MINOR USE ANIMAL DRUG PROGRAM (NRSP-7) NORTH CENTRAL REGION

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: SPECIAL GRANT
• Reporting Frequency: Annual
• Accession No.: 0206965
• Grant No.: 2006-34143-17093
• Proposal No.: 2006-06151
• Project Start Date: Jul 1, 2006
• Project End Date: Jun 30, 2009
• Grant Year: 2006
• Program Code: [SS]- (N/A)

Recipient Organization
IOWA STATE UNIVERSITY
S. AND 16TH ELWOOD
AMES,IA 50011

Performing Department
VETERINARY MEDICINE

Non Technical Summary
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 FDA's 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 an (2) the principal minor diseases of major species. The committee identified the principal diseases for which drugs were not available in the minor species. Without these drugs, animal suffering and mortality would greatly increase, as would the cost of producing animal-derived food products. New projects included in this proposal include work to support the approval of tulathromycin for use in sheep and goats. This antimicrobial should have excellent efficacy against some of the major pathogens of sheep and goats (especially respiratory pathogens which cause millions of dollars in losses annually). An additional new project deals with Regulin in sheep. The active ingredient in Regulin is melatonin. The drug is administered as an implant in the ear of sheep and is widely marketed in Europe and Australia to enhance early breeding and productivity. Lack of Regulin availability places U.S. sheep producers at a selective disadvantage economically.

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

100%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
301	3610	1180	10%
301	3820	1180	10%
311	3610	1180	40%
311	3820	1100	10%
311	3820	1180	30%

Knowledge Area
311 - Animal Diseases; 301 - Reproductive Performance of Animals;

Subject Of Investigation
3610 - Sheep, live animal; 3820 - Goats, meat, and mohair;

Field Of Science
1180 - Pharmacology; 1100 - Bacteriology;

Keywords

minor species

animal drug request(adr)

minor use animal drugprogram

nrsp 7

new animal drug application

fda

amduca legislation

tulathromycin

antimicrobial

regulin

melatonin

Goals / Objectives
1.Identify needs for animal drugs for minor species and minor uses in major species. 2.Generate and disseminate data for the safe, effective, and legal use of drugs intended for use in minor animal species. 3.Facilitate FDA/CVM approvals of drugs for minor species and minor uses. Minor species are all species except dogs, cats, horses, cattle, swine, chickens and turkeys. Minor uses in major species are those that occur infrequently or in limited geographical locations. The primary emphasis of The Program will be on food-and/or fiber- (hair, wool, fur, feathers or hide) producing minor species.

Project Methods
Objective 1 Identify the animal drug needs for minor species and minor uses in major species: Critical and emerging needs will be identified by the Minor Use Program Technical Committee based on information obtained from 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. 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. 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: All projects are initiated by the submission of an Animal Drug Request (ADR) form to a Regional Animal Drug Coordinator. 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 subawards, managed by the Coordinators, to scientists in qualified laboratories at other institutions. A product development meeting will be held for the participating Regional Animal Drug Coordinator(s) and FDA/CVM to identify specific data requirements needed to seek approvals. Regional Animal Drug Coordinators, pharmaceutical sponsor and FDA/CVM. Following research protocol review and refinement with FDA/CVM and the pharmaceutical sponsor, the research may begin. Studies typically required in this phase include efficacy (is the drug effective and at what dose), target animal safety (toxicity), human food safety (drug residues in edible products), and environmental assessment (as required). Objective 3 Facilitate FDA/CVM approvals of drugs for minor species and minor uses: 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.

Progress 07/01/06 to 06/30/09

Outputs
OUTPUTS: The North Central and Western Regions of the Minor Use Animal Drug Program participated in the generation of data essential for the approval of CIDR-G progesterone inserts for the synchronization of estrus in ewes. This was the final study required for approval. The North Central Region also participated in the determination of milk residues in goats with CIDR-G inserts. The NC region sponsored a study of the efficacy of lasalocid as a coccidiostat in pheasants conducted at the University of Georgia by Dr. Larry McDougald. A Target Animal Safety Study of lasalocid in pheasants was recently completed at Iowa State University. A Target Animal Safety Study of tulathromycin in goats has been completed. PARTICIPANTS: Individuals working on the projects listed were Dr. Lisa Tell at the University of California, Davis, Dr. Dennis Hallford at New Mexico State University, Drs. Larry McDougald and Lorraine Fuller at the University of Georgia, Drs. Michael Yaeger, Eric Burrough, Holly Bender and Kristin Clothier at Iowa State University. The projects have provided training for 2 veterinary summer research scholars, one MS candidate and one Ph.D. candidate. TARGET AUDIENCES: Target audiences for this work include producers of minor animal species, veterinarians serving the needs of these producers and manufacturers and suppliers of products for use in minor animal species. Consumers also have a critical interest in these projects because they provide information on animal welfare and the safety of pharmaceutical products used in minor animal species. PROJECT MODIFICATIONS: Terms of the award specify that all studies be conducted under GLP or GCP guidelines and that they be submitted for review by the FDA/Center for Veterinary Medicine.

Impacts
The work with CIDR-G progesterone inserts for sheep will allow the marketing of the product in the U.S. as soon as the supplier can add sheep to the label. The other studies conducted have demonstrated the safety and efficacy of lasalocid in pheasants as well as the safety of Draxxin for use in goats.

Publications

• Fuller, L., R. Griffith and L.R. McDougald. 2008. Efficacy of lasalocid against coccidiosis in Chinese ring-necked pheasants. Avian Diseases 52:632-34.

Progress 07/01/07 to 06/30/08

Outputs
OUTPUTS: The in-life phase of a Target Animal Safety study of tulathromycin in goats was completed at Iowa State University. A study to determine the Efficacy of lasalocid against coccidiosis in pheasants was completed at the University of Georgia Poultry Science Department in cooperation with the North Central Region, NRSP-7. A human food safety study to evaluate milk progesterone levels in goats with CIDR-G inserts was completed at New Mexico State University with funding and assistance from the Western and North Central Regions of NRSP-7. The reports for all three of these studies are being prepared for submission to the FDA/CVM. Work continued to satisfy FDA/CVM concerns over the CIDR-G HFS study in sheep. Protocols were written for the Target Animal Safety and Human Food Safety of lasalocid in pheasants. Protocols were also written for CIDR-G Efficacy in goats and Target Animal Safety, Human Food Safety and Efficacy of Tulathromycin in goats. These study protocols were submitted to the FDA/CVM Office of New Animal Drug Evaluation for review. PARTICIPANTS: Partner organizations for the work included The University of Georgia Poultry Science Department (Dr.Larry McDougald), New Mexico State University (Dr. Dennis Hallford)and University of California, Davis (Dr. Lisa Tell). Training/professional development were provided to one graduate student and two veterinary summer scholars. TARGET AUDIENCES: Target audiences include manufacturers of CIDR-G inserts for sheep and goats, Draxxin for use in goats and lasalocid for use in pheasants. Producers of the animal species named above will benefit from the knowledge gained. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Preliminary conclusions from the studies indicate: 1. That progesterone levels in milk of goats with CIDR-G inserts are less than or equal to progesterone levels in milk of normal pregnant goats. If validated, this indicates that such milk is safe for human consumption. 2. That tulathromycin (Draxxin) is safe for use in both dairy and meat goats. 3. That lasalocid is efficacious for use against coccidiosis in pheasants.

Publications

• No publications reported this period

Progress 07/01/06 to 06/30/07

Outputs
OUTPUTS: Funding from the North Central Region NRSP-7 supported the Human Food Safety (tissue residue) for CIDRg inserts in sheep perfomed at the Department of Rangeland Sciences at New Mexico State University. The study report was submitted earlier but the FDA/CVM requested an additional freezer stability study for progesterone in sheep tissues. This study was completed and submitted. Final acceptance of this work will complete the required experimental data package required for supporting approval for CIDRg inserts in sheep in the U.S. The North Central Region supported the milk residue portion of the Human Food Safety studies for CIDRg inserts in goats. The in-life portion of this study was performed at the University of California, Davis and the analytical phase was performed at New Mexico State University. The tissue residue portion of the HFS studies is planned for 2008. The North Central Region designed and supported the studies necessary for demonstration of the Efficacy of Lasalocid as a coccidiostat in ring-necked pheasants. This work was completed at the University of Georgia Department of Poultry Science. A final report is expected in early 2008. Additional study protocols prepared were for Efficacy, Target Animal Safety and Human Food Safety studies for tulathromycin in goats. These studies are planned for 2008. PARTICIPANTS: Dr. Dennis Hallford at New Mexico State Uiversity performed the Human Food Safety studies on CIDRg intravaginal inserts for use in sheep and the subsequent freezer stability studies. Dr. Dennis Hallford at New Mexico State University performed the assay validation and analysis of progesterone milk residues in dairy goats following removal of CIDRg inserts. Drs. Lisa Tell and Joan Rowe at the University of California, Davis collaborated on the in-life phase of the CIDR milk residue study in goats. This study was a cooperative effort between the NC and Western NRSP-7 Regions with funding shared between the two units. Dr. Larry McDougald at the University of Georgia, Dept. of Poultry Science performed the efficacy trial for lasalocid in ring-necked pheasants. The NC Region of NRSP-7 supported the analysis and QA/QC phases of this study. Dr. Thomas McQuistion at Millikin University collaborated on this study. Dr. Michael Yeager at Iowa State University collaborated on the preparation of the Target Animal Safety protocol preparation. This study is set to begin in Feb., 2008. Protocol review for all studies was coordinated by Dr. Margaret Oeller, NRSP-7 liaison at the FDA/Center for Veterinary Medicine, Rockville, MD and protocol review was provided by the Office of New Animal Drug Evaluation at the FDA/CVM. TARGET AUDIENCES: Target audiences for the efforts of the NRSP-7 program are the producers and consumers concerned with minor animal species. These include the members of the sheep, goat, game bird, aquaculture and many other industries.

Impacts
Data was generated from the Human Food Safety (tissue residue)studies for CIDRg inserts in sheep. The study demonstrated that 24 h after withdrawal, no detectable exogenous progesterone remaining in liver tissues. Levels of progesterone in skeletal muscle were identical to those found in untreated ewes. The stability studies demonstrated that progesterone is stable in frozen sheep tissues. This study was completed and submitted. Final acceptance of this work will complete the required experimental data package required for supporting approval for CIDRg inserts in sheep in the U.S. Submission of protocols to the FDA/CVM and support of additional studies listed above will enable that work to proceed in 2008.

Publications

• No publications reported this period