r00003 - Food and Drug Administration

1





1

2

3

4 FDA/CENTER FOR VETERINARY MEDICINE

5 STAKEHOLDER MEETING

6

7

8

9 April 28, 1999

10

11

12

13

14 Johnson County Community College

15 Overland Park, Kansas

16

17

18

19

20

21

22

23

24

25







2





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.







7





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







9





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







10





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







11





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







12





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.







13





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







14





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







15





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.







16





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







17





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







18





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







19





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







20

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







70





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







71





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







72





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







73





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







74

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







75





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







76





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







77





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







78





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







79





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







80





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.







81

1 So finally we've got a handful of

2 very short recommendations, quick recommendations

3 we'd like to make on where to proceed from here.

4 If the report to Congress does not

5 include it, we would hope CVM, at its earliest

6 possible date, would help us by further enumerating

7 the original and supplemental ADAAs that have been

8 approved since ADAA's enactment, the number that

9 were approved with one or no field investigation,

10 the total approvals since implementation compared

11 with the total approvals for the two years prior to

12 implementation, the number of combination approvals

13 by species since ADAA's enactment and the number of

14 pending ADAAs for which the Agency has agreed to

15 require one or no field investigation, and the

16 number of combination approvals by species that are

17 pending.

18 Whatever is in the report, we'll

19 have to see it; whatever's not, we need to see it.

20 The tracking system we've already

21 mentioned.

22 One other thing we've talked about

23 in the past is we do think there should be some

24 type of annual review with stakeholders of ADAA

25 implementation, perhaps a little more informal than







82





1 a session like this, to talk about the concerns,

2 need the substantial evidence rule promulgated and

3 we also need the Agency to please adopt a proactive

4 stance for minor use minor species provisions.

5 This committee did some very good work, but the

6 fact that it does not yet have administration

7 endorsing it is concerning to us if we try to move

8 forward with implementing some of those

9 provisions.

10 Thank you for your time.

11 DR. ALDERSON: Can we get a copy

12 of the specific requests, the numbers that you

13 would like?

14 MR. BRANDENBERGER: This is all

15 marked up, but I'll certainly mail something to you

16 tomorrow.

17 MR. BREEN: Our next speaker is

18 David Bossman, President of the American Feed

19 Industry Association.

20 MR. BOSSMAN: Good afternoon. My

21 name is David Bossman. I am the President of the

22 American Feed Industry Association.

23 I'm going to submit my formal

24 remarks and questions or answers to the questions

25 in writing so we don't have to go through all this







83





1 today, and maybe we can even save a little time.

2 Much of the comments as per a

3 stakeholder would be similar do what we did last

4 fall. There's just a few things that I'd like to

5 mention. The relationship that AFIA has with CVM,

6 we consider very good, and we appreciate that

7 ongoing communication in doing that.

8 Some of the specifics that I

9 wanted to briefly mention on the ADAA. We need the

10 regs for the BSD, we need the regs for the feed

11 bill licensing, and we need the minor species. We

12 we've heard those mentioned a few times today, and

13 we'll have a more important or written documents of

14 that as part of our submission.

15 The other issue is the funding for

16 the state inspections. In order to have uniform

17 inspections from one state to the other, we're

18 going to need that funding. The relationship

19 between FDA and AVCO and the industry is pretty

20 unique. And as you drop off one of the states, the

21 regulatory inspection scheme certainly doesn't hold

22 as well as it could.

23 The final point that I'd like to

24 bring out -- and certainly we've heard about it

25 many, many times today -- and that's Dr. Henney's







84





1 priority on risk assessment or science-based

2 approach. In my mind, the real reason to do

3 that -- and we've heard a lot of different comments

4 about that, but the real reason to do that is for

5 consumer confidence in the food supply. Anything

6 less than that distorts why you are doing

7 something.

8 And there's as Barb talked about

9 what they're doing in Europe because it was a slow

10 news day could really happen here. I had the

11 Europeans in my office last week, and they said the

12 same thing. They lost their opportunity for a

13 science-based approach. We don't dare do that. If

14 we can't stand on the science, we don't have

15 anything to stand on. The emotion and the politics

16 just will not ride today. We have to be able to

17 use the science. And good science is good

18 science. We found the Europeans, their science,

19 they'll drag out a scientist who will say anything,

20 and everybody can guy buy one. We haven't gotten

21 to that point here and we don't dare get to that

22 point.

23 It's interesting to note the

24 English -- I don't even remember what her title

25 was -- not too long ago said that the deaths







85





1 because of Viagra, which was last year's headlines,

2 were significantly higher than the headlines of two

3 years prior which was BSE. And that's true.

4 People do know that there is a risk. There is a

5 risk to everything. They understand that risk

6 assessment works, and as long as we stand on the

7 science, we can live with that.

8 Thank you very much for the

9 opportunity to be here.

10 (Applause.)

11 MR. BREENE: Our next speaker is

12 Robert Sinclair.

13 MR. SINCLAIR: Good afternoon. My

14 name is Bob Sinclair. My wife, Jane, and I are

15 from West Bloomfield, Michigan. We are here with

16 our colleague, Jean Townsend from John's Island,

17 South Carolina. We'd like to thank the CVM for the

18 opportunity to attend this meeting and offer some

19 views.

20 As consumers and dog owners, we

21 feel strongly that the communication efforts of the

22 FDA can be improved so that users of animal health

23 products can have better access to understandable

24 and timely information. The quality of life of the

25 hundred million-plus American companion animals and







86





1 their owners and households will benefit when the

2 agency treats information about animal health

3 products the way it treats information about human

4 health products.

5 Question 2 in the March 22nd

6 Federal Register notice, let me offer two

7 comments. First, FDA can improve the timeliness

8 of publishing adverse drug experience reports,

9 particularly when new drugs are introduced in the

10 market. Delays in the exchange of information

11 between the FDA and consumers can have serious

12 implications for the companion animals that they

13 care for.

14 Many manufacturers are required to

15 submit ADAA reports to the Agency. Availability of

16 evaluations of these reports to the general public,

17 in our view, should not await preparation and

18 subsequent publication of annual summaries.

19 An example, Pfizer introduced

20 Rimidil Purprophen for dogs in January 1997.

21 Clearly ADE reports were received during the '97

22 calendar year, but the '97 FDA summary of ADE

23 reports on veterinary drugs was not published until

24 October 29, 1998. Dog owners were denied access to

25 this important information for an unacceptably long







87





1 period of time, in our view. For months during

2 which the volume of ADE reports about Rimidil was

3 building, owners were purchasing and administering

4 the drug to their pets with little knowledge about

5 adverse effects. Dear Doctor letters may be

6 issued, and they were, and label changes may occur,

7 and they did, but there is no assurance that

8 balanced risk/benefit information is available to

9 consumers. Lack of information about Rimidil's

10 potentially toxic side effects seriously affected

11 the quality of life of our toy poodle, Misty, and

12 caused the death of Jean Townsend's chocolate lab,

13 George.

14 We detailed Misty's story in

15 reports submitted last October, and in February

16 Georgia's necropsy report was sent to Pfizer and to

17 the FDA/CVM.

18 Second, various means can be

19 employed to disseminate balanced information about

20 animal health products to consumers. Internet web

21 site updates plus post read line bulletins to

22 veterinary facilities and other communication

23 techniques come to mind.

24 In view of the time, I'm going to

25 edit this on the fly and go right on to the next







88

1 point.

2 Question 3 in the notice asks,

3 "What actions do you propose for educating the

4 public about the concept of balancing risks against

5 benefits in public health decision-making?" We

6 have several responses to this question.

7 Direct to consumer so-called DTC

8 advertising posts, we believe FDA can re-institute

9 its earlier policy requiring that DTC advertising

10 of human and animal prescription drugs in all media

11 include a brief summary -- quote, "a brief

12 summary" -- of hazards and contraindications.

13 After broadcast advertising restrictions were eased

14 on August 8th, 1997, it became apparent that

15 procedures are not in place to assure that balanced

16 information is, in fact, delivered in all media.

17 Unbalanced TV commercials encourage animal owners

18 to unknowingly demand drugs like Rimidil that may

19 cause their pets to suffer lethal or sublethal side

20 effects. Coupled with unavailability of label

21 information or patient information leaflets, animal

22 owners hoping to help their pets cannot evaluate

23 the risks versus the benefits and make informed

24 decisions.

25 We suggest a new regulation. We







89





1 suggest that FDA can initiate rule-making towards a

2 federal regulation requiring that consumer

3 information prepared and supplied by the

4 manufacturer must absolutely be delivered to animal

5 owners when prescription drugs are purchased.

6 Drugs suppliers and veterinary practitioners who

7 fail to provide such information to animal owners

8 would be held in violation of this regulation. And

9 obviously means to monitor compliance and enforce

10 the proposed regulation would be required.

11 Blister pack and tube packaging

12 include inserts that do provide information, but

13 many animal prescription drugs are dispensed in

14 small vet-supplied containers without either label

15 information or PILs, containing balanced

16 risk/benefit information. Typically these

17 containers indicate the name of the drug, the

18 dosage and the condition for which it was

19 prescribed. Animal owners are not assured receipt

20 of accurate guidelines advising that their animals

21 should be carefully and objectively monitored.

22 We -- Jean and I -- we never

23 received such guidance about Rimidil. The only

24 information that was provided verbally to us was

25 that Rimidil is, quote, "safer than aspirin and has







90





1 less GI effects." Something clearly is wrong in

2 the risk/benefits communication process between the

3 manufacturer/distributor, the veterinarian, and the

4 consumer/owner of the animal receiving the drug.

5 A veterinary drug database. Many

6 users don't understand possible risks without

7 personally conducting exhaustive research which

8 they may or may not be able to pursue. Information

9 about new human drugs is readily accessible by

10 consumers from the FDA home page, a database of

11 veterinary prescription drug information that can

12 be accessed from the CVM home page we recommend

13 should be created. The FOI summaries don't answer

14 the need. Consumers cannot readily access

15 information about a new animal drugs like Etogesic

16 as they can about a new human drug like Celobrex

17 (phonetics).

18 U.S. approval status reports. We

19 believe the FDA can do a better job of informing

20 the public about the U.S. approval status of drugs

21 approved and being used successfully in other

22 countries. Cartofovet, penicillin polysulfate

23 sodium (phonetics), for example, has been available

24 in Australia, New Zealand, Canada, the United

25 Kingdom and Ireland for years. This therapy for







91





1 osteoarthritis in dogs is not available in the

2 United States, and we do not know how to determine

3 its status.

4 We think the public needs to

5 know. We think the CVM could explain its position

6 on fighting this promotional advertising works

7 advising material to the American public.

8 Here are four copies -- or copies

9 of four letters from the Agency to Pfizer dated

10 April 4, October 8, December 19 and December 21,

11 1998. Each of these letters discussed fair balance

12 and advised that Pfizer was found in violation of

13 the FFDC act and applicable regulations. The

14 public, we believe, deserves to know the results of

15 these actions. Pfizer has claimed Rimidil is safer

16 than aspirin. This is a bogus claim.

17 And I'll skip. I'm getting signs

18 telling me to stop talking. So I'll again edit

19 further on the fly.

20 The claim that Rimidil is safer

21 than aspirin is wrong. That was documented in the

22 October '98 summary of '97 ADE reports highlighted

23 in the January-February issue of the FDA

24 Veterinarian and discussed in articles appearing in

25 recent issues of APC Veterinary News and Dog







92





1 World.

2 The Pfizer commercials continue.

3 The golden retriever is still jumping over garbage

4 cans, leaping to the second floor and sliding down

5 banisters. We think that and merchandising

6 materials, toy dogs, desk pads, calendars, lack

7 fair balance of risk/benefit information.

8 We'd also like to know why -- we'd

9 like CVM to comment on why the U.S. Dosage for

10 Rimidil after one week is twice that in Australia,

11 the United Kingdom and Europe where adverse

12 experiences seem to be less than in this national

13 market.

14 Let me close by describing a

15 personal experience that occurred in March at a

16 specialty show the day before the Detroit Dog

17 Show. A lady that we met brought her six-year-old

18 dog for obedience trials and a beautiful

19 fourteen-year-old along for the ride. In

20 conversation, the owner said that her vet had just

21 put the older dog on Rimidil. We asked why. Her

22 answer? "Oh, no symptoms. She just slowing down a

23 little and the vet said Rimidil is very popular

24 now."

25 Jean, Jane and I are here in part







93





1 seeking closure and for those who record the

2 remote, statistically insignificant judgment, I say

3 that for Misty and George and many others, it was a

4 hundred percent.

5 As you people in CVM well know,

6 the premarket testing rarely indicates the full

7 range of problems. Our plea is simply one for

8 better communications, improvements in the exchange

9 of information about animal drugs.

10 The so-called action plan for the

11 provision of useful prescription medicine

12 information approved for human drugs by Secretary

13 Shalala January 13, '97, we recommend be adopted

14 for animal drugs. What we miss today is the

15 guarantee that information about the drugs we give

16 to our animals is timely, accurate, up-to-date,

17 unbiased, specific, and comprehensive and is

18 presented in an understandable and legible format

19 and is useful.

20 Thank you very much for your time.

21 (Applause.)

22 MR. BREEN: Does the CVM panel

23 have any clarifying questions it wishes to ask?

24 (No response.)

25 MR. BREEN: Then let's proceed







94





1 with the questions. Some of them have

2 been -- excuse me a second.

3 Thank you very much to all

4 speakers.

5 (Applause.)

6 MR. BREEN: Dr. Sundlof will take

7 care of the questions.

8 MR. SUNDLOF: We have one that

9 was originally submitted to the -- by the American

10 Veterinary Medical Association to the telecast and,

11 unfortunately, was not addressed at the telecast.

12 Because it was very specific, the CVM, I thought we

13 would be able to address this question first. It's

14 one to which a number of people alluded to. It

15 talks about the risk assessment. New concept.

16 It says risk assessment is

17 well-recognized as a tool that supports the

18 decision, i.e. the risk management tool. The

19 discipline uses scientific data to evaluate risk

20 and was introduced in the 1970s to evaluate human

21 cancer risk. Risk assessment provides what has

22 been qualified by Anne Lammerding of Health Canada,

23 a common, unified work space for people of

24 different backgrounds to contribute to a better

25 understanding of the whole system.

95





1 Risk assessment shows where there

2 are data gaps, serve as a storage vehicle for

3 valuable knowledge as it is accumulated and

4 describe a chain of cause-and-effect events where

5 proposed changes can be evaluated.

6 That's the prologue. And then the

7 first question is given the complexity and the

8 importance of managing potential human health

9 impact of antimicrobial use in food animals, is the

10 FDA planning to conduct a risk assessment to define

11 these risks to human health and derive these

12 benefits associated with risk assessment in concert

13 with its intention to the proposed antimicrobial

14 framework? And the answer is yes.

15 Next question -- maybe I should

16 expand. Yeah, we expect to have our risk

17 assessment completed this summer, and so we'll be

18 coming out -- we are very far along in it. In

19 fact, we had two of our people down at CDC just

20 this week going through their files collecting the

21 kind of data that is going to be required to try

22 and associate the actual human health problems with

23 antimicrobial resistance, we'll go back and use the

24 data from the NARM system to look at animals, look

25 at human resistance, and we will have a risk







96





1 assessment that we'll go out and we want a lot of

2 input from all our stakeholders, especially in the

3 scientific community, on that risk assessment so

4 that we're sure that we feel confident that it was

5 done properly. We're doing this in conjunction

6 with a consultant who is very well respected within

7 the risk assessment community. His name is David

8 Voss.

9 And let me just say that this risk

10 assessment will apply to food-borne pathogens and

11 will not address commensal organisms like

12 enterococcus. That's a more difficult and

13 challenging risk assessment to perform. We intend

14 to do that subsequent to getting this first one

15 out, which we think the food-borne entero-pathogens

16 are easier to model. So, yes, we certainly support

17 that. We think we have the actual data so that we

18 can minimize the uncertainty in that risk

19 assessment. So that's the answer to that question.

20 The second one, USDA has recently,

21 recently completed a risk assessment on Salmonella

22 enteritidis that will serve as a prototype for

23 future risk assessments of microbial hazards. The

24 risk assessment for E. coli is being conducted by

25 the same agency. The USDA and FDA since then are







97





1 cooperating on a complete risk assessment of

2 Escherichia in food. Question: Do you envision

3 the Center for Veterinary Medicine working

4 cooperatively with the USDA to conduct the risk

5 assessment on the human health impact of

6 antimicrobial use in food-producing animals?

7 Let me say that, as I indicated

8 earlier, we are working with a consultant. We are

9 participating with the USDA in their risk

10 assessment consortium. In fact, our risk

11 assessment model, I think, has been addressed at

12 that consortium. So a number of the people working

13 in USDA on risk assessment, in addition to the

14 Office of Risk Assessment Analysis within USDA

15 certainly have been informed about the risk

16 assessment, the basis for the risk assessment, and

17 we are seeking your input on this as we will seek

18 broad input. And also, yes, the Center is also

19 looking at it. So we are addressing the issue of

20 risk assessment and we do agree that it's very

21 important to do that, and we certainly concur that

22 the decisions that we make that lead to regulations

23 guidance, et cetera, are based on the best science

24 available. That's first one.

25 I haven't read these in advance,







98





1 so we'll take one more of the ones that have been

2 written and then maybe go to the microphone and

3 kind of go back and forth.

4 This one, it says, "How does CVC

5 propose to focus resources on areas of greatest

6 risk in those areas where risk has not been

7 adequately assessed? For example, antimicrobial

8 use. The answer is the FDA, I think we just did

9 that. I'm going to say that we really do try and

10 focus our enforcement efforts on those areas of

11 highest risk. But not totally. And the reason is

12 because we can't let the -- it's like the broken

13 window theory of crime, that if you allow some

14 minor indiscretions to continue, it escalates and

15 you have a deteriorating system that loses

16 credibility. So we try and focus on those with the

17 greatest risk, but we don't ignore some of the

18 other ones as well.

19 So since we already did that one,

20 I'll just read one more and then we will go to the

21 floor.

22 This one says, "What can or will

23 be done to improve consumer veterinarian

24 manufacturers' relationship with regard to

25 informing consumers about possible adverse effects







99





1 of medications so that veterinarian -- so often

2 veterinarians administer drugs, particularly newly

3 introduced ones, without accompanying literature

4 that gives sufficient warning about what side

5 effects to be on the alert for and really

6 emphasizes the side effects to watch for." And

7 that's very consistent with the presentation that

8 we just heard from Mr. Sinclair. And

9 Dr. Tollefson?

10 DR. TOLLEFSON: I'll answer this

11 one, too. There is another submission by Bob

12 Sinclair, who you just heard speak, and it had to

13 do -- he actually had some very excellent points --

14 with improving the availability and timeliness of

15 ADE reports, particularly for the newly approved

16 products, and I think the, as many of you know, the

17 adverse events, the adverse reactions that we

18 receive come in the initial stages of the marketing

19 of the product -- at least the great majority of

20 them -- and that's been associated with the level

21 of use, the advertising, the fact that it's now

22 getting out into the market where a lot of animals

23 are using the drug, and we discover the adverse

24 reactions.

25 We have been trying to improve the







100





1 timeliness of reporting those adverse reaction

2 reports, the summaries, et cetera. It's directly

3 linked to resources. The FY 2000 budget is not

4 going to give us much relief on that. We will be

5 submitting information for the 2001 link report on

6 adverse reactions. It's directly linked to the

7 consumer advertising. We're becoming overwhelmed

8 with the amount of information that's getting out

9 there. The request for the new products, although

10 maybe it wasn't accurately expressed at this

11 meeting but Office of New Animal Drugs' proficiency

12 at approving new products, and it's becoming very

13 critical that we do that.

14 Your ideas about creating more

15 animal health information for the consumer is well

16 received. We want to do that in general, you know,

17 link our home page. We think that maybe that's one

18 way to counteract a lot of information that's

19 becoming widespread on the internet where

20 consumers -- anybody can get information that's not

21 always accurate, not so much for approved products

22 as for unapproved products. It's difficult to

23 regulate that area. So we're thinking that if FDA

24 serves as a source of the neutral information, that

25 will induce people to come to us to check the







101





1 claims and so on. But we do appreciate your

2 input.

3 DR. SUNDLOF: Let's go to the

4 audience. If anybody has any questions, let's go

5 to the microphones. I think there are two there.

6 Let's try to come up and ask those questions.

7 In fact, why don't I read another,

8 because I don't see people flocking. I'll go ahead

9 and read. But while I'm doing one, if you think of

10 a burning question, please walk over to the

11 microphones and we'll get to you.

12 This one says, "What is the

13 agency's role" -- I think that's "role" -- "in

14 regulating animal feed additives? Does current

15 science support restricting some drugs, or is it

16 mostly perception? If it's mostly perception, will

17 FDA bow to pressure for regulation anyway?"

18 Well, as I think is well known

19 that there have been some severe restrictions,

20 especially in some European union where certain

21 products were simply banned without a full

22 scientific review. Whether those products were

23 contributing resistance is still an open question,

24 has not been resolved. CVM's position is that we

25 look at drugs and make regulatory actions based on

102





1 their risks to the public. If that risk is

2 unacceptable, then we would take action.

3 Once a drug is approved, though,

4 the burden of proof is on the FDA to establish that

5 it is unsafe. So any action that we would take on

6 any feed additives would have to be based on our

7 true ability to demonstrate that there was a risk.

8 We do have a petition before us

9 right now to take some similar action to banning

10 certain growth-promoting antibiotics in feeds,

11 which was -- there was more than forty

12 organizations and individuals, including a Nobel

13 laureate that was a co-signator to that citizens'

14 petition. So regardless, it is still the

15 responsibility of the FDA to demonstrate that those

16 products are unsafe, and that's our mandate within

17 the law, and we will make those decisions based on

18 data and science.

19 Dr. Jarrett?

20 DR. JARRETT: Further to the

21 comments I made about compliance and enforcement, I

22 noticed in the slides and the overheads that you

23 used compliance and enforcement based on your

24 wishes had the lowest funding and the greatest

25 desire for funding, and I commend you for that.







103





1 Would you like to comment on that further?

2 DR. TOLLEFSON: Yes, it's always

3 been on our wish list. It's difficult. Frequently

4 that concept doesn't sell very well to FDA

5 stakeholders, the increased compliance, and it

6 never really has. We are now addressing it under

7 the brooder term of product quality assurance, so

8 that you bring in to the issue the preapproval

9 instructions, the GMP issues, that sort of thing,

10 so that everything is lumped into one, and we think

11 it may sell better in a congressional format.

12 Again, our funding requests are being broken down

13 into two areas under food safety initiative

14 enhancements and under regular base line FDA

15 requirements. The inspections component and

16 enforcement issues are under both for FY 2001. And

17 I probably sound like a broken record in saying

18 that our hopes are up for 2001, but that is the

19 case. And we're not alone. The other senators

20 also want to do that. So we're hopeful.

21 Does that answer your question at all

22 or do you want specifics?

23 DR. JARRETT: No, no, no. My

24 inference, though, was more to existing regulations

25 and at the field level, product usage and so forth,







104





1 not those -- the professionals that are out there

2 doing it right. The few that are not doing it

3 right --

4 DR. TOLLEFSON: Correct. We get

5 information own those types of activities from a

6 number of sources. We get an awful lot of

7 information from veterinarians, from organizations,

8 practitioner groups, from competing drug sponsors.

9 We do follow those up. We categorize them in terms

10 of the activity, like compounding pharmaceuticals

11 that you mentioned, internet advertisement and

12 sales. And we request to the field; the field

13 follows up on them based on the priority. And we

14 need to compete against all the other agencies.

15 Representatives from the field can tell you that

16 their priorities follow the lines of the user

17 investigations that have to be done. They're under

18 a mandate to be done, so they come first. Then

19 it's prioritized based on public health. We

20 actually have a pretty good relationship with the

21 field. They do a lot of our work.

22 The other part of that problem is

23 you won't get specific information fed back to you

24 on what is going on if the case is developed or

25 warning labels are issued and so on.







105





1 There's actually a fairly good

2 description of that in the folder on our response

3 to the last stakeholders meeting that addresses

4 some of those specific issues.

5 But our request for additional

6 funding will, of course, help that problem, but

7 it's not specifically addressing enforcing current

8 regulations. It's more for statutory inspections

9 that which are not necessarily overlapping.

10 DR. JARRETT: Thank you.

11 MS. LAVENBERG: My name is Donna

12 Lavenberg, and I'm with Bayer. I noticed in one of

13 the handouts that CVM is starting some third-party

14 reviews, and I just had some questions. Are the

15 sponsors aware that a portion of their application

16 may be under review by a third party? Is

17 this -- in what areas are you working? Are you

18 going to continue this effort? Just some more

19 basic information about the program.

20 DR. BEAULIEU: Yes. We're now

21 working on the Food Safety section, particularly

22 the pathology reviews associated with the tox

23 studies. We lost our tox -- our path expertise,

24 and the general consensus was that, resources being

25 as limited at they were, we could not afford to







106





1 invest one complete FDT in keeping that expertise

2 within the organization. So that was an obvious

3 place to reach outside the organization to get that

4 expertise. We are paying for that. So it's still

5 a resource that's counted against our operating

6 budget. It's working well to the extent we have

7 resources to do it. I think we're very happy with

8 the way that process is working and something on

9 the order of half a dozen reviews, maybe, a year is

10 about what we can afford in that.

11 We're interested in expanding that

12 process possibly into other areas of expertise that

13 we're currently deficient in. But the resources to

14 support that are going to have to come from our

15 budget at this point. So our ability to do that is

16 limited. But so far it's available. It's been a

17 favorable experience. We would very much like to

18 expand it. Part of what we would do with our

19 additional resources in the future, if we get them,

20 would be to expand that program.

21 If you guys have -- I know that

22 you suggested one area that we might consider for

23 going outside for expertise was the statistical

24 area because I think you folks viewed that as a

25 potential roadblock. Where we didn't have







107





1 sufficient resources we dealt with that by

2 investing in more in-house resources in that area,

3 and we hope to deal with that situation in the

4 future, too.

5 But if there are other specific

6 areas of expertise that you perceive that are

7 bottlenecks because -- that are holding the

8 applications up, or you would suggest maybe going

9 outside, we would certainly be interested in

10 hearing about those.

11 The food safety portion of the

12 application, in our judgment right now, tends to

13 lend itself best to that approach. We're not

14 looking for a clinical judgment, we're not looking

15 at any effectiveness evaluation, we're looking for

16 the ability to look for someone to make a fairly

17 specific and concrete determination with respect to

18 what a specific study says.

19 MS. LAVENBERGER: Thank you.

20 MR. RIGGS: David Riggs from

21 Watkinsville, Georgia.

22 I attended a conference that was

23 held at the Centers for Disease Control back

24 earlier in the year, and this is a group of

25 molecular scientists that were discussing their







108





1 findings, and I was very impressed with the content

2 of the meeting and the presentations. But the

3 thing that also hit me is that when people are

4 asked, Where did this resistance that these

5 scientists had recognized and had identified, the

6 question came up, Well, where did they come from?

7 And they gave their opinion -- not fact -- as to

8 what the origin of that resistance was, and the

9 thing that I left that meeting with is a very

10 strong suggestion that we need to get the molecular

11 scientists, the epidemiologists and the people in

12 the field, the end users, together, and have those

13 three groups discuss their findings and be

14 challenged when they make particular statements

15 about -- particularly about the origin and

16 evolution of the antimicrobial resistance issue.

17 That being said, my question to

18 CVM is: Do you have any plans at all to bring

19 these groups together? Would this be a part of

20 your working group plan that you have -- that you

21 had mentioned, and, more specifically, in your

22 research priorities, do you have any long-range

23 plans to look more closely at the origin and the

24 evolution of antimicrobial resistance specifically

25 as to the frequency of transfer within related and

109





1 even unrelated bacterial populations?

2 DR. ALDERSON: Within CVM, there

3 are two resources: The intramural and the

4 extramural. And I think if you'll look at what

5 we're doing, particularly in the intramural side, I

6 think it's very basic just addressing the issue

7 that you're talking about. We have hired three

8 outstanding scientists already, fixing to hire two

9 more. We failed last year. We made two offers,

10 and they got more money to stay where they were.

11 So in one way we failed, but in another way we did

12 select good candidates because they got more money

13 to stay where they were. So we are starting down

14 that path again.

15 But the short answer to your

16 question is: We're very focused intramurally

17 particularly and will become more focused

18 extramurally in the next year's round of funding on

19 just the issue you're talking about. Because

20 that's the evolution of resistance. We've got

21 within our facility now the means for us to take

22 samples when they lie down -- well, anywhere in the

23 GI tract without being able to follow that

24 evolution of resistance beginning in the gut of the

25 animal and following the same animals through that







110





1 process. That's where we are. I think our focus

2 is on how do we help the industry address the

3 problems they have and the problems that we're

4 trying to grasp and give advice to the industry on

5 what do we need to do to address the antibiotic

6 resistance issue to make these products available?

7 There was one other part of the

8 question.

9 DR. SUNDLOF: You were wanting to

10 the know if we're going to bring the different

11 disciplines together, the molecular microbiologists

12 and the epidemiologists and other groups that may

13 have particular expertise that could be brought to

14 bear on this issue. And I would just say that we

15 don't have any formal plans right now to convene

16 such a conference, but I think that in the future

17 we will -- we certainly may.

18 It is our intention to bring as

19 many diverse scientific opinions together on this

20 issue as possible. One of the presenters implied

21 that we were only listening to one faction and that

22 that might be epidemiology, and you should be

23 listening more towards people that are bench

24 scientists' point of view.

25 The whole area of antimicrobial







111





1 resistance is extremely complex. It encompasses a

2 wide variety of scientific disciplines and

3 expertise, and we certainly try and listen to all

4 of those to the extent possible. I think some of

5 the comments that Norris was making was in

6 reference to the fact that we need to be bringing

7 more of that expertise into the Center so that we

8 can understand what's being on out there in the

9 scientific community. If you don't understand

10 molecular biology very well, it's hard to take the

11 newest science into account when you're forming

12 regulations or policies or making decisions. So

13 we're trying to build up our own expertise

14 internally just so we can better understand all of

15 the complexities and new science that's going on

16 out there.

17 I think that's a very important

18 comment, and I appreciate it.

19 Did that address your --

20 We have just one more.

21 DR. JARRETT: Are you also going

22 to address the frequency of transfer of resistance

23 from one bacteria to another? Are you going to

24 look at frequency.

25 DR. ALDERSON: Yes, that's part of







112





1 what we're looking at within our research program.

2 Again, I think the issue, as you notice

3 particularly later in the year, and of course the

4 next year our announcements coming up are for

5 extramural funding. You'll see that particular

6 factor very prominent in the advertisement for

7 extramural funds.

8 DR. SUNDLOF: I'd just add to that

9 that the reason that we're not doing a risk

10 assessment on those types of potential resistance

11 issues -- that is, the transfer of resistance from

12 one organism to another organism -- is because we

13 don't feel we have enough science to define that

14 process very readily in risk assessment modeling.

15 So we are very interested in getting more of that

16 information so that when we do our risk assessment

17 as Phase 2, it will be based on a lot more

18 knowledge than we presently have.

19 We have one more question here,

20 and it says: What role do you see for the office

21 of criminal investigation in your science-based

22 regulatory agency?

23 Norris, do you want to take that

24 one?

25 DR. ALDERSON: You don't want me







113





1 to answer that one.

2 DR. SUNDLOF: Well, I think one of

3 the things we were talking about, whether it's the

4 Office of Criminal Investigation or the field, that

5 we're dealing with a lot of very sophisticated

6 issues that deal with the products that we

7 regulate. And certainly the field needs to be able

8 to keep up with all of the latest changes in

9 science and manufacturing technology and et cetera

10 so that they can do an adequate job. I would

11 assume it would be the same for the Office of

12 Criminal Investigations where they are

13 investigating potential criminal activities that

14 involve some fairly sophisticated mechanisms. My

15 favorite one -- this is the one of the cow, where

16 they wired a cow and traced it through a number of

17 sale barns where individuals had told them that

18 they actually used drugs on them and had all this

19 stuff on tape and had video cameras. It was really

20 neat.

21 DR. TOLLEFSON: It's true.

22 (Laughter.)

23 DR. SUNDLOF: It's true. So they

24 do use some fairly sophisticated techniques that

25 you seldom hear about because they want to keep







114





1 that activity away from the public, for obvious

2 reasons.

3 But we certainly think that the

4 issues that we deal with are technically complex

5 and challenging, and that the Office of Criminal

6 Investigations would need some kind of training to

7 maintain currency as the other component.

8 Charles, I am going to turn it

9 back over to you.

10 MR. BREEN: I'd like to thank

11 everybody very much for your attendance and

12 participation here today.

13 Did you have anything more to

14 say?

15 DR. SUNDLOF: I'm supposed to

16 summarize.

17 Dave Lynch and company have been

18 faithfully taking down notes, too, and trying to

19 summarize what they thought the main points that

20 were raised today are. And Jackie Pace was also

21 involved in that.

22 There was broad support for strong

23 science base, and we're encouraged by that, since

24 that's one of the Commission's major emphasis.

25 The risk assessment was very







115





1 important, and there seems to be a lot of support

2 for CVM making sure that their decisions are based

3 on a valid risk assessment.

4 Continued partnering with

5 stakeholders. We heard a strong sense that

6 partnering was an essential part of doing business.

7 Continued development of judicious

8 use of principles. Absolutely CVM supports that.

9 Support and enhancement and

10 expansion of the National Antimicrobial Monitoring

11 System and surveillance, that is also a view that

12 we certainly share and we will be asking for

13 additional funds through the Food Safety Initiative

14 to increase the robustness of that program.

15 Enforce current regulations. We

16 heard this a lot at our last stakeholders meeting,

17 and we heard it again today. We will go back and

18 again discuss this and try and apply the resources

19 necessary against the -- where we think the

20 enforcement activities need to be.

21 Inclusion of veterinarians and

22 practitioners and producers in the decision-making

23 process. We heard that today, and we certainly

24 support broad public input into decisions.

25 Support for the use of

116





1 compassionate investigation of new animal drug

2 applications, where certain diseases impact a

3 relatively small percentage of the animals, but

4 when diseases do occur, people need drugs, and

5 anything we can do to help with that process is

6 something that we've tried to do and will continue

7 to do.

8 Request for regulations on VFDs,

9 licensing and minor species document. I think

10 we'll be seeing some of those fairly soon because

11 we have come quite a long way on those.

12 Veterinary drug database on the

13 worldwide web. That's something that we need to be

14 considering. I'll be very honest that CVM has not

15 had a lot of requests for this kind of information

16 before, but we've been approving a lot of new drugs

17 for companion animals lately, and as a result of

18 that, maybe this is an area that we haven't spent

19 enough time on.

20 We really appreciate your coming

21 out and making those statements. We may not have

22 been as responsive as we should had you not been

23 here. So certainly we'll try and work on that.

24 Better communication between FDA and consumers.

25 And, again, good suggestions.







117





1 So that's it.

2 Okay, Charles.

3 MR. BREEN: Thank you.

4 I won't repeat myself, but having

5 the last word is a privilege. I would just like to

6 say the stakeholder meetings isn't just a walk,

7 it's a good idea.

8 Thank you.

9 (Applause.)

10 (The proceedings concluded at 4:54

11 p.m.)

12

13

14

15

16

17

18

19

20

21

22

23

24

25







118





1 C E R T I F I C A T E

2

3 I, LINDA R. BURT, a Certified Shorthand

4 Reporter of the State of Kansas, do hereby certify:

5 That said proceedings were was taken

6 down by me in shorthand at the time and place

7 hereinbefore stated and was thereafter reduced to

8 typewriting under my direction;

9 That the foregoing transcript is a true

10 record to the best of my ability of the statements

11 given;

12 That I am not a relative or employee or

13 attorney or counsel of any of the parties or a

14 relative or employee of such attorney or counsel or

15 financially interested in the action.

16 WITNESS my hand and seal this _____ day

17 of _______________________, 1999.

18

19

20

21 __________________________

22 LINDA R. BURT, C.S.R.

23 Certified Shorthand Reporter

24 State of Kansas

25