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