband and myself live and work every day.  I 
          21    think all of us -- CVM and the pork producers -- 
          22    have a common goal of food safety and the 
          23    preservation of public health.  There needs to be 
          24    an effective mechanism, how we work together to 
          25    help reach that goal.  We need to better understand 



                                                               52


           1    the constraints that the agency works under, and 
           2    you need to better understand our business and how 
           3    we work.  One of the most important outcomes of 
           4    these types of meetings is to talk about how that 
           5    mechanism can be developed.
           6                     I would also like to say a few 
           7    things about what I saw at the last Veterinary 
           8    Medicine Advisory Committee meeting.  CVM had 
           9    gathered an impressive group of experts and 
          10    advisors.  However there was only one practitioner 
          11    on the committee that had any idea of how 
          12    veterinary medicine works in everyday practice, and 
          13    that person chaired the meeting, which limited his 
          14    ability to offer input.  If the VMAC is to be 
          15    effective, let it contribute the real life 
          16    understanding of veterinary medicine that CVM 
          17    needs.  Speaker after speaker tried to offer that 
          18    input during the first day, but when it came to the 
          19    discussions of the Committee during the second day, 
          20    there was no indication that what we had tried to 
          21    convey had any effect on the outcome.
          22                     I recently had the opportunity to 
          23    travel to Europe to talk with Swedish producers, 
          24    scientists, officials and veterinarians about how 
          25    they raise pigs and use antibiotics.



                                                               53


           1                     One of the things I learned was 
           2    that they're relying more on politics than they are 
           3    on science.  In fact, science is basically on the 
           4    run in Europe.  Many of their policies are based on 
           5    marketing decisions and posturing of one country 
           6    against the others.  This is not a good example for 
           7    the CVM and their science-based decision-making.
           8                     In a recent issue of Meat 
           9    International, a trade magazine for international 
          10    meat associations, there was an interview with Anne 
          11    Birgitte Lundholt, the managing director of Danske 
          12    Slagterier, the federation of producers and 
          13    slaughterhouses in Denmark.  When she was asked 
          14    about the EU ban of certain antibiotics as growth 
          15    promoters and what the effect has been on 
          16    production, she said, "Scientifically growth 
          17    promoters do not seem to be a problem, but we find 
          18    it impossible to explain to the average consumer 
          19    that medicine has to be given to healthy pigs.  It 
          20    [banning growth promoters] is against our normal 
          21    philosophy of following science."
          22                     When we talked with Danske 
          23    Slagterier during our trip, we were told of the 
          24    Danish plan to stop  using all growth promotant 
          25    antimicrobials, even nursery-age pigs.  The 



                                                               54


           1    scientists told us that it was strictly a political 
           2    decision that was the result of a slow news time 
           3    during last summer. 
           4                     The last thing we need to learn in 
           5    this discussion is that as we talk about the basis 
           6    of science for decisions is that we all need to 
           7    maintain our advocacy for the role of sound 
           8    science.  The Centers for Disease Control has 
           9    become an advocate for the European philosophy.  
          10    During the VMAC meeting we were told that we had 
          11    better move along with this issue because we didn't 
          12    know what it was like to stand by the bed of a 
          13    dying child.  The CDC's Dr. Angulo was quoted in 
          14    the Food Chem News as saying that he, -- and then 
          15    presumably the CDC, was fully supportive of the 
          16    recent CSPI petition to ask for the banning of all 
          17    subtherapeutic uses of antimicrobials.
          18                     I'll let the scientists argue 
          19    that, because, as you can tell, my name doesn't 
          20    have all the letters behind it; I just raise pigs.  
          21    What I have to offer is my opinion that the CVM 
          22    needs to be an advocate for its positions.  If it 
          23    wants to stand on scientific judgment, then it 
          24    should be ready to express that policy and refute 
          25    the ones that don't.  Numerous scientific bodies 



                                                               55


           1    have said that the risk of agricultural uses of 
           2    antimicrobials has not been determined, but there 
           3    is no imminent hazard.  We need to stand by our 
           4    positions on sound science and become its advocate 
           5    or we will find ourselves that we could be in a 
           6    period of slow news and be forced to abandon it 
           7    strictly because of policies.
           8                     The National Pork Producers 
           9    Council is spending our pork producer checkoff 
          10    dollars to try to supply some of the scientific 
          11    answers we need, and we offer all the help we can 
          12    help you in continuing those efforts.
          13                     Thank you. 
          14                     (Applause.) 
          15                     MR. ROGERS:  Before we dismiss 
          16    this panel, I'd like to ask the FDA group if you 
          17    have any clarifying questions of any of the 
          18    panelists.  
          19                     (No response.)
          20                     MR. ROGERS:  Hearing none, thank 
          21    you so much for your input.
          22                     (A short recess was taken.)
          23                     MR. BREEN:  We'll get started for 
          24    the last session.  
          25                     First of all, my name is Charles 



                                                               56


           1    Breen, and I'll be filling in for Mike Rogers this 
           2    afternoon.  As you'll notice, there's a difference 
           3    between the previous man standing over here in the 
           4    dark suit and myself.
           5                     To continue, Dr. James A. Jarrett, 
           6    Executive Vice President of the American 
           7    Association of Bovine Practitioners.  
           8                     DR. JARRETT:  Thank you, David.  
           9    I'm Jim Jarrett.  I'm the Executive Vice President 
          10    of the American Association of Bovine 
          11    Practitioners.
          12                     AAVP is an organization of over 
          13    5500 veterinarians, each with at least some 
          14    interest and involvement in cattle medicine.  We 
          15    have members who are highly specialized in their 
          16    practice and members who see only one or two cows a 
          17    week; so we are quite varied in our interest.
          18                     We all share the knowledge that 
          19    all of our bovine patients are only one conception 
          20    away from McDonalds.  They are all part of the 
          21    human food chain, all of them.  We all share a 
          22    sense of responsibility for the health of the 
          23    nation's cattle herd and the wholesomeness of the 
          24    human food that it produces.  We believe this food 
          25    to be as safe as is humanly possible to make it.  



                                                               57


           1    This is supported by the fact that the incidence of 
           2    food-borne illness as a result of anything that 
           3    happens at the farm level is at an all-time low.
           4                     We support our other animal 
           5    agriculture interests that have gone before me 
           6    today.  And at the risk of saying "Me, too," and 
           7    sitting down, I will continue.  But we will be 
           8    supportive -- where is Paul? -- all of you guys, 
           9    and appreciate what you had to say as well.
          10                     Our mission is to prevent pain and 
          11    suffering in our patients and to ensure that the 
          12    pathogen level in food for animals is as low as is 
          13    humanly possible to make it.
          14                     To do this, from time to time we 
          15    need various therapeutic agents.  This brings us in 
          16    closer contact with the FDA/CVM than any other 
          17    public agency, including the IRS.  We appreciate 
          18    the opportunity for input.  
          19                     DR. TOLLEFSON:  We've never been 
          20    compared to the IRS. 
          21                     DR. JARRETT:  We appreciate the 
          22    opportunity for to give input.  We are encouraged 
          23    by the report of the following of the stakeholders 
          24    meeting in August of 1998.
          25                     Today I've been encouraged by 



                                                               58


           1    statements such as risk-benefit ratio.  I've been 
           2    encouraged by statements that refer to a global 
           3    economy, and would stress the need to keep American 
           4    agricultural on a level playing field with our 
           5    producing comrades around the world.
           6                     I am encouraged by a proposed 
           7    increase in the dollars for outreach and 
           8    enforcement as depicted by Dr. Sundlof slide 
           9    earlier today.
          10                     Some of our members have the 
          11    perception that FDA serves only the consumer 
          12    interest and perceived needs using questionable to 
          13    marginal science.  As an example, the current 
          14    intense activity over antimicrobial resistance is 
          15    being an issue that, at the moment, has limited 
          16    human health impact.  Much of the action assumes 
          17    that there is a problem or a hazard to human health 
          18    that has yet to be demonstrated.
          19                     We have concerns that many actions 
          20    and decisions seem to be based on marginal science 
          21    at best and false information to emotionalism at 
          22    worst.  However, based on the premises that  there 
          23    might be a problem, animal agriculture is being 
          24    proactive with its efforts to formulate such things 
          25    as prudent or judicious use guidelines and 



                                                               59


           1    distributing them to our end user members.  We are 
           2    making available to the practitioner database and 
           3    data information on the selection dosage and usage 
           4    of antimicrobial agents, including the choice of 
           5    drugs as well as the dosage, terms of therapy and 
           6    such information.  This information is and will be 
           7    made available to the practitioner to use as he or 
           8    she makes decisions about controlling pain and 
           9    suffering in our food animal patients at the same 
          10    time.
          11                     However, we vigorously oppose any 
          12    formulary or any edict that might tell or take away 
          13    any of the responsibility or the decision-making 
          14    power of the practitioner in the field.
          15                     This brings me to respond to the 
          16    five questions.  Some of this response will be a 
          17    repeat from the last meeting in August, and I 
          18    apologize for this.
          19                     The first question, though, I am 
          20    impressed, though, that all these questions begin 
          21    with the phrase, "What actions do you propose?" 
          22    There have been many actions proposed by previous 
          23    speakers, and I'm sure by those who will follow as 
          24    well as some of the comments that I will have.
          25                     I'm most concerned about how we 



                                                               60


           1    incorporate true science in a risk-based 
           2    decision-making process, as related to the first 
           3    question.
           4                     Monitoring is certainly a part of 
           5    any concern or any evaluation of antibiotics or 
           6    therapeutic agents.  We certainly support some kind 
           7    of monitoring program; however, we have concerns 
           8    about how samples might be selected and collected 
           9    and how the results might be used.  We would 
          10    encourage -- and I would encourage this as a part 
          11    of all five responses -- the inclusion of 
          12    veterinarians and other livestock producers with 
          13    experience at the production level in the 
          14    decision-making process, along with non-agency 
          15    experts that have already been alluded to.
          16                     The second question refers to the 
          17    actions needed or suggested to help in the exchange 
          18    and integration of scientific information.  We 
          19    would suggest, as I have before, the utilization of 
          20    the existing channels of communication, such as the 
          21    American Association of Bovine Practitioners, the 
          22    American Association of Swine Practitioners, the 
          23    American Veterinary Medical Association, and yes, 
          24    Dennis's poultry veterinarians, along with many 
          25    other existing groups that are there with excellent 



                                                               61


           1    communicating channels already in place.  Again, 
           2    the inclusion in this one as well of non-agency 
           3    experts and outside assistance in formulating 
           4    education programs.
           5                     Number 3 deals with educating the 
           6    public about risk versus benefits.  I take this to 
           7    mean that there will be such a program and praise 
           8    the Agency for this.  This should include such 
           9    information as resistance versus a shift in 
          10    susceptibility.  We feel it should identify some of 
          11    the weakest public health links and concentrate 
          12    efforts on these.  Antimicrobial resistance may or 
          13    may not be the weakest current public health link 
          14    as it applies to food animal agriculture.  And 
          15    again, including outside experts and outside 
          16    assistance as actions are formulated.
          17                     Question 4 focuses on action to --  
          18    focus resources on areas of greatest risk.  Here I 
          19    would like to repeat some of the statements that I 
          20    made at the August meeting.  Many and most of our 
          21    members would like to see the agency enforce 
          22    current regulations before enacting new ones and 
          23    feel that the enforcement of current regulations 
          24    would go a long way toward helping to alleviate 
          25    some of the problems currently seen.



                                                               62


           1                     I'm encouraged by the increased 
           2    funding that is being asked for in the area of this 
           3    effort and the recent requests of CVM-FDA for 
           4    funding to be applied in the area of surveillance 
           5    and enforcement.  
           6                     Most of the problems that we deal 
           7    with today are caused by a few producers and 
           8    veterinarians.  Any action in the area of bringing 
           9    this under control, we feel, must help in terms of 
          10    solving the overall problem.
          11                     As an example of some of these 
          12    problems, I could state just recently a request for 
          13    all the members of the AABP in several states to be 
          14    supplied to a compounding pharmacist.  I did not do 
          15    this and don't plan to.  I would, in addition, 
          16    quote -- or, rather, relate the fact that at a 
          17    recent -- within the last three or four months at a 
          18    major veterinary meeting in the exhibit hall, three 
          19    booths promoting compounding pharmacists.  This 
          20    kind of activity can do nothing but, in our 
          21    feeling, deter and deliver the wrong message to our 
          22    clients and to many veterinarians in the field.
          23                     Question No. 5 refers to 
          24    additional action items to enhance communication.  
          25    Again, I would repeat, the involvement of existing 



                                                               63


           1    channels of communication such as the organizations 
           2    that are here today; and I would, again, as I did 
           3    at the August meeting, encourage the exchange on a 
           4    one-on-one basis between members of the agency and 
           5    personnel in the field.
           6                     In summary, I would like to 
           7    enforce or encourage the enforcement of existing 
           8    regulations before new ones are formulated.  I 
           9    would like to encourage the allowing of time for 
          10    current industry changes to take effect, 
          11    particularly in microbial resistance in such areas 
          12    as prudent use, and I would commend the agency for 
          13    listening to its stakeholders in meetings such as 
          14    this today and look forward to the resulting 
          15    actions and changes as a result.
          16                     Thank you. 
          17                     (Applause.) 
          18                     MR. BREEN:  Richard Wood, 
          19    Executive Director of Food Animal Concerns Trust.
          20                     MR. WOOD:  Thank you for the 
          21    opportunity to respond to the questions related to 
          22    the FDA Modernization Act.
          23                     I am Richard Wood.  I am the 
          24    Executive Director of FACT, or Food Animal Concerns 
          25    Trust.



                                                               64


           1                     FACT is a consumer organization  
           2    with about 30,000 constituents nationwide.  We 
           3    advocate farm management systems that promote the 
           4    safety of meat, poultry and eggs.  We have a food 
           5    safety policy program that is based on our review 
           6    of scientific literature, and our farm projects.  
           7    We now have one project working with thirteen farms 
           8    in Pennsylvania as well as in Hawaii where we have 
           9    a Salmonella control program for an egg-layer 
          10    system, and we're now working on a niche marketing 
          11    project with hog farmers in the Midwest.
          12                     Coming to the FDA questions.  As a 
          13    consumer-based organization, we must rely on the 
          14    scientific research of others.  We are not 
          15    scientists, but that does not exclude us from this 
          16    table.  For all of our experience, we do bring to 
          17    the table critical real-life questions about the 
          18    safety of the food we eat.  As we turn to the 
          19    federal regulatory agencies, our questions become 
          20    expectations as to how these agencies will address 
          21    our food safety concerns.  Granted, we could each 
          22    develop a clinical list of expectations, but in our 
          23    best moments as consumers we have some expectations 
          24    that are not content filled as far as precise 
          25    content, but they are filled in terms of outcome.  



                                                               65


           1    There are expectations in terms of outcome.  
           2                     Our expectations are that the 
           3    regulatory agencies will gather all the data 
           4    necessary to make a well-founded decision; that 
           5    they will conduct unbiased research to the greatest 
           6    extent possible; thirdly, that they'll provide a 
           7    decision-making process that is transparent, giving 
           8    opportunity for input and feedback from all the 
           9    affected parties along the way; fourth, that the 
          10    regulatory agencies will have the power to 
          11    implement and enforce the resolutions fairly across 
          12    the board wherever the threat or the need exists; 
          13    and, fifth, that there will not be delay in the 
          14    face of a food safety threat immediately related to 
          15    public health.  
          16                     It is in this context that I'd 
          17    like to address the questions put before us by the 
          18    FDA.
          19                     FDA Question 1:  What actions do 
          20    you propose the Agency take to expand its 
          21    state-of-the-art Science?  The FDA Center for 
          22    Veterinary Medicine is about to implement a 
          23    framework document that many have talked about 
          24    today.  I probably should have put this speech away 
          25    and pulled out my framework speech, because that 



                                                               66


           1    does seem to be the topic at hand.  I do have some 
           2    comments about it.  But in the context of relating 
           3    to the FDA questions, we do strongly support the 
           4    framework document and want to see it implemented.  
           5    I probably should sit down.  But that's the 
           6    position. 
           7                     We also have a whole list of 
           8    questions that we have raised, both publicly and 
           9    through our comments about the framework document, 
          10    as other groups have questions.  Some have 
          11    questions as to whether or not the framework is 
          12    based on good science.  We see the framework as a 
          13    helpful expression both of what works and what 
          14    needs to be replicated in the Agency, and also an 
          15    expression of what doesn't work within the Agency 
          16    as it addresses food safety issues.
          17                     What works?  Well, the framework 
          18    proposes to gather a wide range of data regarding 
          19    the sale of antibiotics and their use on farms.  
          20    The pharmaceutical companies are being asked to 
          21    provide sales information.  CVM is also proposing 
          22    to initiate on-farm monitoring for antibiotic 
          23    resistance, in addition to the information secured 
          24    through the National Antimicrobial Monitoring 
          25    Systems, or NARMS.  Gathering actual use data 



                                                               67


           1    should make it possible to link antibiotic use with 
           2    decreased susceptibility when an event occurs to a 
           3    particular drug, and thereby to make possible 
           4    realistic mitigation strategies.
           5                     In our view this proposal is a 
           6    model for how the FDA should go about making its 
           7    decisions, and it's part of the answer to their 
           8    first question regarding expanding its scientific 
           9    capabilities.  Gather all the data necessary to 
          10    make a well-founded decision.
          11                     However, the framework fails as a 
          12    model when it comes to the FDA implementing their 
          13    proposals across the board wherever the need may 
          14    exist.  This is where you say they've gone to far, 
          15    and we say they haven't gone far enough.  The 
          16    framework proposal is essentially prospective, 
          17    addressing only new animal drug applications.
          18                     Our expectation is that this 
          19    response to potential antibiotic resistance should 
          20    be applied to all animal antibiotic approvals, past 
          21    and future.  With approximately fifty million 
          22    pounds of antibiotics already going to the farm 
          23    each year, all approvals should be included within 
          24    one post-approval resistance monitoring scheme, and 
          25    that would then create a level playing field for 



                                                               68


           1    all antibiotics used with food animals.
           2                     Question 2.  What actions do you 
           3    propose to facilitate the exchange and integration 
           4    of scientific information?  In our view, consumers 
           5    expect that a food safety regulatory agency will 
           6    conduct unbiased and thorough research.
           7                     We all know that lack of funding 
           8    is major a limiting factor of the FDA.  It's 
           9    heartening to see the bar graph where there is 
          10    increased research funding thanks to some of the 
          11    initiatives that are going on.  But there are some 
          12    endemic problems, in our view, that would not be 
          13    fixed by more money.  This has to do with the 
          14    duplication of roles within the Agency and among 
          15    the regulatory agencies.  We were glad to hear the 
          16    commissioner address that concern earlier today.
          17                     In response to Question 2, for 
          18    there to be an exchange and integration of the 
          19    scientific information, clear roles and authority 
          20    must exist.  FDA through FDAMA is presented with an 
          21    excellent opportunity to take further steps to 
          22    clarify how research is conducted within the agency 
          23    and how it coordinates its efforts with other 
          24    governmental agencies, like the ARS and FSIS and 
          25    others.  



                                                               69


           1                     We call for continuing 
           2    preservation of the Joint Commission and the Joint 
           3    Council on Food Safety. 
           4                     Second of all, we encourage the 
           5    exchange of scientific information between the FDA 
           6    and academia and industry researchers.  FACT calls 
           7    on the FDA to maintain and expand its own expertise 
           8    and research base, that part of the pyramid that 
           9    was laid out by Dr. Sundlof.
          10                     I recently had the opportunity to 
          11    visit the CVM lab in Maryland, where the agency is 
          12    addressing a number of animal health issues.  What 
          13    impressed me most during my visit, as a lay person, 
          14    were areas in which CVM research was addressing 
          15    critical animal health questions where neither 
          16    academia nor industry research was to be found.  
          17    Isn't that the way it's supposed to be?  The focus 
          18    on the exchange and integration of scientific 
          19    exchange of information, we call on the FDA to 
          20    maintain its own unique contribution to the process 
          21    of scientific research.  
          22                     Moving on to Question 4:  What 
          23    actions do you propose to enable FDA to focus 
          24    resources on areas of greatest risk?  First we feel 
          25    that FDA must maintain its focus on priorities 



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           1    established through the Food Safety Program and 
           2    also projects established by its own actions.  As a 
           3    consumer group we hold the FDA accountable for what 
           4    it says it's going to do.  The FDA is part of the 
           5    President's Food Safety Initiative.  FACT expects 
           6    the Center for Veterinary Medicine to fulfill the 
           7    food safety priorities as assigned.  Sometimes we 
           8    look at the bar graphs and say that's stuff we have 
           9    to do.  Well, it's there because we wanted it to 
          10    happen, along with others, apparently, across the 
          11    nation.  
          12                The CVM must also fulfill commitments 
          13    that it has made in other areas, such as enforcing 
          14    the mammalian to ruminant feeding ban and 
          15    implementing regulations related to antibiotic 
          16    resistance.  As priorities, these are areas that 
          17    should be held harmless from shortfalls in FDA 
          18    funding.  
          19                     Second, in terms of Question 4, 
          20    risk assessment should be conducted within a time 
          21    frame that allows for regulatory response as soon 
          22    as possible.  In our view, as we've experienced 
          23    risk assessments among regulatory agencies, risk 
          24    assessments have too often become the science of 
          25    the delay.  CVA is less guilty of this, quite 



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           1    frankly, than other FDA centers or agencies, but to 
           2    use an example from another area, in December of 
           3    1996, the FSIS began a risk assessment of 
           4    Salmonella enteritidis in shell eggs.  We supported 
           5    that assessment.  We provided that assessment 
           6    volumes of material.  And maybe we provided them 
           7    too much material, because two years passed and no  
           8    risk assessment was published.  In May 1998, an 
           9    ANPR was published as a joint FSIS-CFSAN effort, 
          10    but still no risk assessment was published.  
          11    Findings from the risk assessment was published 
          12    after the deadline for comments on the ANPR and 
          13    findings from the risk assessments then had to be 
          14    incorporated back to the ANPR.  To date there's 
          15    been no further public movement toward a rule on SE 
          16    and shell eggs.
          17                     We applaud CVM for moving in a 
          18    timely fashion on both the BSE rule and
          19    implementing the framework document. 
          20                     Third, FACT is concerned about CVM 
          21    reliance on third parties to perform its reviews.  
          22    At several points in the Compliance Plan, the FDA 
          23    refers to the need to rely on third parties to 
          24    essentially speed up the drug approval process, a 
          25    necessary goal.  While FDAMA allows CVM to work 



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           1    with third parties, we do not support an 
           2    arrangement where the sponsor selects and pays for 
           3    the contractor.  FDA, we feel, needs to control the 
           4    review process, even if third party contracts are 
           5    established.  
           6                     Finally, in response to the 
           7    funding question.  It may seem that we've not 
           8    helped very much.  We want a food safety 
           9    initiative.  What's that?  3.5 million at least?  
          10    We want enforcement of the BSE regulations.  Ching.  
          11    We want post-approval surveillance of all 
          12    antibiotics.  Ching.
          13                     Quite frankly, as consumers we can 
          14    only point to the need from our perspective.  There 
          15    are numerous areas of CVM cost that we have not 
          16    identified, particularly with the implementation of 
          17    ADAA.  But we bring to you our priorities and 
          18    concerns.  Even though we are not in a position to 
          19    say what to cut, we are in a position to work for 
          20    adequate funding for this Center as it addresses 
          21    food safety.
          22                     Finally, the last question.  FACT 
          23    supports FDA's objective of obtaining input from 
          24    external stakeholders and encourages the continued 
          25    use of its advisory committees for that purpose, as 



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           1    well as meetings such as today.  We expect that the 
           2    decision-making process at the FDA will be 
           3    transparent, with feedback coming from all 
           4    stakeholders, including consumer groups.  For 
           5    consumer groups, the FDA Office of Consumer Affairs 
           6    is invaluable and the web site is helpful as well, 
           7    even though many of the decisions facing CVM and 
           8    FDA require scientific expertise, we call on the 
           9    FDA to continue to involve lay people in the 
          10    process.  Science without a connection to people's 
          11    experience is an abstraction and will lead the 
          12    agency in meaningless directions.  
          13                     Thank you.
          14                     (Applause.)
          15                     MR. BREEN:  Our next speaker is 
          16    Joel Brandenberger, Vice President of Legislative 
          17    Affairs for the National Turkey Federation.
          18                     MR. BRANDENBERGER:  Thank you.
          19                     My name is Joel Brandenberger, 
          20    Vice President of Legislative Affairs for the 
          21    National Turkey Federation.  I represent, 
          22    obviously, the processors and producers of turkey 
          23    nationally.  We really do appreciate the 
          24    opportunity to be here today.  In fact, we've done 
          25    this with folks from CVM in a number of different 



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           1    venues over time.  Maybe for fun we ought to do 
           2    each other's presentation and see how it turns out.
           3                     I'm going to focus primarily on 
           4    some of the questions regarding implementation of 
           5    the Animal Drug Availability Act.  But before I get 
           6    to that, I would like to take just a moment to 
           7    endorse some things that Rich Carnevale said, from 
           8    AHI, Barb and Paul and Dr. Waddell -- I guess he's 
           9    gone now -- and endorse their comments, 
          10    specifically as they concern risk assessment and 
          11    the antibiotic framework.  Some of the gains which 
          12    we're about to talk about that have been made by 
          13    the ADAA could be put at risk if we make regulatory 
          14    changes to the approval process for antibiotics 
          15    that are not based on real risk and sound science.  
          16    I think the desire of the stakeholders to see a 
          17    comprehensive, qualitative risk assessment 
          18    conducted required in implementation of any changes 
          19    in the antibiotics approval process is clear.
          20                     I guess from our point, speaking 
          21    not just for the National Turkey Federation, but I 
          22    know I speak for everyone in the Coalition for 
          23    Animal Health on this, we would encourage FDA/CVM 
          24    to sit down with the stakeholders and to see if 
          25    there's a way this could be done.  We are confident 



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           1    and hopeful it could be done in a way and 
           2    fashionably not slow.  Also the overall time frame 
           3    for addressing the antibiotic resistance issue.   
           4    But I think you would see in a lot of the
           5    stakeholders a much higher degree of confidence if 
           6    such a risk assessment were conducted. 
           7                     Okay.  To ADAA Implementation.  I 
           8    think, you know, ADAA covered a lot.  I think we're 
           9    going to focus today, speaking both for the 
          10    National Turkey Federation and for the National 
          11    Coalition for Animal Health on the efficacy 
          12    provisions.  That's the core of the bill.  That's 
          13    why we got involved with the stakeholders in 
          14    pushing for the package.  It's clear from the way 
          15    it was constructed that that was Congress's primary 
          16    intent.  Very briefly the efficacy provisions that 
          17    we're talking about here are, one, to remove the 
          18    presumption that multiple field investigations are 
          19    needed; to replace that assumption with one that 
          20    either no or one field investigation may be all 
          21    that is needed in many circumstances.  Require CVM 
          22    to justify more than one field investigation by 
          23    written order specific to the drug and its intended 
          24    use.  Eliminate efficacy requirements for 
          25    combination drugs when all of the drugs or active 



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           1    ingredients are previously approved and all have at 
           2    least one claim in the combination.  And I should 
           3    mention that efficacy should still apply when two 
           4    or more antibacterials are used in combination, at 
           5    least for the feed and water drugs.  
           6                     So two and a half years after 
           7    passage, how is CVM doing?  How do we, as 
           8    stakeholders who worked so closely with them view 
           9    the success record on implementation of this Act.
          10                     Well, let's start with the good 
          11    news first.  That has to do with the combination 
          12    drug section which, taken as a whole, appears to be 
          13    a working exactly as the ADAA's authors intended.  
          14    I had a chance to read some articles recently and 
          15    visit with some folks at CVM about that.  We're 
          16    extremely pleased that we have seen, since ADA 
          17    became law, more than forty combination drugs 
          18    approved.  Roughly 75 percent of those are 
          19    production drugs.  Parochially speaking, the vast 
          20    majority have been poultry drugs, and even more 
          21    parochially we're even more pleased that four of 
          22    them have been combination turkey drugs.  We should 
          23    also mention that there have been several cattle 
          24    approvals, and we have heard that there are some 
          25    swine approvals coming down the line.  So, you 



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           1    know, we think that, on balance, it's working 
           2    well.  I'm not going to say that every application 
           3    is going smoothly, because I'm sure if I indicated 
           4    that I would hear from a lot of our pharmaceutical 
           5    allied members tomorrow with some story.  But I 
           6    think there's every indication that the combination 
           7    proposals are being looked at to be ensure that 
           8    combination drugs are being used for appropriate 
           9    therapy, that there no human safety residue 
          10    questions involved, and that the answer to those 
          11    questions are yes to the appropriate therapy mode, 
          12    and CVM is to be commended and congratulated, in 
          13    fact. 
          14                     The good news that is tempered in 
          15    a couple of issues.  Dispersal of combination 
          16    approvals is obviously going to have a limited life 
          17    span.  There's a limited, finite number of approved 
          18    drugs out there for which these combinations can be 
          19    used.  At some point all of the available 
          20    combinations will end and we will see the dispersal 
          21    approvals begin to slow down.
          22                     That brings us to the question 
          23    about other provisions.  I can't -- when I 
          24    originally started preparing for this presentation 
          25    I originally thought we were going to have to take 



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           1    a hard look and raise some of the questions that 
           2    we've raised in previous forums about whether less 
           3    than three field investigations could really be 
           4    used in those circumstances.  After a while a lot 
           5    of the anecdotal information that we've had in the 
           6    past that we've had some problems.  There are a lot 
           7    of old stories.  I'm not going to torture you with 
           8    stories about instances where we've seen turkey 
           9    drugs slowed by what we think is needless efficacy 
          10    requirements.  But I've got to say this:  CVM has 
          11    apparently completed, at least internally, its 
          12    report to Congress that was required in the FY '99 
          13    Agricultural Appropriations Bill.  Hopefully very 
          14    soon we'll see that publicly.  We've seen some 
          15    preferences to date that 78 percent of the 
          16    applications have been approved at some point by 
          17    the ADAA.  We hope that's accurate.  We're going to 
          18    love to look for it and see how that's counted, how 
          19    they're measuring these improvements.  We hope it's 
          20    good news.  
          21                     What we've seen to this point has 
          22    raised a couple of concerns, though.  Last October, 
          23    Congress proposed several questions to CVM in the 
          24    context of a House Commerce Committee hearing about 
          25    this very question.  One of the answers was really 



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           1    disturbing.  When they were asked to give the 
           2    number of ADAAs in which less than three field 
           3    investigations were used, the first line is, We 
           4    don't have a field in our tracking system that 
           5    allows us to measure this accurately.  Well, it was 
           6    pretty clear from the way Congress handled the ADAA 
           7    that measuring this was going to be pretty 
           8    important.  So let me at least first suggest that 
           9    perhaps that the tracking system be amended so 
          10    there is such a field in the future and we can get 
          11    an accurate measure of this.  Because I think it 
          12    was important to Congress; I know it was important 
          13    to the coalition, and this is a question that's not 
          14    going to go away, I think, until we can get an 
          15    accurate measurement of this.
          16                     They did report in theirs answer 
          17    to Congress that there had been at least seven 
          18    supplemental ADAAs for food animals that had been 
          19    approved for drugs with less than three 
          20    investigations.  That's encouraging.  There was 
          21    also a claim in the response to Congress that 
          22    seventeen ADAAs, including nine for food animals 
          23    that had less than three and sometimes no field 
          24    investigations.
          25                     The question I come back to is I 



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           1    think a breakdown on exactly how many 
           2    investigations -- you know, obviously we want to 
           3    reveal the drug, but in general how many we were 
           4    talking about would be extremely useful.
           5                     I think we also have to mention 
           6    that the substantial evidence regulation, the 
           7    second major implementing regulation for ADAA, is 
           8    approximately six months overdue.  We recognize 
           9    this all is not entirely the Agency's fault, but we 
          10    need to see the regulation at some point.  And we 
          11    are a little curious about the claim that, in part, 
          12    the delay is we were waiting to see what happened 
          13    with the arsenical.  The omnibus appropriations 
          14    bill did not pass until October, but the House 
          15    first action on this was June 10th, and there was 
          16    every indication from June on that this was going 
          17    to be part of the bill.
          18                     I want to endorse what Rich said 
          19    about compassionate use of INADs.  I think there 
          20    was at least one instance in our industry that this 
          21    could be have been very useful.  This is not just 
          22    to pick on CVM.  I say this to every pharmaceutical 
          23    company that's here:  Please, someone step up and 
          24    use the binding presubmission conference as it was 
          25    envisioned in the ADAA.  



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           1                     So finally we've got a handful of