Annual/Termination Reports:

[12/22/2009] [06/28/2010] [06/29/2010] [11/10/2010] [07/12/2011] [12/21/2011] [06/15/2012] [01/26/2013] [06/30/2001] [03/12/2014] [08/01/2014]

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see attached meeting minutes

Brief Summary of Minutes

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Brief Summary of Minutes

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

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Brief Summary of Minutes

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

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Brief Summary of Minutes

See attached meeting minutes file.

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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

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.

Accomplishments

WESTERN  DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Western Region Projects:<br /> ADR#325  Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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.<br /> <br /> ADR#350  Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. <br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder<br /> This project has been transferred to the Northeastern Region.<br /> <br /> ADR#338  Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135  Erythromycin in Salmonids<br /> 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.<br /> <br /> Active Collaborative Projects:<br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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. <br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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. <br /> <br /> Other Projects/Activities:<br /> Quality Assurance: Nothing to report.<br /> <br /> 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.<br /> 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. <br /> <br /> 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. <br /> <br /> 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.<br /> 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.<br /> <br /> New Projects:<br /> Moxidectin in Goats<br /> Tulthromycin in Dairy Goats: <br /> UC Davis summer student has been identified and funding for her position has been awarded. <br /> <br /> Laboratory Report:<br /> 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. <br /> <br /> Usefulness of the Findings:<br /> 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.<br /> <br /> 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. <br /> <br /> Critical Review:<br /> 1. Work accomplished under the original project<br /> 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:<br /> a. Determination and prioritization of minor-use needs and data requirements.<br /> b. Review, analysis and evaluation of minor-use research proposals.<br /> c. Development and assembly of data for minor-use registrations.<br /> d. Preparation and submission of petitions for drug registrations. <br /> 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. <br /> <br /> 2. The degree to which objectives have been met<br /> 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.<br /> <br /> 3. Incomplete work or areas needing further investigation<br /> 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.<br /> <br /> NORTHEAST REGION: DR. PAUL BOWSER <br /> Progress of the work and principal accomplishments<br /> <br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> 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).<br /> <br /> Work planned for next year:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> Data from the Ovadine work is being summarized for publication. We are also investigating the potential of indexing Ovadine. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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.<br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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:<br /> <br /> 1. To identify animal drug needs for minor species and minor uses in major species.<br /> 2. To generate and disseminate data for safe and effective therapeutic applications, and<br /> 3. To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met:<br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation:<br /> 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.<br /> <br /> North Central  Dr. Ronald W. Griffith<br /> Progress of the work and principal accomplishments<br /> Goat CIDR-G Tissue Residue<br /> 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. <br /> <br /> Goat CIDR-G Effectiveness<br /> 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.<br /> <br /> Lasalocid in Pheasants Efficacy<br /> The study was completed in 2007 and the study report submitted this summer. Undergoing final stages of review. Keeping fingers crossed.<br /> <br /> Lasalocid in Pheasants TAS<br /> A second high-dose group study was completed in July. The study report is currently being prepared. <br /> <br /> Draxxin Target Animal Safety in Goats<br /> The study report has been submitted to the FDA/CVM. Dr. Kris Clothier has a manuscript accepted by the Journal of Pharmacology and Therapeutics.<br /> <br /> Draxxin Tissue Residue<br /> Study report undergoing QA audit.<br /> <br /> Draxxin Efficacy in Goats<br /> 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.<br /> <br /> Fenbendazole TAS in Pheasants<br /> Protocol has been submitted to ONADE and is under final review. Birds are scheduled to arrive the third week in May.<br /> <br /> Fenbendazole HFS<br /> 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.<br /> <br /> Fenbendazole Reproductive Safety<br /> 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?<br /> <br /> Ivermectin Cattle Fever Tick Efficacy <br /> 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.<br /> <br /> SOUTHERN  DR. THOMAS VICKROY<br /> Progress of the work and principal accomplishments<br /> 1. ADR#279: Lasalocid for Coccidiosis in Pheasants<br /> 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.<br /> <br /> 2. ADR#280: Fenbendazole in Game Birds (pheasants, bobwhite quail, partridge)<br /> 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. <br /> 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.<br /> 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.<br /> 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). <br /> <br /> 3. ADR#352: Ivermectin Efficacy against Cattle Fever Tick in southern Texas<br /> 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.<br /> <br /> Update on Other Programmatic Efforts and Changes<br /> 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.<br /> 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.<br /> <br /> 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.<br /> <br /> Work Planned<br /> 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. <br />

Publications

Presentations<p><br /> Groocock, Geoffrey H., Emily R. Cornwell, Rodman G. Getchell, Gregory A. Wooster, Paul R. Bowser. 2010. Efficacy of iodophore disinfection of viral hemorrhagic septicemia virus (VHSV) on walleye (Sander vitreus) eggs. Annual Meeting of the New York Chapter of the American Fisheries Society. Lake George, New York. 10-12 February 2010.<br /> <br /> Groocock, G.H., E.R. Cornwell, R.G. Getchell, G.A. Wooster, and P.R. Bowser. 2010. Iodophor Disinfection of Walleye (Sander vitreus) Eggs. 35th Eastern Fish Health Workshop. Shepherdstown, WV. 24-28 May 2010.<br /> <br /> Publications<p><br /> Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther. doi: 10.1111/j.1365-2885.2011.01300.x<br /> <br /> Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 34, 448-454.<br /> <br /> Emily R. Cornwell, Geoffrey H. Groocock, Rodman G. Getchell, and Paul R. Bowser. 2010. Residual tannic acid destroys virucidal properties of iodine. North American Journal of Aquaculture 73(1):8-12.<br /> <br /> Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2011) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther. doi: 10.1111/j.1365-2885.2011.01304.x. <br /> <br /> Tell, L. A., Brooks, J. W., Lintner, V., Matthews, T., and Kariyawasam, S. (2011) Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia, J Vet Diagn Invest 23, 1009-1013.<br />

Impact Statements

1. 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.
2. 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.
3. The Environmental Assessment study data for erythromycin in salmonids INAD I-00613 were accepted by FDA/CVM on 1/12/11.
4. On 2/11/11, the tissue residue depletion study of Nuflor Gold in sheep submitted by NRSP-7/MUADP was accepted by FDA/CVM.
5. 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.
6. 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.

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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

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.

Accomplishments

REPORTS FROM THE REGIONS<br /> <br /> WESTERN  DR. LISA TELL<br /> Active Regional Projects:<br /> ADR#325  Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. <br /> <br /> ADR#350  Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. <br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder<br /> This project has been transferred to the Northeastern Region.<br /> <br /> ADR#338  Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135  Erythromycin in Salmonids<br /> 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. <br /> <br /> Collaborative Projects:<br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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.<br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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.<br /> <br /> Other Projects/Activities:<br /> Quality Assurance: Nothing to report.<br /> <br /> 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.<br /> <br /> 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. <br /> <br /> 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 published. <br /> <br /> 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.<br /> <br /> New Projects:<br /> 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.<br /> <br /> Laboratory Report:<br /> Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. <br /> <br /> Usefulness of the Findings:<br /> 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.<br /> <br /> Work Planned for Remainder of the Year:<br /> 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.<br /> <br /> Critical Review:<br /> 1. Work accomplished under the original project<br /> 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:<br /> a. Determination and prioritization of minor-use needs and data requirements.<br /> b. Review, analysis and evaluation of minor-use research proposals.<br /> c. Development and assembly of data for minor-use registrations.<br /> d. Preparation and submission of petitions for drug registrations. <br /> 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. <br /> <br /> 2. The degree to which objectives have been met<br /> 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.<br /> <br /> 3. Incomplete work or areas needing further investigation<br /> 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.<br /> <br /> NORTHEAST REGION: DR. PAUL BOWSER <br /> Progress of the work and principal accomplishments:<br /> <br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> 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).<br /> <br /> Work planned for next year:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> Data from the Ovadine work is being summarized for publication. We are also investigating the potential of indexing Ovadine. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> 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.<br /> 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.<br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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:<br /> To identify animal drug needs for minor species and minor uses in major species.<br /> To generate and disseminate data for safe and effective therapeutic applications, and<br /> To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met:<br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation:<br /> 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.<br /> <br /> North Central  Dr. Ronald W. Griffith<br /> Progress of the work and principal accomplishments<br /> <br /> Goat CIDR-G Tissue Residue<br /> 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. <br /> <br /> Goat CIDR-G Effectiveness<br /> 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.<br /> <br /> Lasalocid in Pheasants Efficacy<br /> The study was completed in 2007 and the study report submitted this summer. Undergoing final stages of review. Keeping fingers crossed.<br /> <br /> Lasalocid in Pheasants TAS<br /> A second high-dose group study was completed in July. The study report is currently being prepared. <br /> Draxxin Target Animal Safety in Goats<br /> The study report has been submitted to the FDA/CVM. Dr. Kris Clothier has a manuscript accepted by the Journal of Pharmacology and Therapeutics.<br /> <br /> Draxxin Tissue Residue<br /> Study report undergoing QA audit.<br /> <br /> Draxxin Efficacy in Goats<br /> 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.<br /> <br /> Fenbendazole TAS in Pheasants<br /> Protocol has been submitted to ONADE and is under final review. Birds are scheduled to arrive the third week in May.<br /> <br /> Fenbendazole HFS<br /> 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.<br /> <br /> Fenbendazole Reproductive Safety<br /> 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?<br /> <br /> Ivermectin Cattle Fever Tick Efficacy <br /> 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 <br /> Southern region where R. microplus is the species of tick.<br /> <br /> SOUTHERN  DR. THOMAS VICKROY<br /> Overview of Projects in Progress<br /> 1. ADR#352: Ivermectin Efficacy against Cattle Fever Tick in southern Texas <br /> 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.<br /> <br /> 2. ADR#279: Lasalocid for Coccidiosis in Pheasants <br /> 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.<br /> <br /> 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.<br /> <br /> Update on Other Programmatic Efforts and Changes<br /> 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.<br /> <br /> 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.<br />

Publications

Presentations<p><br /> Emily R. Cornwell, Geoffrey H. Groocock, Rodman G. Getchell, and Paul R. Bowser. 2010. Residual tannic acid destroys virucidal properties of iodine. North American Journal of Aquaculture 73(1):8-12.<br /> <br /> Grismer B, Rowe JD, Carlson J, Wetzlich S, Kieu H, Tell L. Pharmacokinetics of a single subcutaneous injection of tulathromycin in lactating dairy goats (Capra hircus). UC Davis STAR student presentation, September 24, 2011<br /> <br /> Rivera S, Tell L. Pharmacokinetics of ceftiofur crystalline free acid in sheep following subcutaneous single-dose administration. Proceedings of the 33rd Annual House Officer Seminar Day, VMTH, University of California Davis, Large Animal/Avian-Exotics/Lab Animal/Primate Presentations, March 11, 2011.<br /> <br /> Publications<p><br /> Doré E, Angelos JA, Rowe JD, Carlson JL, Wetzlich SE, Kieu HT, Tell LA. Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus). J Vet Pharmacol Ther, 34(1):25-30, 2011.<br /> <br /> Leavens TL, Tell LA, Clothier KA, Griffith RW, Baynes RE, Riviere JE. Development of physiologically based pharmacokinetic (PBPK) model to predict tulathromycin distribution in goats. The Toxicologist, 50th Annual Meeting of the Society of Toxicology Annual Meeting, Washington DC, Vol 120(2), March 2011.<br /> <br /> Romanet J, Smith GW, Leavens TL, Baynes RE, Wetzlich SE, Riviere JE, Tell, LA. Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats. In preparation. Planned submission to AJVR, 2011.<br /> <br /> Tell LA, Brooks JW, Lintner V, Matthews T, Kariyawasam S. Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia. J Vet Diagn Invest, 23(5):1009-1013, 2011.<br /> <br /> Topic Popovic, N., T. Howell, J.G. Babish and P.R. Bowser. 2011. Cross-sectional study of hepatic CYP1A and CYP3A enzymes in sunshine bass, channel catfish and Nile tilapia following oxytetracycline treatment. Research in Veterinary Science. In press.<br /> <br /> Young G, Smith GW, Leavens TL, Wetzlich SE, Baynes RE, Mason SE, Riviere JE, Tell LA. Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats. Res Vet Sci, 90(3):477-479, 2011.<br />

Impact Statements

1. 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.
2. The Environmental Assessment study data for erythromycin in salmonids INAD I-00613 were accepted by FDA Center for Veterinary Medicine on 1/12/11.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

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Report Information

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

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.

Accomplishments

NORTHEAST REGION: DR. PAUL BOWSER <br /> Progress of the work and principal accomplishments:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> <br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> 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).<br /> <br /> Work planned for next year:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> 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. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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. Our protocol is under review by CVM FDA.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> 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.<br /> 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. <br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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:<br /> To identify animal drug needs for minor species and minor uses in major species.<br /> To generate and disseminate data for safe and effective therapeutic applications, and<br /> To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/<br /> Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met: <br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation: <br /> 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.<br /> <br /> WESTERN  DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> ADR#325  Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. <br /> <br /> ADR#350  Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. Update 5/1/2012: Awaiting advice from CVM regarding how to move forward on this project or abort this project and go back to Nuflor Injectable Solution project.<br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#338  Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135  Erythromycin in Salmonids<br /> 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. Update 5/1/2012: Awaiting final amendment of EA by CVM.<br /> <br /> Collaborative Projects:<br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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. Update 5/1/2012: Waiting confirmation to be able to submit this study to CVM after QA audit at ISU. <br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. Update 5/1/2012: Awaiting update from Casandra Plummer to see if we need to enroll additional California dairy goats in the study summer of 2012. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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. <br /> <br /> Other Projects/Activities:<br /> 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.<br /> <br /> 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. <br /> <br /> Quality Assurance: Nothing to report.<br /> <br /> New Projects:<br /> 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. Update 5/1/2012: Manuscript in preparation. <br /> <br /> Laboratory Report:<br /> Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. <br /> Usefulness of the Findings:<br /> <br /> 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.<br /> <br /> Work Planned for Remainder of the Year:<br /> 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.<br /> <br /> Critical Review:<br /> 1. Work accomplished under the original project<br /> 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:<br /> a. Determination and prioritization of minor-use needs and data requirements.<br /> b. Review, analysis and evaluation of minor-use research proposals.<br /> c. Development and assembly of data for minor-use registrations.<br /> d. Preparation and submission of petitions for drug registrations. <br /> <br /> 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. <br /> <br /> 2. The degree to which objectives have been met<br /> 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.<br /> <br /> 3. Incomplete work or areas needing further investigation<br /> 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.<br /> <br /> NORTH CENTRAL  DR. RONALD W. GRIFFITH<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> <br /> Goat CIDR-G Effectiveness<br /> 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.<br /> <br /> Lasalocid in Pheasants TAS<br /> The study report has been submitted to the FDA/CVM.<br /> <br /> Draxxin Tissue Residue<br /> The study report is nearing submission.<br /> <br /> Draxxin Efficacy in Goats<br /> Trying to figure out what type of study will be acceptable to the FDA/CVM to demonstrate efficacy. <br /> <br /> Fenbendazole HFS<br /> The study report has been submitted for QA audit and should be submitted to the FDA/CVM soon.<br /> <br /> Fenbendazole TAS in Pheasants<br /> 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.<br /> <br /> Fenbendazole Reproductive Safety<br /> 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.<br /> <br /> Ivermectin Cattle Fever Tick Efficacy <br /> 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.<br /> <br /> Pregnant Mare Serum Gonadotrophin-ADR 0353<br /> 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. <br /> <br /> SOUTHERN  DR. THOMAS VICKROY<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> 1. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279)<br /> 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.<br /> <br /> 2. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352)<br /> 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. <br /> <br /> 3. Fenbendazole in Game Birds (ADR#280)<br /> 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.<br /> <br /> Update on Other Programmatic Efforts and Changes<br /> 1. NRSP-7 Website: <br /> 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. <br /> 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.<br /> <br /> <br />

Publications

PRESENTATIONS<br /> Breyer, K.E., R.G. Getchell, G.H. Groocock, L.L. Coffee, G.A. Wooster, P.R. Bowser, H..G. Ketola. 2012. Garlic (Allicin): More Than Just Flavor For Your Fish! 37th Annual Eastern Fish Health Workshop. Lake Placid, New York. 23-27 April 2012.<br /> <br /> PUBLICATIONS<br /> Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2012) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 35, 113-120.<br /> <br /> Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2012) Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos), J Vet Pharmacol Ther. (In Press)<br /> <br /> Groocock, G.H., Getchell, R.G., Cornwell, E.R. Frattini, S.A., Wooster, G.A. and Bowser, P.R. (2012) Iodophor Disinfection of Walleye Eggs Exposed to Viral Hemorrhagic Septicemia Virus type IVb. North American Journal of Aquaculture. (In Press)<br /> <br /> Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2012) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther 35, 121-131.<br /> <br /> Topic Popovic, N., T. Howell, J.G. Babish and P.R. Bowser. 2012. Cross-sectional study of hepatic CYP1A and CYP3A enzymes in sunshine bass, channel catfish and Nile tilapia following oxytetracycline treatment. Research in Veterinary Science 93:283-291<br /> <br />

Impact Statements

1. Through its collaborative efforts with the FDA Center for Veterinary Medicine, MUADP substantiates the safe and effective use of pharmaceutical products to minor species producers in the U.S., which allows them to remain competitive in the global marketplace. The U.S. imports a significant number of minor species food products and without the therapeutics provided through the research activity of the MUADP, the U.S. producers cannot remain competitive with foreign suppliers.
2. To date 351 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 Approval. Currently there are 18 active research projects involving nine animal species and 12 different drugs.
3. On July 1, 2011, the Food and Drug Administration (FDA) announced 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 data, contained in Public Master File (PMF) 5988, were compiled by the Minor Use Animal Drug Program/National Research Support Project 7.
4. In 2012, data from NRSP-7 was used in support of the FDA approval of Chloramine-T safety 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.
5. From inception to 2012, regional coordinators have published 162 peer-reviewed articles relating to the use of therapeutic drugs in minor species. Such publications benefit stakeholders by providing veterinarians with the necessary information to allow the extra-label use of these drugs on minor species.
6. Since its inception in 1982, Congress has appropriated only $11 million for the program. In return MUADP has generated publication of 36 Public Master Files (PMF) in the Federal Register, an average of 1.4 per year. These PMF have supported FDA approval for 42 drug products for use in minor food species.
7. Without the MUADP American producers of minor species would not have safe and effective products to keep their livestock healthy or their food products safe. Agricultural production of minor species is critically important to numerous regional economies in the U.S. This diverse aggregation of minor species represents approximately $4.4 billion in food and fiber farm gate revenues annually. Processing, use, and export of minor species food and fiber products represent an additional $34 billion economic impact to the U.S. Through a productive MUADP/NRSP-7, producers and veterinarians will continue to have the necessary information to prevent disease-related losses, to reduce pain and suffering in important species, and avoid contamination of our foods with drug residues.

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Report Information

Participants

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;

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;

Paul R. Bowser, MUADP/NRSP-7/Cornell.edu;

Ron Griffith, MUADP/NRSP-7/Iowa State, rgriffit@iastate.edu;

Thomas Vickroy, MUADP/NRSP-7/U FL, vickroy@vetmed.ufl.edu;

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).

Brief Summary of Minutes

12:00 PM INTRODUCTIONS 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 What’s 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, offical 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.
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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 Chairwoman’s 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 Chairman’s 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 we’d 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?

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.

OTHER BUSINESS

NONE BROUGHT FORWARD

SPRING Meeting It was tentatively decided to schedule the spring meeting in concert with the outcome 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.

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

RESPECTFULLY SUBMITTED: /s/ John G. Babish, Ph.D.
Date: 1/26/13
Minor Use Animal Drug Program/NRSP-7 National Coordinator

Accomplishments

REPORTS FROM THE REGIONS<br /> NORTHEAST REGION: DR. PAUL BOWSER <br /> Progress of the work and principal accomplishments:<br /> <br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> 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).<br /> <br /> Work planned for next year:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> 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. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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. Our protocol is under review by CVM FDA.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> 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.<br /> <br /> 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. <br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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. <br /> <br /> The mission of NRSP-7 is:<br /> To identify animal drug needs for minor species and minor uses in major species.<br /> To generate and disseminate data for safe and effective therapeutic applications, and<br /> To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/<br /> Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met: <br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation: <br /> 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.<br /> <br /> WESTERN – DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> ADR#325 – Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. <br /> <br /> ADR#350 – Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. Update 5/1/2012: Awaiting advice from CVM regarding how to move forward on this project or abort this project and go back to Nuflor Injectable Solution project.<br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#338 – Spectramast™ LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135 – Erythromycin in Salmonids<br /> 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. Update 5/1/2012: Awaiting final amendment of EA by CVM.<br /> Collaborative Projects:<br /> <br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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. Update 5/1/2012: Waiting confirmation to be able to submit this study to CVM after QA audit at ISU. <br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. Update 5/1/2012: Awaiting update from Casandra Plummer to see if we need to enroll additional California dairy goats in the study summer of 2013. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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. <br /> <br /> Other Projects/Activities:<br /> Quality Assurance: Nothing to report.<br /> <br /> 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.<br /> <br /> 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. <br /> <br /> New Projects:<br /> 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. Update 5/1/2012: Manuscript in preparation. <br /> <br /> Laboratory Report:<br /> Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. <br /> <br /> Usefulness of the Findings:<br /> 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.<br /> Work Planned for Remainder of the Year:<br /> 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.<br /> Critical Review:<br /> 1. Work accomplished under the original project<br /> 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:<br /> a. Determination and prioritization of minor-use needs and data requirements.<br /> b. Review, analysis and evaluation of minor-use research proposals.<br /> c. Development and assembly of data for minor-use registrations.<br /> d. Preparation and submission of petitions for drug registrations. <br /> 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. <br /> <br /> 2. The degree to which objectives have been met<br /> 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.<br /> <br /> 3. Incomplete work or areas needing further investigation<br /> 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.<br /> <br /> <br /> NORTH CENTRAL – DR. RONALD W. GRIFFITH<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> <br /> Goat CIDR-G Effectiveness<br /> 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.<br /> <br /> Lasalocid in Pheasants TAS<br /> The study report has been submitted to the FDA/CVM.<br /> <br /> Draxxin Tissue Residue<br /> The study report is nearing submission.<br /> <br /> Draxxin Efficacy in Goats<br /> Trying to figure out what type of study will be acceptable to the FDA/CVM to demonstrate efficacy. <br /> <br /> Fenbendazole HFS<br /> The study report has been submitted for QA audit and should be submitted to the FDA/CVM soon.<br /> <br /> Fenbendazole TAS in Pheasants<br /> 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.<br /> <br /> Fenbendazole Reproductive Safety<br /> 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 MacFarlane’s incubators. This information will be included as part of the Target Animal Safety study.<br /> <br /> Ivermectin Cattle Fever Tick Efficacy <br /> 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.<br /> <br /> Pregnant Mare Serum Gonadotrophin-ADR 0353<br /> 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. <br /> <br /> <br /> SOUTHERN – DR. THOMAS VICKROY<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> 1. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279)<br /> 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. <br /> <br /> 2. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352)<br /> 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. <br /> <br /> 3. Fenbendazole in Game Birds (ADR#280)<br /> 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.<br /> Update on Other Programmatic Efforts and Changes<br /> <br /> 1. NRSP-7 Website: <br /> 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. <br /> <br /> 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.<br />

Publications

Publications for Project Period 10/09 to 11/12<br /> 1. Topic Popovic, N., Howell, T., Babish, J. G., and Bowser, P. R. (2012) Cross-sectional study of hepatic CYP1A and CYP3A enzymes in hybrid striped bass, channel catfish and Nile tilapia following oxytetracycline treatment, Res Vet Sci 92, 283-291.<br /> <br /> 2. Tell, L. A., Stephens, K., Teague, S. V., Pinkerton, K. E., and Raabe, O. G. (2012) Study of nebulization delivery of aerosolized fluorescent microspheres to the avian respiratory tract, Avian Dis 56, 381-386.<br /> <br /> 3. Romanet, J., Smith, G. W., Leavens, T. L., Baynes, R. E., Wetzlich, S. E., Riviere, J. E., and Tell, L. A. (2012) Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats, Am J Vet Res 73, 1634-1640.<br /> <br /> 4. Mehl, M. L., Tell, L., Kyles, A. E., Chen, Y. J., Craigmill, A., and Gregory, C. R. (2012) Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats, J Vet Pharmacol Ther 35, 139-146.<br /> <br /> 5. Lee, K. A., Tell, L. A., and Mohr, F. C. (2012) Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos), Avian Dis 56, 704-710.<br /> <br /> 6. Leclere, M., Magdesian, K. G., Cole, C. A., Szabo, N. J., Ruby, R. E., Rhodes, D. M., Edman, J., Vale, A., Wilson, W. D., and Tell, L. A. (2012) Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses, J Vet Pharmacol Ther 35, 541-549.<br /> <br /> 7. Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2012) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther 35, 121-131.<br /> <br /> 8. Hope, K. L., Tell, L. A., Byrne, B. A., Murray, S., Wetzlich, S. E., Ware, L. H., Lynch, W., Padilla, L. R., and Boedeker, N. C. (2012) Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in American black ducks (Anas rubripes), Am J Vet Res 73, 620-627.<br /> <br /> 9. Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2012) Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos), J Vet Pharmacol Ther.<br /> <br /> 10. Cornwell, E. R., Anderson, G. B., Wooster, G. A., Getchell, R. G., Groocock, G. H., Casey, J. W., Bain, M. B., and Bowser, P. R. (2012) Low prevalence of Cyprinid Herpesvirus 3 Found in common carp (Cyprinus carpio carpio) collected from nine locations in the Great Lakes, J Wildl Dis 48, 1092-1096.<br /> <br /> 11. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2012) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 35, 113-120.<br /> <br /> 12. Bowser, P. R., Casey, J. W., Casey, R. N., Quackenbush, S. L., Lofton, L., Coll, J. A., and Cipriano, R. C. (2012) Swimbladder Leiomyosarcoma in Atlantic salmon (Salmo salar) in North America, J Wildl Dis 48, 795-798.<br /> <br /> 13. Young, G., Smith, G. W., Leavens, T. L., Wetzlich, S. E., Baynes, R. E., Mason, S. E., Riviere, J. E., and Tell, L. A. (2011) Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats, Res Vet Sci 90, 477-479.<br /> <br /> 14. White, S. D., Bourdeau, P., Bruet, V., Kass, P. H., Tell, L., and Hawkins, M. G. (2011) Reptiles with dermatological lesions: a retrospective study of 301 cases at two university veterinary teaching hospitals (1992-2008), Veterinary dermatology 22, 150-161.<br /> <br /> 15. Tell, L. A., Brooks, J. W., Lintner, V., Matthews, T., and Kariyawasam, S. (2011) Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia, J Vet Diagn Invest 23, 1009-1013.<br /> <br /> 16. Strunk, A., Imai, D. M., Osofsky, A., and Tell, L. A. (2011) Dysgerminoma in an eastern rosella (Platycercus eximius eximius), Avian Dis 55, 133-138.<br /> <br /> 17. Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2011) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther.<br /> <br /> 18. Kline, Y., Clemons, K. V., Woods, L., Stevens, D. A., and Tell, L. A. (2011) Pharmacokinetics of voriconazole in adult mallard ducks (Anas platyrhynchos), Medical mycology 49, 500-512.<br /> <br /> 19. Hawkins, M. G., Taylor, I. T., Byrne, B. A., Armstrong, R. D., and Tell, L. A. (2011) Pharmacokinetic-pharmacodynamic integration of orbifloxacin in Japanese quail (Coturnix japonica) following oral and intravenous administration, J Vet Pharmacol Ther 34, 350-358.<br /> <br /> 20. Goetting, V., Lee, K. A., and Tell, L. A. (2011) Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature, J Vet Pharmacol Ther 34, 521-556.<br /> <br /> 21. Dore, E., Angelos, J. A., Rowe, J. D., Carlson, J. L., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2011) Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 34, 25-30.<br /> <br /> 22. Cornwell, E. R., Eckerlin, G. E., Getchell, R. G., Groocock, G. H., Thompson, T. M., Batts, W. N., Casey, R. N., Kurath, G., Winton, J. R., Bowser, P. R., Bain, M. B., and Casey, J. W. (2011) Detection of viral hemorrhagic septicemia virus by quantitative reverse transcription polymerase chain reaction from two fish species at two sites in Lake Superior, J Aquat Anim Health 23, 207-217.<br /> <br /> 23. Cornwell, E. R., Cinelli, M. J., McIntosh, D. M., Blank, G. S., Wooster, G. A., Groocock, G. H., Getchell, R. G., and Bowser, P. R. (2011) Epizootic Nocardia infection in cultured weakfish, Cynoscion regalis (Bloch and Schneider), J Fish Dis 34, 567-571.<br /> <br /> 24. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 34, 448-454.<br /> <br /> 25. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther.<br /> <br /> 26. Young, G., Smith, G. W., Leavens, T. L., Wetzlich, S. E., Baynes, R. E., Mason, S. E., Riviere, J. E., and Tell, L. A. (2010) Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats, Res Vet Sci.<br /> <br /> 27. Tell, L. A., Clemons, K. V., Kline, Y., Woods, L., Kass, P. H., Martinez, M., and Stevens, D. A. (2010) Efficacy of voriconazole in Japanese quail (Coturnix japonica) experimentally infected with Aspergillus fumigatus, Medical mycology 48, 234-244.<br /> <br /> 28. Rowe, J. D., Tell, L. A., Carlson, J. L., Griffith, R. W., Lee, K., Kieu, H., Wetzlich, S., and Hallford, D. (2010) Progesterone milk residues in goats treated with CIDR-G((R)) inserts, J Vet Pharmacol Ther 33, 605-609.<br /> <br /> 29. Hope, K. M., Casey, R. N., Groocock, G. H., Getchell, R. G., Bowser, P. R., and Casey, J. W. (2010) Comparison of quantitative RT-PCR with cell culture to detect viral hemorrhagic septicemia virus (VHSV) IVb infections in the Great Lakes, J Aquat Anim Health 22, 50-61.<br /> <br /> 30. Clothier, K. A., Jordan, D. M., Loynachan, A. T., and Griffith, R. W. (2010) Safety evaluation of tulathromycin use in the caprine species: tulathromycin toxicity assessment in goats, J Vet Pharmacol Ther 33, 499-502.<br /> <br /> 31. Bain, M. B., Cornwell, E. R., Hope, K. M., Eckerlin, G. E., Casey, R. N., Groocock, G. H., Getchell, R. G., Bowser, P. R., Winton, J. R., Batts, W. N., Cangelosi, A., and Casey, J. W. (2010) Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping, PLoS One 5, e10156.<br /> <br /> 32. Spitsbergen, J. M., Blazer, V. S., Bowser, P. R., Cheng, K. C., Cooper, K. R., Cooper, T. K., Frasca, S., Jr., Groman, D. B., Harper, C. M., Law, J. M., Marty, G. D., Smolowitz, R. M., St Leger, J., Wolf, D. C., and Wolf, J. C. (2009) Finfish and aquatic invertebrate pathology resources for now and the future, Comp Biochem Physiol C Toxicol Pharmacol 149, 249-257.<br /> <br /> 33. Rowe, J. D., Tell, L. A., and Wagner, D. C. (2009) Animal safety report on intravaginal progesterone controlled internal drug releasing devices in sheep and goats, J Vet Pharmacol Ther 32, 303-305.<br /> <br /> 34. Nguyen, K. Q., Hawkins, M. G., Taylor, I. T., Wiebe, V. J., and Tell, L. A. (2009) Stability and uniformity of extemporaneous preparations of voriconazole in two liquid suspension vehicles at two storage temperatures, Am J Vet Res 70, 908-914.<br /> <br /> 35. Kosoff, R. E., Chen, C. Y., Wooster, G. A., Getchell, R. G., Bowser, P. R., Clifford, A., Craig, J. L., Lim, P., Wetzlich, S. E., Craigmill, A. L., and Tell, L. A. (2009) Florfenicol residues in three species of fish after 10-day oral dosing in feed, J Aquat Anim Health 21, 8-13.<br /> <br /> 36. Davis, J. L., Smith, G. W., Baynes, R. E., Tell, L. A., Webb, A. I., and Riviere, J. E. (2009) Update on drugs prohibited from extralabel use in food animals, J Am Vet Med Assoc 235, 528-534.<br /> <br /> 37. Bowser, P. R., Kosoff, R. E., Chen, C. Y., Wooster, G. A., Getchell, R. G., Craig, J. L., Lim, P., Wetzlich, S. E., Craigmill, A. L., and Tell, L. A. (2009) Florfenicol residues in Nile tilapia after 10-d oral dosing in feed: effect of fish size, J Aquat Anim Health 21, 14-17.<br /> <br /> 38. Smith, G. W., Davis, J. L., Tell, L. A., Webb, A. I., and Riviere, J. E. (2008) Extralabel use of nonsteroidal anti-inflammatory drugs in cattle, J Am Vet Med Assoc 232, 697-701.<br /> <br />

Impact Statements

1. Through its collaborative efforts with the FDA Center for Veterinary Medicine, MUADP substantiates the safe and effective use of pharmaceutical products to minor species producers in the U.S., which allows them to remain competitive in the global marketplace. The U.S. imports a significant number of minor species food products and without the therapeutics provided through the research activity of the MUADP, the U.S. producers cannot remain competitive with foreign suppliers.
2. To date 351 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 Approval. Currently there are 18 active research projects involving nine animal species and 12 different drugs.
3. On July 1, 2011, the Food and Drug Administration (FDA) announced 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 data, contained in Public Master File (PMF) 5988, were compiled by the Minor Use Animal Drug Program/National Research Support Project 7.
4. In 2012, data from NRSP-7 was used in support of the FDA approval of Chloramine-T safety 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.
5. From inception to 2012, regional coordinators have published 162 peer-reviewed articles relating to the use of therapeutic drugs in minor species. Such publications benefit stakeholders by providing veterinarians with the necessary information to allow the extra-label use of these drugs on minor species.
6. Since its inception in 1982, Congress has appropriated only $11 million for the program. In return MUADP has generated publication of 36 Public Master Files (PMF) in the Federal Register, an average of 1.4 per year. These PMF have supported FDA approval for 42 drug products for use in minor food species.
7. Without the MUADP American producers of minor species would not have safe and effective products to keep their livestock healthy or their food products safe. Agricultural production of minor species is critically important to numerous regional economies in the U.S. This diverse aggregation of minor species represents approximately $4.4 billion in food and fiber farm gate revenues annually. Processing, use, and export of minor species food and fiber products represent an additional $34 billion economic impact to the U.S. Through a productive MUADP/NRSP-7, producers and veterinarians will continue to have the necessary information to prevent disease-related losses, to reduce pain and suffering in important species, and avoid contamination of our foods with drug residues.

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Report Information

Participants

Amy Omer, FDA/CVM, Amy.Omer@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;
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;
Paul R. Bowser, MUADP/NRSP-7/Cornell.edu;
Phil Elzer, AA/LSU Ag Center, Pelzer@agcenter.lsu.edu;
Rod Getchell, MUADP/NRSP-7/Cornell U, rgg4@cornell.edu;
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

12:00 PM INTRODUCTIONS
Introductions and meeting organization
Dr. John G. Babish started the meeting with a thank you to Drs. Omar and Bailey for their 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 NIFA/USDA, Administrative Advisors, and National Coordinator.

NIFA/USDA – Dr. Gary Sherman
1). Historically, MUADP/NRSP-7 enjoyed line item Special Grant funding from Congress (administered under NIFA's special grant authority) but this ended 3 years ago when 'earmarks' were greatly reduced.

2) MUADP/NRSP-7 is currently supported by Hatch funding. It was by virtue of the Program's legitimacy as an NRSP that, when special grant funding ended, there was a secondary (Hatch) Authority under which some funding could be made available to the program, at the discretion of the directors of the system of US Agricultural Experiment Stations (AESs).

3) NIFA and Congress continue to support and fund the Hatch program. The Hatch Act authority provides funds to be distributed by NIFA on a formula basis to Ag Experiment Stations co-located at Land Grant colleges and universities. NRSPs and MultiState Committees, proposed and administered by AES Directors, are supported as a specified apportionment from Hatch funds. AES directors determine levels of funding for NRSPs and Multi-State Committees based on available funds.

4) NIFA Budget cuts for 2013 include loss of $180 M in mandatory funding that was not renewed, and the effects of Sequester. The ~18% overall cut to NIFA is expected to be applied roughly evenly across all NIFA programs. The Hatch program will likely experience this % decrease and this should be expected to impact Hatch sub-programming like NRSPs.

5) Efforts continue to search for a Western Region Administrative advisor for NRSP-7

6) NIFA is cognizant of the exploratory efforts underway related to a possible merger with IR-4. The Agency will consider consensus restructuring possibilities if and when the leaderships of both NRSP-7 and IR-4/NRSP-4 come to one or more mutually agreed upon potential merger strategy(ies).

7) Dr. Sherman, NIFA Liaison to NRSP-7, reminded the group that Secretary Vilsack and President Obama continue to strongly support revitalization of rural America. It is therefore appropriate to emphasize the roll of the MUADP in supporting a diversified, growing and vibrant rural economy.

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 shared his outline of a proposed evaluation for merging the IR-4 Minor Use Pesticide Program with the Minor Use Animal Drug Program. These steps were presented in the outline form below to the group.

Merging the MUADP/NRSP-7 into the IR-4 Minor Use Pesticide Program in Three Steps

Relationship #1
MUADP and IR-4 Share Some Resources – Primary goal is to develop a greater understanding of the working of the two organizations

MUADP Include pesticides into the Mission Statement as below

• To identify animal drug and pesticide 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.

Action Items:

1. Identify immediate and long-term pesticide needs for minor species.

2. MUADP and IR-4 Establish Informal Relationship between MUADP Regional Coordinators and IR-4 GLP units.

a. Identify IR-4 GLP units capable of performing audits and reviews of current studies
b. Can the IR-4 GLP units satisfy FDA/CVM requirements for MUADP
c. Costing of IR-4 GLP audits

3. Identify RFPs to fund a joint drug/pesticide program

4. Continue efforts to incorporate both programs into the FY 12 Farm Bill

5. Establish relationship with shareholders of a joint program

6. Make decision on moving to #2 or #3 below in 3 months and incorporate this decision into the MUADP renewal plans.

Relationship #2
MUADP and IR-4 Begin integration of work

Modify Mission Statement accordingly

• To identify animal drug and pesticide needs for minor species and minor uses in major species,

• To generate and disseminate data for safe and effective therapeutic applications of drugs and pesticides, and

• To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.

Action Items:
1. MUADP and IR-4 develop a list of potential animal pesticide projects for FDA/CVM and EPA approvals

2. MUADP establishes contacts at EPA

3. Assessment of protocols and resources necessary to begin the merger of the two programs

4. Explore AES and NIFA mechanisms for joining the programs.
Relationship #3

Complete inclusion of pesticides into the Mission Statement

• To identify animal drug and pesticide needs for minor species and minor uses in major species,

• To generate and disseminate data for safe and effective therapeutic applications of drugs and pesticides, and

• To facilitate FDA/CVM and EPA approvals for drugs and pesticides identified as a priority for a minor species or minor use.

Action Items:

1. MUADP and IR-4 more forward on either or both AES and NIFA paths for funding.

OTHER BUSINESS
NONE BROUGHT FORWARD

FALL Meeting
The final decision on the timing of the meeting will be made when the federal budget situation becomes clearer and discussed at monthly teleconferences.

As there was no further business, the meeting was adjourned at 2:45 pm.

RESPECTFULLY SUBMITTED:
/s/John G. Babish, Ph.D. Date: 6/30/13
Minor Use Animal Drug Program/NRSP-7 National Coordinator

Accomplishments

REPORTS FROM THE REGIONS<br /> WESTERN – DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> <br /> ADR#325/INAD 10-958 – Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. Update 04/2013: No new progress on this project.<br /> <br /> ADR#350 – Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. Update 04/2130: No new progress on this project.<br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#338 – Spectramast™ LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135 – Erythromycin in Salmonids<br /> 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. Update 04/2013: Awaiting final amendment of EA by CVM.<br /> <br /> Collaborative Projects:<br /> <br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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). Update 04/2013: HFS report received concurrence from CVM, April 2014.<br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. Update 04/2013: Nothing new to report. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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 04/2013: In March, 2013 an ERA amendment was requested by CVM for the HFS technical report but this study will result in a technical section incomplete due to some analytical challenges and freezer stability requirements. <br /> <br /> Other Projects/Activities:<br /> Quality Assurance: Since the Fall of 2012, we had a FDA Inspection and our efforts have been focused on addressing SOP revisions and internal operations. <br /> <br /> 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 completed. Manuscript being resubmitted to another journal as JVPT would only accept as a brief communication. <br /> <br /> 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. Update 11/2012: This method has been validated for goats and cattle. All of the samples have been analyzed. Manuscript in preparation.<br /> <br /> Another study is being initiated to evaluate flunixin use in goats and milk residues. <br /> Plasma samples from a goat study study lead by Jamie Boehmer at the Office of Research evaluating inflammatory markers and flunixin are currently being analyzed. Dr. Tell is in contact with Dr. Boehmer to get this study published. <br /> <br /> Tulathromycin pharmacokinetics in dairy goats: A UC Davis summer student, Bernadette Grismer, performed this study. A total of 448 samples (328 milk; 120 plasma) have been analyzed. Update 04/2013: Manuscript complete. Submission in process.<br /> <br /> Laboratory Report:<br /> Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. <br /> <br /> Usefulness of the Findings:<br /> 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.<br /> <br /> Work Planned for Remainder of the Year:<br /> Goat banamine milk residue study (non GLP), tulathromycin multidose goat study (non GLP), and get all protocols and SOPs in order and accordance with FDA Fall 2012 audit.<br /> <br /> Critical Review:<br /> 1. Work accomplished under the original project<br /> 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:<br /> <br /> a. Determination and prioritization of minor-use needs and data requirements.<br /> b. Review, analysis and evaluation of minor-use research proposals.<br /> c. Development and assembly of data for minor-use registrations.<br /> d. Preparation and submission of petitions for drug registrations. <br /> <br /> 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. <br /> <br /> 2. The degree to which objectives have been met<br /> 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.<br /> <br /> 3. Incomplete work or areas needing further investigation<br /> 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.<br /> <br /> NORTH CENTRAL – DR. RONALD W. GRIFFITH<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> <br /> Goat CIDR-G Effectiveness<br /> The study report is still in preparation. <br /> <br /> Lasalocid in Pheasants Target Animal Safety<br /> We have a technical section incomplete letter from ONADE. The problems should be correctable and re-submission of an amended report is scheduled. The work has been published in the Avian Diseases journal.<br /> <br /> Lasalocid in Pheasants Human Food Safety<br /> The study protocol for the in-life phase at Iowa State was submitted from the Southern Region and we have received protocol concurrence. The FDA had questions on the analytical method and we had planned to complete method validation beginning in June, 2013. The method validation is on-hold pending guidance from the FDA primarily concerning requirements for a quality assurance unit. It probably will not be possible to complete the method validation this year.<br /> <br /> Draxxin Tissue Residue<br /> ONADE asked for additional data and clarification for the study report. The Western Region is leading the response effort.<br /> <br /> Draxxin Efficacy in Goats<br /> This is now largely in the hands of the FDA/CVM. <br /> <br /> Fenbendazole Human Food Safety in Pheasants<br /> The Western and North Central Regions combined to do this study. We were recently informed that this technical section is complete. <br /> <br /> Fenbendazole Target Animal Safety in Pheasants<br /> We received a technical section incomplete letter on the study report. Additional data, clarification and justification of study procedures will be necessary. The reproductive safety portion of the work was not acceptable but the label will just state that reproductive safety has not been demonstrated. A paper covering this work and the reproductive safety data has been submitted to Avian Diseases.<br /> <br /> Ivermectin Cattle Fever Tick Efficacy <br /> 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 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 the ticks appear to have been completely eradicated from those animals and the pasture they were on. Treatment of a second herd infested with Rhipicephalus annulatus began in April 2012. Bulls were added to that herd after the start of the treatment regimen in the cows. The bulls were not ingesting the medicated protein/mineral blocks and remained infested for a period of time during the early breeding season. However, this herd and pasture is now considered to be free of cattle fever ticks.. A study at a third herd will begin when the tick burden becomes high enough. The quarantine zone remains under extreme drought conditions. We are planning on having a quality assurance monitor re-visit the project and do a more extensive monitoring of the study. The right of reference from Merial is remains unresolved.<br /> <br /> Pregnant Mare Serum Gonadotrophin-ADR 0353<br /> 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. No further action at this point.<br /> <br /> SOUTHERN – DR. THOMAS VICKROY<br /> Progress of Work and Principal Accomplishments:<br /> <br /> 1. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279)<br /> This project is a collaborative effort between the North-Central Region (Iowa State University) and the Southern Region (University of Florida) of MUADP. A tissue residue depletion study protocol (number 2012-235-HFS) was submitted in September to the INAD exemption file for a project to investigate the use of lasalocid (Avatec®) Type A medicated article for the control of coccidiosis associated with infection by Eimeria colchici, E. duodenalis or E. phasiani in pheasants. The protocol is currently under review with a response expected within the next one to two weeks. If approved, the study will be performed jointly by the North-Central and Southern regions. The in-life phase of studies will be conducted at Iowa State under the supervision of Dr. Ron Griffith and the Southern Region will carry out marker (lasaloicd) residue analyses of all tissue samples. Pending CVM concurrence with the study protocol and the analytical method, this project is tentatively set to begin with the in-life phase studies in late Spring of 2013.<br /> <br /> 2. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352)<br /> This 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. Preliminary work at the Southern Region has continued on this project, although the project faces several major hurdles before it can be considered for possible concurrence by the CVM. The primary role of the Southern Region has been to determine levels of ivermectin in medicated feed blocks that are formulated by the Texas-based company Postive Feeds, Inc. These blocks, which will be used for oral drug delivery to free-range cattle in pastures, contain a complex mixture of nutrients, minerals and numerous other ingredients, including molasses as a taste enhancer. We have adapted the approved regulatory method for ivermectin analysis to determine ivermectin levels in formulated feed blocks. During the past six months, we have continued to determine ivermectin content in block samples from different lots of medicated blocks. Based on our preliminary work, it appears that Postive Feeds has developed a manufacturing process that yields fairly consistent drug levels throughout the block matrix, although work continues on that front. <br /> <br /> 3. Fenbendazole in Game Birds (ADR#280)<br /> 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.<br /> <br /> Update on Other Programmatic Efforts and Changes<br /> <br /> 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 helps organize monthly teleconferences among the regional coordinators and administrators. The next teleconference is scheduled to be held in May 2013.<br /> <br /> 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.<br /> <br /> Summary Review of Progress<br /> <br /> 1. Work accomplished under the original project - the objective of this program is to conduct safety, efficacy or residue-related studies that facilitate drug clearances (tolerances, exemptions and registrations)for minor and specialty food animal species. This work is conducted in cooperation with appropriate state, federal and industry personnel to (a) determine and prioritize minor-use needs and data requirements, (b) review, analyze and evaluate minor-use species research proposals, (c) develop and organize data for minor-use animal species drug registrations, and (d) prepare and submit petitions for drug registrations. <br /> <br /> 2. The degree to which objectives have been met – Relative to the aforementioned objectives, considerable progress has been made for each of the active projects listed above. However, the degree to which these objectives have been met varies from project to project. 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.<br /> <br /> 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 Southern 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.<br /> <br /> NORTHEAST REGION: DR. PAUL BOWSER <br /> Progress of the work and principal accomplishments:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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. Two manuscripts on this work have been published in the peer-reviewed literature.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> In all cases, the findings to date over the course of these projects serve as the foundation for continued work on these compounds. <br /> <br /> Work planned for next year:<br /> <br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> 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. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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. Our protocol is under review by CVM FDA.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> 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.<br /> 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. <br /> Publications issued or manuscripts approved during the year: (see “Principal Publications” at end of report)<br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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:<br /> To identify animal drug needs for minor species and minor uses in major species.<br /> To generate and disseminate data for safe and effective therapeutic applications, and<br /> To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/ Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met: <br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation: <br /> 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.<br /> <br /> <br /> <br />

Publications

1. Topic Popovic, N., Howell, T., Babish, J. G., and Bowser, P. R. (2012) Cross-sectional study of hepatic CYP1A and CYP3A enzymes in hybrid striped bass, channel catfish and Nile tilapia following oxytetracycline treatment, Res Vet Sci 92, 283-291.<br /> <br /> 2. Tell, L. A., Stephens, K., Teague, S. V., Pinkerton, K. E., and Raabe, O. G. (2012) Study of nebulization delivery of aerosolized fluorescent microspheres to the avian respiratory tract, Avian Dis 56, 381-386.<br /> <br /> 3. Romanet, J., Smith, G. W., Leavens, T. L., Baynes, R. E., Wetzlich, S. E., Riviere, J. E., and Tell, L. A. (2012) Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats, Am J Vet Res 73, 1634-1640.<br /> <br /> 4. Mehl, M. L., Tell, L., Kyles, A. E., Chen, Y. J., Craigmill, A., and Gregory, C. R. (2012) Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats, J Vet Pharmacol Ther 35, 139-146.<br /> <br /> 5. Lee, K. A., Tell, L. A., and Mohr, F. C. (2012) Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos), Avian Dis 56, 704-710.<br /> <br /> 6. Leclere, M., Magdesian, K. G., Cole, C. A., Szabo, N. J., Ruby, R. E., Rhodes, D. M., Edman, J., Vale, A., Wilson, W. D., and Tell, L. A. (2012) Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses, J Vet Pharmacol Ther 35, 541-549.<br /> <br /> 7. Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2012) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther 35, 121-131.<br /> <br /> 8. Hope, K. L., Tell, L. A., Byrne, B. A., Murray, S., Wetzlich, S. E., Ware, L. H., Lynch, W., Padilla, L. R., and Boedeker, N. C. (2012) Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in American black ducks (Anas rubripes), Am J Vet Res 73, 620-627.<br /> <br /> 9. Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2012) Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos), J Vet Pharmacol Ther.<br /> <br /> 10. Cornwell, E. R., Anderson, G. B., Wooster, G. A., Getchell, R. G., Groocock, G. H., Casey, J. W., Bain, M. B., and Bowser, P. R. (2012) Low prevalence of Cyprinid Herpesvirus 3 Found in common carp (Cyprinus carpio carpio) collected from nine locations in the Great Lakes, J Wildl Dis 48, 1092-1096.<br /> <br /> 11. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2012) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 35, 113-120.<br /> <br /> 12. Bowser, P. R., Casey, J. W., Casey, R. N., Quackenbush, S. L., Lofton, L., Coll, J. A., and Cipriano, R. C. (2012) Swimbladder Leiomyosarcoma in Atlantic salmon (Salmo salar) in North America, J Wildl Dis 48, 795-798.<br /> <br /> 13. Young, G., Smith, G. W., Leavens, T. L., Wetzlich, S. E., Baynes, R. E., Mason, S. E., Riviere, J. E., and Tell, L. A. (2011) Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats, Res Vet Sci 90, 477-479.<br /> <br /> 14. White, S. D., Bourdeau, P., Bruet, V., Kass, P. H., Tell, L., and Hawkins, M. G. (2011) Reptiles with dermatological lesions: a retrospective study of 301 cases at two university veterinary teaching hospitals (1992-2008), Veterinary dermatology 22, 150-161.<br /> <br /> 15. Tell, L. A., Brooks, J. W., Lintner, V., Matthews, T., and Kariyawasam, S. (2011) Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia, J Vet Diagn Invest 23, 1009-1013.<br /> <br /> 16. Strunk, A., Imai, D. M., Osofsky, A., and Tell, L. A. (2011) Dysgerminoma in an eastern rosella (Platycercus eximius eximius), Avian Dis 55, 133-138.<br /> <br /> 17. Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., and Riviere, J. E. (2011) Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats, J Vet Pharmacol Ther.<br /> <br /> 18. Kline, Y., Clemons, K. V., Woods, L., Stevens, D. A., and Tell, L. A. (2011) Pharmacokinetics of voriconazole in adult mallard ducks (Anas platyrhynchos), Medical mycology 49, 500-512.<br /> <br /> 19. Hawkins, M. G., Taylor, I. T., Byrne, B. A., Armstrong, R. D., and Tell, L. A. (2011) Pharmacokinetic-pharmacodynamic integration of orbifloxacin in Japanese quail (Coturnix japonica) following oral and intravenous administration, J Vet Pharmacol Ther 34, 350-358.<br /> <br /> 20. Goetting, V., Lee, K. A., and Tell, L. A. (2011) Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature, J Vet Pharmacol Ther 34, 521-556.<br /> <br /> 21. Dore, E., Angelos, J. A., Rowe, J. D., Carlson, J. L., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2011) Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 34, 25-30.<br /> <br /> 22. Cornwell, E. R., Eckerlin, G. E., Getchell, R. G., Groocock, G. H., Thompson, T. M., Batts, W. N., Casey, R. N., Kurath, G., Winton, J. R., Bowser, P. R., Bain, M. B., and Casey, J. W. (2011) Detection of viral hemorrhagic septicemia virus by quantitative reverse transcription polymerase chain reaction from two fish species at two sites in Lake Superior, J Aquat Anim Health 23, 207-217.<br /> <br /> 23. Cornwell, E. R., Cinelli, M. J., McIntosh, D. M., Blank, G. S., Wooster, G. A., Groocock, G. H., Getchell, R. G., and Bowser, P. R. (2011) Epizootic Nocardia infection in cultured weakfish, Cynoscion regalis (Bloch and Schneider), J Fish Dis 34, 567-571.<br /> <br /> 24. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther 34, 448-454.<br /> <br /> 25. Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Tell, L. A. (2011) Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus), J Vet Pharmacol Ther.<br /> <br /> 26. Young, G., Smith, G. W., Leavens, T. L., Wetzlich, S. E., Baynes, R. E., Mason, S. E., Riviere, J. E., and Tell, L. A. (2010) Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats, Res Vet Sci.<br /> <br /> 27. Tell, L. A., Clemons, K. V., Kline, Y., Woods, L., Kass, P. H., Martinez, M., and Stevens, D. A. (2010) Efficacy of voriconazole in Japanese quail (Coturnix japonica) experimentally infected with Aspergillus fumigatus, Medical mycology 48, 234-244.<br /> <br /> 28. Rowe, J. D., Tell, L. A., Carlson, J. L., Griffith, R. W., Lee, K., Kieu, H., Wetzlich, S., and Hallford, D. (2010) Progesterone milk residues in goats treated with CIDR-G((R)) inserts, J Vet Pharmacol Ther 33, 605-609.<br /> <br /> 29. Hope, K. M., Casey, R. N., Groocock, G. H., Getchell, R. G., Bowser, P. R., and Casey, J. W. (2010) Comparison of quantitative RT-PCR with cell culture to detect viral hemorrhagic septicemia virus (VHSV) IVb infections in the Great Lakes, J Aquat Anim Health 22, 50-61.<br /> <br /> 30. Clothier, K. A., Jordan, D. M., Loynachan, A. T., and Griffith, R. W. (2010) Safety evaluation of tulathromycin use in the caprine species: tulathromycin toxicity assessment in goats, J Vet Pharmacol Ther 33, 499-502.<br /> <br /> 31. Bain, M. B., Cornwell, E. R., Hope, K. M., Eckerlin, G. E., Casey, R. N., Groocock, G. H., Getchell, R. G., Bowser, P. R., Winton, J. R., Batts, W. N., Cangelosi, A., and Casey, J. W. (2010) Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping, PLoS One 5, e10156.<br /> <br /> 32. Spitsbergen, J. M., Blazer, V. S., Bowser, P. R., Cheng, K. C., Cooper, K. R., Cooper, T. K., Frasca, S., Jr., Groman, D. B., Harper, C. M., Law, J. M., Marty, G. D., Smolowitz, R. M., St Leger, J., Wolf, D. C., and Wolf, J. C. (2009) Finfish and aquatic invertebrate pathology resources for now and the future, Comp Biochem Physiol C Toxicol Pharmacol 149, 249-257.<br /> <br /> 33. Rowe, J. D., Tell, L. A., and Wagner, D. C. (2009) Animal safety report on intravaginal progesterone controlled internal drug releasing devices in sheep and goats, J Vet Pharmacol Ther 32, 303-305.<br /> <br /> 34. Nguyen, K. Q., Hawkins, M. G., Taylor, I. T., Wiebe, V. J., and Tell, L. A. (2009) Stability and uniformity of extemporaneous preparations of voriconazole in two liquid suspension vehicles at two storage temperatures, Am J Vet Res 70, 908-914.<br /> <br /> 35. Kosoff, R. E., Chen, C. Y., Wooster, G. A., Getchell, R. G., Bowser, P. R., Clifford, A., Craig, J. L., Lim, P., Wetzlich, S. E., Craigmill, A. L., and Tell, L. A. (2009) Florfenicol residues in three species of fish after 10-day oral dosing in feed, J Aquat Anim Health 21, 8-13.<br /> <br /> 36. Davis, J. L., Smith, G. W., Baynes, R. E., Tell, L. A., Webb, A. I., and Riviere, J. E. (2009) Update on drugs prohibited from extralabel use in food animals, J Am Vet Med Assoc 235, 528-534.<br /> <br /> 37. Bowser, P. R., Kosoff, R. E., Chen, C. Y., Wooster, G. A., Getchell, R. G., Craig, J. L., Lim, P., Wetzlich, S. E., Craigmill, A. L., and Tell, L. A. (2009) Florfenicol residues in Nile tilapia after 10-d oral dosing in feed: effect of fish size, J Aquat Anim Health 21, 14-17.<br /> <br /> 38. Smith, G. W., Davis, J. L., Tell, L. A., Webb, A. I., and Riviere, J. E. (2008) Extralabel use of nonsteroidal anti-inflammatory drugs in cattle, J Am Vet Med Assoc 232, 697-701.<br /> <br />

Impact Statements

1. Through its collaborative efforts with the FDA Center for Veterinary Medicine, MUADP substantiates the safe and effective use of pharmaceutical products to minor species producers in the U.S., which allows them to remain competitive in the global marketplace. The U.S. imports a significant number of minor species food products and without the therapeutics provided through the research activity of the MUADP, the U.S. producers cannot remain competitive with foreign suppliers.
2. To date 351 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 Approval. Currently there are 18 active research projects involving nine animal species and 12 different drugs.
3. On July 1, 2011, the Food and Drug Administration (FDA) announced 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 data, contained in Public Master File (PMF) 5988, were compiled by the Minor Use Animal Drug Program/National Research Support Project 7.
4. In 2012, data from NRSP-7 was used in support of the FDA approval of Chloramine-T safety 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.
5. From inception to spring 2012, regional coordinators have published 162 peer-reviewed articles relating to the use of therapeutic drugs in minor species. Such publications benefit stakeholders by providing veterinarians with the necessary information to allow the extra-label use of these drugs on minor species.
6. Since its inception in 1982, Congress has appropriated only $11 million for the program. In return MUADP has generated publication of 36 Public Master Files (PMF) in the Federal Register, an average of 1.4 per year. These PMF have supported FDA approval for 42 drug products for use in minor food species.
7. Without the MUADP American producers of minor species would not have safe and effective products to keep their livestock healthy or their food products safe. Agricultural production of minor species is critically important to numerous regional economies in the U.S. This diverse aggregation of minor species represents approximately $4.4 billion in food and fiber farm gate revenues annually. Processing, use, and export of minor species food and fiber products represent an additional $34 billion economic impact to the U.S. Through a productive MUADP/NRSP-7, producers and veterinarians will continue to have the necessary information to prevent disease-related losses, to reduce pain and suffering in important species, and avoid contamination of our foods with drug residues.

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Report Information

Participants

Amy Omer, FDA/CVM, Amy.Omer@fda.hhs.gov;
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;
Paul R. Bowser, MUADP/NRSP-7/Cornell.edu;
Rod Getchell, MUADP/NRSP-7/Cornell U, rgg4@cornell.edu;
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

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. 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), Margaret Smith (Cornell University, AES) and Phil Elzer (LSU, AES). The attending NIFA representative was Dr. Gary Sherman (Washington, DC) and the FDA liaisons were Drs. Meg Oeller and Amy Omer (Rockville, MD). Absent wer administrative advisor Dr. Frances D. Galey (Western Region) and Regional Coordinator Thomas Vickroy (Southern Region).

12:00 PM INTRODUCTIONS - Introductions and meeting organization

Dr. John G. Babish started the meeting, as custom, with a thank you to Drs. Omar and Bailey for their 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 NIFA/USDA, Administrative Advisors, the National Coordinator, FDA/CVM and the Regional Coordinators.

NIFA/USDA – DR. GARY SHERMAN

Funding for the FY 2013 NRSP-7 Hatch Multistate projects have all been awarded to CA, FL, IA and NY. If grantees have not received the funds in their Treasury ASAP accounts, they should follow-up with NIFA's Financial Operations Division who has purview over fund certification. Emails should be sent to ASAPCustomerService@nifa.usda.gov. Grantees should provide the award number (per NIFA Award Face Sheet), and their ASAP account number when sending inquiries. We have not received any information regarding the FY 2014 Appropriation to date.

Even if this were a good year, it is way too early in the FY-14 budget cycle to expect to see distributions to states for the FY14. Because we are once again functioning on a CR, we are not permitted any prognostication about the timing of potential release of FY-14 distributions. Finally, what the Experiment Station System likely did was vote to fund at a projected level. Ultimately funding for any off the top subprogram in Hatch may be different if/when a budget is signed into law for FY-14.

Dr. Sherman, upon request, repeated his outline of the funding history of the MUADP delivered last spring.

1). Historically, MUADP/NRSP-7 enjoyed line item Special Grant funding from Congress (administered under NIFA's special grant authority) but this ended 3 years ago when 'earmarks' were greatly reduced.

2) MUADP/NRSP-7 is currently supported by Hatch funding. It was by virtue of the Program's legitimacy as an NRSP that, when special grant funding ended, there was a secondary (Hatch) Authority under which funding could be made available to the program, at the discretion of the directors of the system of US Agricultural Experiment Stations (AESs).

3) NIFA and Congress continue to support and fund the Hatch program. The Hatch Act authority provides funds to be distributed by NIFA on a formula basis to Ag Experiment Stations co-located at Land Grant colleges and universities. NRSPs and MultiState Committees, proposed and administered by AES Directors, are supported as a specified apportionment from Hatch funds. AES directors determine levels of funding for NRSPs and Multi-State Committees based on available funds.

4) NIFA Budget cuts for 2013 include loss of $180 M in mandatory funding that was not renewed, and the effects of Sequester. The ~18% overall cut to NIFA is expected to be applied roughly evenly across all NIFA programs. The Hatch program will likely experience this % decrease and this should be expected to impact Hatch sub-programming like NRSPs.

5) Efforts continue to search for a Western Region Administrative advisor for NRSP-7

6) NIFA is cognizant of the exploratory efforts underway related to a possible merger with IR-4. The Agency will consider consensus restructuring possibilities if and when the leaderships of both NRSP-7 and IR-4/NRSP-4 come to one or more mutually agreed upon potential merger strategy(ies).

7) Dr. Sherman, NIFA Liaison to NRSP-7, reminded the group that Secretary Vilsack and President Obama continue to strongly support revitalization of rural America. It is therefore appropriate to emphasize the roll of the MUADP in supporting a diversified, growing and vibrant rural economy.

REPORT FROM THE ADMINISTRATIVE ADVISORS - DR. JOHN BAKER (CHAIR)

Dr. Baker reported that the Fall meeting of ESCOP on September 25, 2013, NRSP7 was approved for $325,000 for FY2014. Here are the official ESCOP NRSP actions taken during the fall ESCOP meeting, held on September 25, 2013 in Columbus, OH:

• NRSP_temp281 (now NRSP8) was approved for a new five-year term (10/2014 to 9/2019) with an annual OTT budget of $500,000.

• NRSP1 was approved for an increase from $50,000 to $75,000. New distributions: $53,410 should go to Colorado State for impact reporting and $21,590 goes to Rutgers to support the NIMSS system.

• All other NRSP OTT budgets will remain the same for FY2014 (assuming no cuts from sequestration):

• NRSP3: $50,000

• NRSP4: $481,182

• NRSP6: $150,000

• NRSP7: $325,000

• NRSP9: $175,000

Dr. Baker reviewed the renewal process and outlined anticipated changes for this year. The NRSP-7 one-year proposal is due January 15th of 2014 and he and Dr. Babish have been working through the outline to complete the proposal on time.

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

One-Year Renewal

The NRSP-7 membership discussed at length either the 1-year renewal or 5-year renewal after the response from IR-4. The main issue facing NRSP-7 is the loss of funding in the USDA budget a number of years ago. The AES have been keeping the project alive for the last several years through “off the top” funds, which is at a reduced level than the previous USDA funding. There are serious concerns the project can remain viable if funding is reduce with the renewal (new guidelines, maintenance funding).

The application for renewal was submitted in Sept 2013 and the final application is due Jan 15th, 2014.

The decision to go with a I year renewal was based on the following:

1. Continue discussions with IR-4 in the area of collaboration. Even though they would remain separate projects there are opportunities for collaboration and cooperation between the two projects. A 1-year renewal would allow this process to move forward.

2. To provide time for one final appeal to Congress re Farm Bill, USDA and FDA for stable funding (and increased in funding). This would also allow more time for the engagement of stakeholders in this process. Emphasize prudent use of antimicrobials in veterinary medicine necessitates the continuation of the MUADP.

3. Increase stakeholder base through inclusion of natural product manufacturers, pesticide manufacturers, etc.

4. CDC publications and news releases. They have come down hard on antibiotic use in veterinary medicine. I'm attaching a copy of their publication. See especially pages 36-37. While coming down hard on the use of antibiotics in veterinary medicine, they emphasize a more controlled use. This should be our position in describing the critical need for the program - more control over the use of antibiotics in minor species. Maybe this position by the CDC could serve NRSP7 in much the same way reregistration served the IR-4. Anyway, we have to come out ahead of this position and not be run over by it.

5. USDA and FDA need to realize that if the project closes there are ramifications. First off is the loss of faculty commitment, infrastructure and personnel that cannot easily be turned back on. Second, the loss of NRSP-7 is a serious food safety concern. This is (in my opinion) is the only viable option to get approval for pharmaceuticals used in minor species. Failure to do so leads to off label and sometimes illegal use of pharmaceuticals in minor species with subsequent risk to human health.

Again, NRSP-7 is on life support right now. Reduction of funding from the AES by moving the project to maintenance support makes it difficult for the project to continue.

The application for renewal was submitted in Sept 2013 and the final application is due Jan 15th, 2014. The Sept application was sent around earlier this morning.

Schedule: Our funding for 2014 has been approved. The one-year renewal is for FY2015. If we are not approved for continued funding, we get one year (2016) to dismantle the program.

FDA Announced Minor Use/Minor Species (MUMS) Grant Program Request for Applications Open Period due January 3, 2014

REPORT FROM FDA/CVM - DRS. MEG OELLER AND DOROTHY BAILEY

Erythromycin Salmonids I-006013 – Environmental Assessment hopefully can be done by FDA/CVM; After that, NRSP7 will probably be done with this project

CIDR Goats I-011389 - Dr. Griffiths is working diligently with FDA/CVM to see what data for efficacy can be submitted. Conference call with CVM has occurred and Dr. Oeller is hopeful that the data that exists can be submitted and hopefully accepted.

Fenbendazole Pheasants I-010062 – Dr. Oeller says that she can address the efficacy portion and the Environmental. I believe Dr. Griffiths has sent the Response for Target Animal Safety to CVM.

Lasalocid Pheasants I-009096 - From what I understand, there are challenges with getting the old method bridged due to availability of materials. Dr. Vickroy had submitted a validation protocol. Not sure if there is a clear path to get this method validated.

Tulathromycin Goats I-011512 - If Human Food Safety is to be done, entire animal study needs to be repeated. A protocol for efficacy has not been established. This project needs to be put on low priority.

Tulathromycin Sheep I-011513 - Not planning to pursue this one.

Nuflor Gold Sheep I-011836 Drs. Oeller and Baileuy are going to look into what can be combined with the old Nuflor and Nuflor Gold. Otherwise, this project would also be put on hold.

DEVELOPMENT OF NEW ACTION ITEMS

Going forward on funding, renewal discussions for monthly teleconferences

OTHER BUSINESS - NONE BROUGHT FORWARD

SPRING Meeting 2014 - The final decision on the timing of the meeting will be made during discusions at monthly teleconferences.

As there was no further business, the meeting was adjourned at 3:05 pm.

RESPECTFULLY SUBMITTED:

/s/John G. Babish, Ph.D. Date: 3/12/14
Minor Use Animal Drug Program/NRSP-7 National Coordinator

Accomplishments

REPORTS, DISCUSSIONS AND NEW PROJECT PROPOSALS FROM THE REGIONS <br /> <br /> WESTERN REGION – DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> <br /> ADR#325 – Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. Update 12/2013: No new progress on this project.<br /> <br /> ADR#350 – Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. Update 12/2013: No new progress on this project.<br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> <br /> ADR#338 – Spectramast™ LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed. <br /> <br /> ADR#135 – Erythromycin in Salmonids<br /> 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. Update 12/2013: Awaiting final amendment of EA by CVM.<br /> <br /> Collaborative Projects:<br /> <br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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). Update 12/2013: HFS report received concurrence from CVM, April 2014.<br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. Update 12/2013: Nothing new to report. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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 04/2013: In March, 2013 an ERA amendment was requested by CVM for the HFS technical report but this study will result in a technical section incomplete due to some analytical challenges and freezer stability requirements. 12/2013: Nothing new to report. <br /> <br /> Other Projects/Activities:<br /> <br /> Quality Assurance: Since the Fall of 2012 FDA Inspection, and our efforts have been focused on addressing SOP revisions and internal operations. At this time these efforts are on hold due to funding challenges.<br /> <br /> Excede in Sheep: Study has been completed in domestic sheep. Manuscript has been accepted for pulication in AJVR.<br /> <br /> 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. Update 12/2013: Samples were reanalyzed and the data is currently being evaluated.<br /> Multidose flunixin Administration in Goats: This study was initiated to evaluate multi dose flunixin use in goats and milk residues. The study has been completed and the data is being analyzed. Initial study results were presented at the 2013 STAR meeting. <br /> <br /> Plasma samples from a goat study study lead by Jamie Boehmer at the Office of Research evaluating inflammatory markers and flunixin have been analyzed. Dr. Tell is in contact with Dr. Boehmer and the manuscript is currently being written.<br /> <br /> Tulathromycin pharmacokinetics in dairy goats: A UC Davis summer student, Bernadette Grismer, performed this study. A total of 448 samples (328 milk; 120 plasma) have been analyzed. Update 12/2013: Manuscript accepted by JVPT and is on line via early release.<br /> <br /> A food animal medicine resident (Matt Cuneo) performed a research study looking at a two time dose administration of tulathromycin in dairy goats. The samples are currently being analyzed. Initial results will be presented at UC Davis Goat Day 2014.<br /> <br /> Laboratory Report:<br /> Most of the activity continues as sample analysis in the laboratory. Results and plans are reported under separate projects above. <br /> <br /> Usefulness of the Findings:<br /> The findings from most of the current studies (non-GLP) will be utilized to fulfill the mission of generating data relative to drug use in minor food animal species.<br /> <br /> Work Planned for Remainder of the Year:<br /> <br /> Finish sample analysis for goat flunixin and tulathromycin studies. Publish data for all of these <br /> <br /> NORTHEAST REGION: DR. PAUL BOWSER <br /> <br /> Progress of the work and principal accomplishments:<br /> <br /> Species Grouping Project:<br /> <br /> INAD 10-320 Oxytetracycline in Fish<br /> <br /> INAD 10-823 Romet-30 in Fish<br /> <br /> INAD 11-145 Florfenicol in Fish<br /> <br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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. Two manuscripts on this work have been published in the peer-reviewed literature.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids:<br /> 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. <br /> <br /> Usefulness of the findings:<br /> <br /> In all cases, the findings to date over the course of these projects serve as the foundation for continued work on these compounds. <br /> <br /> Work planned for next year:<br /> <br /> Species Grouping Project:<br /> <br /> INAD 10-320 Oxytetracycline in Fish<br /> <br /> INAD 10-823 Romet-30 in Fish<br /> <br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> 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. <br /> <br /> Strontium Marking of Fish Otoliths<br /> 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. Our protocol is under review by CVM FDA.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> 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.<br /> <br /> 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. <br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> <br /> 1) Work accomplished under the original project:<br /> 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:<br /> <br /> To identify animal drug needs for minor species and minor uses in major species.<br /> <br /> To generate and disseminate data for safe and effective therapeutic applications, and<br /> <br /> To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> <br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> <br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/<br /> Romet-TC and Aquaflor as test articles.<br /> <br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> <br /> 2) The degree to which the objectives have been met: <br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation: <br /> 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.<br /> <br /> SOUTHERN – DR. THOMAS VICKROY<br /> <br /> Progress of Work and Principal Accomplishments:<br /> <br /> Active Regional Projects:<br /> <br /> 1. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279)<br /> 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.<br /> <br /> 2. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352)<br /> 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. <br /> <br /> 3. Fenbendazole in Game Birds (ADR#280)<br /> 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.<br /> Update on Other Programmatic Efforts and Changes<br /> <br /> 1. NRSP-7 Website: <br /> 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. <br /> <br /> 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.<br /> <br /> NORTH CENTRAL – DR. RONALD W.GRIFFITH<br /> <br /> Goat CIDR-G Effectiveness<br /> The study report is still in preparation.<br /> <br /> Lasalocid in Pheasants Target Animal Safety<br /> We have a technical section incomplete letter from ONADE. We are waiting on the outcome of the fenbendazole TAS technical report before re-submitting this one. The work has been published in the Avian Diseases journal.<br /> <br /> Lasalocid in Pheasants Human Food Safety<br /> The study protocol for the in-life phase at Iowa State was submitted from the Southern Region and we have received protocol concurrence. The FDA had questions on the analytical method and we had planned to complete method validation beginning in June, 2013. The method validation is on-hold pending guidance from the FDA primarily concerning requirements for GLP studies for the MUADP. The study itself has been given a lower priority due to lack of funding and uncertainty over GLP issues.<br /> <br /> Draxxin Tissue Residue<br /> ONADE asked for additional data and clarification for the study report. The Western Region is leading the response effort.<br /> <br /> Draxxin Efficacy in Goats<br /> This is now largely in the hands of the FDA/CVM. Zoetis may be working on this.<br /> Fenbendazole Human Food Safety in Pheasants<br /> The Western and North Central Regions combined to do this study. The technical section is complete.<br /> <br /> Fenbendazole Target Animal Safety in Pheasants<br /> We received a technical section incomplete letter on the study report. Additional data, clarification and justification of study procedures have been submitted. The reproductive safety portion of the work was not acceptable but the label will just state that reproductive safety has not been demonstrated. A conference call is scheduled for Dec. 23 with the stats reviewer to address one of their concerns. A paper covering this work and the reproductive safety data was submitted to Avian Diseases and is currently in press.<br /> <br /> Ivermectin Cattle Fever Tick Efficacy<br /> This project is being done 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 as well as with Postive Feeds, Ltd. A conference call was held in November to discuss how to proceed with this portion of the project. Two herds (pastures) have been totally cleared of cattle fever ticks and additional data is available on pastures with low tick burdens on which the cattle were fed the ivermectin tubs. It was concluded that a study report covering the data we have to date will be prepared and submitted to the FDA/CVM The right of reference from Merial is remains unresolved.<br /> <br /> Pregnant Mare Serum Gonadotrophin-ADR 0353<br /> 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. No further action at this point.<br /> <br /> <br /> <br />

Publications

1. Wu, H., Baynes, R. E., Leavens, T., Tell, L. A., and Riviere, J. E. (2013) Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle, J Vet Pharmacol Ther 36, 248-257.<br /> <br /> 2. Washburn, K. E., Fajt, V. R., Lawhon, S. D., Adams, L. G., Tell, L. A., and Bissett, W. T. (2013) Caprine abscess model of tulathromycin concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis following subcutaneous or intrachamber administration, Antimicrobial agents and chemotherapy 57, 6295-6304.<br /> <br /> 3. Spitsbergen, J. M., Frattini, S. A., Bowser, P. R., Getchell, R. G., Coffee, L. L., Wolfe, M. J., Fisher, J. P., Marinovic, S. J., and Harr, K. E. (2013) Epizootic neoplasia of the lateral line system of lake trout (Salvelinus namaycush) in New York's Finger Lakes, Vet Pathol 50, 418-433.<br /> <br /> 4. Snook, T. S., White, S. D., Hawkins, M. G., Tell, L. A., Wilson, L. S., Outerbridge, C. A., and Ihrke, P. J. (2013) Skin diseases in pet rabbits: a retrospective study of 334 cases seen at the University of California at Davis, USA (1984-2004), Veterinary dermatology.<br /> <br /> 5. Shelver, W. L., Tell, L. A., Wagner, S., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., and Smith, D. J. (2013) Comparison of ELISA and LC-MS/MS for the Measurement of Flunixin Plasma Concentrations in Beef Cattle after Intravenous and Subcutaneous Administration, J Agric Food Chem 61, 2679-2686.<br /> <br /> 6. McDonnel, S. J., Tell, L. A., and Murphy, B. G. (2013) Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats, J Vet Pharmacol Ther.<br /> <br /> 7. Macpherson, M. L., Giguere, S., Hatzel, J. N., Pozor, M., Benson, S., Diaw, M., Sanchez, L. C., Vickroy, T. W., Tell, L., Wetzlich, S., and Sims, J. (2013) Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis, J Vet Pharmacol Ther 36, 59-67.<br /> <br /> 8. Grismer, B., Rowe, J. D., Carlson, J., Wetzlich, S. E., and Tell, L. A. (2013) Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus), J Vet Pharmacol Ther.<br /> <br /> 9. Goetting, V., Lee, K. A., Woods, L., Clemons, K. V., Stevens, D. A., and Tell, L. A. (2013) Inflammatory marker profiles in an avian experimental model of aspergillosis, Medical mycology 51, 696-703.<br /> <br /> 10. DeDonder, K. D., Gehring, R., Baynes, R. E., Tell, L. A., Vickroy, T. W., Apley, M. D., and Riviere, J. E. (2013) Effects of new sampling protocols on procaine penicillin G withdrawal intervals for cattle, J Am Vet Med Assoc 243, 1408-1412.<br /> <br /> 11. Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., and Tell, L. A. (2013) Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos), J Vet Pharmacol Ther 36, 122-129.<br /> <br /> 12. Cornwell, E. R., Labuda, S. L., Groocock, G. H., Getchell, R. G., and Bowser, P. R. (2013) Experimental Infection of Koi Carp with viral hemorrhagic septicemia virus type IVb, J Aquat Anim Health 25, 36-41.<br /> <br /> 13. Cornwell, E. R., Bellmund, C. A., Groocock, G. H., Wong, P. T., Hambury, K. L., Getchell, R. G., and Bowser, P. R. (2013) Fin and gill biopsies are effective nonlethal samples for detection of viral hemorrhagic septicemia virus genotype IVb, J Vet Diagn Invest 25, 203-209.<br /> <br /> 14. Coffee, L. L., Casey, J. W., and Bowser, P. R. (2013) Pathology of tumors in fish associated with retroviruses: a review, Vet Pathol 50, 390-403.<br /> <br /> 15. Coffee, L. L., Bogdanovic, L. B., Cushing, T. L., and Bowser, P. R. (2013) Pharyngeal odontoma in an adult walleye (Sander vitreus), Vet Pathol 50, 483-487.<br />

Impact Statements

1. Through its collaborative efforts with the FDA Center for Veterinary Medicine, MUADP substantiates the safe and effective use of pharmaceutical products to minor species producers in the U.S., which allows them to remain competitive in the global marketplace. The U.S. imports a significant number of minor species food products and without the therapeutics provided through the research activity of the MUADP, the U.S. producers cannot remain competitive with foreign suppliers.
2. The Minor Use Animal Drug Program has received over 354 Animal Drug Requests submitted by researcher investigators at federal, state, and university laboratories, veterinarians, and animal industry personnel for approval of a specific drug for the control of a certain disease in an animal industry.
3. In the 31 years of the Program, data supplied by the Program provided for the modification of 52 label claims to include minor species, an overall average of 1.6 per year. Included in these approvals were one for rabbits, nine for game birds, 16 for fish, lobster and shrimp, 15 for meat and dairy goats, eight for bison and reindeer, one for foxes and two for honey bees. Even with the estimated increased cost per drug approval in recent years, the NRSP-7 program continues to demonstrate remarkable efficiency and cost effectiveness. Compared to an average investment of the pharmaceutical industry of $10 to $25 million for adding a label claim to an existing veterinary drug, information generated for additional label claims by the NRPS-7 program costs only approximately 15 to 35% of pharmaceutical industry costs.
4. On July 1, 2011, the Food and Drug Administration (FDA) announced 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 data, contained in Public Master File (PMF) 5988, were compiled by the Minor Use Animal Drug Program/National Research Support Project 7.
5. In 2012, data from NRSP-7 was used in support of the FDA approval of Chloramine-T safety 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.
6. Without the MUADP American producers of minor species would not have safe and effective products to keep their livestock healthy or their food products safe. Agricultural production of minor species is critically important to numerous regional economies in the U.S. This diverse aggregation of minor species represents approximately $4.4 billion in food and fiber farm gate revenues annually. Processing, use, and export of minor species food and fiber products represent an additional $34 billion economic impact to the U.S. Through a productive MUADP/NRSP-7, producers and veterinarians will continue to have the necessary information to prevent disease-related losses, to reduce pain and suffering in important species, and avoid contamination of our foods with drug residues.
7. NRSP-7 has published 206 articles in peer-reviewed journals, averaging 6.6 per year over the term of the program. For the last five years, however, publications have nearly doubled to 10.6 per year. Thus, although FDA/CVM drug approvals have waned due to increasing costs, the Program has increased its efforts to supply critical data needs to minor species producers. The data generated by the Program is also shared with the Food Animal Residue Avoidance Database (FARAD) program to further increase visibility.
8. The use of the Internet to optimize communications with stakeholders and program participants continues to improve in this rapidly changing medium. Since inception in 1999, the NRSP-7 website has been visited 11,950 times for an average of 4.1 hits per day, an increase of 30% over the last review period. NRSP-7 believes that this represents a significant degree of interaction with stakeholders as well as the public at large.
9. Approvals and projects that have changed the outlook of two industries include the approvals of lincomycin hydrochloride water-soluble powder and tylosin tartrate powder for control of American Foulbrood in honey bees. These approvals represent a significant therapeutic addition to an industry working to reverse the declining honey bee population. The potential effect on the industry is important. Secondly, the ivermectin/molasses block formulation study currently being conducted in Texas for the control of Cattle Tick Fever, has the potential of averting a major threat to the U.S. cattle population. Several efficacy studies have supported the use of this novel formulation in cattle tick control. NRSP-7 labs in the Southern Region have worked with producers to assure a uniform distribution of ivermectin in the molasses blocks, insuring that cattle will receive uniform dosing.

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Report Information

Participants

Omer, Amy Omer@fda.hhs.gov FDA/CVM;

Galey, Francis (AA) FGaley@uwyo.edu UWY;

Sherman, Gary gsherman@nifa.usda.gov USDA/CSRESS;

Babish, John (NC) jgb7@cornell.edu MUADP/NRSP-7;

Tell, Lisa (RC); latell@ucdavis.edu MUADP/NRSP-7/UC Davis;

Smith, Margaret (AA) mes25@cornell.edu Cornell/NY AES;

Oeller, Meg margaret.oeller@ fda.hhs.gov FDA/CVM;

Bowser, Paul, R. (RC); prb4@cornell.edu MUADP/NRSP-7/Cornell U;

Elzer, Phil (AA) Pelzer@agcenter.lsu.edu LSU;

Getchell, Rod (RC) rgg4@cornell.edu MUADP/NRSP-7/Cornell U;

Griffith, Ronald (RC) rgriffit@iastate.edu MUADP/NRSP-7/Iowa State;

Vickroy, Thomas (RC) vickroy@vetmed.ufl.edu MUADP/NRSP-7/U FL;

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. Ronald Griffith (Iowa State University), and Dr. Paul Bowser (Cornell University). The Administrative Advisors present were Drs. Margaret Smith (Cornell University, AES), Phil Elzer (LSU, AES) and Francis Galey (UWY, AES). The attending NIFA representative was Dr. Gary Sherman (Washington, DC) and the FDA liaisons were Drs. Meg Oeller, Dorothy Bailey, and Amy Omer (Rockville, MD). Absent was administrative advisor Dr. John Baker.

Brief Summary of Minutes

12:00 PM INTRODUCTIONS - Introductions and meeting organization

Dr. John G. Babish started the meeting, as custom, with a thank you to Drs. Omar and Bailey for their 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 Administrative Advisors, the National Coordinator, FDA/CVM, NIFA/USDA, and Accomplishments from the Regional Coordinators,

REPORT FROM THE ADMINISTRATIVE ADVISORS - DR. JOHN BAKER (CHAIR)

Dr. Baker was unable to attend the meeting, but had contacted Dr. Babish earlier in the day with the news that he had been selected as the new Dean of the College of Veterinary Medicine for Michigan State University. Both Drs. Baker and Babish recommended Dr. Margaret Smith as the new chair of the Administrative Advisors. Dr. Smith agreed and stated she was honored by the consideration. She also stated that she would work hard within the AES system to move NRSP-7 forward into a new era of funding.

REPORT FROM THE NATIONAL COORDINATOR - DR. JOHN G. BABISH

The central issue facing NRSP-7 is the loss of funding in the NIFA/USDA budget a number of years ago. The Hatch funds have been used to leverage support from stakeholders for the last several years, but these funds are at a reduced level from the previous NIFA/USDA funding. Our Hatch funding for 2014 has been approved. Due to a change in AES Guidelines on Hatch funds, however, this award is not continued for an additional year if our five-year proposal is not approved,.

During our one-year renewal term the Program has outlined the following tasks:

1. Since the inclusion of the MUADP in the 2014 Farm Bill, the Program will work to identify Congressional support for stable and increased funding. Emphasize prudent use of antimicrobials in veterinary medicine necessitates the continuation of the MUADP.

2. Increase stakeholder base through inclusion of natural product manufacturers, pesticide manufacturers, etc.

3. Utilize CDC publications and news releases. The CDC has come down hard on antibiotic use in veterinary medicine. While strongly discouraging the use of antibiotics in veterinary medicine, they emphasize a more controlled use. This should be our position in describing the critical need for the program - more control over the use of antibiotics in minor species. Maybe this position by the CDC could serve NRSP7 in much the same way reregistration served the IR-4. Anyway, we have to come out ahead of this position and not be run over by it.

4. USDA and FDA need to realize that if the project closes there are ramifications. First off is the loss of faculty commitment, infrastructure and personnel that cannot easily be turned back on. Second, the loss of NRSP-7 is a serious food safety concern. This is (in my opinion) is the only viable option to get approval for pharmaceuticals used in minor species. Failure to do so leads to off label and sometimes illegal use of pharmaceuticals in minor species with subsequent risk to human health.

REPORT FROM FDA/CVM - DRS. MEG OELLER, AMY OMER AND DOROTHY BAILEY

1. Project Progress

• Erythromycin – Environmental Assessment (EA) pending with CVM due date of 7/13/2014. All other technical sections complete; Safety and effectiveness are for Chinook salmon only.
o Next steps: Need to reach out to Chris Moffitt to see if data exists to expand this indication. Need to contact Bimeda to discuss their progress on the CMC technical section.

• CIDR-g – TAS, Human Food Safety (HFS) and Environmental technical sections are complete.Next steps: Effectiveness study report is nearing completion.

• Fenbendazole – HFS technical section complete. Target Animal Safety (TAS) technical section response submitted on 6/4/2014; CVM due date 12/2/2014.
o Next steps: Request for Categorical exclusion denied; working on response. Need to request reaffirmation of Effectiveness technical section.

• Lasalocid – Effectiveness technical section complete.
o Next steps: TAS response is closely related to fenbendazole TAS response; waiting for feedback on fenbendazole response. Categorical exclusion request is currently being prepared. HFS still pending.

• Ivermectin – Right of reference still pending; when it happens CVM will renegotiate requirements based on existing data.
o Next steps: Working to get Merial and Postive Feeds to the table discuss path forward.

• SrCl – TAS protocol received concurrence from ONADE. Northeast region received OMUMS grant funding for TAS study.
o Next steps: CVM to utilize existing data to support effectiveness technical section. CVM investigating how to prepare an environmental assessment as a white paper argument.

• Tulathromycin in Goats – TAS and Environmental technical sections complete.
o Next steps: On hold.
• Tulathromycin in Sheep – Environmental technical section complete. Zoetis terminated designation.
o Next steps: On hold.

• Nuflor Gold in Sheep – On hold.

2. Revisit prioritization of completion of these projects.

3. GLP Issues - What next steps are needed to move forward on the status of GLP concerns? Should we set up a meeting between University principals and Bernadette? Do the regional coordinators believe Meg’s draft document is at least in part a feasible resolution to the issue? If the proposed budget allows for QA staffing, what affect will this have on the outlook of GLP studies at the universities?

NIFA/USDA – DR. GARY SHERMAN

Dr. Sherman noted that NIFA is cognizant of the exploratory efforts underway related to expanding the objectives of the program. Additionally, Dr. Sherman reminded the group that Secretary Vilsack and President Obama continue to strongly support revitalization of rural America. It is therefore appropriate to emphasize the roll of the MUADP in supporting a diversified, growing and vibrant rural economy.

Dr. Sherman then restated from the Fall meeting that funding for the FY 2014 NRSP-7 Hatch Multistate projects have all been awarded to CA, FL, IA and NY. He added that If grantees have not received the funds in their Treasury ASAP accounts, they should follow-up with NIFA's Financial Operations Division who has purview over fund certification. Emails should be sent to ASAPCustomerService@nifa.usda.gov. Grantees should provide the award number (per NIFA Award Face Sheet), and their ASAP account number when sending inquiries. We have not received any information regarding the FY 2014 Appropriation to date.

Accomplishments

WESTERN REGION – DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> <br /> ADR#325 – Florfenicol (Nuflor® Injectable Solution) for sheep for respiratory disease <br /> 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. Update 12/2013: No new progress on this project.<br /> <br /> ADR#350 – Florfenicol (Nuflor Gold®) for sheep for respiratory disease<br /> 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. Update 06/2014: No new progress on this project.<br /> <br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project is not being pursued.<br /> <br /> ADR#338 – Spectramast™ LC Sterile Suspension for Mastitis in Dairy Goats<br /> Project is not being pursued.<br /> <br /> ADR#135 – Erythromycin in Salmonids<br /> 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. Update 06/2014: Awaiting final amendment of EA by CVM.<br /> <br /> Collaborative Projects:<br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> 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). HFS report received concurrence from CVM, April 2014. Update 06/2014: No new progress on this project.<br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS, Milk Residue Study, and Efficacy)<br /> 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. Update 06/2014: Nothing new to report. <br /> <br /> ADR#340 - Tulathromycin in Goats (Collaborative project with the North Central region)<br /> 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 04/2013: In March, 2013 an ERA amendment was requested by CVM for the HFS technical report but this study will result in a technical section incomplete due to some analytical challenges and freezer stability requirements. Update 06/2014: Nothing new to report. <br /> <br /> Other Projects/Activities:<br /> Quality Assurance: Since the Fall of 2012 FDA Inspection, and our efforts have been focused on addressing SOP revisions and internal operations. At this time these efforts are on hold due to funding challenges.<br /> <br /> Excede in Sheep: Study has been completed in domestic sheep. Manuscript has been published.<br /> <br /> 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. Update 12/2013: Samples were reanalyzed and the data is currently being evaluated.<br /> Multidose flunixin Administration in Goats: This study was initiated to evaluate multi dose flunixin use in goats and milk residues. The study has been completed and the data is being analyzed. Initial study results were presented at the 2013 STAR meeting. <br /> Plasma samples from a goat study study lead by Jamie Boehmer at the Office of Research evaluating inflammatory markers and flunixin have been analyzed. Dr. Tell is in contact with Dr. Boehmer and the manuscript is currently being written.<br /> Tulathromycin pharmacokinetics in dairy goats: A UC Davis summer student, Bernadette Grismer, performed this study. A total of 448 samples (328 milk; 120 plasma) have been analyzed. Update 12/2013: Manuscript accepted by JVPT and has been published.<br /> <br /> A food animal medicine resident (Matt Cuneo) performed a research study looking at a two time dose administration of tulathromycin in dairy goats. The samples are currently being analyzed. Initial results will be presented at UC Davis Goat Day 2014. Update 06/20/2014: Analysis of all milk samples just completed. Analysis of serum samples in progress. <br /> <br /> Laboratory Report:<br /> Some of the activity for the region continues as sample analysis in the laboratory mostly for studies focusing on drug use in small ruminants. Statuses of projects are reported under separate projects above.<br /> <br /> Usefulness of the Findings:<br /> The findings from most of the current studies (non-GLP) will be utilized to fulfill the mission of generating data relative to drug use in minor food animal species.<br /> <br /> Work Planned for Remainder of the Year:<br /> Publish data for all of these <br /> <br /> NORTHEAST REGION: DR. RODMAN G. GETCHELL <br /> Progress of the work and principal accomplishments:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Florfenicol in Fish<br /> 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.<br /> <br /> Ovadine (Western Chemical) Disinfection of Fish Eggs:<br /> 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. Two manuscripts on this work have been published in the peer-reviewed literature.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids:<br /> We conducted a cooperative project with Dr. H. George Ketola of the USGS Tunison Laboratory of Aquatic Science, Cortland, NY in which we evaluated the use of allicin as a component of the ration to increase production efficiency in salmonids. More specifically, we determined if allicin in the ration will result in a reduction in losses due to Aeromonas salmonicida in salmonids. We developed a challenge model with A. salmonicida in rainbow trout and conducted two preliminary trials in which allicin was added to the ration at three different concentrations (0.0%, 0.5%, 1.0% and 2.0%). The fish were then challenged with an intraperitoneal injection of Aeromonas salmonicida. Upon preliminary evaluation of the data, there appeared to be some benefit from the addition of allicin at 0.5% and 1.0% and an adverse effect at 2.0%. Future effectiveness trials will involve a challenge with the pathogen administered via the water. The standard target animal safety model (1X, 3X, 5X dose for 3X duration) was utilized to further evaluate the effect of supplementation of allicin to the diet. Fish were fed allicin supplemented rations (0.0%, 0.5%, 1.5% and 2.5%) for 30 days. At the end of the trial select serum chemistry, hematology and histopathology parameters were evaluated. A preliminary evaluation of the data indicated significant (P<0.05) differences between treatments for some of the parameters. Upon microscopic evaluation of select tissues from treated fish, an increase in pigment containing macrophage centers in the posterior region of the kidneys of the fish receiving the highest dose (2.5% for 30 days). This was interpreted to be a possible indication of tissue damage. The presence of a potential adverse effect at the highest dose was consistent with the potential adverse impact of the highest treatment concentration in the challenge studies. <br /> <br /> The effort served as the basis for the Master of Science thesis research for Dr. Kate E. Breyer, a Resident in the Laboratory Animal Medicine Program at Cornell. She successfully defended her Thesis in June of 2013. A manuscript based on these studies has been submitted and is currently under review. <br /> <br /> Usefulness of the findings:<br /> In all cases, the findings to date over the course of the above described projects serve as the foundation for continued work on these compounds. The Human Food Safety Studies completed to date for oxytetracycline, Romet-30 and Florfenicol 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).<br /> <br /> Work planned for next year:<br /> Species Grouping Project:<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> 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.<br /> <br /> Ovadine (PVP-Iodine, Western Chemical) Disinfection of Fish Eggs<br /> 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. <br /> <br /> Strontium Marking of Fish Otoliths<br /> We have developed a project to complete the data package needed to obtain a label or to index the use of Strontium Chloride for marking fish otoliths. Our protocol has been reviewed and accepted by CVM FDA. We submitted an application for funding from the MUMS Program to conduct this project. We were recently informed that our MUMS application was successful. We anticipate the commencement of the Strontium Chloride effort in the fall of 2014 when fish of appropriate size and age become available. This summer we will conduct an assay validation trial for strontium chloride measurements in water.<br /> <br /> Allicin for the reduction of Aeromonas salmonicida infection in salmonids<br /> We completed two efficacy trials and one target animal safety trial in which allicin was added to the ration of rainbow trout as a nutritional supplement to increase production efficiency of fish culture. We do not anticipate any future studies on allicin at this time. <br /> <br /> CRITICAL REVIEW (Northeast Region) <br /> 1) Work accomplished under the original project:<br /> 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:<br /> • To identify animal drug needs for minor species and minor uses in major species.<br /> • To generate and disseminate data for safe and effective therapeutic applications, and<br /> • To facilitate FDA/CVM approvals for drugs identified as a priority for a minor species or minor use.<br /> <br /> Under the framework of this mission, progress has been made in the following areas:<br /> (A) Use of hydrogen peroxide for the control of bacterial gill disease in fish.<br /> (B) Species Grouping in Fish, using the compounds Oxytetracycline, Romet-30/<br /> Romet-TC and Aquaflor as test articles.<br /> (C) Use of Ovadine for the reduction of Viral Hemorrhagic Septicemia Virus on fish eggs.<br /> (D) Uses of allicin as a component of the ration to reduce th impact of Aeromonas salmonicida in salmonids. <br /> (E) We have been successful in obtaining funding through the MUMS program that will augment the NRSP-7 funding and allow the program to undertake a project to evaluate the use of strontium chloride as an otholith marker. <br /> <br /> 2) The degree to which the objectives have been met: <br /> 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. <br /> <br /> 3) Incomplete work or areas needing further investigation: <br /> (A) 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. Further work on species grouping will require securing additional funding.<br /> (B) Discussions with a researcher from U.S. Dept. of Agriculture, Agricultural Research Service Harry K. Dupree - Stuttgart National Aquaculture Research Center (USDA ARS HKD SNARC) suggests there is an interest in investigating the anti-viral properties of copper sulfate for the treatment of baitfish eggs. We have the capability to conduct in vitro work with fish cell cultures and/or in vivo work with baitfish eggs similar to the Ovadine disinfection project. The baitfish industry has asked the HKD SNARC about disinfectants on eggs, so that they could inactivate any viruses on the outside of eggs during hatching (most are outside the egg). <br /> <br /> In some testing this spring, the iodine product Ovadine, at the recommended rate for fish eggs (100 mg/L for 10 min), caused mortalities in golden shiner and fathead minnow eggs. The preliminary results also suggested that Ovadine was toxic to hybrid striped bass and largemouth bass eggs at the recommended dose. This researcher has conducted studies that demonstrate that copper sulfate works well for fungus on eggs and relatively high doses are safe. Their previous drug approval research showed that 10 mg/L copper sulfate is safe and effective for catfish eggs, but they also have used 100 mg/L with good results. Copper sulfate treatment of eggs has been used in the catfish industry as well as with hybrid striped bass and a largemouth bass hatchery. Since copper sulfate is being used for egg fungus, the baitfish industry brought up copper sulfate as a possible disinfectant for fish viruses. We will be proposing an effort to the NRSP7 that will investigate copper sulfate treatment of fish eggs for the control of external viral fish pathogens. <br /> <br /> SOUTHERN – DR. THOMAS VICKROY<br /> Progress of Work and Principal Accomplishments:<br /> Active Regional Projects:<br /> 1. Ivermectin Medicated Feed Block for Control of Cattle Fever Tick in South Texas (ADR#352)<br /> This project is a collaborative effort among the North-Central Region of MUADP (Iowa State University), the Southern Region of MUADP (University of Florida), USDA-ARS, USDA-APHIS, the Texas Animal Health Commission and the Cattle Fever Tick Eradication Program. The study represents a minor use in a major food animal species as determined by FDA-CVM. Work conducted thus far at UF has involved determination of ivermectin content in samples of medicated feed blocks. Analyses have been carried out using a modified version of the approved regulatory method for ivermectin determination in beef liver samples. The method has not yet undergone FDA review for concurrence. The medicated blocks contain a proprietary undisclosed mixture of nutrients, minerals, other ingredients and molasses as a taste enhancer that is used for oral drug delivery to free-range cattle in pastures. Analysis of feed block samples for consistency and reproducibility of ivermectin content has continued during the report period. Unfortunately, the project faces several major hurdles before it can be considered for possible concurrence by the CVM. The most significant problem has been the continued impasse between Texas-based Postive Feeds and Merck-Merial to reach an agreement to support release of a Right of Reference letter. At present, the future direction of this project remains uncertain. <br /> <br /> 2. Lasalocid for Treatment of Coccidiosis in Pheasants (ADR#279)<br /> This project is a collaborative effort between the North-Central Region (Iowa State University) and the Southern Region (University of Florida) of the MUADP. This study remains on hold with no activity during the past six months. At this time, both regions are awaiting guidance from the FDA regarding on-going GLP study requirements as well as future needs for quality assurance oversight of this and other projects. As background, a tissue residue depletion study protocol (number 2012-235-HFS) was submitted in September 2012 to the INAD exemption file for a project to investigate the use of lasalocid (Avatec®) Type A medicated article for the control of coccidiosis associated with infection by Eimeria colchici, E. duodenalis or E. phasiani in pheasants. If this project moves forward, the in-life phase of studies will be conducted at Iowa State under the supervision of Dr. Ron Griffith and the Southern Region will carry out marker (lasalocid) residue analyses of all tissue samples. <br /> <br /> 3. Fenbendazole in Game Birds (ADR#280)<br /> This is a collaborative project among the North-Central, Western and Southern regions, although the Southern region has no direct role related to the in-life studies (North-Central Region) nor the analytical phase (Western Region). For details on the project history, please refer to those regional reports for progress updates.<br /> <br /> Update on Other Programmatic Efforts and Changes<br /> 1. NRSP-7 Website: The Southern Region is responsible for maintaining and updating the NRSP-7 website, including MUMsRx and the RUSTi system that is used for tracking the status of regional projects. The information posted on the website has been updated with recent progress reports but remains in need of a major overhaul. Efforts on the website have been scaled back pending a decision on the future status of the program.<br /> <br /> 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.<br /> <br /> NORTH CENTRAL – DR. RONALD W.GRIFFITH<br /> Goat CIDR-G Effectiveness<br /> The study report is nearing completion.<br /> <br /> Lasalocid in Pheasants Target Animal Safety<br /> We have a technical section incomplete letter from ONADE. We are waiting on the outcome of the fenbendazole TAS technical report before re-submitting this one. The work has been published in the Avian Diseases journal.<br /> <br /> Lasalocid in Pheasants Human Food Safety<br /> The study protocol for the in-life phase at Iowa State was submitted from the Southern Region and we have received protocol concurrence. The FDA had questions on the analytical method and we had planned to complete method validation beginning in June, 2013. The method validation is on-hold pending guidance from the FDA primarily concerning requirements for GLP studies for the MUADP. The study itself has been given a lower priority due to lack of funding and uncertainty over GLP issues.<br /> <br /> Draxxin Efficacy in Goats<br /> This is now largely in the hands of the FDA/CVM. Zoetis may be working on this.<br /> <br /> Fenbendazole Target Animal Safety in Pheasants<br /> We received a technical section incomplete letter on the study report. Additional data, clarification revised statistical analysis and justification of study procedures have been submitted. The reproductive safety portion of the work was not acceptable but the label will just state that reproductive safety has not been demonstrated. A paper covering this work and the reproductive safety data has been published in Avian Diseases.<br /> <br /> Ivermectin Cattle Fever Tick Efficacy<br /> This project is being done 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 as well as with Postive Feeds, Ltd. A conference call was held in November to discuss how to proceed with this portion of the project. Two herds (pastures) have been totally cleared of cattle fever ticks and additional data is available on pastures with low tick burdens on which the cattle were fed the ivermectin tubs. It was concluded that a study report covering the data we have to date will be prepared and submitted to the FDA/CVM The right of reference from Merial is remains unresolved.<br /> <br /> Pregnant Mare Serum Gonadotrophin-ADR 0353<br /> 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. No further action at this point.<br />

Publications

Publications During this Period<br /> <br /> 1) Rivera-Garcia, S., Angelos, J. A., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Van Liew, D. B., and Tell, L. A. (2014) Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep, Am J Vet Res 75, 290-295.<br /> <br /> 2) McDonnel, S. J., Tell, L. A., and Murphy, B. G. (2014) Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats, J Vet Pharmacol Ther 37, 196-200.<br /> <br /> 3) Kinney, M. E., Lamberski, N., Wack, R., Foster, R., Neely, M., Tell, L., and Gehring, R. (2014) Population pharmacokinetics of a single intramuscular administration of tulathromycin in adult desert tortoises (Gopherus agassizii), J Vet Pharmacol Ther 37, 500-507.<br /> <br /> 4) Grismer, B., Rowe, J. D., Carlson, J., Wetzlich, S. E., and Tell, L. A. (2014) Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus), J Vet Pharmacol Ther 37, 205-208.<br /> <br /> 5) Griffith, R., Yaeger, M., Hostetter, S., Tell, L. A., Wetzlich, S., Vickroy, T., Lillie, B., MacFarlane, W., Laudenslager, T., Whitley, E., Dzikamunhenga, R., and Larson, W. (2014) Safety of fenbendazole in Chinese ring-necked pheasants (Phasianus colchicus), Avian Dis 58, 8-15.<br /> <br /> 6) Groocock, G.H., Getchell, R.G., Cornwell, E.R. Frattini, S.A. Wooster, G.A. and Bowser, P.R. (2013) Iodophor disinfection of walleye eggs exposed to viral hemorrhagic septicemia virus type iVB. North American Journal of Aquaculture. 75:25-33.<br /> <br /> 7) Wu, H., Baynes, R. E., Leavens, T., Tell, L. A., and Riviere, J. E. (2013) Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle, J Vet Pharmacol Ther 36, 248-257.<br /> <br /> 8) Washburn, K. E., Fajt, V. R., Lawhon, S. D., Adams, L. G., Tell, L. A., and Bissett, W. T. (2013) Caprine abscess model of tulathromycin concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis following subcutaneous or intrachamber administration, Antimicrobial Agents and Chemotherapy 57, 6295-6304.<br /> <br /> Abstracts and Presentations<br /> <br /> 1. Smith J, Angelos J, Rowe J, Carlson J, Lee, L, Tell LA. Pharmacokinetics of flunixin meglumine in plasma and milk of domestic goats (Capra aegagrus hircus) following single subcutaneous dosing. UC Davis Goat Day, Davis, CA, February 1, 2014, UC Davis 36th Annual House Officer Seminar Day, Davis, CA, March 21st, 2014 and ACVIM Annual Meeting, Nashville, TN, June 4-7, 2014. <br /> <br /> 2. Breyer, K.E. 2013. Evaluating the efficacy of a low-dose Garlic Compound (Allicin) Against Infection With Aeromonas salmonicida In Rainbow Trout. Master Of Science Thesis, Cornell University. 45 Pp.<br /> <br /> 3. Breyer, K.E. , Getchell, R., Wooster, G., Ketola, G., and Bowser, P. (2013) Evaluating the efficacy of a low-dose garlic compound against Aeromonas salmonicida in Rainbow trout. 2013 Clinical Investigator’s Day, Cornell University, Ithaca, New York. 18 March 2013. (Keb: Honorable Mention Award). <br /> <br /> 4. Breyer, K.E. , Getchell, R., Wooster, G., Ketola, G., and Bowser, P. (2013) Update! Garlic (Allicin): More than just flavor for your fish. 38th Eastern Fish Health Workshop, Gettysburg, PA. 29 April – 3 May 2013. <br /> <br />

Impact Statements

1. The Minor Use Animal Drug Program has received over 356 Animal Drug Requests submitted by researcher investigators at federal, state, and university laboratories, veterinarians, and animal industry personnel for approval of a specific drug for the control of a certain disease in an animal industry.
2. In the 32 years of the Program, data supplied by the Program provided for the modification of 52 label claims to include minor species, an overall average of 1.6 per year. Included in these approvals were one for rabbits, nine for game birds, 16 for fish, lobster and shrimp, 15 for meat and dairy goats, eight for bison and reindeer, one for foxes and two for honey bees. Even with the estimated increased cost per drug approval in recent years, the NRSP-7 program continues to demonstrate remarkable efficiency and cost effectiveness. Compared to an average investment of the pharmaceutical industry of $10 to $25 million for adding a label claim to an existing veterinary drug, information generated for additional label claims by the NRPS-7 program costs only approximately 20 to 50% of pharmaceutical industry costs.
3. NRSP-7 has published 211 articles in peer-reviewed journals, averaging 6.6 per year over the term of the program. The data and publications generated by the Program are also shared with the Food Animal Residue Avoidance Database (FARAD) program to further increase visibility.
4. Without the MUADP American producers of minor species would not have safe and effective products to keep their livestock healthy or their food products safe. Agricultural production of minor species is critically important to numerous regional economies in the U.S. This diverse aggregation of minor species represents approximately $4.4 billion in food and fiber farm gate revenues annually. Processing, use, and export of minor species food and fiber products represent an additional $34 billion economic impact to the U.S. Through a productive MUADP/NRSP-7, producers and veterinarians will continue to have the necessary information to prevent disease-related losses, to reduce pain and suffering in important species, and avoid contamination of our foods with drug residues.
5. The use of the Internet to optimize communications with stakeholders and program participants continues to improve in this rapidly changing medium. Since inception in 1999, the NRSP-7 website has been visited 12,690 times for an average of 2.3 visits per day. NRSP-7 believes that this represents a significant degree of interaction with stakeholders as well as the public at large.
6. Approvals and projects that have changed the outlook of two industries include the approvals of lincomycin hydrochloride water-soluble powder and tylosin tartrate powder for control of American Foulbrood in honey bees. These approvals represent a significant therapeutic addition to an industry working to reverse the declining honey bee population. The potential effect on the industry is important. Secondly, the ivermectin/molasses block formulation study currently being conducted in Texas for the control of Cattle Tick Fever, has the potential of averting a major threat to the U.S. cattle population. Several efficacy studies have supported the use of this novel formulation in cattle tick control. NRSP-7 labs in the Southern Region have worked with producers to assure a uniform distribution of ivermectin in the molasses blocks, insuring that cattle will receive uniform dosing.

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