Duration: 10/01/2004 to 09/30/2009

Administrative Advisor(s):

NIFA Reps:

Non-Technical Summary

Statement of Issues and Justification

Stakeholders identify critical national need in minor use therapeutics - In 1976, the Food and Drug Administration (FDA) initiated an extensive study of the minor use of animal drugs through the efforts of a minor use/minor species drug committee. This committee, comprised of representatives of the FDAs then Bureau of Veterinary Medicine and Bureau of Foods, the U.S. Department of Agriculture (USDA), the pharmaceutical industry, and animal producer groups identified the scope of the problem as a lack of approved drugs for (1) diseases of minor species and (2) the principle minor diseases of major species. The committee identified the principal diseases for which drugs were not available in the minor species. Additionally, the committee recognized that the livestock industry in the United States relies heavily on the judicious use of drugs for the treatment of diseases in food animals. Without these drugs, animal suffering and mortality would greatly increase, as would the cost of producing animal-derived food products. However, before a drug can be marketed for use in a food animal species, it must be shown to be safe to the human consumer of the animal-derived food, and safe and efficacious in the target animal.

The process of generating the safety and efficacy data necessary for FDA/CVM approval of a drug is costly and time-consuming. In 1999, the estimated cost to a pharmaceutical company for research necessary to obtain FDA/CVM approval for a new drug exceeded $20 million, and required 8 to 10 years of concentrated research effort (Ringer et al., 1999). More recently, issues relating to (1) increased costs in the development of analytical methods, (2) concerns over antimicrobial resistance in human medicine, and (3) increased environmental testing have increased veterinary drug approval costs dramatically (Lathers, 2003). Drug approvals are generally species and disease specific and additional label claims also come with considerable added expense. Pharmaceutical company estimates place the cost of adding a label claim to an FDA/CVM approved drug at $2 to $8 million (Brown, 2003).

Because of this substantial investment in time and resources, pharmaceutical companies must be assured that the drug will have a reasonable potential for profit. Therefore most drug approvals are sought only for those animal species that are produced in sufficient numbers to support large volume sales, specifically cattle, swine, chickens and turkeys. There is little economic incentive for pharmaceutical firms to generate data necessary to seek FDA/CVM approval of drugs in minor species; hence, very few drugs are available for management of diseases in these species. Inequities in drug availability represent serious management and economic problems for producers for minor species. Today, more than half of all commercially led pharmaceutical R&D in the veterinary medical field is focused on developing products for companion animals, and the emphasis on this sector is likely to increase in coming years, as companion animals live longer, and more diseases of old age are diagnosed and treated (Lathers, 2003).

The FDA/CVM was aware that veterinarians and livestock producers were using unapproved drugs without the safeguards that approved drugs carry. Such unapproved drug use could not only cause detrimental effects to the animals being treated, but could also lead to the persistence of drug residues in animal products intended for human consumption. A definite need was established for approval of minor use veterinary drugs and the scope of the problem was defined. This need was also affirmed by various grower organizations.

In 1982, the IR-4 Animal Drug Program was established as part of the overall IR-4 Minor Use Pesticide Management Program. Since that time the animal portion established itself as a national means of securing approved drugs and as a conduit between the animal industries and the FDA/CVM.

In December 1990, the USDA/CSRS requested a peer review of the IR-4 program, including both the pesticide portion and the minor use animal component. A reorganization of the minor use animal drug section was one of the recommendations of the Review Team. This Change was carried out with the development of a separate Minor Use Animal Drug Technical Committee that reported to the IR-4 Administrative Advisors.

In 1992, IR-4 Administrative Advisors recommended that with the change from interregional Projects (IRs) to National Research Support Projects (NRSPs), as well as the experience gained under the reorganized IR-4 Project, that the two programs (pesticide and animal) be separated into two projects. In 1993, NRSP-7 was thus created as the Minor Use Animal Drug Program.

Animal producers are the primary stakeholders in the NRSP-7 program, but pharmaceutical companies may be considered significant stakeholders as well. Other groups with interest in minor animal drug use include veterinarians and regulators. The active participation of animal producers and pharmaceutical companies is essential for the success of the program. However, to one degree or another, NRSP-7 involves all stakeholders. NRSP-7 producer stakeholders are represented by the following 58 organizations in 10 categories: American Association of Wildlife Veterinarians, American Association of Zoo Veterinarians, American Farm Bureau, American Feed Industry Association, American Pet Product Manufacturers Association, Inc., American Rabbit Breeders Association, American Sheep Industry Association, American Veterinary Medical Association, Animal Health Institute, Animal Drug Alliance, Arkansas Bait and Ornamental Fish Growers Association, Catfish Farmers of America, Center for Veterinary Medicine, Florida Tropical Fish Farms Association, Inc., Food Animal Concerns Trust, International Association of Aquatic Animal Medicine, International Association of Fish and Wildlife Agencies, North American Deer Farmers Association, North American Gamebird Association, Inc., National Pork Producers Council, National Cattlemen's Beef Association, National Fisheries Institute, National Turkey Federation, Pacific Coast Shellfish Growers Association, and the National Aquaculture Association.

Prerequisite Criteria

How is the NRSP consistent with the mission?

How does the NRSP pertain to a national issue?

Rationale

Priority Established by ESCOP/ESS

Relevance to Stakeholders

Implementation

Objectives

1. <p>Objective 1 - Identify the animal drug needs for minor species and minor uses in major species<p>Critical and emerging needs will be identified by the Minor Use Animal Drug Program Technical Committee based on information obtained from stakeholders represented by animal industry groups and producer organizations, scientific and professional groups, literature surveillance, and research originating within the program. To further refine specific project objectives, contacts will be made with key, knowledgeable representatives from producer organizations, scientific and professional groups, government agencies, and pharmaceutical companies. Workshops and symposia also may be sponsored by the Minor Use Animal Drug Program to gather information about priority needs and emerging issues. p>Highest priority will be given to research projects that address drugs or compounds that are required to prevent or treat disease, or for reproductive management. Drugs intended for the prevention or treatment of disease or for the modification of specific physiological functions in minor species, or to treat or prevent minor diseases in major food animal species are selected over drug requests for nonfood animals.
   
2. <p>Objective 2 - Generate and disseminate data for the safe, effective, and legal use of drugs used primarily in therapy or reproductive management of minor animal species. <p>All projects are initiated by the submission of an Animal Drug Request (ADR) form to a the National or Regional Animal Drug Coordinator. The ADRs will be forwarded to the FDA/CVM to request comments regarding the extent of the data package that would be required for drug/compound approval (e.g. target animal safety, efficacy, residue depletion, and/or environmental assessment studies-see below). The appropriate pharmaceutical sponsor in cooperation with the efforts of NRSP-7 will seek to gain approvals of the drug compound. Pending favorable initial review by both parties, the ADR will be ranked according to priority for the funding by the program. Upon receipt of the reviews from FDA/CVM and the pharmaceutical sponsor, a decision can be made to fund the project. The project objectives may be directed toward generating sufficient data to seek FDA/CVM approval of the drug (Objective #3), or when that is not practicable, toward generating data sufficient to support safe, effective and legal use under the AMDUCA legislation. Research not conducted in the laboratories of the Regional Animal Drug Coordinators will be conducted under subcontracts, managed by the Coordinators, to scientists in qualified laboratories at other institutions.
   
3. <p>Objective 3 - Facilitate FDA/CVM approvals of drugs for minor species and minor uses. <p>Upon completion of each required study, reports of results and all raw data will be submitted to the Regional Animal Drug Coordinator for review prior to submission to FDA/CVM. Following acceptance of the data by FDA/CVM, a Public Master File will be established which is in the public domain, the notice of which will be published in the Federal Register. The pharmaceutical sponsor may refer to the Public Master File in support of a New Animal Drug Application (NADA), and ultimately the labeling of the drug for the use in the minor species, or for the minor use. <p>Moreover, NRSP-7 functions through the coordination of efforts among animal producers, pharmaceutical manufacturers, FDA/CVM, USDA/Cooperative State Research, Education, and Extension Service, universities, state agricultural experiment stations and veterinary medical colleges though out the country. The steps involved in this coordination of efforts are described in Table 1.
   
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Projected Outcomes

Management, Budget and Business Plan

Research for the Minor Use Animal Drug Program is funded through a USDA special research grant administered by CSREES in cooperation with the NRSP-7 Technical Committee. Support for NRSP-7 also comes from pharmaceutical companies, universities, and state agricultural experiment stations. Currently, there are no off-the-top Regional Research funds allocated to the Minor Use Program. The program receives significant in-kind support from several sources including the institutions conducting the research (state agriculture experiment stations, colleges of veterinary medicine, federal laboratories), animal producer groups through contributions of animals for research, and pharmaceutical companies. Perhaps the most significant of this in-kind support comes through the cooperation of the pharmaceutical companies that provide access to their proprietary data package prepared for the drug approval in a major species, estimated at $20 million (Ringer et al. 1999). In addition, the pharmaceutical sponsors complete the approval package by adding the new use of the drug to their current label, and often contribute to the program in the form for drug research, as well as direct financial aid. Without the generous support of the pharmaceutical manufactures, this program would not be possible.

The Regional Animal Coordinators are not compensated by salary for time contributed to the Minor Use Animal Drug Program. In two cases, secretarial and/or technical support services are budgeted from the Program. Funding is provided for the National Drug Coordinators part-time salary and the maintenance of an office.

The breakdown of funding by source for NRSP-7 is presented in Table 2. Since 1982, grants have been awarded from appropriated USDA funds in the amount of $240,000 per year for fiscal years 1982-85; $229,000 per year for fiscal years 1986-1989; $226,000 for fiscal year 1990; $450,000 for fiscal year 1991; $464,000 per year for fiscal years 1992 and 1993; $611,000 for fiscal year 1994; $550,000 per year for fiscal years 1995-2000; $548,970 in fiscal year 2001; and $588,000 in fiscal years 2002 and 2003.

The non-federal funds and sources provided for NRSP-7 since 1991 included $156,099 state appropriations, $29,409 industry contributions and $11,365 miscellaneous in 1991; $265,523 state appropriations, $1,182 product sales, $10,805 industry contributions and $59 miscellaneous in 1992; $212,004 state appropriations, $315 industry contributions and $103 miscellaneous in 1993; $157,690 state appropriations and $7,103 miscellaneous in 1994; $84,359 state appropriations in 1995; $191,835 non-federal support in 1996; $357,099 non-federal support in 1997; $104,596 state appropriations and $97,375 industry contributions in 1998; $317,225 state appropriations and $9,678 industry contributions, and $7,000 miscellaneous in 1999; $349,250 state appropriations and $9,500 industry contributions in 2000; $87,000 state appropriations and $38,850 industry contributions in 2001; and $137,720 state appropriations and $30,480 industry contributions in 2002. Figures for federal funding were similar to 2002 for 2003, however there were no industry funds in 2003.

In the 22 years of the Minor Use Animal Drug program, a total of $9,116,000 has been granted through federal funding and an additional 41 percent, on average, has been obtained through nonfederal funds. The average total expenditure per completed research for a drug approval or publication of a Public Master File was $398,000. This figure includes submissions currently under review at FDA/CVM as well as the 30 projects listed in Table 3. Average federal expenditures per completed research for a drug approval or publication of a Public Master File was $304,000. Compared to an average investment of the pharmaceutical industry of $2 to $8 million for adding a label claim to an existing veterinary drug, information generated for additional label claims by the NRPS-7 program costs only approximately 10 to 40% of pharmaceutical industry costs.

Integration

Public Master Files and New Animal Drug Allowances

The goal of the NRSP-7 educational and outreach plan is to provide stakeholder access to information regarding program goals, accomplishments and impacts through a variety of channels. One form of outreach consists of the publication of the efficacy, target animal safety and drug residue depletion data generated as a Public Master File in the Federal Register and as a New Animal Drug Allowance (NADA). Publication in the Federal Register places the safety and efficacy studies in the public domain and a New Animal Drug Allowance provides the producer stakeholder the availability of the drug for the claimed minor use. Table 3 lists the 30 Public Master Files and New Animal Drug Allowances developed from data generated by NRSP-7.

Outreach, Communications and Assessment

Presentations and publications

Presentations, abstracts, publications and doctoral dissertations represent yet another form of communication to the stakeholders. Over the last 15 years, NRSP-7 has produced 63 presentations, publications, abstracts and dissertations. NRSP-7 has averaged five presentations/abstract per year and three peer-reviewed publications per year for the last five years.

Website

The Technical Committee has worked to develop the NRSP-7 website (www.NRSP7.org) as a communication tool for dissemination of information generated by the program. The site provides for the submission of Animal Drug Requests (ADR's), operational information and monitoring of project progress by Technical Committee members, access to the MUMS (Minor Use Minor Species) program and links to a variety of stakeholders' websites. The use of the Internet to optimize communications with stakeholders and program participants continues to improve in this rapidly changing medium. Since inception in 1999, the NRSP-7 website has been visited 4522 times for an average of three hits per day. NRSP-7 believes that this represents a significant degree of interaction with stakeholders as well as the public at large.

Sharing NRSP-7 information with FARAD

Another form of dissemination of NRSP-7 data is the publication of drug pharmacokinetic and residue depletion studies through FARAD (Food Animal Residue Avoidance Database). FARAD is a computer-based decision support system designed to provide livestock producers, extension specialists, and veterinarians with practical information on how to avoid drug, pesticide and environmental contaminant residue problems. The FARAD website (www.FARAD.org) provides:

Current label information including withdrawal times of all drugs approved for use in food-producing animals in the United States.

Official tolerances for drug and pesticides in tissues, eggs and milk.

Database with approximately 5000 scientific articles with data on residues, pharmacokinetics and the fate of chemicals in food animals.

By providing FARAD with information developed on minor use animal drug residue depletion and pharmacokinetics, NRSP-7 affords the stakeholder yet another conduit for obtaining critical information to avoid illegal and potentially hazardous drug residues in food animals.

Steps to improve communications

Several changes have recently been incorporated in an effort to enhance communication both within the program and with stakeholders. First, monthly teleconferences are held by the Technical Committee to discuss potential projects, interactions with stakeholders and progress in studies. Second, stakeholders will be invited to be active non-voting participants in the annual spring meeting. The nature of the participation is ad hoc and representatives from different stakeholder groups are invited on a rotating basis, without representation from a single or specific group "assigned" to the committee. The meetings will take place within the Washington, DC area to provide the opportunity for the participating stakeholders to visit key legislators on behalf of NRSP-7.

Informatics will be better utilized to increase/improve communication with NRSP-7 participants and stakeholders. Improvements to web usage include posting pdf versions of publications and or dissertations that have been supported through NRSP7 funds as well as links to other appropriate pages (partners, producer and/or pharmaceutical company websites). Existing brochures and any newly developed media information packages should likewise be posted. Stakeholders can be surveyed using the web site monitoring capabilities.

Projected Participation

View Appendix E: Participation

Literature Cited

Brown, S. 2003. Pfizer Animal Health, personnel communication.

Lathers, C.M. 2003. Opinion: Challenges and opportunities in animal drug development: a regulatory perspective. Nat Rev Drug Discov 2(11):1-4.

Ringer, R.K., Miller, L.M. and Saylor, W.W. 1999. Minor-use animal drug program  A national agricultural program to approve animal drugs for minor species and uses. JVAMA 214(11)1636-1637.

Attachments

Land Grant Participating States/Institutions

CA, FL, NY

Non Land Grant Participating States/Institutions

Iowa State University - College of Vet Med