Annual/Termination Reports:

[07/09/2005] [12/05/2005] [08/01/2006] [11/03/2006] [05/01/2007] [05/08/2008] [10/15/2008] [02/20/2009]

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From NRSP-7, Drs. L. Gary Adams, John G. Babish, John C. Baker, David G. Thawley, Paul R. Bowser, Arthur L. Craigmill, Ronald W. Griffith, and Alistair I. Webb. USDA/CREESS representative Dr. Larry R. Miller, FDA/CVM liaison Dr. Meg Oeller and Alpharma representatives Drs James P. Peters, Mark LaVorgna, Ronald Dalrymple, James T. Skinner, Scott Wassink, and Denny Hausmann.

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ATTENDANCE
The NRSP-7 technical committee is made up of a National Coordinator, 4 Regional Coordinators, 4 regional Administrative Advisors, and liaisons from USDA and FDA. The National Coordinator is Dr. John Babish (Cornell University). The Regional Coordinators are Dr. Arthur Craigmill (University of California, Davis), Dr. Alistair Webb (University of Florida), Dr. Ronald Griffith (Iowa State University), and Dr. Paul Bowser (Cornell University). The Administrative Advisors are Dr. Kirklyn Kerr (University of Connecticut), Dr. Garry Adams (Texas A&M), Dr. David Thawley (University of Nevada), and Dr. John Baker (Michigan State University). The USDA representative is Dr. Gary Sherman (Washington, DC) and the FDA liaison is Dr. Meg Oeller (Rockville, MD). Dr. Craigmill was unable to attend and was represented by his Regional Coordinator-elect, Dr. Lisa Tell. Dr. Kerr was also unable to attend. This meeting was attended by the National NADA coordinator for Aquaculture, Rosalie "Roz" Schnick as well as by stakeholders and several reviewers and managers from FDA/CVM.

Brief Summary of Minutes

Accomplishments

REGIONAL COORDINATORS' REPORTS<br /> Northeast Region: Dr. Paul Bowser <br /> Hydrogen Peroxide Project:<br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> During this reporting period one manuscript based on this project has been published in the peer-reviewed scientific literature. No additional work has been performed on this project during this study period.<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 /> A primary constraint in the availability of therapeutic compounds for the Aquaculture Community is the relatively large number of fish species that are currently cultured or that have significant potential as commercial species. Currently, research in support of a label for a therapeutic compound must be performed separately for each species for which the label is desired. We have undertaken a project designed to show the similarities in how drugs are handled by different fish species with the goal of supporting a species (crop) grouping concept for fish. We have conducted these studies in a collaborative effort with the Western Region NRSP7. Within this context, to date we have completed the following preliminary Human Food Safety/Tissue Depletion Studies using the following test articles as model compounds:<br /> <br /> Oxytetracycline:<br /> 1. Walleyes, freshwater fish, 15C and 20C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater fish, 20C and 25C<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> <br /> Romet-30:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass (would not accept the ration; see below)<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> <br /> Florfenicol:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater, 20C, 25C<br /> <br /> Data from these species will be compared to data currently available where available for the cold water species, rainbow trout (freshwater) and Atlantic salmon (marine). Data from studies of Oxytetracycline in the four species indicated above has been published in several peer-reviewed manuscripts. <br /> In addition to the species grouping effort with Oxytetracycline, we completed one cold water temperature Human Food Safety/Tissue Depletion Study in rainbow trout. This study was completed at the request of CVM/FDA. The study involved medicating market size rainbow trout and following elimination of the test article in the edible portion of the fish (filet with skin on, but descaled). The study was conducted at 8C. Oxytetracycline concentration in the edible portion never exceeded the 2.0 mg/Kg action level at any time during the study.<br /> Several attempts were made to conduct human food safety studies or Romet-30 in hybrid striped bass. Although extremely active feeding on a non-medicated ration was observed during acclimation, the hybrid striped bass refused to consume the Romet-medicated ration on all attempts to initiate a trial. As a result, hybrid striped bass were eliminated from our testing matrix for Romet-30. The Sponsor has reported that they have developed a product that circumvents the palatability problem and we anticipate efforts to complete the Human Food Safety/Tissue Elimination studies in that species. <br /> More recently, we have completed Human Food Safety/Tissue Depletion Studies using Aquaflor (Florfenicol, Schering-Plough; 10 mg drug/kg fish/day for 10 days) as a model compound, with studies completed in walleyes (20C, 25C), tilapia (25C, 30C) and hybrid striped bass (20C, 25C). <br /> In a related effort requested by the sponsor (Schering-Plough), we have evaluated the question of fish size using our standard testing protocol for Human Food Safety/Tissue Elimination studies. This study was also conducted in light of the recent communication with the sponsor that they anticipate a label dose of 15 mg drug/Kg fish/day for 10 days for the treatment of Streptococcus infection in tilapia. The in-life portion of the Tilapia size studies have been completed:<br /> <br /> 1. Tilapia  100 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 2. Tilapia  250 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 3. Tilapia  500 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> <br /> Samples from these studies are being analyzed in a cooperative effort with the Western Region NRSP7.<br /> <br /> Usefulness of the findings:<br /> 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 (Florfenicol) in trout, salmon and catfish.<br /> <br /> <br /> North Central Region: Dr. Ronald W. Griffith<br /> 1. CIDRg in sheep:<br /> Dr. Dennis Hallford at New Mexico State University has submitted the results of the tissue residue study to CVM. CVM has requested additional data on the stability of progesterone in liver and muscle tissues of normal ewes to demonstrate that there was no loss of progesterone in these tissues when stored frozen for up to 6 months. Dr. Lynn Friedlander at CVM recently gave us some guidance as to the specifics of the stability assays that were needed. Dr. Hallford has submitted a draft protocol for the stability study to CVM for review. A teleconference to discuss the protocol is being scheduled. Dr. Hallford is currently preparing to collect tissues and would like to begin the stability study at the end of May 2006 if possible.<br /> 2. CIDRg in goats:<br /> The Western Region is taking the lead in this project. Dr. Hallford has obtained normal goat milk and has reported that he is nearly ready with the validation of progesterone in milk. He has not yet attempted the validation in goat meat and liver. The North Central Region will help out with this project as needed.<br /> 3. Nuflor in veal calves:<br /> No current activity with these studies.<br /> <br /> <br /> WESTERN REGION: DRS. ARTHUR L. CRAIGMILL/LISA TELL<br /> ADR#325 - Florfenicol for sheep for respiratory diseases.<br /> Project is on hold awaiting confirmation of additional data required. Funds expended to date on this project exceed $200,000 of Western Region expenses. Of interest in this process is that the time and money spent on method validation exceeded the amount spent on analyzing the actual samples. <br /> ADR#324 - Progesterone Ciders for goats. <br /> The TAS study is complete and we are awaiting a report from the principal investigator. <br /> ADR#272 - Romet for gamebirds.<br /> The PBPK model for the birds will be accomplished during the summer of 2006. Whole animal studies have been run in all species for serum pharmacokinetics of midazolam, the CYP3 market substrate. <br /> ADR#299 - Pirlimycin for dairy goats.<br /> No progress since last meeting.<br /> ADR#295 - Strontium chloride for Salmonids. <br /> Nothing to report from Steve Schroeder the PI.<br /> ADR#311 - Lincomycin for honeybees<br /> Data were accepted by CVM and a Public Master File has been published.<br /> <br /> SOUTHERN REGION: DR. ALISTAIR I. WEB<br /> The GLP inspections of our ivermectin assay and in vivo sections by the Western Region have been completed and all issues addressed satisfactorily.<br /> RABBITS<br /> ADR #107 Ivermectin & Rabbits<br /> The assay has been validated and the in vivo depletion stage is completed. The assay is being bridged with beef [species the residue method was developed in]. <br /> <br /> FISH<br /> ADR #271 CRUDE CARP PITUITARY<br /> The TAS report has not found favor with FDA. The author is preparing a rebuttal and we will see if the report is salvageable. What is groups view on funding any repeat on the project given this and low likelihood of a manufacturer being found. <br /> <br /> ADR#235 Ovaprim<br /> UFL Tropical Fish [Roy Yanong] and Syndel are working with CVM to define needs. At present our only involvement is to provide GLP support for any TAS studies. This may be an alternative to CCPE as a spawning aid.<br /> <br /> ADR #236 metomidate<br /> Following a teleconference with CVM, UFL Tropical Fish [Roy Yanong] has been evaluating behavioral changes as markers of efficacy of metomidate for sedation during transport. Pilot studies have not been promising. This may push them back to studying cortisol depression as an index of stress relief. My anesthesiologist hat is concerned as this group of drugs has a potent depressant effect on adrenal function in mammals, which would confound their study.<br /> <br /> BIRDS<br /> ADR #280 FENBENDAZOLE & GAMEBIRDS<br /> The TAS report is nearly complete but lacks investigators final input and QA . We are waiting for Western Regions depletion assay results and it is hoped that there will be a fast turn round in submitting that to CVM.<br /> <br /> DEER<br /> ADR #210 Fenbendazole & Red Deer & ADR  216 Fenbendazole & Fallow <br /> We had an in-person conference with CVM and Intervet to spell out requirements but Intervet is seeking more clarification  especially TAS kinetic requirements. Plan at the moment is that NRSP-7 will do the TAS and human safety and the efficacy, conducted by Intervet, will follow  risk there is if the effective dose is higher that that used in the two former studies they would have to be repeated. The investigator for the TAS and human safety work has been identified but has cooling ardor. Intervet have limited their interest to white tailed deer but I have made it clear to FDA NRSP-7s goal is for Cervid. In the conference studies of WTD, red deer/elk and fallow deer would gain a Cervid label.<br /> <br /> ADR #294 Lasalocid And Deer / ADR #298 Lasalocid And Goats<br /> A teleconference was held November 18th 2005 to define requirements and develop budgets. Like the FBZ project, Alpharma will do the efficacy after the TAS and Human safety with the same risks involved. We have investigators lined up for both deer and goat work at UFL. Problem is that Alpharma will only proceed if there is a zero withdrawal time<br /> <br />

Publications

(1) Smith, G. W., Gehring, R., Craigmill, A. L., Webb, A. I., and Riviere, J. E. Extralabel intramammary use of drugs in dairy cattle. J Am Vet Med Assoc 2005, 226, 1994-6.<br /> (2) KuKanich, B., Gehring, R., Webb, A. I., Craigmill, A. L., and Riviere, J. E. Effect of formulation and route of administration on tissue residues and withdrawal times. J Am Vet Med Assoc 2005, 227, 1574-7.<br /> (3) Haskell, S. R., Payne, M., Webb, A., Riviere, J., and Craigmill, A. L. Antidotes in food animal practice. J Am Vet Med Assoc 2005, 226, 884-7.<br /> (4) Gehring, R., van der Merwe, D., Pierce, A. N., Baynes, R. E., Craigmill, A. L., and Riviere, J. E. Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle. Am J Vet Res 2005, 66, 108-12.<br /> (5) Gehring, R., Haskell, S. R., Payne, M. A., Craigmill, A. L., Webb, A. I., and Riviere, J. E. Aminoglycoside residues in food of animal origin. J Am Vet Med Assoc 2005, 227, 63-6.<br /> <br />

Impact Statements

1. Since the first drug approval in 1984 under the former IR-4 program, NRSP-7 has been responsible for generating 31 Public Master File (PMF) publications in the Federal Register, an average of 1.5 per year during its 21 years of funding.
2. Seven data packages have been submitted for review by the Food and Drug Center for Veterinary Medicine. Among those submitted this year were data packages for human food safety/tissue elimination kinetics studies of oxytetracycline in tilapia, walleye, summer flounder, and hybrid striped bass were submission to the Center for Veterinary Medicine for review. Additionally, the Human Food Safety studies of florfenicol for the treatment of respiratory infections in sheep were completed and a final report has been sent to FDA/CVM for review.
3. To date 341 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 14 active research projects involving nine animal species and 11 different drugs.

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PARTICIPANTS
The NRSP-7 technical committee is made up of a National Coordinator, 4
Regional Coordinators, 4 regional Administrative Advisors, and liaisons from USDA and
FDA. The National Coordinator is Dr. John Babish (jgb7@conrell.edu Cornell
University). The Regional Coordinators are Dr. Arthur Craigmill
(alcraigmill@ucdavis.edu University of California, Davis), Dr. Alistair Webb
(Webb@ufl.edu University of Florida), Dr. Ronald Griffith (rgriffit@iastate.edu Iowa State
University), and Dr. Paul Bowser (prb4@cornell.edu Cornell University). The
Administrative Advisors are Dr. Kirklyn Kerr (Kirklyn.Kerr@uconn.edu University of
Connecticut), Dr. Garry Adams (gadams@cvm.tamu.edu Texas A&M), Dr. David
Thawley (thawley@cabnr.unr.edu University of Nevada), and Dr. John Baker
(Baker@anr.msu.edu Michigan State University). The USDA representative is Dr. Gary
Sherman (gsherman@CSREES.USDA.GOV Washington, DC) and the FDA liaison is
Dr. Meg Oeller (margaret.oeller@fda.hhs.gov Rockville, MD). Dr. Craigmill was unable
to attend and was represented by his Regional Coordinator-elect, Dr. Lisa Tell
(latell@ucdavis.edu University of California, Davis). Drs. Kerr and Thawley were also
unable to attend. This meeting was also attended by the National NADA coordinator for
Aquaculture, Rosalie "Roz" Schnick (RozSchnick@centurytel.net). Our host
representatives were Drs. William Gingerich and Randy Hines (rkhines@usgs.gov).

Brief Summary of Minutes

TOUR OF THE FACILITIES AND RESEARCH PROGRAMS
Dr. Randy Hines conducted a tour of the facilities that included detailed presentations of all current projects as well as an historical perspective.


PRESENTATION BY NATIONAL NADA COORDINATOR FOR AQUACULTURE
Roz Schnick gave a presentation, Aquaculture Drug Approval Highlights of Progress. She described the achievements of several different entities, including the Upper Midwest Environmental Sciences Center, conducting studies to support drug approvals. Roz reported significant progress on projects exploring claims for Aqui-Sê (anesthetic), chloramine-T, Florfenicol, formalin, hydrogen peroxide, 17 alpha methyltestosterone, and oxytetracycline. She also described a survey that she conducted to identify unmet label claims in the public sector. Results will soon be distributed to the 38 participating states through the Drug Approval Working Group. Ms. Schnick also described her internet-based drug matrix database, which provides general information and reports on the status of studies supporting aquaculture drug development.


FDAS NRSP-7 LIAISON REPORT
Dr. Oeller reported on CVM current events including an update on MUMS, personnel changes in Office of MUMS, Animal Drug User Fee Act (ADUFA), minor use determinations and CVM commitment to Minor Species. On the status of implementing MUMS regulations, Dr. Oeller indicated that the final designation regulations and the proposed small numbers for determining minor use are both pending. The proposed Indexing regulations have been published and the comment period closes 12/20/06. The Office of MUMS has received over 50 Designation requests and has granted 38 of them to date.

With regard to the personnel changes in the Office of MUMS, Dr. Oeller indicated that the transition period for Dr. Bernadette Dunham to take over the position of Dr. Bealieu has begun with completion scheduled for January 2007.

On the Animal Drug User Fee Act (ADUFA), Dr. Oeller indicated that waivers for minor species and minor uses are still available and the ADUFA renewal for NRSP-7 has been granted.

As related by Dr. Oeller, Minor Use Determinations are currently being done on a case-by-case basis and that they are important for ADUFA waivers, Conditional Approval and Designation. The task of Minor Use Determinations will be easier when the small number for minor use is officially determined.

In closing, Dr. Oeller emphasized that CVM will (1) continue to support the attempts to get drugs approved for minor species and minor uses, (2) support NRSP-7 through its FDA liaison, (3) provide waiver from ADUFA fees while providing the same quality of service as for those who must pay. Through the Office of Minor Use/Minor Species, CVM will make designations, administer grants, review indexing request, make minor use determinations, and provide outreach to sponsors, industry groups and the public.

Accomplishments

REGIONAL COORDINATORS' REPORTS<br /> Northeast Region: Dr. Paul Bowser <br /> Hydrogen Peroxide Project:<br /> <br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> No additional work has been performed on this project during this study period.<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 /> A primary constraint in the availability of therapeutic compounds for the Aquaculture Community is the relatively large number of fish species that are currently cultured or that have significant potential as commercial species. Currently, research in support of a label for a therapeutic compound must be performed separately for each species for which the label is desired. We have undertaken a project designed to show the similarities in how drugs are handled by different fish species with the goal of supporting a species (crop) grouping concept for fish. We have conducted these studies in a collaborative effort with the Western Region NRSP7. Within this context, to date we have completed the following preliminary Human Food Safety/Tissue Depletion Studies using the following test articles as model compounds:<br /> <br /> Oxytetracycline:<br /> 1. Walleyes, freshwater fish, 15C and 20C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater fish, 20C and 25C<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> 5. Rainbow Trout, cold water trial (8C)<br /> <br /> Romet-30:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass (would not accept the ration;see below)<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> <br /> <br /> Florfenicol (10 mg/Kg/d, 10d):<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater, 20C, 25C<br /> <br /> Florfenicol (Effect of fish size)<br /> 1. Tilapia  100 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 2. Tilapia  250 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 3. Tilapia  500 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d <br /> <br /> Several attempts were made to conduct human food safety studies or Romet-30 in hybrid striped bass. Although extremely active feeding on a non-medicated ration was observed during acclimation, the hybrid striped bass refused to consume the Romet-medicated ration on all attempts to initiate a trial. As a result, hybrid striped bass were eliminated from our testing matrix for Romet-30. The Sponsor has reported that they have developed a product that circumvents the palatability problem and we anticipate efforts to complete the Human Food Safety/Tissue Elimination studies in that species. <br /> <br /> Samples from several of the Florfenicol studies are currently being analyzed in a cooperative effort with the Western Region NRSP7.<br /> <br /> USEFULNESS OF THE FINDINGS:<br /> In all cases, the findings 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) in trout, salmon and catfish.<br /> <br /> WORK PLANNED FOR NEXT YEAR:<br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> No additional work is planned for this project in the upcoming 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 conducting Efficacy Studies, with a focus on oxytetracycline during the coming year. These studies will be performed 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 salmonids and for the 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 /> During the coming year we anticipate the completion of tissue assays for samples generated from Human Food Safety/Tissue Elimination Studies of Aquaflor in Hybrid Striped Bass and Tilapia.<br /> <br /> Rofenaid in Pheasants INAD 10-804<br /> We are considering the conduct of an efficacy trial of Rofeniad for the treatment of coccidia in pheasants.<br /> <br /> Minor Species Efforts in Goats<br /> Preliminary efforts are underway to establish a minor species project in the Northeast Region that will focus on needs of the goat industry. This effort will be under the leadership of Dr. Mary Smith, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University. Specific details of this study are still in the developmental stages.<br /> <br /> <br /> North Central Region: Dr. Ronald W. Griffith<br /> CIDRg in sheep. Dr. Dennis Hallford at New Mexico State University is completing the assays for determination of progesterone stability in frozen liver and muscle tissue. Interestingly, when fresh liver is spiked with exogenous progesterone, the liver enzyme systems continue to function. Assays for progesterone in liver tissue indicate that only background levels are detected within 1 hour of spiking. The stability assay in frozen liver tissue only needed to be conducted out to 30 days and that portion of the study is completed. Dr. Hallford is continuing to assay for progesterone levels in frozen muscle tissue and will likely complete this in January. <br /> <br /> Lasalocid in ring-necked pheasants. A product development conference with ONADE and Alpharma is scheduled for October 18, 2006. A protocol for determination of efficacy has been submitted to CVM. The efficacy studies are being done in cooperation with Dr. Thomas McQuistion in Milliken University in Decatur, Ill. That study should get underway next spring barring any unforeseen developments.<br /> <br /> Draxxin in goats and sheep. A product development meeting between the NC Region, ONADE, Meg Oeller and Pfizer was held on October 2, 2006. Protocols for Efficacy, Target Animal Safety, and Human Food Safety (tissue residues) have been submitted to CVM for studies in goats. Once those protocols are reviewed, they will be adapted for sheep. The efficacy study requires significant revision since ONADE is going to require a moderately large field trial. <br /> <br /> CIDRg in goats. The assay for progesterone in milk is ready to be validated Dr. Dennis Hallford at New Mexico State University.<br /> <br /> Bioclip for shearing sheep. No response from Merial on this project. This product is currently licensed for use in Australia. It is injected subcutaneously into sheep. It causes a wool break and the wool is then shed. A net is placed around the sheep at the same time Bioclip is injected and the net keeps the wool in place. After about a month, the net and fleece are removed. The product works best in Merino or half-Merino sheep.<br /> <br /> Regulin for sheep. CEVA is interested but has not decided whether they wish to pursue approval for Regulin in the US. I have protocol approval from ISUs IACUC but have not written any protocols or requested a product development conference. Regulin is a melatonin implant that is approved for use in Australia. It is used to stimulate sheep to come into estrus sooner and has the added benefit of increasing the number of lambs conceived per ewe. <br /> <br /> Nuflor in veal calves. No recent activity.<br /> <br /> <br /> WESTERN REGION: DR. LISA TELL<br /> Progress of Work and Principal Accomplishments:<br /> ACTIVE Regional Projects:<br /> ADR#325 - Florfenicol for sheep for respiratory disease.<br /> Funds expended to date on this project exceed $200,000 of Western Region resources. CVM response regarding submitted MIC data has been received. MIC data accepted for publication in JAVMA.<br /> ADR#324 - Progesterone CIDRs for Goats<br /> The TAS study is complete. Report from the principal investigator is in progress.<br /> ADR#272 - Romet for Gamebirds<br /> See species grouping report.<br /> ADR#299 - Pirlimycin for Dairy Goats<br /> No progress since last meeting, move to inactive projects. <br /> ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder<br /> Nothing to report from the region.<br /> ADR#338  Spectramast" LC Sterile Suspension for Mastitis in Dairy Goats<br /> This project is ready to proceed with the support of Pfizer. Dr. Rowe as indicated interest in being involved with this study.<br /> ADR#135  Erythromycin in Salmonids<br /> Environmental safety report is in progress. Eric Rosenblum met with Christine Moffit and Meg Oeller. Eric Rosenblum is awaiting reference data for the EA. Once he receives these references he should be close to providing a rough draft version. <br /> ADR# 311 Lincomycin soluble powder for foulbrood disease in Honeybees.<br /> <br /> Collaborative Projects:<br /> ADR#280 - Fenbendazole in game birds (Pheasants, bobwhite quail, partridge)<br /> See Southern Region report.<br /> Species Grouping Fish: <br /> Samples currently undergoing analysis for florfenicol, see Dr. Bowsers report, NER. In our laboratory so far this year, for the fish species grouping project we have analyzed 90 plasma and 335 muscle. WR Laboratory personnel are currently working on the remaining 25 muscle samples from trial 2005-3 and 2005-4 (120 each) and the remainder of the muscle samples from 2004-1 (90). <br /> <br /> Other Projects:<br /> Species Grouping:<br /> Krsity Cortright is entering her second year of veterinary school, and has finished her work on the in vitro and in vivo studies. Her paper on the first portion of the in vitro modeling has been accepted for publication in JVPT. Whole animal studies have been run in all species for serum pharmacokinetics of midazolam, the CYP3 marker substrate. Scott Wetzlich has worked out a good method for extracting parent midazolam and metabolites from tissues and has analyzed 1000 liver, muscle, and fat samples. Kristy finished the PBPK modeling this summer using these tissue data to compete her Ph.D. work. <br /> <br /> Related and Unfunded Projects:<br /> Nuflor veal calf  Dr. Griffiths samples are complete. <br /> <br /> New Projects:<br /> Nothing to report at this time.<br /> <br /> <br /> SOUTHERN REGION: DR. ALISTAIR I. WEB<br /> PROJECTS IN PROGRESS:<br /> The GLP inspections of our ivermectin assay and in vivo sections by the Western Region has been completed and all issues addressed satisfactorily.<br /> <br /> RABBITS<br /> ADR  107 Ivermectin & Rabbits<br /> <br /> The in-vivo human safety has been completed and the tissues are currently being assays. Hopefully that will be completed by the new year and reports prepared for submission to FDA-CVM. <br /> <br /> FISH<br /> ADR - 271 Crude Carp Pituitary<br /> The author has not submitted a revised report that could address FDA-CVMs concerns. a rebuttal and we will see if the report is salvageable. What is groups view on funding any repeat on the project given this and low likelihood of a manufacturer being found.<br /> ADR  235 Ovaprim<br /> <br /> UFL Tropical Fish [Roy Yanong] and Syndel are working with CVM to define needs. At present our only involvement is to provide GLP support for any TAS studies. This may be an alternative to CCPE as a spawning aid.<br /> ADR  236 Metomidate<br /> <br /> Following a teleconference with CVM, UFL Tropical Fish [Roy Yanong] has been evaluating behavioral changes as markers of efficacy of metomidate for sedation during transport. Pilot studies have not been promising. This may push them back to studying cortisol depression as a index of stress relief. My anesthesiologist hat is concerned as this group of drugs has a potent depressant effect on adrenal function in mammals which would confound their study.<br /> <br /> BIRDS<br /> ADR - 280 Fenbendazole & Gamebirds <br /> The TAS report is nearly complete but lacks investigators final input and QA . We have received the Western Regions depletion assay results and are preparing a packet for submission to FDA-CVM.<br /> <br /> DEER<br /> ADR  210 Fenbendazole & Red Deer & ADR  216 Fenbendazole & Fallow <br /> <br /> Intervet have indicated that they want us to carry out the human safety part of the approval. We have started negotiations with Dr.Shane Donley on conducting the in-vivo work with Western Region but I have made it clear to FDA-CVM that NRSP-7s goal is for Cervid. In the product conference we were told that studies of WTD, red deer/elk and fallow deer would gain a Cervid label.<br /> <br /> ADR - 294 Lasalocid And Deer / ADR - 298 Lasalocid And Goats<br /> <br /> Problem is that Alpharma will only proceed if there is a zero withdrawal time. We are starting to mount an assay and will carry out initial pilots on two deer and two goats to see if the lasalocid levels are below tolerance.<br /> <br /> WORK PLANNED FOR THE REMAINDER OF THE YEAR: <br /> " Maintain lab and staff at GLP level<br /> " Submit early in the new year the all ivermectin for rabbit reports and all fenbendazole reports.<br /> " Organize studies for gaining approval of fenbendazole & lasalocid in deer, and lasalocid in goats.<br /> " Prepare, in coordination with the National Coordinator, INAD submissions for studies conducted under the aegis of the Southern Region. Initial preparation of written responses to CVM review of all of the data submitted for each project. This is often a time consuming and unrecognized activity associated with the completion of each project and may require considerable correspondence and conversation.<br /> " Continued collaborative work with the other regions is anticipated and may include unplanned studies to address critical needs and opportunities to collect data.<br /> " Continue the development of the NRSP-7 web site with full activation of the RUSTi database.<br /> <br /> New / Proposed Projects:<br /> Last meeting I reported: Fasinex® in deer continues to interest us but gathers dust while we see how other deer projects go. Trichlorbendazole is a drug that Novartis has approved for sheep, cattle and deer in Europe. It is especially being requested for red and fallow deer which are unnatural hosts for Fascioloides and it is frequently fatal. Novartis have perked up on this but say their tox package is old and may have a rough passage through FDA. The lure of MUMS and possibility of major species extension later may get them to play. Given problems with deer approvals I would recommend this be put on hold until we have a production line in place.<br /> We have received an ADR for moxidectin in deer from NCSU. Either our invermectin assay or their analytic lab maybe be able to handle the residue assays  Southern region cannot handle this project at this time.<br /> Another possible goat project is flunixin or some other NSAID for relief of pain. Comment re-Southern Region accepting any new projects hold here too.<br /> <br /> Web Site<br /> The NRSP-7.org web has continued to function well but is need of some development such as PowerPoint Presentations. The University is cranking-up security and is centralizing control of IT. We are concerned but we have been model citizens plus we actually got our original permission to host the web site without obvious use of the ufl.edu domain from the current head of IT. The MUMSRx web database continues to be updated  it alone receives 1-2 hits each day. Rusti is now fully functional and Laura has returned to full-time work. We will be working with each coordinator to get active projects fully entered into the system. <br /> <br />

Publications

(1) Payne, M. A., Craigmill, A., Riviere, J. E., and Webb, A. I. Extralabel use of penicillin in food animals. J Am Vet Med Assoc 2006, 229, 1401-3.<br /> (2) Smith, G. W., Gehring, R., Craigmill, A. L., Webb, A. I., and Riviere, J. E. Extralabel intramammary use of drugs in dairy cattle. J Am Vet Med Assoc 2005, 226, 1994-6.<br /> (3) KuKanich, B., Gehring, R., Webb, A. I., Craigmill, A. L., and Riviere, J. E. Effect of formulation and route of administration on tissue residues and withdrawal times. J Am Vet Med Assoc 2005, 227, 1574-7.<br /> (4) Haskell, S. R., Payne, M., Webb, A., Riviere, J., and Craigmill, A. L. Antidotes in food animal practice. J Am Vet Med Assoc 2005, 226, 884-7.<br /> (5) Gehring, R., van der Merwe, D., Pierce, A. N., Baynes, R. E., Craigmill, A. L., and Riviere, J. E. Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle. Am J Vet Res 2005, 66, 108-12.<br /> (6) Gehring, R., Haskell, S. R., Payne, M. A., Craigmill, A. L., Webb, A. I., and Riviere, J. E. Aminoglycoside residues in food of animal origin. J Am Vet Med Assoc 2005, 227, 63-6.<br /> <br />

Impact Statements

1. Since the first drug approval in 1984 under the former IR-4 program, NRSP-7 has been responsible for generating 31 Public Master File (PMF) publications in the Federal Register, an average of 1.5 per year during its 21 years of funding.
2. Seven data packages have been submitted for review by the Food and Drug Center for Veterinary Medicine. Among those submitted this year were data packages for human food safety/tissue elimination kinetics studies of oxytetracycline in tilapia, walleye, summer flounder, and hybrid striped bass were submission to the Center for Veterinary Medicine for review. Additionally, the Human Food Safety studies of florfenicol for the treatment of respiratory infections in sheep were completed and a final report has been sent to FDA/CVM for review.
3. To date 341 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 14 active research projects involving nine animal species and 11 different drugs.

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Report Information

Participants

PARTICIPANTS
NAME AFFILIATION EMAIL ADDRESS
A. Adams CVM/ONADE/HFV-131 Aadams1@cvm.fda.gov
Alistair Webb NRSP-7/U FL Webb@ufl.edu
Andrew Beaulieu CVM/ONADE/OMUMS abeaulieu@cvm.fda.gov
Art Craigmill NRSP-7/UC DAvis alcraigmill@ucdavis.edu
Charise Kasser CVM/OSC/HFV-212 ckasser@cvm.fda.gov
Charles Eirkson CVM/ONADE/HFV-103 ceirkson@cvm.fda.gov
Cindy Wolf U Minnesota wolf006@umn.edu
Denise Petty U of FL/CVM pettyd@ufl.edu
Doris J. Newton USDA/ERS DNEWTON@ers.usda.gov
Eric Silberhorn CVM/ONADE/HFV-103 esilberk@cvm.fda.gov
Evert Byington USDA/ARS exb@ars.usda.gov
Garry Adams AA/CVM/Texas A&M gadams@cvm.tamv.edu
Harlan Howard CVM/ONADE/HFV-126 hhoward@cvm.fda.gov
James Nitao CVM/ONADE/Hfr-140 jnitao@cvm.fda.gov
Joan Gotthardt CVM/ONADE/HFV-130 jgotthar@cvm.fda.gov
John Babish NRSP-7 jgb7@cornell.edu
John C. Baker AA/MI College of Vet Med baker@cvm.msu.edu
John Machado CVM/OSC/HFV-228 jmachado@cvm.fda.gov
Larry Miller USDA-CSREES lmiller@csrees.usda.gov
Lisa Tell NRSP-7/UC Davis latell@ucdavis.edu
Lynn G. Friedlander FDA/CVM lfriedla@cvm.fda.gov
Meg Oeller FDA/CVM moeller@cvm.fda.gov
Michael Popek CVM/ONADE/DMT mpopek@cvm.fda.gov
Paul Rodgers American Sheep Industry Assn prodgers2@earthlink.net
Ron Griffith NRSP-7 rgriffit@iastate.edu
Roz Schnick MSU RozSchnick@centurytel.net
Sibyl Wright USDA/FSIS SIBYL.WRIGHT@FSIS.USDA.GOV
Susan Storey CVM/ONADE/HFV-131 sstorey@cvm.fda.gov

Brief Summary of Minutes

Accomplishments

REGIONAL COORDINATORS' REPORTS<br /> Northeast Region: Dr. Paul Bowser <br /> WORK COMPLETED<br /> Hydrogen Peroxide Project:<br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> No additional work has been performed on this project during this study period.<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 /> A primary constraint in the availability of therapeutic compounds for the Aquaculture Community is the relatively large number of fish species that are currently cultured or that have significant potential as commercial species. Currently, research in support of a label for a therapeutic compound must be performed separately for each species for which the label is desired. We have undertaken a project designed to show the similarities in how drugs are handled by different fish species with the goal of supporting a species (crop) grouping concept for fish. We have conducted these studies in a collaborative effort with the Western Region NRSP7. Within this context, to date we have completed the following preliminary Human Food Safety/Tissue Depletion Studies using the following test articles as model compounds:<br /> <br /> Oxytetracycline:<br /> 1. Walleyes, freshwater fish, 15C and 20C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater fish, 20C and 25C<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> 5. Rainbow Trout, cold water trial (8C)<br /> <br /> Romet-30:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass (would not accept the ration;<br /> see below)<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> <br /> Florfenicol (10 mg/Kg/d, 10d):<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater, 20C, 25C<br /> <br /> Florfenicol (Effect of fish size)<br /> 1. Tilapia  100 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 2. Tilapia  250 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 3. Tilapia  500 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d <br /> Several attempts were made to conduct human food safety studies or Romet-30 in hybrid striped bass. Although extremely active feeding on a non-medicated ration was observed during acclimation, the hybrid striped bass refused to consume the Romet-medicated ration on all attempts to initiate a trial. As a result, hybrid striped bass were eliminated from our testing matrix for Romet-30. The Sponsor has reported that they have developed a product that circumvents the palatability problem and we anticipate efforts to complete the Human Food Safety/Tissue Elimination studies in that species. <br /> <br /> Samples from all of the above noted Florfenicol studies are currently being analyzed in a cooperative effort with the Western Region NRSP7.<br /> <br /> WORK PLANNED FOR THE COMING YEAR<br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> No additional work is planned for this project in the upcoming 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 conducting Efficacy Studies, with a focus on oxytetracycline during the coming year. These studies will be performed 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 salmonids and for the 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 /> During the coming year we anticipate the completion of the remaining tissue assays for samples generated from Human Food Safety/Tissue Elimination Studies of Aquaflor (Florfenicol) in Hybrid Striped Bass and Tilapia.<br /> <br /> Rofenaid in Pheasants INAD 10-804<br /> We are considering the conduct of an efficacy trial of Rofeniad for the treatment of coccidia in pheasants.<br /> <br /> Minor Species Efforts in Goats<br /> Preliminary efforts are underway to establish a minor species project in the Northeast Region that will focus on needs of the goat industry. This effort will be under the leadership of Dr. Mary Smith, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University. Specific details of this study are still in the developmental stages.<br /> <br /> North Central Region: Dr. Ronald W. Griffith<br /> Sheep CIDR-g Tissue Residue Stability<br /> This study is being performed by Dr. Dennis Hallford at New Mexico State University in cooperation with both the Western and North Central Regions. The assays for the freezer stability of progesterone have been completed, the data has been reviewed by the NC Region coordinator and submitted to the Western Region for QA documentation. Conclusions of the tissue residue study are that exogenous progesterone from the CIDR-g intravaginal insert are essentially zero 24 hours following removal of the CIDR-g. Fresh liver tissue has a high capacity for metabolizing progesterone. No residues were found in fresh (non-frozen) liver tissue spiked with exogenous progesterone and processed within 30 minutes of the addition of the progesterone. Progesterone is stable in frozen muscle tissues and frozen/thawed muscle tissues for at least 6 months following addition of exogenous progesterone. The data package from this study should be ready for submission to CVM shortly.<br /> <br /> Goat CIDR-g Tissue and Milk Residue <br /> The milk residue assay has been validated but the protocol for this study has not been written and obviously has not been submitted for review. Dr. Dennis Hallford is currently altering the sheep protocol to fit goats. He plans on doing both the in-life and analytical phase of the liver and muscle tissue portions of the study entirely at New Mexico State University using Boer-cross goats. For the milk residue portion of the study, he plans on doing the analytical phase but has requested that the in-life phase be done either by the Western or North Central Regions. He has demonstrated that progesterone is stable in frozen goat milk. As long as the milk is frozen shortly after (within 30 minutes) of collection, the assay should be valid.<br /> <br /> Draxxin Efficacy in Goats<br /> Two different protocols have been submitted to CVM for review. ONADE requested a natural exposure model in two different geographic locations within the U.S. using Arepresentative breeds@ and a total of 60 treated and 30 to 60 non-treated goats. ONADE also asked for antimicrobial susceptibility testing on at least 30 isolates of each bacterial species recovered from these goats. Texas A&M University will be one geographic site and Iowa State University will be the second site. A preliminary study this spring is planned to ascertain if enough goats can be Amanaged@ poorly enough to induce natural respiratory disease at a rate that will make this a practical study.<br /> <br /> The second protocol submitted is a lung pharmacokinetic model. This study proposes to recover pulmonary fluids from treated goats over a period of time and then assay these fluids for tulathromycin levels. This would be coupled with antimicrobial susceptibility testing of 50 to 100 isolates of Mannheimia haemolytica, Pasteurella multocida and Mycoplasma species from diverse geographic locations within the U.S. The lung fluid samples will be obtained at Iowa State University and analysed by LCMS at U.C., Davis. The antimicrobial susceptibility testing will be done at Texas A&M by Dr. Mitzy Libal.<br /> <br /> Draxxin Target Animal Safety<br /> The protocol has been submitted to CVM for review.<br /> <br /> Draxxin Tissue Residue<br /> The protocol has been submitted to CVM for review.<br /> <br /> Lasalocid Efficacy in Pheasants<br /> The protocol has been submitted to CVM for review. This study was originally going be done in cooperation with Dr. Thomas McQuistion. However, the number of pheasants required by ONADE for the study exceeded the capacity of the facilities at Milliken University. We are now planning on working with Dr. Larry McDougald at the University of Georgia. Inocula from two different geographic locations within the U.S. will be tested in two separate trials.<br /> <br /> Bioclip in Sheep<br /> No response from Merial to our inquiries.<br /> <br /> Regulin (melatonin) implants for sheep<br /> No activity to report. CEVA representative will be moving to Kansas City this spring. Contact will be made at that time to determine if CEVA is interested in supporting approval.<br /> <br /> LCMS Purchase<br /> Financial support is being provided for purchase of an LCMS for the Western Region Lab.<br /> <br /> <br /> WESTERN REGION: DR. LISA TELL<br /> PROGRESS OF WORK AND PRINCIPAL ACCOMPLISHMENTS:<br /> ADR #325 - Florfenicol for Sheep (Treatment for Respiratory Disease) - During this reporting period the Tissue Residue Depletion after Multiple Subcutaneous Administration of Florfenicol in Sheep results were presented by Scott Wetzlich at the 10th EAVPT (European Association of Veterinary Pharmacology and Toxicology) meeting, September 17-22, 2006 in Turin, Italy. The MIC data that was submitted for this study was re-summarized, geographically mapped (to demonstrate regions in California that were represented) and resubmitted to CVM for review. We also requested that CVM review a historical product development call where it was stated that they would accept MIC data from Europe as part of the package. At this time, based on an informal response from CVM, it appears that we will not be able to progress any further with this project.<br /> <br /> ADR #324 - Progesterone CIDRs for Goats - The Target Animal Safety Study Final Report is finished and is now undergoing quality assurance review. The development of the efficacy protocol is underway. Drs. Tell, Rowe, Griffith, and Craigmill have requested a conference call with CVM to receive guidance for the protocol.<br /> <br /> ADR #135  Erythromycin in Salmonids - FDA/CVM has contacted the Study Director, Dr. Christine Moffitt, stating that the Technical Section has been accepted as soon as there is an authorization letter from Abbott for CVM to use their proprietary toxicology data as the basis for the ADI. Once that is established, the Technical Section Complete letters for effectiveness, target animal safety, and human food safety will be complete. Dr. Moffitt is also reviewing the draft Environmental Assessment Report.<br /> <br /> ADR # 311 Lincomycin Soluble Powder For Treating Foulbrood Disease in Honeybees. - Efficacy Study - a pilot study was reviewed and comments provided. The pivotal study was conducted at the same time and used the same protocol as the tylosin study which was accepted. Final study report is pending. Target Animal Safety - Technical section completed (letter dated11/23/2001). Human Food Safety - Also done at the same time and used the same protocol as the tylosin study which was accepted. Final study report pending. Dr. Oeller will submit a paper to address antimicrobial resistance (Guidance 152) and will also address the human gut flora issues. She will probably send all human food safety submissions in together. Environmental Assessment  Dr. Oeller will use the same Veterinary International Committee on Harmonization guidance that was used for the tylosin environmental submission.<br /> <br /> COLLABORATIVE PROJECTS:<br /> ADR #280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge) - See report from the Southern Region by Dr. Alistair Webb.<br /> <br /> Species Grouping Fish Project - During this reporting period there were no new samples submitted. There were 10 trials total. All feed and plasma samples from all trials have been analyzed. Muscle samples from 3 trials were completed this year. Muscle samples from 2 trials are pending (One of which is the abandoned trial). Sample analysis is ongoing. For more information please refer to the Northeast report by Dr. Paul Bowser. <br /> <br /> Progesterone CIDR for Sheep - Ms. Sandy Ogletree is currently working on the quality assessment for the human food safety report sent from Dr. Dennis Halford.<br /> <br /> NEW PROJECTS:<br /> 1. Working with Dr. Ron Griffith on the tulathromycin (DRAXXIN®) study in sheep and goats (see North Central Region Report).<br /> 2. Florfenicol in goats being pursued with Dr. Rowe.<br /> <br /> WORK PLANNED FOR THIS YEAR (2007)<br /> The completion of the projects listed above is the primary work planned for this year. If there are no funds identified for the 2007 fiscal year, the laboratory will go into hibernation mode. During this time, we will work on assay development using the liquid chromatography/mass spectrometer, finish the fish samples, and investigate the needs for the tulathromycin assay.<br /> <br /> PUBLICATIONS ISSUED OR MANUSCRIPTS APPROVED SINCE THE LAST MEETING<br /> Cortright, K.A. and Craigmill, A.L. Cytochrome P450-dependent metabolism of midazolam in hepatic microsomes from chickens, turkeys, pheasant and bobwhite quail. J Vet Pharmacol Therap 29(6)469-476, 2006.<br /> <br /> SOUTHERN REGION: DR. ALISTAIR I. WEB<br /> SOUTHERN REGION<br /> CURRENT PROJECTS<br /> RABBITS<br /> ADR  107 Ivermectin & Rabbits - The in-vivo human safety has been completed and assay has been validated. Analyses of the incurred samples will be completed by winter and reports prepared for submission to FDA-CVM. <br /> FISH<br /> ADR - 271 Crude Carp Pituitary - The author has submitted a revised report that might address FDA-CVMs concerns.<br /> <br /> ADR  235 Ovaprim - UFL Tropical Fish [Roy Yanong] and Syndel are working with CVM to define needs. At present our only involvement is to provide GLP support for any TAS studies. This may be an alternative to CCPE as a spawning aid. There is no activity by the investigators. <br /> ADR  236 Metomidate - There is no activity by the investigator [Yanong UFL]<br /> <br /> BIRDS<br /> ADR - 280 Fenbendazole & Gamebirds - The TAS report continues to be incomplete but lacks investigators final input and QA . We have received the Western Regions depletion assay results and are preparing a packet for submission to FDA-CVM.<br /> <br /> DEER<br /> ADR  210 Fenbendazole & Red Deer & ADR  216 Fenbendazole & Fallow - Intervet have indicated that they want to carry out a dose study before moving on this project<br /> ADR - 294 Lasalocid And Deer / ADR - 298 Lasalocid And Goats - Problem is that Alpharma will only proceed if there is a zero withdrawal time. We are starting to mount an assay and will carry out initial pilots on two deer and two goats to see if the lasalocid levels are below tolerance.<br /> <br /> WORK PLANNED FOR THE COMING PERIOD <br /> " Maintain lab and staff at GLP level<br /> " Submit early in the new year the all ivermectin for rabbit reports and all fenbendazole reports.<br /> " Organize studies for gaining approval of fenbendazole & lasalocid in deer, and lasalocid in goats.<br /> " Prepare, in coordination with the National Coordinator, INAD submissions for studies conducted under the aegis of the Southern Region. Initial preparation of written responses to CVM review of all of the data submitted for each project. This is often a time consuming and unrecognized activity associated with the completion of each project and may require considerable correspondence and conversation.<br /> " Continued collaborative work with the other regions is anticipated and may include unplanned studies to address critical needs and opportunities to collect data.<br /> " Continue the development of the NRSP-7 web site with full activation of the RUSTi database.<br /> WEB SITE MAINTENANCE<br /> The NRSP-7.org web has continued to function well but is need of some development such as PowerPoint Presentations. The University is cranking-up security and is centralizing control of IT. We are concerned but we have been model citizens plus we actually got our original permission to host the web site without obvious use of the ufl.edu domain from the current head of IT. The MUMSRx web database continues to be updated  it alone receives 1-2 hits each day. Rusti is now fully functional and Laura has returned to full-time work. We will be working with each coordinator to get active projects fully entered into the system. <br /> <br /> <br /> NEW / PROPOSED PROJECTS:<br /> With no funding in sight, no new projects are under consideration with primary effort being made to complete existing studies.<br /> <br />

Publications

(1) Needham, M. L., Webb, A. I., Baynes, R. E., Riviere, J. E., Craigmill, A. L., and Tell, L. A. Current update on drugs for game bird species. J Am Vet Med Assoc 2007, 231, 1506-8.<br /> (2) Payne, M. A., Craigmill, A., Riviere, J. E., and Webb, A. I. Extralabel use of penicillin in food animals. J Am Vet Med Assoc 2006, 229, 1401-3.<br /> <br />

Impact Statements

1. Since the first drug approval in 1984 under the former IR-4 program, NRSP-7 has been responsible for generating 32 Public Master File (PMF) publications in the Federal Register, an average of 1.4 per year during its 23 years of funding.
2. Data from NRSP-7 was used in support of the FDA approval of hydrogen peroxide as 35% PEROX-AID® (New Animal Drug Application 141-255). This formulation was approved as an external microbicide for the control of mortality in freshwater-reared finfish eggs due to saprolegniasis, for the control of mortality in freshwater-reared salmonids due to bacterial gill disease associated with Flavobacterium branchiophilum, and for the control of mortality in freshwater-reared coolwater finfish and channel catfish due to external columnaris disease associated with Flavobacterium columnare (Flexibacter columnaris).
3. Tissue stability studies of progesterone implants for estrus synchronization in sheep have been completed.
4. Compared to an average investment of the pharmaceutical industry of $2 to $8 million for adding a label claim to an existing veterinary drug, information generated for additional label claims by the NRPS-7 program costs only approximately 10 to 40% of pharmaceutical industry costs.
5. To date 342 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 14 active research projects involving nine animal species and 11 different drugs.

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Report Information

Participants

Brief Summary of Minutes

Accomplishments

Publications

Impact Statements

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Report Information

Participants

The NRSP-7 technical committee, which is made up of a National Coordinator, four Regional Coordinators, four regional Administrative Advisors, and liaisons from USDA and FDA. In attendance were the National Coordinator, Dr. John Babish (Cornell University), the Regional Coordinators, Dr. Lisa Tell (University of California, Davis), Dr. Alistair Webb (University of Florida), Dr. Ronald Griffith (Iowa State University), and Dr. Paul Bowser (Cornell University), Administrative Advisors Dr. Garry Adams, Chairman of Administrative Advisors (Texas A&M) and Dr. John Baker (Michigan State University), and the FDA liaison Dr. Meg Oeller (Rockville, MD).
NAME AFFILIATION EMAIL ADDRESS
Alistair Webb NRSP-7/U FL Webb@ufl.edu
Garry Adams AA/CVM/Texas A&M gadams@cvm.tamv.edu
Gary Sherman USDA/CSRESS gsherman@CSREES.USDA.GOV
John G. Babish NRSP-7 jgb7@cornell.edu
John C. Baker AA/MI College of Vet Med baker@cvm.msu.edu
Lisa Tell NRSP-7/UC Davis latell@ucdavis.edu
Meg Oeller FDA/CVM moeller@cvm.fda.gov
Ron Griffith NRSP-7 rgriffit@iastate.edu

Brief Summary of Minutes

Accomplishments

NORTHEASTERN REGION - DR. PAUL BOWSER<br /> Progress of the work and principal accomplishments:<br /> Hydrogen Peroxide Project:<br /> INAD 9493 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish.<br /> No additional work has been performed on this project during this study period.<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 /> A primary constraint in the availability of therapeutic compounds for the Aquaculture Community is the relatively large number of fish species that are currently cultured or that have significant potential as commercial species. Currently, research in support of a label for a therapeutic compound must be performed separately for each species for which the label is desired. We have undertaken a project designed to show the similarities in how drugs are handled by different fish species with the goal of supporting a species (crop) grouping concept for fish. We have conducted these studies in a collaborative effort with the Western Region NRSP7. Within this context, to date we have completed the following preliminary Human Food Safety/Tissue Depletion Studies using the following test articles as model compounds:<br /> Oxytetracycline:<br /> 1. Walleyes, freshwater fish, 15C and 20C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater fish, 20C and 25C<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> 5. Rainbow Trout, cold water trial (8C)<br /> Romet-30:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass (to be completed;see below)<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> Florfenicol (10 mg/Kg/d, 10d):<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater, 20C, 25C<br /> Florfenicol (Effect of fish size)<br /> 1. Tilapia  100 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 2. Tilapia  250 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 3. Tilapia  500 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d <br /> Several attempts were made to conduct human food safety studies for Romet-30 in hybrid striped bass. These attempts were unsuccessful due to lack of feed acceptance by the fish due to apparent palatability problems. Since that time, the Sponsor had developed and marketed a product (Romet-TC) designed to circumvent palatability problems. In two attempts with this new product, we found that hybrid striped bass would not accept a ration medicated with Romet-TC. Therefore, we will not include hybrid striped bass in our efforts with Romet. <br /> Usefulness of the findings:<br /> In all cases, the findings 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) in trout, salmon and catfish.<br /> Work planned for next year:<br /> ADR 259 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. (INAD 9493)<br /> No additional work is planned for this project in the upcoming 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 conducting 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 /> 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 /> Target animal safety studies have been completed in both rainbow trout and walleye. Information collected during these studies constituted the subject of eight manuscripts in the peer-reviewed literature and several presentations at scientific meetings. Our raw data and a peer reviewed publication (see Saez and Bowser 2000 below) describing discharge kinetics of hydrogen peroxide from a fish hatchery were provided to the U.S. Geological Survey Upper Midwest Environmental Sciences Center, La Crosse, Wisconsin, for their use in the recent submission that resulted in a label for hydrogen peroxide. We also provided reprints of our eight peer reviewed publications to the Sponsor in response to their request as they prepared their all other relevant information submission.<br /> <br /> (B) Species Grouping in Fish<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> Our efforts have focused on evaluation of a species grouping concept for finfish. Within this effort we have conducted Human Food Safety/Tissue Elimination Studies as follows:<br /> <br /> Oxytetracycline<br /> Tilapia (25C, 30C) - completed<br /> Walleye (15C, 20C) - completed<br /> Hybrid Striped Bass (20C, 25C) - completed<br /> Summer Flounder (17C, 20C)  completed<br /> <br /> Results of studies conducted in the above four fish species are summarized in the publication:<br /> <br /> Chen, C.-Y., R.G.Getchell, G.A.Wooster, A.L. Craigmill and P.R. Bowser. 2004. Oxytetracycline residues in four species of fish after 10-day oral dosing in feed.Journal of Aquatic Animal Health 16:208-219.<br /> <br /> Rainbow Trout, cold water trial (8C) - completed<br /> Romet-30<br /> Tilapia (25C, 30C) - completed<br /> Walleye (20C, 25C)  completed<br /> Summer Flounder (17C, 20C)  completed<br /> <br /> Results of studies conducted in the above three fish species are summarized in the publication:<br /> Kosoff, R.E., C.-Y. Chen, G.A. Wooster, R.G. Getchell, A.Clifford, A.L. Craigmill and P.R. Bowser. 2007. Sulfadimethoxine and Ormetoprim Residues in Three Species of Fish After 5-day Oral Dosing in Feed. Journal of Aquatic Animal Health 19:109-115<br /> <br /> Hybrid Striped Bass (20C, 25C) - did not accept feed medicated with Romet-30; palatability problems; two additional trials were attempted with feed medicated with Romet-TC (a product developed to avoid palatability problems). These additional studies were also unsuccessful because of lack of feed acceptance due to apparent palatability problems by the hybrid striped bass. No further work with Romet-30 or Romet-TC is currently planned.<br /> <br /> Aquaflor (10 mg/Kg/d X 10 days) Tilapia (25C, 30C) - completed<br /> Walleye (20C, 25C) - completed<br /> Hybrid Striped Bass (20C, 25C) - completed <br /> Aquaflor (15 mg/Kg/d X 10 days)<br /> Tilapia<br /> 100 gm fish - completed<br /> 250 gm fish - completed <br /> 500 gm fish - completed <br /> <br /> Results of studies conducted with Aquaflor are summarized in the following two publications that are currently in review:<br /> Kosoff, R.E., C.-Y. Chen, G.A. Wooster, R.G. Getchell, A. Clifford, J.L. Craig, P. Lim, S.E. Wetzlich, A.L. Craigmill, L.A. Tell and P.R. Bowser. 2008. Florfenicol Residues in Three Species of Fish After10-day Oral Dosing in Feed. Journal of Aquatic Animal Health. In press<br /> <br /> Bowser, P.R., R.E. Kosoff, C.-Y. Chen, G.A. Wooster, R.G. Getchell, J.L. Craig, P. Lim, S.E. Wetzlich, A.L. Craigmill, and L.A. Tell. 2008. Florfenicol Residues in Nile Tilapia After 10-day Oral Dosing in Feed: Effect of Fish Size. Journal of Aquatic Animal Health. In press<br /> <br /> Our protocol employed the optimum culture temperature for each fish species, plus one additional lower temperature at which the species might be cultured in an economically viable manner. A preliminary evaluation of our data suggests that Oxytetracycline and Romet-30 were eliminated from the edible portion of the fish at rates that will very likely be within the current label for salmonids and channel catfish.<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 /> 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 /> NORTH CENTRAL REGION - DR. RONALD W. Griffith<br /> SHEEP CIDR-G<br /> Sheep CIDR-g Tissue Residue Stability<br /> This study was performed by Dr. Dennis Hallford at New Mexico State University in cooperation with both the Western and North Central Regions. The study report was not accepted due to the instability of progesterone in fresh liver tissues such that freezer stability could not be documented. ONADE is currently trying to demonstrate by reference that plasma progesterone levels decrease dramatically once the CIDR-G inserts are removed and use this to infer that overall tissue residues are markedly reduced. Muscle tissue progesterone levels were demonstrated to be at normal background levels 24 hr. after CIDR removal<br /> GOAT CIDR-G<br /> Goat CIDR-g Milk Residue <br /> These studies are being supported by both the NC and Western Regions of NRSP-7. The in-life phase of milk residue study was performed at UC-Davis in fall 2007 and the analytical phase was performed by Dr. Hallford at New Mexico State University. The data from the study has been submitted for QA to the Western Region and the study report should be submitted shortly. The data indicate that progesterone levels in the milk of pregnant does are greater than progesterone levels in the milk of CIDR-treated does. Dr. Hallford plans on performing the tissue residue portion of the study this fall but wanted to wait for resolution of the sheep tissue residue issues. I have encouraged him to submit the goat protocol so that we can get it reviewed in time to begin the study.<br /> Goat CIDR-g Tissue Residue<br /> Currently planned for Fall 2009. Dennis Hallford plans to perform both the in-life phase and residue analysis.<br /> Goat CIDR-g Effectiveness<br /> Re-revision of the protocol is underway. Hopefully study will begin in late summer/fall 2009.<br /> TULATHROMYCIN<br /> Draxxin Target Animal Safety in Goats<br /> The in-life phases of the study were completed on March 22, 2008. The tissues from the untreated control and high-dose-group goats were examined for histopathology. Some minor lesions were observed in both groups and it was decided to examine the tissues from the 1X and 3X groups just in case ONADE would want that data. All the goats remained in good health except for one untreated control goat that developed respiratory disease. A few of the goats had some scattered gross lesions that seemed to be related to infectious processes rather than any toxic effects of the drug. In addition to the TAS portion of the study, we collected tissues and plasma for tulathromycin analysis for publication purposes.<br /> Draxxin Efficacy in Goats<br /> The protocol for a natural exposure model has been accepted by CVM. However, the studies were predicted to take at least three years to complete and require a significant portion of the financial resources of the NC Region. An alternative protocol based upon determination of AUC/MIC was prepared and submitted. However, ONADE wanted us to base statistical significance by comparison to cattle AUC/MIC. We were asked to provide an alternative target for determining effectiveness. It was decided that we needed some preliminary analytical and MIC data in order to set a realistic target. We have procured and tested a small group of bacterial isolates for MICs. The MICs are very close to those described for cattle. Plasma samples were collected from 6 goats and these have been analyzed for tulathromycin levels. <br /> Draxxin Tissue Residue<br /> The protocol has been reviewed by ONADE and there were relatively few comments. The protocol was amended and sent to Scott Wetzlich who will be doing the analysis. The methods for tissue extraction and tulathromycin analysis is currently being developed. This study can begin whenever the assays are validated. We will have tissues from goats at 2-, 3-, 4- and 5-weeks post treatment for determination of a target end point for the tissue residue study. <br /> LASALOCID<br /> Lasalocid Efficacy in Pheasants<br /> The study was performed by Drs. Larry McDougald and Lorraine Fuller at the University of Georgia with the assistance of Dr. Thomas McQuistion from Milliken University. A draft of the final report and an associated paper for publication was received on April 16, 2008. The full study report has been requested several times. <br /> Lasalocid TAS in Pheasants<br /> The protocol for this study was submitted to ONADE for review and was returned in early July. Drs. McDougald and Fuller have agreed to perform this study as well. <br /> Lasalocid Human Food Safety in Pheasants<br /> This project was traded to the Western Region in exchange for the CIDR-G goat effectiveness study. <br /> MELATONIN<br /> Regulin (melatonin) implants for sheep<br /> No activity to report. There does not seem to be much interest in this product either from the manufacturer or the sheep and goat industry.<br /> EPIDERMAL GROWTH FACTOR<br /> Bioclip for Sheep<br /> No activity to report. <br /> TRICLABENDAZOLE<br /> Fasinex (Triclabendazole) for Deer and Elk <br /> No Activity to report.<br /> SOUTHERN REGION  DR. ALISTAIR I. WEB<br /> Projects in Progress:<br /> RABBITS<br /> ADR  0107 Ivermectin & Rabbits<br /> The human safety and target animal safety reports are being prepared. This task is being treated as secondary to the fenbendazole in gamebirds.<br /> FISH<br /> ADR - 0271 Crude Carp Pituitary<br /> The project appears dead from FDA/CVMs perspective. Query change RUSTi status to dead?<br /> BIRDS<br /> ADR - 0280 Fenbendazole & Gamebirds<br /> The human safety report has been re-vamped and been brought to this meeting for UC-Davis QA The TAS report continues to be incomplete but lacks investigators final input and QA we are [planning a 90 day completion. . If critics are happy, this will be submitted to FDA within 45 days. <br /> DEER<br /> ADR  0210 Fenbendazole & Red Deer & ADR  0216 Fenbendazole & Fallow <br /> Intervet have indicated that they want to carry out a dose study before moving on this project. This is with Don Davis at TAMU. The Intervet merger has given all involved brain freeze.<br /> <br /> ADR - 0294 Lasalocid and Deer / ADR - 0298 Lasalocid and Goats<br /> A Problem is that Alpharma will only proceed if there is a zero withdrawal time. We are well into validating an assay and will carry out initial pilots on two deer and two goats to see if the lasalocid levels are below tolerance. See below for TAMU collaboration.<br /> The assay method has been finalized and validation starting for pheasants, goats and deer. The time table for that will be discussed at the meeting.<br /> BEES<br /> ADR  0343 Remebee and Honey bees<br /> This is a project that is in development with Beeologics for a Israel Acute Paralysis Virus [IAPV] specific double strand RNA product for prevention of collapsing colony disorder. The company has obtained an INAD and is setting up a teleconference with FDA/CVM next month after which NRSP-7s role may become clear. UFL has signed a non-disclosure agreement with Beeologics covering Remebee. Its status in RUSTi is pending.<br /> <br /> Work Planned for the remainder of the Year: <br /> " Maintain lab and staff at GLP level<br /> " Submit by the new year the all ivermectin for rabbit reports and all fenbendazole reports.<br /> " Organize collaborative studies for gaining approval of fenbendazole & lasalocid in deer, and lasalocid in goats.<br /> " Prepare, in coordination with the National Coordinator, INAD submissions for studies conducted under the aegis of the Southern Region. Initial preparation of written responses to CVM review of all of the data submitted for each project. This is often a time consuming and unrecognized activity associated with the completion of each project and may require considerable correspondence and conversation.<br /> " Continued collaborative work with the other regions is anticipated and may include unplanned studies to address critical needs and opportunities to collect data.<br /> " Continue the development of the NRSP-7 web site with possible re-implementation of the RUSTi database.<br /> New / Proposed Projects:<br /> With no assured funding in sight, no new projects are under consideration with primary effort being made to complete existing studies and we are trying to collaborate with TAMU to start work on lasalocid deer & goat projects.<br /> Web Site<br /> The NRSP-7.org web has continued to function well but is need of some development such as PowerPoint Presentations. The University is cranking-up security and is centralizing control of IT. We are concerned but we have been model citizens plus we actually got our original permission to host the web site without obvious use of the ufl.edu domain from the current head of IT. The MUMSRx web database continues to be updated  it alone receives 1-2 hits each day. RUSTi is alive but with loss of biological scientist we have kept a low profile. Further development will have to wait upon programs choice of a successor on the current coordinators retirement in May 2010.<br /> Coordinator Retirement<br /> It appears that UFL and TAMU have groups interested in this despite some reservations about funding. <br /> WESTERN  DR. LISA TELL<br /> ACTIVE REGIONAL PROJECTS:<br /> Progress of Work and Principal Accomplishments:<br /> ACTIVE Regional Projects:<br /> ADR#325 - Florfenicol for sheep for respiratory disease <br /> Schering-Plough has been contacted and is interested in pursuing a bioequivalence study for the sheep using the new formulation. We are currently waiting for a response from Dr. Oeller regarding setting up a conference call with the investigators, manufacturer and CVM. <br /> ADR#324 - Progesterone CIDRs for Goats (TAS and Milk Residue Study)<br /> Target Animal Safety report has been accepted by FDA/CVM (February 20, 2008). Milk residue study has been completed. Raw data for goat milk progesterone concentrations have been sent to UC Davis by Dr. Dennis Hallford from New Mexico State University. The QA of Dr. Hallfords data has been completed. The final report submitted by Drs. Rowe and Hallford is now undergoing QA review. This report will be sent to FDA/CVM in October 2008.<br /> ADR# 235 - Lasalocid in Ring-Necked Pheasants (Human Food Safety/Residue Study)<br /> The general protocol has been written except for the final details regarding the analytical methods and formulation of the premixed medicated feed. A study director has been identified from UC Davis Center for Laboratory Science. A location for mixing the feed has been identified. The UC Davis animal care and use protocol has been submitted. The protocol will be submitted to CVM for concurrence in October or November. <br /> ADR#272 - Romet for Gamebirds<br /> See species grouping report.<br /> ADR#299 - Pirlimycin for Dairy Goats<br /> Project on hold until funding is identified and CIDR goat studies are completed.<br /> ADR#295 - Strontium Chloride for Salmonids. Steve Schroeder<br /> There is nothing to report. Status of the project needs to be changed.<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 /> ADR#135  Erythromycin in Salmonids<br /> Mark Gaikowski with the U.S. Geological Survey (Upper Midwest Environmental Sciences Center in La Crosse, Wisconsin) is working in conjunction with NRSP-7 to revise and review specific sections of the Environmental Assessment Report for resubmission to CVM. In order to address the CVM comments, a pilot chronic toxicity study with Daphnia magna, is currently underway, using erythromycin thiocyanate (ERTT) and diphenhydramine (DERT). The report for this study is being finalized and should be completed soon. The no observed effect concentration (NOEC) developed from this study was similar to the data from the Ceriodaphnia study included in the environmental assessment (EA). The USGS is also planning to complete a follow-up ERTT study this fall with Daphnia to supplement the initial work. Another study on ERTT physical chemistry has been completed and the transformation kinetic sample results should be processed by October 1 with a draft manuscript done in December. This manuscript will be revised into a final report to include with the EA. The ultimate goal of these studies is to produce data that will address CVMs concerns regarding chronic toxicity to aquatic insects. Another study to evaluate ERTT microbial toxicity has been completed and another study to evaluate DERT is in process. These studies will identify physio-chemical properties of erythromycin and determine the microbial toxicity of various erythromycin transformation products. Once again, these results will be used to address the concerns expressed by CVM. The last study to be considered is characterization of leaching of erythromycin from feed, feces, and sediment.<br /> ADR# 311 Lincomycin soluble powder for foulbrood disease in Honeybees<br /> Waiting for the data summary for CVM submission. Dr. Margaret Oeller is assisting to facilitate this CVM submission. <br /> Collaborative Projects:<br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> See Southern Region Report.<br /> Ms. Ogletree and Dr. Webb met in February 2008 and discussed concerns regarding the QA portion of this project. Dr. Webb will be submitting additional information. <br /> Species Grouping Fish: <br /> See North Eastern Region Report.<br /> Sample analysis for florfenicol is complete and the two manuscripts have been accepted for publication.<br /> ADR#324  Progesterone CIDRs for Goats: Efficacy Study<br /> See North Central Region Report.<br /> The study protocol was submitted to CVM by Dr. Griffith. The UC Davis portion of the study is to be performed in Fall of 2009. UC Davis Animal Care and Use protocol for this study has been approved. <br /> <br /> ADR#340 - Tulathromycin in Goats<br /> QA review of the TAS protocol was done by Ms. Sandra Ogletree. The analytical method for plasma samples from goats was established and we analyzed 440 samples from the TAS and preliminary PK studies. Emphasis will now shift back to establishing and validating the tissue methods. <br /> <br /> Other Projects:<br /> Avian Species Grouping:<br /> Kristy Cortright finished work on the in vitro and in vivo studies. She is completing work for her PhD.<br /> CEFTIOFUR CRYSTALLINE FREE ACID<br /> Excede in Goats: <br /> In collaboration with Drs. Rowe and Angelos, Dr. Elizabeth Dore (UC Davis 3rd year Food Animal Resident) completed a study evaluating the use of Excede in lactating and non-lactating goats. The data from this study were compiled and presented at two scientific venues for which Dr. Dore received a resident award at one of the meetings. The serum and milk samples have been analyzed and the PK data modeled. Dr. Dore is currently working on the manuscript and the manuscript will be submitted to JVPT for publication. <br /> New Projects:<br /> Nothing to report at this time.<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 /> The submission of the Milk Residue CIDR-G data to CVM and starting the CIDR-G Efficacy study are the primary goals. We will also continue to work to have the approved tulathromycin method established on the LCMS and begin analyzing samples for Dr. Griffith. Species grouping work for fish will continue, if the fish will consume the medicated Romet feed. Obtaining CVM concurrence for a florfenicol bioequivalence study will also be a major focus. Lasalocid avian food residue study to be performed in 2009. <br /> <br />

Publications

Impact Statements

1. Since the first drug approval in 1984 under the former IR-4 program, NRSP-7 has been responsible for generating 33 Public Master File (PMF) publications in the Federal Register, an average of 1.4 per year during its 24 years of funding. The mean total expenditure per completed research for a drug approval or publication of a PMF was $454,000. Average federal expenditures per completed research for a drug approval or publication of a Public Master File was $346,000. NRSP-7 continues to demonstrate remarkable efficiency and cost effectiveness. Compared to an average investment of the pharmaceutical industry of $2 to $8 million for adding a label claim to an existing veterinary drug, information generated for additional label claims by the NRPS-7 program costs only approximately 10 to 40% of pharmaceutical industry costs.
2. To date 342 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 14 active research projects involving nine animal species and 11 different drugs. Approximately 23% of the active projects involve ruminant species, 15% avian, 38% aquatic and 23% other species such as rabbits and honey bees. While a majority of Public Master Files (53%) involved ruminant species, current active projects are more evenly divided among additional species.

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Report Information

Participants

Participants: Babish, John - Cornell University (jgb7@cornell.edu); Tell, Lisa (latell@ucdavis.edu) - University of California, Davis; Webb, Alistair (Webb@ufl.edu) - University of Florida; Griffith, Ronald (rgriffit@iastate.edu) - Iowa State University; Bowser, Paul (prb4@cornell.edu) - Cornell University; Adams, Garry (gadams@cvm.tamu.edu) - Texas A&M; Baker, John (Baker@anr.msu.edu) - Michigan State University; and; Sherman, Gary (gsherman@CSREES.USDA.GOV) - USDA/CSREES; Oeller, Meg (moeller@cvm.fda.gov) - FDA/CVM; Lutschaunig, Mark (MLutschaunig@avma.org) - American Veterinary Medical Association; Luke, Gina - American Veterinary Medical Association; Smith, Brian (Bsmith@aavmc.org) - American Association of Veterinary Medical Colleges; Engelbach, Karl (kmengelbach@ucdavis.edu) - UC Davis; Miller, Diane (dlm72@cornell.edu)  Cornell University; Bryant. Dustin (dustinbryant@meyersandassociates.com) - Meyers and Associates for Texas A&M University; Schnick. Rosalie (RozSchnick@centurytel.net) - National Coordinator for Aquaculture New Animal Drug Applications; Rybolt, Michael  The National Turkey Federation.

Brief Summary of Minutes

Accomplishments

ACCOMPLISHMENTS FROM THE REGIONS AND NEW PROJECTS:<br /> Northeastern  Dr. Paul R. Bowser<br /> Progress of the work and principal accomplishments:<br /> Hydrogen Peroxide Project:<br /> <br /> INAD 9493 Hydrogen Peroxide as a Therapeutic Compound for Bacterial Gill Disease in Fish. No additional work has been performed on this project during this study period.<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 /> A primary constraint in the availability of therapeutic compounds for the Aquaculture Community is the relatively large number of fish species that are currently cultured or that have significant potential as commercial species. Currently, research in support of a label for a therapeutic compound must be performed separately for each species for which the label is desired. We have undertaken a project designed to show the similarities in how drugs are handled by different fish species with the goal of supporting a species (crop) grouping concept for fish. We have conducted these studies in a collaborative effort with the Western Region NRSP7. Within this context, to date we have completed the following preliminary Human Food Safety/Tissue Depletion Studies using the following test articles as model compounds:<br /> <br /> Oxytetracycline:<br /> 1. Walleyes, freshwater fish, 15C and 20C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater fish, 20C and 25C<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> 5. Rainbow Trout, cold water trial (8C)<br /> <br /> Romet-30:<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass (would not accept ration; Species removed from Romet trials)<br /> 4. Summer Flounder, saltwater fish, 17C and 20C<br /> <br /> Florfenicol (10 mg/Kg/d, 10d):<br /> 1. Walleyes, freshwater fish, 20C and 25C<br /> 2. Tilapia, freshwater fish, 25C and 30C<br /> 3. Hybrid Striped Bass, saltwater, 20C, 25C<br /> <br /> Florfenicol (Effect of fish size)<br /> 1. Tilapia  100 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 2. Tilapia  250 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d<br /> 3. Tilapia  500 gm, freshwater fish, <br /> 25C, 15 mg/Kg, 10d <br /> <br /> Several attempts were made to conduct human food safety studies for Romet-30 in hybrid striped bass. Additional trials where the new Romet-TC was used were also met with a lack of palatability. Therefore, we will not include hybrid striped bass in our efforts with Romet. <br /> Usefulness of the findings:<br /> <br /> In all cases, the findings 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) in trout, salmon and catfish.<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 /> Future work is being hampered by a lack of funds in the Northeast Region. Should funding become available, we propose to conduct 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 /> Other:<br /> We are also considering the development of a project that centers on the question of disinfection of fish eggs to prevent the vertical transmission of Viral Hemorrhagic Septicemia Virus. <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 /> Target animal safety studies have been completed in both rainbow trout and walleye. Information collected during these studies constituted the subject of eight manuscripts in the peer-reviewed literature and several presentations at scientific meetings. Our raw data and a peer reviewed publication (see Saez and Bowser 2000 below) describing discharge kinetics of hydrogen peroxide from a fish hatchery were provided to the U.S. Geological Survey Upper Midwest Environmental Sciences Center, La Crosse, Wisconsin, for their use in the recent submission that resulted in a label for hydrogen peroxide. We also provided reprints of our eight peer reviewed publications to the Sponsor in response to their request as they prepared their all other relevant information submission. The manuscripts provided were the following:<br /> <br /> Tort, M.J., A.J. Kuhl, G.A. Wooster and P.R. Bowser. 1998. Modification of tolerance of walleye (Stizostedion vitreum) to bath treatment with hydrogen peroxide. Journal of the World Aquaculture Society 29:499-504.<br /> <br /> Saez, J.A. and P.R. Bowser. 2000. Hydrogen peroxide concentrations in hatchery culture units and effluent during and after treatment. North American Journal of Aquaculture 63:74-78.<br /> <br /> Tripi, C.M. and P.R. Bowser. 2001. Toxicity of hydrogen peroxide to pre-exposed young-of-the-year walleye (Stizostedion vitreum): effects of water quality and age of fish. Journal of the World Aquaculture Society 32:416-421.<br /> <br /> Tort, M.J., C. Jennings-Bayshore, D. Wilson, G.A. Wooster and P.R. Bowser. 2002. Assessing the effects of increasing hydrogen peroxide dosage on rainbow trout(Onchorhynchus mykiss) gills utilizing a digitized scoring methodology. Journal of Aquatic Animal Health 14:95-103.<br /> <br /> Tort, M.J., D. Pasnik, C. Fernandez-Cobas, G.A. Wooster and P.R. Bowser. 2002. Quantitative scoring of gill pathology of walleyes (Stizostedion vitreum) exposed to hydrogen peroxide. Journal of Aquatic Animal Health 14:154-159.<br /> <br /> Tort, M.J., C. Fletcher, G.A. Wooster, and P.R. Bowser. 2003. Stability of hydrogen peroxide in aquaria as a fish disease treatment. Journal of Applied Aquaculture 14:(3/4) 37-45.<br /> <br /> Tort, M.J., G.A. Wooster and P.R. Bowser. 2003. Effects of Hydrogen Peroxide on Hematology and Blood Chemistry Parameters of Walleye (Stizostedion vitreum). Journal of the World Aquaculture Society 34:236-242<br /> <br /> Tort, M.J., D. Hurley, C. Fernanzez-Cobas, G.A. Wooster and P.R. Bowser. 2005. Effects of hydrogen peroxide treatment on catalase and glutathione activity in walleye (Sander vitreus). Journal of the World Aquaculture Society 36(4):576-585.<br /> <br /> (B) Species Grouping in Fish<br /> INAD 10-320 Oxytetracycline in Fish<br /> INAD 10-823 Romet-30 in Fish<br /> INAD 11-145 Aquaflor (Florfenicol) in Fish <br /> Our efforts have focused on evaluation of a species grouping concept for finfish. Within this effort we have conducted Human Food Safety/Tissue Elimination Studies as follows:<br /> <br /> Oxytetracycline<br /> Tilapia (25C, 30C) - completed<br /> Walleye (15C, 20C) - completed<br /> Hybrid Striped Bass (20C, 25C) - completed<br /> Summer Flounder (17C, 20C)  completed<br /> Results of studies conducted in the above four fish species are summarized in the publication:<br /> <br /> Chen, C.-Y., R.G.Getchell, G.A.Wooster, A.L. Craigmill and P.R. Bowser. 2004. Oxytetracycline residues in four species of fish after 10-day oral dosing in feed. Journal of Aquatic Animal Health 16:208-219.<br /> <br /> Rainbow Trout, cold water trial (8C) - completed<br /> <br /> Romet-30<br /> Tilapia (25C, 30C) - completed<br /> Walleye (20C, 25C)  completed<br /> Summer Flounder (17C, 20C)  completed<br /> <br /> Results of studies conducted in the above three fish species are summarized in the publication:<br /> Kosoff, R.E., C.-Y. Chen, G.A. Wooster, R.G. Getchell, Clifford, A.L. Craigmill and P.R. Bowser. 2007. Sulfadimethoxine and Ormetoprim Residues in Three Species of Fish After 5-day Oral Dosing in Feed. Journal of Aquatic Animal Health 19:109-115<br /> <br /> Hybrid Striped Bass (20C, 25C) - did not accept feed medicated with Romet-30; palatability problems; two additional trials were attempted with feed medicated with Romet-TC (a product developed to avoid palatability problems). These additional studies were also unsuccessful because of lack of feed acceptance due to apparent palatability problems by the hybrid striped bass. No further work with Romet-30 or Romet-TC is currently planned.<br /> Aquaflor (10 mg/Kg/d X 10 days)<br /> Tilapia (25C, 30C) - completed<br /> Walleye (20C, 25C) - completed<br /> Hybrid Striped Bass (20C, 25C) - completed <br /> Aquaflor (15 mg/Kg/d X 10 days)<br /> Tilapia<br /> 100 gm fish - completed<br /> 250 gm fish - completed <br /> 500 gm fish - completed <br /> <br /> Results of studies conducted with Aquaflor are summarized in the following two publications that have been accepted for publication:<br /> Kosoff, R.E., C.-Y. Chen, G.A. Wooster, R.G. Getchell, A. Clifford, J.L. Craig, P. Lim, S.E. Wetzlich, A.L. Craigmill, L.A. Tell and P.R. Bowser. 2009. Florfenicol Residues in Three Species of Fish After 10-day Oral Dosing in Feed. Journal of Aquatic Animal Health. In press<br /> <br /> Bowser, P.R., R.E. Kosoff, C.-Y. Chen, G.A. Wooster, R.G. Getchell, J.L. Craig, P. Lim, S.E. Wetzlich, A.L. Craigmill, and L.A. Tell. 2009 Florfenicol Residues in Nile Tilapia After 10-day Oral Dosing in Feed: Effect of Fish Size. Journal of Aquatic Animal Health. In press<br /> <br /> Our protocol employed the optimum culture temperature for each fish species, plus one additional lower temperature at which the species might be cultured in an economically viable manner. A preliminary evaluation of our data suggests that Oxytetracycline and Romet-30 were eliminated from the edible portion of the fish at rates that will very likely be within the current label for salmonids and channel catfish.<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. Additional work is currently being impacted by a lack of funds in the Northeast Region.<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 /> Principal Publications (during the past year):<br /> Kosoff, R.E., C.-Y. Chen, G.A. Wooster, R.G. Getchell, A. Clifford, J.L. Craig, P. Lim, S.E. Wetzlich, A.L. Craigmill, L.A. Tell and P.R. Bowser. 2008. Florfenicol Residues in Three Species of Fish After 10-day Oral Dosing in Feed. Journal of Aquatic Animal Health. In press<br /> <br /> Bowser, P.R., R.E. Kosoff, C.-Y. Chen, G.A. Wooster, R.G. Getchell, J.L. Craig, P. Lim, S.E. Wetzlich, A.L.Craigmill, and L.A. Tell. 2008. Florfenicol Residues in Nile Tilapia After 10-day Oral Dosing in Feed:Effect of Fish Size. Journal of Aquatic Animal Health.In press<br /> <br /> <br /> NORTH CENTRAL  DR. RONALD W. GRIFFITH<br /> Sheep CIDR-G Tissue Residue Study<br /> This study was performed by Dr. Dennis Hallford at New Mexico State University in cooperation with both the Western and North Central Regions. NRSP-7 was informed on January 5, 2009 that the study report had been accepted by the Office of New Animal Drug Evaluation. This completed the data package required of NRSP-7 for approval of CIDR-Gs in sheep for a zero time withdrawal period. <br /> <br /> Goat CIDR-G Milk Residue <br /> These studies are being supported by both the NC and Western Regions of NRSP-7. The in-life phase of milk residue study was performed at UC-Davis in fall 2007 and the analytical phase was performed by Dr. Hallford at New Mexico State University. The study report has been recently submitted to the FDA/CVM. The data indicate that progesterone levels in the milk of pregnant goats are greater than progesterone levels in the milk of CIDR-treated goats. <br /> <br /> Goat CIDR-G Tissue Residue<br /> Currently planned for Fall 2009. Dr. Dennis Hallford at New Mexico State University plans to perform both the in-life phase and residue analysis.<br /> <br /> Goat CIDR-G Effectiveness<br /> Re-revision of the protocol is underway. Hopefully study will begin in late summer/fall 2009.<br /> <br /> Draxxin Target Animal Safety in Goats<br /> The in-life phases of the study were completed on March 22, 2008. The tissues from the untreated control and high-dose-group goats were examined for histopathology. Some minor lesions were observed in both groups and it was decided to examine the tissues from the 1X and 3X groups just in case ONADE would want that data. All the goats remained in good health except for one untreated control goat that developed respiratory disease. A few of the goats had some scattered gross lesions that seemed to be related to infectious processes rather than any toxic effects of the drug. In addition to the TAS portion of the study, we collected tissues and plasma for tulathromycin analysis for publication purposes.<br /> <br /> Draxxin Efficacy in Goats<br /> The protocol for a natural exposure model has been accepted by CVM. However, the studies were predicted to take three to six years to complete and require a significant portion of the financial resources of the NC Region. An alternative protocol based upon determination of AUC/MIC was prepared and submitted. However, ONADE wanted us to base statistical significance by comparison to cattle AUC/MIC. We were asked to provide an alternative target for determining effectiveness. It was decided that we needed some preliminary analytical and MIC data in order to set a realistic target. We have procured and tested a small group of bacterial isolates for MICs. The MICs are very close to those described for cattle. Plasma samples were collected from 6 goats and these have been analyzed for tulathromycin levels. <br /> <br /> Draxxin Tissue Residue<br /> The protocol has been reviewed by ONADE and there were relatively few comments. The protocol was amended and sent to Scott Wetzlich (Western Region NRSP-7) who will be doing the analysis. The methods for tissue extraction and tulathromycin analysis are currently being developed and validated. This study can begin whenever assay validation is complete. We will have tissues from goats at 2-, 3-, 4- and 5-weeks post treatment for determination of a target end point for the tissue residue study. <br /> <br /> Lasalocid Efficacy in Pheasants<br /> The study was performed by Drs. Larry McDougald and Lorraine Fuller at the University of Georgia with the assistance of Dr. Thomas McQuistion from Milliken University. A draft of the final report and an associated paper for publication was received on April 16, 2008. The full study report has been received and forwarded to Sandy Ogletree at UC-Davis for QA. <br /> Lasalocid TAS in Pheasants<br /> The protocol for this study was submitted to ONADE for review and was returned in early July. Drs. McDougald and Fuller have agreed to perform this study as well. <br /> Lasalocid Human Food Safety in Pheasants<br /> The protocol for this project is being revised and the study may be conducted in 2009 if the assay is validated.<br /> <br /> Regulin (melatonin) implants for sheep<br /> No activity to report. There does not seem to be much interest in this product either from the manufacturer or the sheep and goat industry.<br /> <br /> Bioclip for Sheep<br /> No activity to report. Does not seem to be much interest.<br /> Fasinex (Triclabendazole) for Deer and Elk <br /> No Activity to report. A major obstacle is that the drug is not currently marketed for cattle in the U.S.<br /> <br /> WESTERN  DRS. LISA TELL<br /> PROGRESS OF WORK AND PRINCIPAL ACCOMPLISHMENTS:<br /> ACTIVE Regional Projects:<br /> ADR#325 - Florfenicol for sheep for respiratory disease <br /> Schering-Plough has been contacted and is interested in pursuing a bioequivalence study for the sheep using the new formulation. We are preparing to re-initiate communication with FDA/CVM to find out what is needed and possibly repeat the studies.<br /> <br /> ADR#324 - Progesterone CIDRs for Goats (TAS and Milk Residue Study)<br /> Target Animal Safety report has been accepted by FDA/CVM (February 20, 2008). Milk residue study has been completed. The final technical report was sent to FDA/CVM in December 2008.<br /> <br /> ADR#272 - Romet for Gamebirds<br /> See species grouping report.<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 /> There is nothing to report. Status of the project needs to be changed.<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 /> Mark Gaikowski with the U.S. Geological Survey (Upper Midwest Environmental Sciences Center in La Crosse, Wisconsin) is working in conjunction with NRSP-7 to revise and review specific sections of the Environmental Assessment Report for resubmission to CVM. <br /> Work continues to summarize the physical chemistry of erythromycin thiocyanate. All samples have been processed and analyzed. Because of the physical characteristics of ERTT, an empirical pKa could not be established. However, it is expected that a derived pKa will be calculated. A draft manuscript is presently in preparation. <br /> The report for the range-finding chronic toxicity study for Daphnia magna is in USGS review and should be finalized in the first quarter of 2009. A regulated chronic toxicity study will be initiated the week of Jan 26, 2009. The chronic study will provide the pivotal toxicity endpoint for the EA. The resultant final study report will likely be completed in the second quarter of 2009.<br /> ADR# 311 Lincomycin soluble powder for foulbrood disease in Honeybees<br /> Dr. Margaret Oeller is coordinating the data summary/report preparation for CVM submission. <br /> Collaborative Projects:<br /> <br /> ADR#280 - Fenbendazole in Game Birds (Pheasants, bobwhite quail, partridge)<br /> See Southern Region Report.<br /> Ms. Ogletree and Dr. Webb met in February 2008 and discussed concerns regarding the QA portion of this project. Dr. Webb will be submitting his final report to FDA/CVM in January 2009.<br /> Species Grouping Fish: <br /> See North Eastern Region Report.<br /> Sample analysis for florfenicol is complete and the two manuscripts have been accepted for publication.<br /> <br /> ADR# 235-Lasalocid in Ring-Necked Pheasants<br /> See North Central Region Report. The study director for this study was reverted back to Dr. Ronald Griffith of the North Central Region and is currently under quality assurance review (by Ms. Sandy Ogletree) for the efficacy portion of the study.<br /> ADR#324  Progesterone CIDRs for Goats: Efficacy Study<br /> See North Central Region Report.<br /> The study protocol was submitted to CVM by Dr. Griffith. The UC Davis portion of the study is to be performed in Fall of 2009. UC Davis Animal Care and Use protocol for this study has been approved. <br /> <br /> ADR#340 - Tulathromycin in Goats<br /> The plasma method was established and our laboratory analyzed 440 samples from the TAS and preliminary PK studies. Emphasis will now shift back to establishing and validating the tissue methods. At this time, the Western region is working on establishing the approved analytical method in our laboratory. Validations of liver and muscle are nearly complete. Validation of kidney is underway and fat will follow shortly.<br /> <br /> Other Projects:<br /> Avian Species Grouping<br /> Kristy Cortright finished work on the in vitro and in vivo studies. She is completing her last manuscript resulting from her PhD thesis. The manuscript should be published this year.<br /> <br /> Excede in Goats: <br /> In collaboration with Drs. Rowe and Angelos, Dr. Elizabeth Dore (UC Davis 3rd year Food Animal Resident) completed a study evaluating the use of Excede in lactating and non-lactating goats. The data from this study were compiled and presented at two scientific venues for which Dr. Dore received a resident award at one of the meetings. The serum and milk samples have been analyzed and the PK data modeled. Dr. Dore is currently working on the manuscript and the manuscript will be submitted to JVPT for publication. <br /> New Projects:<br /> Nothing to report at this time.<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 /> This year our primary goals are to start the CIDR-G Efficacy study, continue the method validation and analyses for the goat tulathromycin project, and finish up the salmonid erythromycin environmental assessment. Obtaining CVM concurrence for a florfenicol bioequivalence study will also be a major focus. <br /> <br /> Publications issued or manuscripts approved since the last meeting:<br /> Rowe, J, Tell, L, and Wagner, D. Animal safety report on intravaginal progesterone controlled internal drug releasing devices (CIDRs) in sheep and goats. J Vet Pharmacol Therap, In Press.<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 /> SOUTHERN  DR. ALISTAIR I. WEBB<br /> Projects in Progress:<br /> RABBITS<br /> ADR  0107 Ivermectin & Rabbits<br /> The human safety and target animal safety reports are being prepared. This task is being treated as secondary to the fenbendazole in gamebirds.<br /> <br /> FISH<br /> ADR - 0271 Crude Carp Pituitary<br /> The project is dead with no response to FDA/CVMs concerns from the investigator.<br /> BIRDS<br /> ADR - 0280 Fenbendazole & Gamebirds<br /> The human safety report has been submitted to FDA-CVM. The concerns of UC-Davis QA resulted in (a) withdrawal of quail part of the report [QA problem with Webbs dual role as study director and QA inspector plus very problematic withdrawal conclusions; (b) letters from site personnel submitted to try and mitigate lack of in vivo QA inspection; (c) in vitro section QA was certified. The TAS report continues to be incomplete but lacks investigators final input and QA we are planning a 60-day completion. This will be submitted to FDA within 30 days. <br /> <br /> DEER<br /> ADR  0210 Fenbendazole & Red Deer & ADR  0216 Fenbendazole & Fallow <br /> Intervet / Schering Plough are still working on their combined project pipeline priorities so this project id on hold.<br /> <br /> ADR - 0294 Lasalocid and Deer / ADR - 0298 Lasalocid and Goats<br /> Problem is that Alpharma will only proceed if there is a zero withdrawal time. We are well into validating an assay and will carry out initial pilots on two deer and two goats to see if the lasalocid levels are below tolerance. See below for TAMU collaboration.<br /> The assay method has been had problems with recovery and there is no internal standard available. Once this is solved formal validation for pheasants, goats and deer will be carried out.<br /> Dr Fajt [TAMU] has sent a draft of the HFS protocol for lasalocid in goats. It is being reviewed and hopefully can soon be submitted to FDA. TAMU is developing a drug development program and will probably have its own QA unit.<br /> <br /> BEES<br /> ADR  0343 Remebee and Honey bees<br /> The Remebee project is with Beeologics for an Israel Acute Paralysis Virus [IAPV] specific double strand RNA product for prevention of collapsing colony disorder. The company has obtained an INAD and following a teleconference with FDA/CVM last month has gained both EA exclusion and approval for consumption of honey from treated hives [treatment has to end before honey flow. NRSP-7s role is of a possible advisor until FDA considers all the data submitted to determine what gaps there are and how large.<br /> <br /> Work Planned for the remainder of the Year: <br /> " Maintain lab and staff at GLP level<br /> " Submit by summer all the ivermectin for rabbit reports and the TAS in gamebirds fenbendazole reports.<br /> " Organize collaborative studies for gaining approval of fenbendazole & lasalocid in deer, and lasalocid in goats.<br /> " Prepare, in coordination with the National Coordinator, INAD submissions for studies conducted under the aegis of the Southern Region. Initial preparation of written responses to CVM review of all of the data submitted for each project. This is often a time consuming and unrecognized activity associated with the completion of each project and may require considerable correspondence and conversation.<br /> " Continued collaborative work with the other regions is anticipated and may include unplanned studies to address critical needs and opportunities to collect data.<br /> " Continue the development of the NRSP-7 web site with possible re-implementation of the RUSTi database.<br /> <br /> New / Proposed Projects:<br /> With no assured funding in sight, no new projects are under consideration with primary effort being made to complete existing studies and we are trying to collaborate with TAMU to start work on lasalocid deer & goat projects.<br /> Web Site<br /> <br /> The NRSP-7.org web has continued to function well but is need of some development such as PowerPoint Presentations. The University is cranking-up security and is centralizing control of IT. We are concerned but we have been model citizens plus we actually got our original permission to host the web site without obvious use of the ufl.edu domain from the current head of IT. The MUMSRx web database continues to be updated  it alone receives 1-2 hits each day. RUSTi is alive but with loss of biological scientist we have kept a low profile. Further development will have to wait upon programs choice of a successor on the current coordinators retirement in May 2010.<br /> <br />

Publications

PEER-REVIEWED PUBLICATIONS<br /> (1) Spitsbergen, J. M., Blazer, V. S., Bowser, P. R., et al. Finfish and aquatic invertebrate pathology resources for now and the future. Comp Biochem Physiol C Toxicol Pharmacol 2009, 149, 249-57.<br /> <br /> (2) Wesley, I. V., Larsen, S., Hurd, H. S., McKean, J. D., Griffith, R., Rivera, F., Nannapaneni, R., Cox, M., Johnson, M., Wagner, D., and de Martino, M. Low prevalence of Listeria monocytogenes in cull sows and pork. J Food Prot 2008, 71, 545-9.<br /> <br /> (3) Smith, G. W., Davis, J. L., Tell, L. A., Webb, A. I., and Riviere, J. E. Extralabel use of nonsteroidal anti-inflammatory drugs in cattle. J Am Vet Med Assoc 2008, 232, 697-701.<br /> <br /> (4) Hurd, H. S., Brudvig, J., Dickson, J., Mirceta, J., Polovinski, M., Matthews, N., and Griffith, R. Swine health impact on carcass contamination and human foodborne risk. Public Health Rep 2008, 123, 343-51.<br /> <br /> (5) Hawkins, M. G., Taylor, I. T., Craigmill, A. L., and Tell, L. A. Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits. J Vet Pharmacol Ther 2008, 31, 423-30.<br /> <br /> (6) Groocock, G. H., Grimmett, S. G., Getchell, R. G., Wooster, G. A., and Bowser, P. R. A survey to determine the presence and distribution of largemouth bass virus in wild freshwater bass in New York State. J Aquat Anim Health 2008, 20, 158-64.<br /> <br /> (7) Bartlett, S. L., Wooster, G. A., Sokolowski, M. S., Dove, A. D., and Bowser, P. R. Naturally occurring bacteraemia in American lobsters, Homarus americanus Milne-Edwards, in Long Island Sound. J Fish Dis 2008, 31, 19-25.<br /> <br /> (8) Needham, M. L., Webb, A. I., Baynes, R. E., Riviere, J. E., Craigmill, A. L., and Tell, L. A. Current update on drugs for game bird species. J Am Vet Med Assoc 2007, 231, 1506-8.<br /> <br />

Impact Statements

1. Since the first drug approval in 1984 under the former IR-4 program, NRSP-7 has been responsible for generating 33 Public Master File (PMF) publications in the Federal Register, an average of 1.4 per year during its 24 years of funding.
2. In 2008, 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.
3. To date 342 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.

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