SAES-422: NRSP007

NRSP007: A National Agricultural Program for Minor Use Animal Drugs

Annual/Termination Reports (SAES-422): [12/22/2009] [06/28/2010] [06/29/2010] [11/10/2010] [07/12/2011] [12/21/2011] [06/15/2012]

Date of Annual Report: 12/22/2009

Report Information:

Annual Meeting Dates: 11/19/09 to 11/20/09

Period the Report Covers: 10/2009 to 09/2010

Participants:

see attached meeting minutes

Brief Summary of Minutes of Annual Meeting:

URL: Copy of minutes

Accomplishments:

Impact Statements:

Last Modified: 25-Jan-2010

Date of Annual Report: 06/28/2010

Report Information:

Annual Meeting Dates: 03/25/10 to 03/26/10

Period the Report Covers: 10/2009 to 09/2010

Participants:

Brief Summary of Minutes of Annual Meeting:

Meeting minutes, part 1. See next listed meeting report for part 2. Entire minutes file was too big to be uploaded as one report.

URL: Copy of minutes

Accomplishments:

Impact Statements:

Last Modified: 30-Jun-2010

Date of Annual Report: 06/29/2010

Report Information:

Annual Meeting Dates: 06/29/10 to 06/29/10

Period the Report Covers: 10/2009 to 09/2010

Participants:

Brief Summary of Minutes of Annual Meeting:

March 25 and 26 meeting minutes, part 2. See previous meeting/report file for part 1.

URL: Copy of minutes

Accomplishments:

Impact Statements:

Last Modified: 30-Jun-2010

Date of Annual Report: 11/10/2010

Report Information:

Annual Meeting Dates: 10/04/10 to 10/10/10

Period the Report Covers: 10/2009 to 09/2010

Participants:

Brief Summary of Minutes of Annual Meeting:

See attached meeting minutes file.

URL: Copy of minutes

Accomplishments:

Impact Statements:

Last Modified: 10-Nov-2010

Date of Annual Report: 07/12/2011

Report Information:

Annual Meeting Dates: 03/31/11 to 04/01/11

Period the Report Covers: 10/2010 to 09/2011

Participants:

Bernadette Dunham, FDA/CVM, Bernadette.dunham@fda.hhs.gov
Dorothy Bailey , FDA/CVM, Dorathy.bailey@cvm.fda.gov
Francis D. Galey, AA/WO AES, FGaley@uwyo.edu
Gary Sherman, USDA/CSRESS, gsherman@nifa.usda.gov
Joan gotthardt, FDA/CVM, Joan.gotthardt@cvm.fda.gov
John Babish, MUADP/NRSP-7, jgb7@cornell.edu
John C. Baker, AA/MI AES, Baker@anr.msu.edu
Lisa Tell, MUADP/NRSP-7/UC Davis, latell@ucdavis.edu
Margaret Smith, AA/NY AES, mes25@cornell.edu
Meg Oeller, FDA/CVM, moeller@cvm.fda.gov
Ron Griffith, MUADP/NRSP-7/Iowa State, rgriffit@iastate.edu
Stuart Jeffrey, FDA/CVM, Stuart.jeffrey@cvm.fda.gov
Thomas Vickroy, MUADP/NRSP-7/U FL, vickroy@vetmed.ufl.edu

Brief Summary of Minutes of Annual Meeting:

Introductions and meeting organization Dr. John G. Babish started the meeting with a round of introductions followed by a description of the programs ongoing efforts to increase funding and dealing with increasing research costs, and more rigorous regulatory requirements that have evolved over the programs twenty-six year existence. Dr. Babish then outlined the format of the meeting as an interaction between CVM reviewers and Regional Coordinators to discuss both general issues as Good Laboratory Practice inspections and specific concerns in recent protocol or research submissions.

Welcome from Dr. Bernadette Dunham Dr. Dunham, the Director of the FDA Center for Veterinary Medicine (CVM), welcomed everyone and began the discussion with her vision of changes within CVM and the future of the MUMS and MUADP. In her remarks, she again stressed the need for collaboration with stakeholders and the need to demonstrate to the leaders at USDA and in the Congress the impact of the program on both animal and public health.

Again this year, Dr. Dunham praised the program members for their efforts to ensure funding through continued lobbying and provided guidance into the most effective ways of establishing strong connections with stakeholders and legislators. She provided insight into the budget process both from the standpoint of the agencies of the executive branch and from the congressional side. Changes in the scope of the program and in the funding mechanisms need to be planned well in advance and must be supported by clear objectives and accomplishments. The MUADP/NRSP-7 program has a good story to tell. Dr. Dunham encouraged the members of the program and their stakeholders to take this important message to the USDA and the congress to encourage their support.

USDA/NIFA Dr. Gary Sherman Dr. Gary Sherman continued his discussion from fall 2010 on the funding methods of the program and the complexities of the budget process. A vote taken by the Technical Committee following this discussion of the MUADP funding category was unanimous to have Dr. Sherman work in concert with the Technical Committee to move the programs current status from noncompetitive to competitive within NIFA/USDA. It was felt that this move would be necessary to support increased funding and maintain viability in the current political climate that discourages Congressional earmarks.

ADMINISTRATIVE REPORTS REPORT FROM THE ADMINISTRATIVE ADVISORS - Dr. John Baker (Chair) Dr. Baker began his report praising the Regional Coordinators for their efforts, Dr. Baker questioned how long the Program could be expected to function under the current funding circumstances of delayed payments to regions and insufficient funds. He went on to suggest possible movement into a competitive grants program at within the AES framework and the development of an action plan roadmap to carry out this objective. Once again, Dr. Baker stressed the need to develop a broader listing of stakeholder groups to align with additional NIFA priorities of sustainable agriculture and support of the rural, family farms.

Report from CVM Dr. Meg Oeller Dr. Oeller began her presentation with a short review of the active projects in each of the regions and discussed any issues regarding these projects with the respective Regional Coordinator.

URL: Copy of minutes

Accomplishments:

WESTERN DR. LISA TELL Progress of Work and Principal Accomplishments:

Active Western Region Projects: ADR#325 Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease The human food safety (HFS) and efficacy studies required by FDA/CVM for the old formulation of florfenicol (Nuflor Injectable Solution) have been completed. All of the data from this project have been published. The data from the HFS study has been organized and a technical report has been written. The final technical report for the human food safety study was reviewed for Quality Assurance in March, 2010. This report was submitted to FDA/CVM in July 2010. On February 11, 2011, FDA/CVM concluded that the tissue residue depletion study was acceptable for supporting a withdrawal period determination, and assigned a 42-day withdrawal period. Other comments from FDA/CVM were that microbial food safety issues still need to be addressed which include the impact of florfenicol on antimicrobial resistance among bacteria of public health concern in or on treated sheep as well as human intestinal flora.

ADR#350 Florfenicol (Nuflor Gold®) for sheep for respiratory disease A pilot study evaluating administration route (IM vs. SC) and doses of 20 (IM) or 40 (SC) mg/kg was performed in September and October of 2009. All of the samples (n=672; 28 samples for 24 animals) have been analyzed. A product development meeting was held on November 18th, 2009 with CVM, the sponsor and the Minor Use Animal Drug Program. Another dose range finding study using the SC route of administration is to be performed. Once the proposed label dose is determined, the Target Animal Safety Study will be performed. This study is currently pending and will not progress until CVM provides further guidance.

ADR#299 - Pirlimycin for Dairy Goats Project on hold until funding is identified and CIDR goat studies are completed.

ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder This project has been transferred to the Northeastern Region.

ADR#338 Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats Project on hold until funding is identified and CIDR goat studies are completed.

ADR#135 Erythromycin in Salmonids The environmental assessment was sent to FDA/CVM for review and they requested a revision of certain sections and that a chronic toxicity study with Daphnia magna is performed. This chronic toxicity study has been performed and will address CVM concerns regarding chronic toxicity to aquatic insects. In addition, a study describing the physiochemical properties of erythromycin has been performed. Because of the physical characteristics of ERTT, an empirical pKa could not be established. The final environmental assessment report for erythromycin in salmonids was completed in May, 2010 and submitted to FDA/CVM for review. The results of this environmental assessment report supports the safe use of erythromycin thiocyanate in all freshwater-reared salmonids at a dose regimen of 100 mg/kg bodyweight/day for 21 to 20 days. Christine Moffitt (author) submitted the White Paper for erythromycin. This was revised and submitted to FDA/CVM in July, 2010. We received notification January 12, 2011 from FDA/CVM that the Final Study Report for the pivotal Daphnia magna chronic toxicity study entitled: Chronic toxicity of erythromycin thiocyanate to Daphnia magna in a flow-through, continuous exposure test system is considered complete. Dr. Oeller is working on the White Paper for this study.

Active Collaborative Projects: ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge) A conference call with Merck/Intervet/SP was held on February 25, 2010. A product development meeting was held with CVM on September 9, 2010 to discuss the development plan for investigating the use of fenbendazole Type A medicated article for the treatment of nematode parasites in pheasants. The HFS protocol was submitted and received concurrence from CVM on 12/08/2010. The TAS study protocol was submitted to FDA/CVM for review in February 2011. Plans are in place to conduct the HFS and TAS studies in the summer of 2011. The Western region will perform the analytical testing of the samples. The analytical laboratory in the Western region has started to re-establish the fenbendazole tissue method for pheasants by testing intra and inter-day precision and accuracy. We are testing liver, muscle (breast and thigh), and skin/fat. In addition to spiked samples we will assay incurred samples to verify the method.

ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region) The quality assurance was performed for the target animal safety study in February and March 2008. A tissue liquid chromatography/mass spectrometry method for analysis of the samples has been validated using 664 spiked samples to validate 4 tissues. Validation of analytical methods for liver, muscle, kidney and fat samples is complete. Plasma (444) and tissue (180) samples from the target animal safety have been analyzed. The quality assurance for the target animal safety report was completed November 2009. Plasma samples from the HFS study have been analyzed and the PK data has been generated. Tissue samples from the HFS study (205) have been analyzed. The method validation report has been submitted to the Central Region for quality assurance review. See North Central region report for further information. Freezer stability of tulathromycin in goat tissues was assessed again to cover a 16 month time span. While the tulathromycin concentrations in the tissues were less than expected in the spiked tissues, incurred samples from both the Target Animal Safety and Human Food Safety studies have shown good stability. The data for the tissue samples freezer stability has been submitted to Dr. Griffith of the Northcentral region for the HFS report.

Other Projects/Activities: Quality Assurance: Nothing to report.

Ceftiofur (Excede) in Sheep: Study has been completed domestic sheep. The serum samples have been analyzed and the pharmacokinetic data modeled. The data was presented at the UC Davis Veterinary Medical Teaching Hospital House Officers Research Seminar day on March 18, 2011. Flunixin in Goats: Two cross-over studies have been completed in domestic goats evaluating IV vs. IM administration. In addition, a pilot study has been completed in lactating goats. All samples are waiting to be analyzed due to challenges with the method.

Cephapirin in Goats: An analytical method for measuring cephapirin in goat serum samples was established in the Western Region analytical laboratory during this reporting period. 105 samples were analyzed from goats that were administered the drug intramammary. No detectable concentrations of cephapirin were found systemically.

Ceftiofur for Treating Arcanobacterium pyogenes Respiratory Infections in Deer: 27 isolates from deer (4 females, 7 males, and 6 unknown sex) ranging from 6 weeks to 14 years of age have been collected. Of these isolates, the MICs for ceftiofur ranged from 0.25-1. All of the isolates were sensitive to ceftiofur. Dr. Albert Ramudo from Pfizer was contacted on November 12th, 2009 regarding Pfizers interest in a label claim. Due to the sensitivities and pathology associated with this organism, this project is not currently being pursued for a label claim for either tulathromycin or ceftiofur. The sensitivity data were compiled and have been submitted to the Journal of Veterinary Diagnostic Investigation for publication. The reviewers comments have been received and addressed. We are currently waiting on favorable acceptance of the manuscript based on the revisions. CIDRs for Deer: Historical conference call with Dr. Albert Ramudo. At this time, Pfizer has indicated that they are not interested in pursuing a label claim for deer. Proposed discussion regarding this project at Spring 2011 Meeting. New Projects: Moxidectin in Goats Tulthromycin in Dairy Goats: UC Davis summer student has been identified and funding for her position has been awarded.

Laboratory Report: Most of the activity continues as establishing new analytical methods and sample analysis in the laboratory. Results and plans are reported under separate projects above.

Usefulness of the Findings: The findings from all of the studies above will be utilized to fulfill the data requirements for the FDA/CVM approval of these drugs for use in minor species.

Work Planned for Remainder of the Year: Over the next year our primary goals are to work on getting the fenbendazole game bird analytical method re-established in our laboratory and analyzing the samples from the Human Food Safety Study (summer of 2011). In addition, we will be working to get the flunixin analytical method for goats established in the laboratory.

Critical Review: 1. Work accomplished under the original project The original objectives of the project were to conduct a national program to obtain minor and specialty animal drug clearances (tolerances, exemptions and registrations) in cooperation with state, federal and industry personnel to include: a. Determination and prioritization of minor-use needs and data requirements. b. Review, analysis and evaluation of minor-use research proposals. c. Development and assembly of data for minor-use registrations. d. Preparation and submission of petitions for drug registrations. Considering these objectives, considerable progress has been made towards achieving them for each of the active projects listed above, particularly in the development of the data (the actual research), its analysis, assembly and interpretation, and submission to the FDA/CVM for review.

2. The degree to which objectives have been met The degree to which these objectives have been met varies from project to project, however, in most all cases there has been progress. Those projects on which there has been no movement are reevaluated during each meeting of the NRSP-7 Technical Committee and decisions made on whether to continue to pursue them or move them into the inactive project list.

3. Incomplete work or areas needing further investigation All of the projects listed above have some work that needs to be completed before they are approved by the FDA/CVM. In some cases this is just the FDA/CVM review, while in others there is work needed by the NRSP-7 project. The NRSP-7 work which is undertaken each year within the Western Region is based on the availability of qualified and interested investigators, the capacity of the regional laboratory to validate methods and analyze samples, and cooperation of the pharmaceutical manufacturers whose products are investigated.

NORTHEAST REGION: DR. PAUL BOWSER Progress of the work and principal accomplishments

Species Grouping Project: INAD 10-320 Oxytetracycline in Fish INAD 10-823 Romet-30 in Fish INAD 11-145 Florfenicol in Fish Efforts on this project consisted of providing administrative support and oversight to the New York State Department of Environmental Conservation in their conduct of field trials under our INAD 10-320 for the use of Oxytetracycline in fish.

Ovadine (Western Chemical) Disinfection of Fish Eggs: We have been an evaluation of the efficacy of Ovadine (PVP-Iodine, Western Chemical) as an egg disinfection compound for fish eggs with a particular emphasis on the reduction of Viral Hemorrhagic Septicemia Genotype IVb from walleye eggs. Our trial will build on preliminary efforts, funded by New York Sea Grant Program, in which we found that the consensus treatment protocol of the Great Lakes Fishery Commission (50 mg/L iodine for 30 minutes) was not completely effective in the elimination of VHSV IVb. A disinfection trial was conducted during the 2010 walleye spawning season with the collaboration of the New York State Department of Environmental Conservation. Treatments included iodine doses of 0, 50 and 100 mg/L for 30 minutes. One publication on this work has been published and a second publication is in development.

Usefulness of the findings: In all cases, the findings to date over the course of these projects serve as the foundation for continued work on these compounds. The Human Food Safety Studies completed to date in fish are consistent with what was expected; namely that the elimination of therapeutic compounds from the edible portion of the fish tested are within the withdrawal times currently specified for labels, or available in the literature for oxytetracycline, Romet-30 and Aquaflor (Florfeniol).

Work planned for next year: Species Grouping Project: INAD 10-320 Oxytetracycline in Fish INAD 10-823 Romet-30 in Fish INAD 11-145 Aquaflor (Florfenicol) in Fish We anticipate our efforts on this project to center around the continued provision of administrative support and oversight of Efficacy Studies of oxytetracycline in a collaborative effort with the New York State Department of Environmental Conservation. The particular focus of the efficacy trials will be for the treatment of bacterial diseases not currently on the label for treatment of bacterial diseases of cool water species such as walleyes, muskellunge and tiger muskellunge (hybrid muskellunge X northern pike). These studies will be initiated when diagnosed field cases can be identified that will lend themselves to the implementation of controlled field studies.

Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs Data from the Ovadine work is being summarized for publication. We are also investigating the potential of indexing Ovadine.

Strontium Marking of Fish Otoliths We are in the early stages of developing a project to complete the data package needed to obtain a label or to index the use of Strontium Chloride for marking fish otoliths.

1. To identify animal drug needs for minor species and minor uses in major species. 2. To generate and disseminate data for safe and effective therapeutic applications, and 3. To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.

2) The degree to which the objectives have been met: Work has focused on a number of important therapeutic compounds in aquatic animals. The work is being conducted in a deliberate manner with the goal of developing appropriate data that will be submitted in support of a label for these compounds. An initial step in this process is the publication of the data in the peer reviewed scientific literature. While we consider it extremely important to have such peer-reviewed information available for the veterinary community, should they consider an extra-label use, the ultimate goal is to secure a label for the product. As an additional goal, the work is being done in a manner that could justify a species grouping concept for finfish cultured in the United States.

3) Incomplete work or areas needing further investigation: The development of a crop (species) grouping concept is seen as imperative for supporting efforts to gain labels for therapeutic compounds for fish. Our work on Oxytetracycline, Romet-30/Romet-TC and Aquaflor (Florfenicol) in fish is proposed to be part of an effort to utilize those compounds as models in this effort. We expect that our efforts in developing a species grouping concept for fish will be a major undertaking in the upcoming years.

North Central Dr. Ronald W. Griffith Progress of the work and principal accomplishments Goat CIDR-G Tissue Residue Study report has been submitted. Mean tissue levels of progesterone 12 hours after CIDR removal were significantly lower than tissue levels in control does without CIDRs.

Goat CIDR-G Effectiveness This study is in full swing. We have received excellent cooperation from producers in a number of states. We currently have over 600 dairy goats enrolled in the study in Iowa, California, Missouri, Minnesota and Wisconsin. On the meat goat side, we have two herds in Iowa and one at Texas A&M Prairieview that have participated. In the fall of 2011, we should have a herd at Florida A&M University and other group of goats at TAMU and possibly a small group of does in Iowa. Target for completion of the in-life phase is 2013.

Lasalocid in Pheasants Efficacy The study was completed in 2007 and the study report submitted this summer. Undergoing final stages of review. Keeping fingers crossed.

Lasalocid in Pheasants TAS A second high-dose group study was completed in July. The study report is currently being prepared.

Draxxin Target Animal Safety in Goats The study report has been submitted to the FDA/CVM. Dr. Kris Clothier has a manuscript accepted by the Journal of Pharmacology and Therapeutics.

Draxxin Tissue Residue Study report undergoing QA audit.

Draxxin Efficacy in Goats PK/PD studies and MIC and killing kinetics data have been obtained. A partial study report on efficacy is being prepared. A manuscript is being prepared. A field trial may be necessary to complete this section.

Fenbendazole TAS in Pheasants Protocol has been submitted to ONADE and is under final review. Birds are scheduled to arrive the third week in May.

Fenbendazole HFS Working with the Lisa Tell in the Western Region on this project. Protocol concurrence has been received. On track to complete in-life phase in late summer or early fall.

Fenbendazole Reproductive Safety We have received two summers worth of hatching data from MacFarlane Pheasants and have requested data be kept for the coming hatching season. They have also provided data comparing hatching data of their own pheasant eggs with those of other producers that were hatched in MacFarlanes incubators. New England flock?

Ivermectin Cattle Fever Tick Efficacy Working in conjunction with Tom Vickroy in the Southern Region. A preliminary draft of a protocol for this study has been circulated for review. Dr. Beto de Leon has responded with some comments and corrections. We are waiting to receive the right of reference from Merial. The preliminary study being conducted by Dr. Davey is in its 31s week. Apparently, the sentinel cattle are still picking up ticks but the treated cattle remain free. It may be difficult to find sufficient numbers of ticky pastures in the northern region where R. annulatus is the species of tick. There are plenty of ticky pastures in the Southern region where R. microplus is the species of tick.

SOUTHERN DR. THOMAS VICKROY Progress of the work and principal accomplishments 1. ADR#279: Lasalocid for Coccidiosis in Pheasants This is a collaborative project between the North-Central and Southern regions. The role of the Southern region will be analysis of all tissue samples. Previous attempts to establish the approved regulatory method were unsuccessful, but will be a necessary pre-requisite before in-life phase of studies can move forward. Preliminary work on establishing and gaining concurrence for a robust and reliable analytical method was halted owing to a higher priority being assigned to the ivermectin project in cattle (ADR#352). Work on this project is slated to resume as quickly as time permits.

2. ADR#280: Fenbendazole in Game Birds (pheasants, bobwhite quail, partridge) This is a collaborative project among the North-Central, Western and Southern regions. A conference call and product development meeting was held with CVM on 9 September 2010. A development plan was discussed for investigating the use of fenbendazole Type A-medicated article for the treatment of nematode parasitic infections in pheasants. a) HFS Protocol: a protocol was drafted, reviewed by Western and North-Central Region Coordinators and submitted to CVM. The HFS protocol received concurrence from CVM on 8 December 2010. The in-life phase studies will be conducted at Iowa State and analytical studies will be conducted at UC Davis. b) TAS Study Protocol: was submitted to FDA/CVM for review by ONADE in February 2011. Plans are in place to conduct TAS studies in the summer of 2011. c) Reproductive Safety Studies: hatching data have been collected and will continue to be collected during the upcoming hatching season for pheasants at one site (McFarlane Farms in Wisconsin) . In addition, we have communicated with and established a second site to collect data for reproductive safety assessment (Mahantongo Farms in Pennsylvania).

3. ADR#352: Ivermectin Efficacy against Cattle Fever Tick in southern Texas This is a collaborative project among the North-Central and Southern regions of NRSP-7 that is classified as a minor use project owing to the small number of affected animals and the geographical isolation of the affected region. A preliminary draft of a protocol for this study has been circulated for review. Dr. Beto Perez de Leon has responded with some comments and corrections. We are waiting to receive the right of reference from Merial. A preliminary study being conducted by Dr. Davey is into week 31 and sentinel cattle are still picking up ticks while treated cattle remain tick free. Problems and obstacles remain including the limited number of pastures laden with R. annulatus in the northern region of the quarantine zone. The Southern region will be responsible for analytical testing of samples and is currently working to establish and validate the approved regulatory method.

Update on Other Programmatic Efforts and Changes 1. Hiring of New Chemist: Mr. Kacy Magee, a chemist with several years of analytical experience, was hired in January of 2011. Mr. Magee has spent considerable effort bringing the lab into a state of GLP compliance and presently is working on the ivermectin analytical method in beef liver. 2. NRSP-7 Website: The Southern Region is responsible for maintaining and updating the NRSP-7 website, including MUMsRx and the RUSTi system for tracking the status of regional projects. In addition, the Southern Region coordinator organizes and coordinates monthly teleconferences among the regional coordinators and administrators. The next teleconference is scheduled tentatively for 2 May 2011 at 12:00pm.

Anticipated Use of Project Outcomes: The findings from all of the studies above will be utilized to fulfill the data requirements for Public Master Files and, ultimately, for FDA/CVM approval of these drugs for use in minor species.

Work Planned Over the next quarter our primary goals are to fully establish the ivermectin method for analysis of samples from the Texas cattle tick fever study and to return to our suspended effort of developing and gaining concurrence of a modified analytical method for lasalocid in pheasants. This will be essential for allowing studies to proceed in the North-Central region.

Impact Statements:

Since its inception in 1982, more than $12.6 million has been allocated to the program through Federal funding. In return NRSP-7/MUADP has generated publication of 36 PMF in the Federal Register. These PMF have, in turn, supported FDA/CVM approvals for 43 drugs for use in minor food species or for minor uses in major species. Compared to an average investment of the pharmaceutical industry of $10 to $25 million for adding a label claim to an existing veterinary drug, expenses for data generated for additional label claims by the NRSP-7/MUADP program are approximately 10 to 35% of pharmaceutical industry costs.
To date 352 drug requests have been submitted to the NRSP-7/MUADP for the development of data in support of the submission of NADA or supplemental NADA. Currently there are 22 active research projects involving nine animal species and 11 different drugs.
The Environmental Assessment study data for erythromycin in salmonids INAD I-00613 were accepted by FDA/CVM on 1/12/11.
On 2/11/11, the tissue residue depletion study of Nuflor Gold in sheep submitted by NRSP-7/MUADP was accepted by FDA/CVM.
The Effectiveness Study of lasalocid in pheasants submitted by NRSP-7/MUADP to FDA/CVM on 7/1/10 was deemed complete by the agency on 3/25/11.
Also in 2011, data from NRSP-7/MUADP was used in support of the FDA/CVM approval of Chloramine-T safety and efficacy studies for control of bacterial gill disease in freshwater-reared salmonids. This formulation is used by immersion for control of mortality in freshwater-reared salmonids due to bacterial gill disease.

Last Modified: 17-Jan-2012

Date of Annual Report: 12/21/2011

Report Information:

Annual Meeting Dates: 11/01/11 to 11/01/11

Period the Report Covers: 10/2010 to 09/2011

Participants:

Participants: Dorothy Bailey , FDA/CVM, Dorathy.bailey@cvm.fda.gov
Gary Sherman, USDA/CSRESS, gsherman@nifa.usda.gov
John Babish, MUADP/NRSP-7, jgb7@cornell.edu
John C. Baker, AA/MI AES, Baker@anr.msu.edu
Lisa Tell, MUADP/NRSP-7/UC Davis, latell@ucdavis.edu
Margaret Smith, AA/NY AES, mes25@cornell.edu
Meg Oeller, FDA/CVM, moeller@cvm.fda.gov
Ron Griffith, MUADP/NRSP-7/Iowa State, rgriffit@iastate.edu
Thomas Vickroy, MUADP/NRSP-7/U FL, vickroy@vetmed.ufl.edu

Brief Summary of Minutes of Annual Meeting:

Introductions and meeting organization

Dr. John G. Babish started the meeting with a thank you to Dr. Bailey for her organizing efforts at FDA/CVM to have the teleconference conducted through the Adobe Connect facilities at Rockville, MD. The National Coordinator then outlined the agenda of the meeting with reports from the Regional Coordinators and presentations from FDA/CVM, NIFA, AA and National Coordinator. Welcome from Dr. Meg Oller for Dr. Bernadette Dunham

Dr. Oller welcomed all to the teleconference on behalf of Dr. Bernadette Dunham, the Director of the FDA Center for Veterinary Medicine. She underscored the budget difficulties Dr. Dunham spoke of at the spring meeting and further stressed the need for collaboration with stakeholders and the need to demonstrate to the leaders at USDA and in the Congress the impact of the program on both animal health and public health.

REPORTS FROM LIAISONS

NIFA/USDA Dr. Gary Sherman Dr. Gary Sherman continued his discussion from spring on the funding methods of the program and the complexities of the budget process. A previous vote taken by the Technical Committee following this spring discussion of the MUADP funding category was unanimous to have Dr. Sherman work in concert with the Technical Committee to move the programs current status from noncompetitive to competitive within NIFA/USDA. It was felt that this move would be necessary to support increased funding and maintain viability in the current political climate that discourages Congressional earmarks. He presented rather positive news on the ability of NIFA to move the MUADP from the Congressional earmarks category of Other Funding to a competitive, non-earmark category. He noted that NIFA simply needs to refrain from requesting that the MUADP be noncompetitive to remove the earmark label and therefore garner stronger Congressional support.

REPORT FROM FDA/CVM - Drs. Meg Oller and Dorothy Bailey

As with previous meetings, Dr. Oeller began her presentation with a short review of the active projects in each of the regions and discussed any issues regarding these projects with the respective Regional Coordinator. Continuing with discussions of regional projects, Dr. Bailey reviewed a table (see below) with the Regional Coordinators on the progress of MUADP submissions to FDA/CVM.

REPORT FROM THE ADMINISTRATIVE ADVISORS - Dr. John Baker (Chair)

Dr. Baker began his report praising the Regional Coordinators for their efforts, Dr. Baker questioned how long the Program could be expected to function under the current funding circumstances of delayed payments to regions and insufficient funds. He went on to suggest possible movement into a competitive grants program within the AES framework and the development of an action plan roadmap to carry out this objective.

He praised the Regional Coordinators for their heroic efforts to keep current projects moving from protocol development to FDA/CVM submission. In his remarks he suggested the possibility of looking at historical projects that could have species added with lower costs than totally new projects. In these cases, the savings would largely be in the shortened time for the development of analytical methods. It was brought up, however, that transfer of analytical methodology across species is not always a straightforward affair. Once again, Dr. Baker stressed the need to develop a broader listing of stakeholder groups to align with additional NIFA priorities of sustainable agriculture and support of the rural, family farms.

REPORT FROM THE NATIONAL COORDINATOR - Dr. John G. Babish

AES approved funding of NRSP-7 for $335,000. These funds will be appropriated from Hatch monies out of the FY12 budget, which has not yet been approved by Congress. Final Federal FY12 Budget will not be forthcoming until the Super Committee completes its mission. It is difficult to estimate what the outcome will be with the action of the SC. It is likely they will not accomplish their mission and an automatic series of draconian budget cuts will go into place. RC should be sure that the communications between their colleges and AES are more fluid than they have been in the past to ensure a more rapid transfer of funds.

Attempts to generate more stakeholder involvement to get behind the FY Farm Bill. Facebook and Google+ efforts are underway. Headquarters has been developing experience in marking through these channels. It is necessary to be able to get your story out through press releases as well as these Social Media sites. Press releases can be done relatively inexpensively (~$129 to $550) through PR Newswire. Desperate need to get our situation out to the world. A copy of the Facebook web site was presented to the attendees (see below).

Enter competitive grants program. NIFA Discussion of Garys points on the structure of the grants and organization. AES Not been done before and a lot of new ground to break here.

URL: Copy of minutes

Accomplishments:

REPORTS FROM THE REGIONS

WESTERN DR. LISA TELL Active Regional Projects: ADR#325 Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease The human food safety (HFS) and efficacy studies required by FDA/CVM for the old formulation of florfenicol (Nuflor Injectable Solution) have been completed. All of the data from this project have been published. The data from the HFS study has been organized and a technical report has been written. The final technical report for the human food safety study was reviewed for Quality Assurance in March, 2010. This report was submitted to FDA/CVM in July, 2010. On February 11, 2011, FDA/CVM concluded that the tissue residue depletion study was acceptable for supporting a withdrawal period determination, and assigned a 42-day withdrawal period. Other comments from FDA/CVM were that microbial food safety issues still need to be addressed which include the impact of florfenicol on antimicrobial resistance among bacteria of public health concern in or on treated sheep as well as human intestinal flora.

ADR#299 - Pirlimycin for Dairy Goats Project on hold until funding is identified and CIDR goat studies are completed.

ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder This project has been transferred to the Northeastern Region.

ADR#338 Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats Project on hold until funding is identified and CIDR goat studies are completed.

Collaborative Projects: ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge) A conference call with Merck/Intervet/SP was held on February 25, 2010. A product development meeting was held with CVM on September, 9, 2010 to discuss the development plan for investigating the use of fenbendazole Type A medicated article for the treatment of nematode parasites in pheasants. The HFS protocol was submitted and received concurrence from CVM on 12/08/2010. The TAS study protocol was submitted to FDA/CVM for review in February 2011. Plans are in place to conduct the HFS and TAS studies in the summer of 2011. The Western region will perform the analytical testing of the samples. We have begun to re-establish the fenbendazole tissue method for pheasants by testing intra and inter-day precision and accuracy. We are testing liver, muscle (breast and thigh), and skin/fat. In addition to spiked samples we will assay incurred samples to verify the method. There were a total of 366 samples analyzed in our laboratory during the summer of 2011 (120 study; 138 stability; 108 validation). The analytical portion of the human food safety report has been written and submitted to Dr. Griffith at Iowa State University.

ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy) The target animal safety study technical report has been accepted by FDA/CVM (February 2008). The milk residue study has been completed and the quality assurance inspection has been completed. The final technical report was sent to FDA/CVM in December 2008 and accepted October 2009. FDA/CVM has provided comments regarding the efficacy protocol. The protocol has been accepted for concurrence. The efficacy study was started at UC Davis and Iowa State University during the Fall of 2009. A quality assurance inspection was performed for the stability of progesterone in goat tissue during frozen storage in September 2009. A quality assurance inspection was performed in October 2009 for CIDR-G Insertion and Removal. All of the raw data from the UC Davis portion of this project was submitted to the Study Sponsor, Dr. Ron Griffith in August, 2010. The CIDR Efficacy study was initiated in August, 2010. A letter dated August 12, 2011 from FDA/CVM stated that the human food safety requirements for the use of CIDR-G in goats have been satisfied for toxicology, residue chemistry, and microbial food safety. The Human Food Safety technical section is complete as of August 12, 2011. A withdrawal period was established as zero and a milk discard time of zero.

ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region) The quality assurance was performed for the target animal safety study in February and March 2008. A tissue liquid chromatography/mass spectrometry method for analysis of the samples has been validated using 664 spiked samples to validate 4 tissues. Validation of analytical methods for liver, muscle, kidney and fat samples is complete. Plasma (444) and tissue (180) samples from the target animal safety have been analyzed. The quality assurance for the target animal safety report was completed November 2009. Plasma samples from the HFS study have been analyzed and the PK data has been generated. Tissue samples from the HFS study (205) have been analyzed. The method validation report has been submitted to the Central Region for quality assurance review. See North Central region report for further information. Tissue samples to re-establish data for freezer stability have been run and the data submitted to Dr. Griffith of the North Central region. A total of 102 freezer stability samples from Iowa State University were analyzed. The analytical data for the Human Food Safety Report has been provided to Dr. Kris Clothier and Dr. Ronald Griffith at Iowa State University.

Other Projects/Activities: Quality Assurance: Nothing to report.

Excede in Sheep: Study has been completed in domestic sheep. The serum samples have been analyzed and the pharmacokinetic data modeled. The data was presented at the UC Davis Veterinary Medical Teaching Hospital House Officers Research Seminar day on March 18, 2011.

Flunixin in Goats: Two cross over studies have been completed in domestic goats evaluating IV vs. IM administration. In addition, a pilot study has been completed in lactating goats. All samples are waiting to be analyzed due to challenges with the method.

CIDRs for Deer: Historical conference call with Dr. Albert Ramudo. At this time, Pfizer has indicated that they are not interested in pursuing a label claim for deer.

New Projects: Pharmacokinetics of tulathromycin in dairy goats: A UC Davis summer student, Bernadette Grismer, performed this study. A total of 448 samples (328 milk; 120 plasma) were analyzed during the summer of 2011.

Laboratory Report: Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above.

Usefulness of the Findings: The findings from all of the studies above will be utilized to fulfill the data requirements for the FDA/CVM approval of these drugs for use in minor species.

Work Planned for Remainder of the Year: We will be working to establish and validate the flunixin analytical method for plasma samples from goats. In addition, we will process any samples relative to the tulathromycin in goats efficacy study.

Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs Data from the Ovadine work is being summarized for publication. We are also investigating the potential of indexing Ovadine.

Allicin for the reduction of Aeromonas salmonicida infection in salmonids We were approached by Dr. George Ketola of the USGS Tunison Laboratory of Aquatic Sciences, Cortland, NY about a potential project to evaluate the ability of allicin, a garlic extract, to reduce the severity of various pathogens of fish. We initiated a collaborative project in which we are evaluating the ability of the allicin to reduce the severity of Aeromonas salmonicida infection in rainbow trout. Dr. Ketola has had a long career of fish nutrition research (the former name of the Cortland facility was the USFWS Tunison Fish Nutrition Laboratory) that spans well over 30 years. In this collaboration, Dr. Ketola formulates the rations and we utilize our biosecure fish research laboratories for the conduct of the challenge trials. The effort will serve as the Master of Science thesis research for Dr. Kate E. Breyer, who is a Resident in the Laboratory Animal Medicine Program at Cornell. She is pursuing the MS degree through the Cornell University Employee Degree Program. Thus, her salary support is from sources other than NRSP7. Our efforts to date have focused on the development of the standard bacterial challenge model to achieve an appropriate level of Aeromonas salmonicida infection. Once the challenge model is established, we will proceed with the experimental trial in which allicin will be formulated into the ration at various concentrations in an effort to determine the effective dose to reduce the bacterial infection. Given the financial limitation we are facing in the NE Region NRSP7, this collaboration between the Tunison Laboratory of Aquatic Sciences and the Laboratory Animal Medicine Program at Cornell is seen as an extremely economic means to conduct this research.

CRITICAL REVIEW (Northeast Region) 1) Work accomplished under the original project: The original objectives of the project were to conduct a national program to obtain minor and specialty animal-drug clearances (tolerances, exemptions and registrations) in cooperation with state, federal and industry personnel. The mission of NRSP-7 is: To identify animal drug needs for minor species and minor uses in major species. To generate and disseminate data for safe and effective therapeutic applications, and To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.

3) Incomplete work or areas needing further investigation: The development of a crop(species) grouping concept is seen as imperative for supporting efforts to gain labels for therapeutic compounds for fish. Our work on Oxytetracycline, Romet-30/Romet-TC and Aquaflor (Florfenicol) in fish is proposed to be part of an effort to utilize those compounds as models in this effort. We expect that our efforts in developing a species grouping concept for fish will be a major undertaking in the upcoming years.

North Central Dr. Ronald W. Griffith Progress of the work and principal accomplishments

Goat CIDR-G Tissue Residue Study report has been submitted. Mean tissue levels of progesterone 12 hours after CIDR removal were significantly lower than tissue levels in control does without CIDRs.

Lasalocid in Pheasants Efficacy The study was completed in 2007 and the study report submitted this summer. Undergoing final stages of review. Keeping fingers crossed.

Lasalocid in Pheasants TAS A second high-dose group study was completed in July. The study report is currently being prepared. Draxxin Target Animal Safety in Goats The study report has been submitted to the FDA/CVM. Dr. Kris Clothier has a manuscript accepted by the Journal of Pharmacology and Therapeutics.

Draxxin Tissue Residue Study report undergoing QA audit.

Fenbendazole TAS in Pheasants Protocol has been submitted to ONADE and is under final review. Birds are scheduled to arrive the third week in May.

Fenbendazole HFS Working with the Lisa Tell in the Western Region on this project. Protocol concurrence has been received. On track to complete in-life phase in late summer or early fall.

SOUTHERN DR. THOMAS VICKROY Overview of Projects in Progress 1. ADR#352: Ivermectin Efficacy against Cattle Fever Tick in southern Texas This is a collaborative project among multiple entities, including the NorthCentral and Southern regions of NRSP7, USDAARS and APHIS. This project is classified as a minor use project owing to the small number of affected animals and the relatively restricted geographical region that is impacted. A protocol was drafted by Dr. Ron Griffith and following revision was submitted to FDA ONADE in July, which responded with a letter of nonconcurrence in September. The primary role of the Southern region will be analytical testing of ivermectin in feed blocks that will be used for drug delivery to cattle in pastures. At this time, we have made necessary modifications of the approved regulatory method for ivermectin analysis in cattle liver in order to determine ivermectin content of a proprietary medicated feed block mixture (molasses/protein/mineral bovine supplement) that is formulated by Postive Feeds. We are in the midst of (1) conducting studies to validate the method for submission to FDA for possible concurrence and (2) using the analytical method to determine the level and consistency of drug content in the formulated feed blocks.

2. ADR#279: Lasalocid for Coccidiosis in Pheasants This is a collaborative project between the NorthCentral and Southern regions. The role of the Southern region will be to carry out drug analyses of all tissue samples. Previous attempts to establish the approved regulatory method were unsuccessful and led to failure of a previous trial. However, we have now solved all of the analytical problems and have a robust and reliable working method that entails what are considered (by me) to be slight and non significant modifications of the regulatory method that is approved for use in cattle liver and other tissues. This is a significant and requisite step that puts us in position to analyze samples from upcoming inlife phase of studies. At present, we are conducting work to validate this method and, once complete, will submit the work to FDA for evaluation. The goal is to obtain method concurrence prior to the initiation of inlife phase studies by the NorthCentral region.

3. ADR#280: Fenbendazole in Game Birds (pheasants, bobwhite quail, partridge) This is a collaborative project among the NorthCentral, Western and Southern regions. At this time, there is no recent progress to report.

Update on Other Programmatic Efforts and Changes 1. NRSP7 Website: The Southern Region is responsible for maintaining and updating the NRSP7 website, including MUMsRx and the RUSTi system for tracking the status of regional projects. In addition, the Southern Region coordinator organizes and coordinates monthly teleconferences among the regional coordinators and administrators. The next teleconference is scheduled tentatively for 6 December 2011 at 12:00pm EST.

2. Anticipated Use of Project Outcomes: The findings from all of the studies above will be utilized to fulfill the data requirements for Public Master Files and, ultimately, for FDA/CVM approval of these drugs for use in minor species.

Impact Statements:

Since its inception in 1982, more than $12.6 million has been allocated to the program through Federal funding. In return NRSP-7/MUADP has generated publication of 36 PMF in the Federal Register. These PMF have, in turn, supported FDA/CVM approval for 43 drugs for use in minor food species or for minor uses in major species. Compared to an average investment of the pharmaceutical industry of $10 to $25 million for adding a label claim to an existing veterinary drug, expenses for data generated for additional label claims by the NRPS-7 program are approximately 10 to 35% of pharmaceutical industry costs.
The Environmental Assessment study data for erythromycin in salmonids INAD I-00613 were accepted by FDA Center for Veterinary Medicine on 1/12/11.
On 2/11/11, the tissue residue depletion study of Nuflor Gold in sheep submitted by NRSP-7 was accepted by FDA Center for Veterinary Medicine.
The Effectiveness Study of lasalocid in pheasants submitted by NRSP-7 to FDA/CVM on 7/1/10 was deemed complete by the agency on 3/25/11.
On July 1, 2011, the FDA Center for Veterinary Medicine published the availability of effectiveness, target animal safety, microbial food safety, residue chemistry, and environmental impact data that may be used in support of a new animal drug application (NADA) or supplemental NADA for use of lincomycin hydrochloride water soluble powder for the control of American foulbrood (Paenibacillus larvae) in honey bees. The Minor Use Animal Drug Program/NRSP-7 compiled the data, contained in Public Master File 5988.
On 8/12/11, the FDA Center for Veterinary Medicine approved the Human Food Safety sections of the CIDR-goat study submitted 11/18/10.
Also in 2011, data from NRSP-7 was used in support of the FDA approval of Chloramine-T safety and efficacy studies for control of bacterial gill disease in freshwater-reared salmonids. This formulation is used by immersion for control of mortality in freshwater-reared salmonids due to bacterial gill disease.
To date 352 drug requests have been submitted to the Minor Use Animal Drug Program for the development of data in support of the submission of a New Animal Drug Application. Currently there are 16 active research projects involving nine animal species and 12 different drugs.

Last Modified: 25-Jan-2012

Date of Annual Report: 06/15/2012

Report Information:

Annual Meeting Dates: 05/01/12 to 05/01/12

Period the Report Covers: 10/2011 to 09/2012

Participants:

Dorothy Bailey, FDA/CVM, dorothy.bailey@fda.hhs.gov
Gary Sherman, USDA/CSRESS, gsherman@nifa.usda.gov
John Babish, MUADP/NRSP-7, jgb7@cornell.edu
John C. Baker, AA/MI AES, Baker@anr.msu.edu
Lisa Tell, MUADP/NRSP-7/UC Davis, latell@ucdavis.edu
Margaret Smith, AA/NY AES, mes25@cornell.edu
Meg Oeller, FDA/CVM, margaret.oeller@ fda.hhs.gov
Paul R. Bowser, MUADP/NRSP-7/Cornell U, prb4@cornell.edu
Ron Griffith, MUADP/NRSP-7/Iowa State, rgriffit@iastate.edu
Thomas Vickroy, MUADP/NRSP-7/U FL, vickroy@vetmed.ufl.edu The USDA's Minor Species Animal Drug Program, National Research Support Project #7 (MUADP/NRSP-7) held its semi-annual spring meeting of the technical committee and administrative advisors on May 1st by teleconference starting at noon and hosted by the FDA Center for Veterinary Medicine (CVM), 7519 Standish Place, Rockville, MD. Absent were administrative advisors Drs. John Liu (Southern Region) and Frances D. Galey (Western Region).

Brief Summary of Minutes of Annual Meeting:

The MUADP/NRSP-7 technical committee is made up of a National Coordinator, four Regional Coordinators, four regional Administrative Advisors, and liaisons from USDA and FDA. The National Coordinator is Dr. John Babish (Cornell University). The Regional Coordinators are Dr. Lisa Tell (University of California, Davis), Dr. Thomas Vickroy (University of Florida), Dr. Ronald Griffith (Iowa State University), and Dr. Paul Bowser (Cornell University). The Administrative Advisors present were Drs. John C. Baker (Michigan State University AES), Chairman of Administrative Advisors (AA) and Margaret Smith (Cornell University, AES). The attending NIFA representative was Dr. Gary Sherman (Washington, DC) and the FDA liaisons were Drs. Meg Oeller and Dorothy Bailey (Rockville, MD). Absent were administrative advisors Drs. John Liu (Southern Region) and Frances D. Galey (Western Region).

Introductions and meeting organization Dr. John G. Babish started the meeting with a thank you to Dr. Bailey for her organizing efforts at FDA/CVM to have the teleconference conducted through the Adobe Connect facilities at Rockville, MD. The National Coordinator then outlined the agenda of the meeting with reports from the Regional Coordinators and presentations from FDA/CVM, NIFA, AA and National Coordinator.

REPORTS FROM LIAISONS

REPORT FROM FDA/CVM - Drs. Meg Oeller and Dorothy Bailey Whats Up at FDA/CVM? 1. Approval of Lincomycin 1.1. Technical Section Complete

2.Effectiveness Erythromycin

3. GFI 61 Update

4. PMF new procedures

5. Problems with Erythromycin CMC

6. Collaboration with OR on goat projects Draxxin, Banamine?

MUADP Stats Update 1. Current MUADP Goat Projects 1.1. Active Projects 1.1.1. Intravaginal progesterone 1.1.2. Tulathromycin/respiratory infections

1.2. Future Projects: 1.2.1. Flunixin?

2. Current MUADP Cattle Project 2.1. Project in progress: 2.1.1. Ivermectin medicated feed blocks for Cattle Fever Ticks 2.1.1.1. Effectiveness trial in progress (pivotal?) 2.1.1.2. Right of reference pending? 3. Current MUADP Sheep Projects 3.1. Projects in progress: 3.1.1. Florfenicol (Nuflor & Nuflor Gold) - respiratory infections 3.1.2. Tulathromycin - respiratory infections 3.1.3. Excede

4. Current MUADP Gamebird Projects 4.1. In Progress:

4.1.1. Fenbendazole: 4.1.1.1. Pheasants 4.1.1.2. Partridges (later) 4.1.1.3. Quail (later)

4.1.2. Lasalocid pheasants

5. Current MUADP Fish Projects: 5.1. Erythromycin/BKD/salmonids 5.2. Species grouping studies 5.3. Strontium chloride /marking/finfish 5.4. PVP iodine fish eggs 5.5. Allicin- antibacterial/immunostimulant

6. Erythromycin/Salmonids Status: 6.1. Effectiveness complete 6.2. Target Animal Safety complete 6.3. Human Food Safety complete 6.4. Environmental Safety EA for CVM review due 8/22/2012 6.5. PMF to publish after EA accepted 6.6. Pharmaceutical co. manufacturing Can we help?

7. MUADP Misc Projects: 7.1. Honey bees: 7.1.1. Lincomycin/American foulbrood - Approved! 7.2. Rabbits: Ivermectin/ear mites??

8. On Hold: 8.1. For Goats: 8.1.1. Pirlimycin for mastitis 8.1.2. Sprectramast for mastitis

8.2. For Fish: CCP for spawning

8.3. For Deer: 8.3.1. Fenbendazole for GI parasites 8.3.2. Lasalocid for coccidiosis

8.4. For Ornamental Fish: 8.4.1. GnRHa & Domperidone for spawning 8.4.2. Metomidate for anesthesia

9. Pending MUADP Work: 9.1. Revise SrCl2 TAS Protocol 9.2. AB resistance submissions for Draxxin 9.3. Ivermectin TAS/HFS/EA negotiation after right of reference 9.4. Florfenicol project clarification 9.5. Coordinate OR & MUADP research 9.6. Complete Erythro PMF 9.7. Identify and post all Complete Technical Sections on PMF Web page

NIFA/USDA Dr. Gary Sherman Dr. Gary Sherman again continued his discussion from fall on the funding methods of the program and the complexities of the budget process. Before the meeting, it was requested Dr. Sherman delve into Senate FY-13 NIFA budget details to determine if MUADP might be buried somewhere within a composite line. At the time of our last call, official Senate markup information, vetted by NIFA, was not yet available, though there were several unofficial versions circulating, which NIFA does not comment on. Taken together, the Senate budget information and explanations below allow me to conclude that MUADP is not embedded anywhere within the FY13 Senate mark-up. Dr. Sherman also restated his remarks from previous teleconferences that the USDA Special Grants category in which the MUADP exists does not require noncompetitive grant status.

REPORT FROM THE ADMINISTRATIVE ADVISORS - Dr. John Baker (Chair) Once again, Dr. Baker stressed the need to develop a broader listing of stakeholder groups to align with additional NIFA priorities of sustainable agriculture and support of the rural, family farms.

REPORT FROM THE NATIONAL COORDINATOR - Dr. John G. Babish Dr. Babish reported that he had learned that MUADP will not have an amendment to the Farm Bill ready in time for the Chairwomans mark. MUADP strategy will be adjusted as a result. Barring any shenanigans or sabotage, the Senate version of the Farm Bill will pass out of the Committee soon. Majority Leader Reid will schedule the bill for Senate floor action sometime between now and when 112th congress adjourns. Whatever that period of time is will be our window of opportunity to advance MUADP in the Senate. I welcome your insights and thoughts about the proposed strategy. I will be calling upon you for your help in the coming weeks.

Senate path forward: 1) pursuit of a Senate bill to formally authorize MUADP (this could be attached as an amendment to the Senate Farm Bill on the floor). 2) pursuit of an amendment to Senate Farm Bill when it goes to the floor.

Senate target is Sen. Amy Klobuchar (D-MN). Should she not champion the bill/amendment then I will move on to the next potential champion. House path forward: 1) pursuit of a House bill to formally authorize MUADP (this could be included in the Chairmans mark). 2) if that fails then seek to include the provision in the House Farm Bill in the amendment phase. 3) if that fails then seek to have it included in the floor debate. 4) if that succeeds then wed urge the senate to recede to the House to adopt the MUADP provision.

House target is Rep. Dennis Cardoza (D-CA-18). He has expressed interest. His staff has assured me that they are working on it.

Minor Use Producer Testimonials It would be tremendously helpful to have testimonials from producers of minor species about the importance of the program. Do we have statements from goat farmers, honey bee producers, game bird farmers, etc. about the importance of having certain drugs available all due to MUADP efforts? Dr. Babish will coordinate this effort.

If we could have a prominent catfish farmer say his successful operation is reliant upon sulfadimethoxine and florfenicol for which MUADP secured the approvals for this could be the linchpin in securing the backing of the delegations from Mississippi, Louisiana, and Alabama. The same can be said for the other minor species.

FALL Meeting It was tentatively decided to schedule the fall meeting in concert with the outcome or progress of the Farm Bill and delay setting a date or location. The final decision on the timing of the meeting will be made when the budget situation becomes clearer. This will be followed on a month-to-month basis and discussed at our monthly teleconferences.

OTHER BUSINESS None brought forward.

There being no further business, the meeting was adjourned at 2:30 pm.

URL: Copy of minutes

Accomplishments:

NORTHEAST REGION: DR. PAUL BOWSER Progress of the work and principal accomplishments: Species Grouping Project: INAD 10-320 Oxytetracycline in Fish INAD 10-823 Romet-30 in Fish INAD 11-145 Florfenicol in Fish

Efforts on this project consisted of providing administrative support and oversight to the New York State Department of Environmental Conservation in their conduct of field trials under our INAD 10-320 for the use of Oxytetracycline in fish.

Ovadine (Western Chemical) Disinfection of Fish Eggs: We have been evaluating the efficacy of Ovadine (PVP-Iodine, Western Chemical) as an egg disinfection compound for fish eggs with a particular emphasis on the reduction of Viral Hemorrhagic Septicemia Genotype IVb from walleye eggs. Our trial will build on preliminary efforts, funded by New York Sea Grant Program, in which we found that the consensus treatment protocol of the Great Lakes Fishery Commission (50 mg/L iodine for 30 minutes) was not completely effective in the elimination of VHSV IVb. A disinfection trial was conducted during the 2010 walleye spawning season with the collaboration of the New York State Department of Environmental Conservation. Treatments included iodine doses of 0, 50 and 100 mg/L for 30 minutes. One publication on this work has been published and a second publication is in press.

Allicin for the reduction of Aeromonas salmonicida infection in salmonids: We are conducting a cooperative project with the USGS Tunison Laboratory of Aquatic Science in which we are evaluating the use of allicin as a nutritional supplement for the reduction of Aeromonas salmonicida in salmonids. We have developed a challenge model with A. salmonicida in rainbow trout and conducted the first trial.

Work planned for next year: Species Grouping Project: INAD 10-320 Oxytetracycline in Fish INAD 10-823 Romet-30 in Fish INAD 11-145 Aquaflor (Florfenicol) in Fish

We anticipate our efforts on this project to center around the continued provision of administrative support and oversight of Efficacy Studies of oxytetracycline in a collaborative effort with the New York State Department of Environmental Conservation. The particular focus of the efficacy trials will be for the treatment of bacterial diseases not currently on the label for treatment of bacterial diseases of cool water species such as walleyes, muskellunge and tiger muskellunge (hybrid muskellunge X northern pike). These studies will be initiated when diagnosed field cases can be identified that will lend themselves to the implementation of controlled field studies.

Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs Data from the Ovadine work is being summarized with one publication and a second manuscript in press. We are investigating the potential of indexing Ovadine.

Allicin for the reduction of Aeromonas salmonicida infection in salmonids We were approached by Dr. George Ketola of the USGS Tunison Laboratory of Aquatic Sciences, Cortland, NY about a potential project to evaluate the ability of allicin, a garlic extract, to reduce the severity of various pathogens of fish. We initiated a collaborative project in which we are evaluating the ability of the allicin to reduce the severity of Aeromonas salmonicida infection in rainbow trout. Dr. Ketola has had a long career of fish nutrition research (the former name of the Cortland facility was the USFWS Tunison Fish Nutrition Laboratory) that spans well over 30 years. In this collaboration, Dr. Ketola formulates the rations and we utilize our biosecure fish research laboratories for the conduct of the challenge trials. The effort will serve as the Master of Science thesis research for Dr. Kate E. Breyer, who is a Resident in the Laboratory Animal Medicine Program at Cornell. She is pursuing the MS degree through the Cornell University Employee Degree Program. Thus, her salary support is from sources other than NRSP7. Given the financial limitation we are facing in the NE Region NRSP7, this collaboration between the Tunison Laboratory of Aquatic Sciences and the Laboratory Animal Medicine Program at Cornell is seen as an extremely economic means to conduct this research. To date we have developed a standard bacterial challenge model to achieve an appropriate level of Aeromonas salmonicida infection following an IP challenge. This was followed by the first trial. Prior to the trial, for 14 days the fish were fed a diet in which allicin was added at 0.0, 0.5, 1.0 or 2.0% of the diet by weight. Fish were fed at 2% body weight per day. In this trial we did not observe a benefit from the addition of allicin to the diet at 0.0, 0.5, 1.0 or 2.0% of the diet when fish were fed at 2% of body weight per day. This protocol was based on a protocol reported in the literature in which the challenge pathogen was Aeromonas hyhdrophila. We will be repeating this trial to confirm the results of the first trial. If we again observe a lack of effect, we may continue the effort, but with a challenge that involves a water borne challenge with the bacterium.

CRITICAL REVIEW (Northeast Region) 1) Work accomplished under the original project: The original objectives of the project were to conduct a national program to obtain minor and specialty animal-drug clearances (tolerances, exemptions and registrations) incooperation with state, federal and industry personnel. The mission of NRSP-7 is: To identify animal drug needs for minor species and minor uses in major species. To generate and disseminate data for safe and effective therapeutic applications, and To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.

Under the framework of this mission, progress has been made in the following areas: (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish. (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/ Romet-TC and Aquaflor as test articles. (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs. 2) The degree to which the objectives have been met: Work has focused on a number of important therapeutic compounds in aquatic animals. The work is being conducted in a deliberate manner with the goal of developing appropriate data that will be submitted in support of a label for these compounds. An initial step in this process is the publication of the data in the peer reviewed scientific literature. While we consider it extremely important to have such peer-reviewed information available for the veterinary community, should they consider an extra-label use, the ultimate goal is to secure a label for the product. As an additional goal, the work is being done in a manner that could justify a species grouping concept for finfish cultured in the United States. 3) Incomplete work or areas needing further investigation: The development of a species grouping concept is seen as imperative for supporting efforts to gain labels for therapeutic compounds for fish. Our work on Oxytetracycline, Romet-30/Romet-TC and Aquaflor (Florfenicol) in fish is proposed to be part of an effort to utilize those compounds as models in this effort. We expect that our efforts in developing a species grouping concept for fish will be a major undertaking in the upcoming years.

WESTERN DR. LISA TELL Progress of Work and Principal Accomplishments:

Active Regional Projects: ADR#325 Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease The human food safety (HFS) and efficacy studies required by FDA/CVM for the old formulation of florfenicol (Nuflor Injectable Solution) have been completed. All of the data from this project have been published. The data from the HFS study have been organized and a technical report has been written. The final technical report for the human food safety study was reviewed for Quality Assurance in March, 2010. This report was submitted to FDA/CVM in July, 2010. On February 11, 2011, FDA/CVM concluded that the tissue residue depletion study was acceptable for supporting a withdrawal period determination, and assigned a 42-day withdrawal period. Other comments from FDA/CVM were that microbial food safety issues still need to be addressed which include the impact of florfenicol on antimicrobial resistance among bacteria of public health concern in or on treated sheep as well as human intestinal flora. Update 5/1/2012: Contacted CVM to see if isolates from other regional sections would be acceptable to get final concurrence for the efficacy section of this project. Awaiting advice from CVM regarding how to move forward on this project.

ADR#338 Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats Project on hold until funding is identified and CIDR goat studies are completed.

ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region) The quality assurance was performed for the target animal safety study in February and March 2008. A tissue liquid chromatography/mass spectrometry method for analysis of the samples has been validated using 664 spiked samples to validate 4 tissues. Validation of analytical methods for liver, muscle, kidney and fat samples is complete. Plasma (444) and tissue (180) samples from the target animal safety have been analyzed. The quality assurance for the target animal safety report was completed November 2009. Plasma samples from the HFS study have been analyzed and the PK data has been generated. Tissue samples from the HFS study (205) have been analyzed. The method validation report has been submitted to the Central Region for quality assurance review. See North Central region report for further information. Tissue samples to re-establish data for freezer stability have been run and the data submitted to Dr. Griffith of the North Central region. A total of 102 freezer stability samples from Iowa State University were analyzed. The analytical data for the Human Food Safety Report has been provided to Dr. Kris Clothier and Dr. Ronald Griffith at Iowa State University. Update 5/1/2012: Currently working on putting the final report together for submission to CVM.

Other Projects/Activities: Excede in Sheep: Study has been completed in domestic sheep. The serum samples have been analyzed and the pharmacokinetic data modeled. The data was presented at the UC Davis Veterinary Medical Teaching Hospital House Officers Research Seminar day on March 18, 2011. Update 5/1/2012: Manuscript in preparation.

Flunixin in Goats: Two cross-over studies have been completed in domestic goats evaluating IV vs. IM administration. In addition, a pilot study has been completed in lactating goats. All samples are waiting to be analyzed due to challenges with the method. Update 5/1/2012: This method has been validated for goats and cattle. Three of the four sets of goat samples have been analyzed. One set of the goat samples remain to be analyzed and two sets of milk samples.

Quality Assurance: Nothing to report.

Laboratory Report: Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. Usefulness of the Findings:

The findings from all of the studies above will be utilized to fulfill the data requirements for the FDA/CVM approval of these drugs for use in minor species. Work Planned for Remainder of the Year: We will be working to establish and validate the flunixin analytical method for milk and tissue samples from goats. In addition, we will process any samples relative to the tulathromycin in goats efficacy study.

Considering these objectives, considerable progress has been made towards achieving them for each of the active projects listed above, particularly in the development of the data (the actual research), its analysis, assembly and interpretation, and submission to the FDA/CVM for review.

NORTH CENTRAL DR. RONALD W. GRIFFITH Progress of Work and Principal Accomplishments: Active Regional Projects:

Goat CIDR-G Effectiveness The study report is in preparation. We have received excellent cooperation from producers in a number of states. There were over 600 dairy goats enrolled in the study in Iowa, California, Missouri, Minnesota and Wisconsin. On the meat goat side, we have two herds in Iowa and one at Texas A&M Prairieview that have participated. We had planned on having more meat-type goats in the study this fall but all of the sites we identified were unable to participate due to lower than expected numbers of breeding females. We contacted smaller herds in Iowa, but they have also reduced numbers. CIDRs seem to be in widespread use in the goat population now that they are readily available for sheep.

Lasalocid in Pheasants TAS The study report has been submitted to the FDA/CVM.

Draxxin Tissue Residue The study report is nearing submission.

Draxxin Efficacy in Goats Trying to figure out what type of study will be acceptable to the FDA/CVM to demonstrate efficacy.

Fenbendazole HFS The study report has been submitted for QA audit and should be submitted to the FDA/CVM soon.

Fenbendazole TAS in Pheasants The study report is in the final stages of preparation and, hopefully, will be submitted for a QA audit very soon. The study was completed in August, 2011. There were some slight differences in the clinical pathology findings but the birds gained weight well, there were no abnormal findings on gross necropsy or histopath, and there were no detectable feathering abnormalities.

Fenbendazole Reproductive Safety We have received three summers worth of hatching data from MacFarlane Pheasants and the data have been submitted to Dorothy Bailey. Fertility drops off dramatically as the egg-laying season progresses but there does not appear to be an effect from feeding 100 ppm fenbendazole to the hens. MacFarlane Pheasants has also provided data comparing hatching data of their own pheasant eggs with those of other producers that were hatched in MacFarlanes incubators. This information will be included as part of the Target Animal Safety study.

Ivermectin Cattle Fever Tick Efficacy Working in conjunction with Tom Vickroy in the Southern Region and a whole host of individuals with the Texas Animal Health Commission, the USDA-APHIS and the Cattle Fever Tick Eradication Program. A study protocol was submitted to ONADE but we received a letter of non-concurrence. The biggest problems are the non-uniformity of the product (how to analyze for potency) and the lack of a precise description of exactly how the product was going to be used and the expected outcomes. The study protocol was altered in accordance with the ONADE comments and it was decided to proceed with the two infested herds under the revised study protocol. Two tick-infested herds were identified. One herd in South Texas which was infested with Rhipicephalus microplus began treatment in November, 2011 and treatment is continuing at this time. Ivermectin has virtually eliminated any tick infestion on treated cattle in that herd. Treatment of the second herd infested with Rhipicephalus annulatus began in April 2012 and no results are available at this time.

Pregnant Mare Serum Gonadotrophin-ADR 0353 A request was received to investigate the feasibility of performing studies to support FDA/CVM approval for Pregnant Mare Serum Gonadotropin to be used as a reproductive aid in small ruminants. A current review of the literature is being prepared with the goal of subsequently requesting a product development conference.

SOUTHERN DR. THOMAS VICKROY Progress of Work and Principal Accomplishments: Active Regional Projects: 1. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279) This pending project is a collaborative effort between the North-Central Region (Iowa State University) and the Southern Region (University of Florida) of MUADP. The primary role of the Southern region is to carry out drug analyses of all tissue samples. Previously, attempts to bridge the approved regulatory method for lasalocid analysis in bovine liver were unsuccessful in liver or skin from pheasants, which led to the failure of a human food safety trial. However, we have now solved all of the analytical problems and have a robust and reliable working method. That method has undergone a partial validation in samples of liver and skin with adhering fat from pheasants. In view of the previous difficulties in mounting a working analytical method, the validated method was submitted to the CVM along with the protocol for the in-life phase of studies. Pending CVM review and concurrence with the study protocol and the analytical method, this project will be in position to move forward with the in-life phase studies in the North-Central Region. The anticipated time line for project start up is October of 2012.

2. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352) Preliminary work has continued slowly on this project. The study represents a minor use in a major food animal species and is a collaborative effort among several agencies and institutions, including the North-Central Region (Iowa State University) and the Southern Region (University of Florida) of the MUADP as well as USDA-ARS and APHIS. The project has not yet received concurrence from the CVM and it is unclear whether it will proceed or be completed. The primary role of the Southern Region is to conduct analytical testing of ivermectin levels in medicated feed blocks that are formulated by Postive Feeds, Inc. These blocks, which will be used for drug delivery to cattle in pastures, contain a complex mixture of nutrients, minerals and numerous other ingredients, including molasses as a taste enhancer. We have been successful in adapting the approved regulatory method for ivermectin analysis in order to determine ivermectin levels in the feed blocks. At this time, we have completed analysis of three batches of medicated blocks, each containing 16 to 24 individual blocks. Work is currently in progress as we continue to analyze medicated blocks for consistency of drug levels.

3. Fenbendazole in Game Birds (ADR#280) This is a collaborative project among the North-Central, Western and Southern regions. The Southern Region has no principal role related to in-life studies (North-Central Region) nor the analytical phase (Western Region), so any progress updates will be contained in those regional reports.

Update on Other Programmatic Efforts and Changes 1. NRSP-7 Website: The Southern Region is responsible for maintaining and updating the NRSP-7 website, including MUMsRx and the RUSTi system for tracking the status of regional projects. In addition, the Southern Region coordinator organizes and coordinates monthly teleconferences among the regional coordinators and administrators. The next teleconference is scheduled tentatively June 2012. 2. Anticipated Use of Project Outcomes: The findings from all of the studies above will be utilized to fulfill the data requirements for Public Master Files and, ultimately, for FDA/CVM approval of these drugs for use in minor species.

Impact Statements:

Last Modified: 08-Aug-2012

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NRSP007: A National Agricultural Program for Minor Use Animal Drugs

Annual/Termination Reports (SAES-422): [12/22/2009] [06/28/2010] [06/29/2010] [11/10/2010] [07/12/2011] [12/21/2011] [06/15/2012]

Date of Annual Report: 12/22/2009

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Date of Annual Report: 06/28/2010

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Date of Annual Report: 06/29/2010

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Date of Annual Report: 11/10/2010

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Date of Annual Report: 07/12/2011

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Date of Annual Report: 12/21/2011

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Date of Annual Report: 06/15/2012

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