NECC1702: Establishment of a Formal Structure for the Minor Use Animal Drug Program

(Multistate Research Coordinating Committee and Information Exchange Group)

Status: Inactive/Terminating

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SAES-422 Reports

Annual/Termination Reports:

[11/14/2017] [11/19/2018] [06/03/2020]

Date of Annual Report: 11/14/2017

Report Information

Annual Meeting Dates: 10/02/2017 - 10/02/2017
Period the Report Covers: 10/01/2017 - 10/02/2017

Participants

Brief Summary of Minutes

Program Status:

The program is now a Multistate Research Coordinating Committee and Information Exchange Group, NECC1702: Establishment of a Formal Structure for the Minor Use Animal Drug Program, under the authority of the Northeastern Regional Association of State Agricultural Experiment Station Directors. Dr. Margaret Smith is the Administrative Advisor.

The group reviewed and discussed the Committee’s three Objectives:

Provide the formal structure necessary to maintain the 88 INADs held in the name of the MUADP.

Continue APHIS funded research on cattle fever tick and sheep drug approvals.

In conjunction with NIFA and stakeholders, identify a stable funding source to work with the FDA/CVM to facilitate their approval of animal health products and provide information for the safe and efficacious use of these materials in specialty animal species.

As part of Objective 3, the group discussed various ways the program could elicit stakeholder involvement and support in the future:

Regular (biannual, quarterly) newsletters to key trade associations

Open meetings via teleconference to allow for engagement from a larger stakeholder base

Outreach via the existing Facebook page

Assuming the program maintains its past structure, the National Coordinator would spearhead these stakeholder engagement activities.

Dr. Smith explained that when a new Coordinating Committee is created within the Agricultural Experiment Station system, a notice is sent to all of the stations to invite interested parties to participate in the new committee. Dr. Enrique Escobar, Assistant Professor and Small Ruminant Extension Specialist at the University of Maryland Eastern Shore, has put his name forward to participate in the committee.

Program Structure:

During this time of transition, the group should take this opportunity to critically examine the structure of the program and design the best structure for completing work in the current regulatory landscape. In the past, most research was conducted by the Regional Coordinators at their respective universities. The group discussed old and new approaches for completing the work of the program, such as:

Contracting out the research to third parties (either CROs or other university researchers), with the Regional Coordinators serving as a Sponsor Representative.

Continuing with the historical approach, with certain regions providing a particular expertise necessary to complete the regulatory research. This approach led to the discussion of what level of Good Laboratory Practice (GLP) compliance would be needed at the 4 historical sites.

GLP compliance:

The program has historically conducted Target Animal Safety Studies and Human Food Safety studies (residue) in support of drug approvals. These 2 study types must be conducted under GLP standards. The group discussed the impact of conducting these studies in the university setting:

Concerns with the difficulty in achieving and maintaining systems that are necessary for GLP compliance

investment of resources (both initial and ongoing),

issues with University management (understanding and support for GLP studies),

Is it the best use of the program’s resources to have all 4 University sites maintain GLP compliance on a continuous basis?

To better understand the current status of GLP compliance, FDA/CVM/ONADE has offered to, in cooperation with the FDA Liaison, perform site feasibility visits of the 4 University sites. The site visits are intended to identify any gaps in the GLP infrastructure at the sites and will provide an opportunity for University management to gain a better understanding of GLP requirements. The goal is to provide support and compliance training/assistance, prior to the program moving forward with new GLP studies. The first 2 Universities slated for visits are Cornell and Iowa State, with plans to conduct the Cornell visit in November 2017. Based on the outcome of these first two visits, the group will discuss any identified gaps and determine how to best design the program’s GLP infrastructure.

Existing projects:

Group discussed need to complete the three highest priority projects:

Fenbendazole/pheasants:
- Human Food Safety = COMPLETE
- Target Animal Safety = COMPLETE.
- Environmental Impact = Contracting with Eric Rosenblum to complete the Environmental Assessment.
- Effectiveness = Work ongoing on White Paper to reaffirm the technical section complete letter received in 1998.

CIDR/goats:
- Human Food Safety = COMPLETE
- Target Animal Safety = COMPLETE.
- Environmental Impact = COMPLETE
- Effectiveness = Group discussed issues with study conducted at several commercial goat farms. Issues with data quality may require that the study be redone. Current plan is to write up the study and submit to ONADE. Based on what conclusions can be made from study, may be able to conduct a small scale study to provide substantial evidence of effectiveness.

Erythromycin/salmonids:
- Human Food Safety = COMPLETE
- Target Animal Safety = COMPLETE
- Environmental Impact = Environmental assessment requires administrative revisions.
- Effectiveness = Work ongoing on White Paper to reaffirm the technical section complete letter received in 1998, so that the indication can be broadened to all salmonids, as opposed to only Chinook.

Status update for other projects:

lasalocid – needs residue method; resubmit target animal safety

strontium chloride – target animal safety currently under review

ivermectin block – no progress made on this for several years; without significant progress on manufacturing and data access issues this project cannot be successful.

Future projects:

Group discussed considerations for how the program should choose projects in the future.

How best can the program elicit and respond to our stakeholders needs for approved products? What constitutes a product request that is actionable?

The program should consider only performing work on products for which there is already a complete manufacturing technical section. The exception to this rule would be for aquaculture projects.

The program should consider only taking on 2-3 projects at a time, with focus on completing ongoing projects prior to initiating new projects.

Funding options:

Group discussed funding options during this time of transition and beyond.

MUMS grants - The program could definitely qualify for MUMS grants to fund research. The impact of indirect costs charged by the universities was discussed. The recommendation was to describe such costs as part of the grant application.

Possibility of being funded through the USDA-NIFA budget. The tactical sciences effort currently being explored could provide a long-term solution to the chronic funding woes. The report of the group is available at: https://nifa.usda.gov/resource/tactical-science-continuing-commitment.

In the meantime, USDA-APHIS is providing a small amount of funding for some exploratory work in sheep and goats through the North Central Region.

Accomplishments

Publications

Impact Statements

Date of Annual Report: 11/19/2018

Report Information

Annual Meeting Dates: 09/17/2018 - 09/18/2018
Period the Report Covers: 10/01/2017 - 09/30/2018

Participants

Amy Omer FDA/CVM Amy.Omer@fda.hhs.gov
John Babish MUADP jgb7@cornell.edu
Lucy Lee FDA/CVM Lucy.Lee@fda.hhs.gov
Margaret Smith Admin Advisor, CUAES mes25@cornell.edu
Meg Oeller FDA/CVM Margaret.Oeller@fda.hhs.gov
Peter Johnson NIFA PJOHNSON@nifa.usda.gov
Rodman G. Getchell Cornell University rgg4@cornell.edu
Ronald Griffith Iowa State University rgriffit@iastate.edu

Brief Summary of Minutes

Minutes Attachment:

MUADP Mtg Sep 2018 Minutes.docx

Accomplishments

<ul> <li>Fenbendazole for pheasants  </li> <ul> <li>TAS: complete</li> <li>HFS: complete (except for tox piece);</li> <li>Effectiveness: outstanding—completed in 2000; must re-affirm data with white paper; goal is that by the end of this calendar year to be submitted;</li> <li>Environmental impact: initially wanted to ask for categorical exclusion from the EA, that request rejected; Eric Rosenblum will put together an exposure assessment report, including relevant information on how pheasants are managed, where leftover feed goes, etc.</li> </ul> <li>Fenbendazole for quail</li> <ul> <li>Effectiveness: (a) farmed quail- completed back in 2000, would need to re-affirm; (b) free-ranging quail- recent study completed, submission being prepared</li> <li>TAS: recent study completed, study designed to cover both farmed and free-ranging quail, submission being prepared</li> <li>Environmental impact/free-ranging quail: Planning a categorical exclusion request (regs say that if the drug is already approved in a species that has similar animal management practices, the proposed new use can be excluded from having to provide an EA).</li> <li>Human food safety: method/validation is currently under review; residue depletion study completed, final study report undergoing QA review</li> <li>The indication for the free-ranging quail = Lots of stakeholders! Lots of resources towards combatting the decrease of quail – especially in Texas !</li> </ul> <li>Erythromycin in salmon</li> <ul> <li>New sponsor to work on CMC technical section; will require a new API (active pharmaceutical ingredient)</li> <li>Still working with Chris Moffitt as conduit between manufacturer and end-users;</li> <li>Effectiveness: TS complete in 2000, when asked for re-affirmations in 2012-13 claim for all salmonids came back as chinook only; ONADE recommended we do another study; hope to write justification</li> <li>TAS:  TS complete in 2000, when asked for re-affirmations in 2012-13 claim for all salmonids came back as chinook only;</li> <li>Have had conversations with ONADE about going back to all salmonids for both EFF and TAS TSs, but with new API, calling into question EVERYTHING;</li> <li>Environmental impact: EA completed back when previous sponsor was involved;  will need to be revised based on removal of proprietary information</li> </ul> <li>Strontium chloride in salmon</li> <ul> <li>TAS:  Rod did TAS study (submitted in Jan 2016; incomplete); TAS will be submitted by the end of the year;</li> <li>Effectiveness, environmental, HFS:  white paper arguments for the rest of the TS; lots of data from the public domain—i.e. public health organizations</li> </ul> <li>Ivermectin block in cattle</li> <ul> <li>Collaboration between= (Texas cattle fever tick, USDA/ARS/APHIS, state veterinary, Postive Feeds)</li> <li>Project was deemed minor use bc it was geographically contained to a small area to eradicate cattle fever tick; this product is not intended to be used outside the quarantine zone</li> <li>TAS, HFS, environmental, effectiveness:  No progress on any of the technical sections</li> <li>Postive Feeds has made no progress on the CMC technical section.  Have recommended that they seek advice from a manufacturing consultant.</li> <li>Is there an option for another legal status? Perhaps legal compounding?</li> <li>Dr. Baca, our USDA contact down in Texas, recently retired; Amy needs to contact Dr. Hallie Hassel</li> <li>Need to have an action plan for this project</li> <li>APHIS will likely want to continue this if at all possible; Mexico has seen ivermectin resistance and tick is spreading along the edges of the quarantine zone</li> </ul> <li>CIDR in goats</li> <ul> <li>TAS, HFS, environmental: 3 TS COMPLETE</li> <li>Effectiveness: did complete effectiveness studies but lots of data errors</li> <li>Write up on the data from the farms that we do have; explain why other farms left out</li> <li>Zoetis approved for use in sheep and goats in other countries</li> <li>Not used in dairy goats</li> </ul> </ul>

Publications

Impact Statements

A grant was prepared and submitted to USDA-NIFA by Rod Getchell for $500,000 over five years, "Increasing the number of safe and effective therapeutics for aquaculture."

Date of Annual Report: 06/03/2020

Report Information

Annual Meeting Dates: 03/04/2020 - 03/04/2020
Period the Report Covers: 10/01/2018 - 09/30/2019

Participants

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

John Babish MUADP/ jgb7@cornell.edu

Margaret Smith NEAES mes25@cornell.edu

Meg Oeller FDA/CVM Margaret.Oeller@fda.hhs.gov

Cat Bens Colorado State University Cat.Bens@colostate.edu

Mark Mirando USDA/NIFA mark.mirando@usda.gov

Rodman G. Getchell Cornell University rgg4@cornell.edu

Ronald Griffith Iowa State University rgriffit@iastate.edu

Amanda Kreuder Iowa State University akreuder@iastate.edu

Participants Attachment:

Annual Report 2019.docx

Brief Summary of Minutes

Executive Summary

The NECC1702 structure has allowed the current 88 INADAs at the Center of Veterinary Medicine to remain active without payment of maintenance fees.

A nine-member Coordinating Committee teleconferences on a regular basis to maintain schedules and information on progress and NIFA grant opportunities.

Coordinating Committee members, Drs. Meg Oeller and Amy Omer of CVM/OMUMS and Dr. Rod Getchell of Cornell University, Northeast Regional Coordinator), attended the IR-4 Priority Setting Workshop in September 2019.

Rod Getchell has maintained communication with aquaculture and pharmaceutical representatives, as well as fish health stakeholders.

Omer completed MUADP’s registration with CVM’s eSubmitter program.

Progress has been made on nine of 13 current projects.

A one-year, $200,000 grant application under USDA-NIFA-AFRI-Funding Opportunity Number 007052 entitled, Therapeutic interventions for disease reduction or treatment was submitted to assess the efficacy of Florfenicol (AQUAFLOR®), Oxytetracycline (TM200), and Hydrogen peroxide (Perox-Aid®) for parasitic diseases of fish.

Detailed cost and time estimates of Efficacy, Target Animal Safety and Human Food Safety studies by the National Coordinator concluded direct costs associated with a single abbreviated new animal drug approval (ANADA) would be approximately $700,000 over five years. Various structures are currently under examination to address stakeholder expectations and support.

Coordinating Committee members have published two-peer review articles and made three presentations of current projects

Accomplishments

NECC1702 Accomplishments and Impacts are related to the following stated objective and activities described in the 6/26/2017 proposal (in italics): 1. Provide the formal structure necessary to maintain the 88 INADAs held in the name of the MUADP. The NECC1702 structure has allowed the current 88 INADAs to remain active within FDA/CVM without payment of maintenance fees. 2. Teleconference and meet with NIFA associates to address the development of a tactical science initiative and formation of a unified Regulatory Systems Support Program. Under the format of NECC1702, the following Coordinating Committee members (Table 1) teleconferenced on a regular basis to discuss funding opportunities and progress on studies. NIFA assigned liaison, Dr. Mark Mirando provides updates on funding opportunities through the agency. Outreach Several members of the MUADP Coordinating Committee (Drs. Meg Oeller and Amy Omer of CVM/OMUMS and Dr. Rod Getchell of Cornell University, Northeast Regional Coordinator) attended the IR-4 Priority Setting Workshopin September 2019. The members observed the priority-setting activities of IR-4, a program whose mission is essentially identical to that of the Minor Use Animal Drug Program (MUADP) but for plants instead of animals. Attendance at this workshop provided an opportunity for the Committee members to understand the process that IR-4 uses to (1) prioritize the research they conduct, and (2) maintain the involvement of their stakeholders in the prioritization process. Dr. Rod Getchell has maintained communication with aquaculture and pharmaceutical representatives, as well as fish health stakeholders. Additionally, he works closely with AADAP and other research partners.  For example, the progress made on our AQUI-S®20E project was presented at the annual meeting of the Aquaculture Drug Approval Coordination Workshop last July. Additionally, Dr. Getchell updates the NECC1702 Coordinating Committee members on his NECC1702 projects during teleconferences.  Table 1. Minor Use Animal Drug Program Coordinating Committee <table width="624"> <tbody> <tr> <td width="180"> Name </td> <td width="222"> Representing </td> <td width="221"> email Address </td> </tr> <tr> <td width="180"> Amanda Kreuder </td> <td width="222"> Iowa State University </td> <td width="221"> akreuder@iastate.edu </td> </tr> <tr> <td width="180"> Amy Omer </td> <td width="222"> FDA/CVM </td> <td width="221"> <a href="mailto:Amy.Omer@fda.hhs.gov">Amy.Omer@fda.hhs.gov</a> </td> </tr> <tr> <td width="180"> Cat Bens </td> <td width="222"> Colorado State University </td> <td width="221"> <a href="mailto:Cat.Bens@colostate.edu">Cat.Bens@colostate.edu</a> </td> </tr> <tr> <td width="180"> John Babish </td> <td width="222"> MUADP/ </td> <td width="221"> <a href="mailto:jgb7@cornell.edu">jgb7@cornell.edu</a> </td> </tr> <tr> <td width="180"> Margaret Smith </td> <td width="222"> NEAES </td> <td width="221"> <a href="mailto:mes25@cornell.edu">mes25@cornell.edu</a> </td> </tr> <tr> <td width="180"> Mark Mirando </td> <td width="222"> USDA/NIFA </td> <td width="221"> <a href="mailto:mark.mirando@usda.gov">mark.mirando@usda.gov</a> </td> </tr> <tr> <td width="180"> Meg Oeller </td> <td width="222"> FDA/CVM </td> <td width="221"> <a href="mailto:Margaret.Oeller@fda.hhs.gov">Margaret.Oeller@fda.hhs.gov</a> </td> </tr> <tr> <td width="180"> Rodman G. Getchell </td> <td width="222"> Cornell University </td> <td width="221"> <a href="mailto:rgg4@cornell.edu">rgg4@cornell.edu</a> </td> </tr> <tr> <td width="180"> Ronald Griffith </td> <td width="222"> Iowa State University </td> <td width="221"> <a href="mailto:rgriffit@iastate.edu">rgriffit@iastate.edu</a> </td> </tr> </tbody> </table> Process Improvement Dr. Omer completed MUADP’s registration with CVM’s eSubmitter program. The CVM eSubmitter tool is an electronic, question-based submission tool that allows animal drug sponsors to electronically and securely submit information to CVM. All animal drug sponsors must use eSubmitter to submit information to CVM’s Office of New Animal Evaluation (ONADE).  Having the ability to submit to CVM electronically will provide increased efficiencies in the creation and delivery of submissions to CVM.  Additionally, as a registered eSubmitter user, MUADP will now qualify for shortened reactivation or resubmission review times on certain critical submissions, as defined by the latest Animal Drug User Fee Act (ADUFA III). 3. Continue research on current outstanding projects. Thirteen projects are presently active in the Program (Table 2). Details of progress on nine of those this year are provided below. Table 2. Current Projects <table> <tbody> <tr> <td> Drug </td> <td> Formulation </td> <td> Species </td> <td> Indication </td> </tr> <tr> <td> Fenbendazole </td> <td> Premix </td> <td> Gamebirds </td> <td> GI Parasites </td> </tr> <tr> <td> Strontium chloride </td> <td> Immersion </td> <td> Salmonids </td> <td> Otolith Marking </td> </tr> <tr> <td> Progesterone </td> <td> CIDR1 </td> <td> Goats </td> <td> Estrus synchronization </td> </tr> <tr> <td> Tulathromycin </td> <td> Injection </td> <td> Goats </td> <td> Respiratory Infection </td> </tr> <tr> <td> Chlortetracycline </td> <td> Oral </td> <td> Lambs </td> <td> Respiratory Infection </td> </tr> <tr> <td> Ivermectin </td> <td> Medical Block </td> <td> Beef Cattle </td> <td> Rhipicephalus microplus </td> </tr> <tr> <td> Vaccinal Immunity </td> <td> Soluble vaccine </td> <td> Sheep </td> <td> Haemonchus contortus </td> </tr> <tr> <td> Vaccinal Immunity </td> <td> Soluble vaccine </td> <td> Sheep </td> <td> Corynebacterium pseudotuberculosis </td> </tr> <tr> <td> AQUI-S®20E </td> <td> Liquid </td> <td> Striped bass </td> <td> Sedative </td> </tr> <tr> <td> AQUI-S®20E </td> <td> Liquid </td> <td> Pompano </td> <td> Sedative </td> </tr> <tr> <td> Lasalocid </td> <td> Premix </td> <td> Pheasants </td> <td> Coccidiosis </td> </tr> <tr> <td> Tulathromycin </td> <td> Injection </td> <td> Sheep </td> <td> Respiratory Infection </td> </tr> <tr> <td> Erythromycin </td> <td> Premix </td> <td> Salmonids </td> <td> Bacterial Kidney DiseaseControlled internal drug release </td> </tr> </tbody> </table>  1CIDR = controlled internal drug release   1. Fenbendazole in quail: MUADP continues collaboration with our research partners, Dr. Ron Kendall of Texas Tech University and Merck Animal Health, to generate the data necessary to obtain FDA approval of fenbendazole-medicated feed for the treatment of nematodes in quail.  This project has impact for both wild quail and farmed quail. Wild quail populations have declined by more than 85% in the last five decades. While many causes for the decline have been proposed, this project addresses the potential role of parasitism. Field studies conducted by Dr. Kendall have shown that fenbendazole is effective against common parasites in quail. The ongoing research will also support FDA approval for the use of fenbendazole in farmed quail. There are currently no anthelmintics approved for use in quail. Successful completion of this project will provide access to a class of therapeutic drugs previously unavailable to quail farmers.  1.1 Environmental MUADP worked with research partner, Merck Animal Health, to justify a claim of categorical exclusion from the requirement to conduct an Environmental Assessment for the use of fenbendazole in quail.  The claim was denied by CVM, with a request for additional information.  MUADP and Merck are working to address CVM’s requests. 1.2 Human Food Safety In April 2019, MUADP, with research partner Dr. Ron Kendall of Texas Tech University, submitted a revised protocol for a tissue residue depletion study for fenbendazole in quail.  CVM requested additional revisions to the protocol. In August 2019, MUADP submitted for CVM review the revised Method SOP and Validation Report.  CVM determined that the tissue method for fenbendazole in quail was adequately validated and acceptable for use in a residue depletion study. 1.3 Target Animal Safety and Effectiveness Dr. Ron Kendall has conducted both a Target Animal Safety study and an Effectiveness study for the use of fenbendazole in quail.  The MUADP is preparing these data sets for submission to CVM.   2. Strontium Chloride immersion for salmon: MUADP continues collaboration with our research partner, Syndel USA, to generate the data necessary to obtain FDA approval of strontium chloride hexahydrate immersion for the skeletal marking of freshwater salmonid fry and fingerlings. Fishery managers need a method to chemically mark salmon to determine migration patterns while avoiding the stress of tagging or other physical markings. While there are other drug products approved for skeletal marking in salmon, this project provides a non-antimicrobial alternative. 2.1 Target Animal Safety Dr. Rod Getchell, Northeast Regional Coordinator for the MUADP, completed a GLP Target Animal Safety study evaluating strontium chloride hexahydrate immersion for the skeletal marking of freshwater salmonid fry and fingerlings.In May 2019, CVM determined that the Target Animal Safety technical section was complete for this indication.   3. Efficacy of CIDRs for synchronization of estrus in goats:  No progress to report.   4. Tulathromycin (Draxxin) Tissue Residue in Goats: 4.1 Target Animal Safety The ultimate objective of this project is to perform studies in support of FDA/CVM approval of a label claim for Draxxin in goats. In the summer and fall of 2017, Dr. Joe Smith conducted work to determine the pharmacokinetics of Draxxin in infected vs uninfected goats (Abstract of presentation at the ACVIM meeting below). In addition, selected target tissues were harvested from the uninfected goats and frozen for determination of tissue residue levels in preparation for conducting a required Human Food Safety study. 4.2 Publication Preliminary evaluation of a Pasteurella multocida respiratory disease induction model for goats Comparative Medicine (In Press)   5. Efficacy of oral chlortetracycline for control of naturally acquired respiratory disease in feeder lambs: 5.1 Principal investigators Katelyn Ternus, Dawson LaBorde, Ron Griffith, Paul Plummer, Kelly Still Brooks. 5.2 Objective The purpose of this study was to evaluate if medicating feeder lambs with oral chlortetracycline (CTC) decreases the prevalence of clinical and subclinical respiratory disease. 5.3 Methods This study was conducted as a blinded, randomized clinical trial enrolling 160 weaned feeder lambs with natural exposure to ovine respiratory disease. The efficacy of CTC for control of ovine respiratory disease was evaluated through overall average daily gain, ruminal core body temperature, ante mortem clinical respiratory disease scores, post mortem lung lesion scores, and pulmonary tissue culture. Current project efforts are focused on preparation and laboratory analysis of the banked biologic samples. The ovine plasma CTC concentration determinations have been completed by Scott Wetzlich (UC Davis) and the raw data has been returned to the research team. Dr. Fufa Bari completed DNA library preparation of a subset of the bronchoalveolar lavage samples last fall; viral metagenomic sequencing was run at the ISU VDL and the bioinformatics analysis has been returned to the research team. These samples will be submitted for tetracycline resistance marker shotgun sequencing at the end of the summer (2018) when the 16s samples are ready for assay. DNA prep for the water biofilm samples is nearly complete and DNA prep of the BAL, fecal, cecal, and rumen samples will be performed this summer, with bulk submission of all samples for 16s sequencing slated for this fall. Coordination is in progress to complete the quantitative feed tetracycline analysis through Zoetis this summer.   6. Ivermectin Molasses/Protein/Mineral Tubs for Eradication of Cattle Fever Ticks: 6.1 Report The study report for this project has been compiled and organized. Plans are to return the report to Dr.Dan Baca for submission to the FDA/CVM. However, the manufacturer has not reached an agreement with Merial for the right of reference and the manufacturer has also not been able to complete the Chemistry and Manufacturing Component. The latter was to be performed before or at least early in the work.   7. Extended Vaccinal Immunity to Haemonchus contortus in Sheep: 7.1 Principal Investigators Matt Brewer and Doug Jones. 7.2 Methods 24 sheep were divided into 4 experimental groups: adjuvant only (ADJ), soluble vaccine (SOL), implant with dextran adjuvant (DD), or implant with Quil A adjuvant (DQ). Sheep were infected with 4500 larvae 9 months post-vaccination (12 sheep) or 9000 larvae one year post-vaccination, and necropsied 50-60 days post infection.  7.3 Results Implanted sheep had lower adult worm counts and all vaccinated sheep had decreased egg counts. Vaccination was also associated with a modest increase in PCV. FAMACHA scoring did not reveal any dramatic differences between control and vaccinated animals. Implanted animals had ELISA endpoint titers that were orders of magnitude greater than control animals 55 weeks post-vaccination.  IHC revealed serum antibodies binding to a variety of worm tissues, including the gut and body wall. Statistical analysis, additional IHC, and measurement of cytokines (recall responses) are underway.  We have identified a suitable source of refined Haemonchus gut antigen for future experiments. A manuscript describing these results is in preparation. 7.4 Figure Figure 1 in the attached report shows results of evaluating Haemonchus contortus vaccine as adjuvant only (ADJ), soluble vaccine (SOL), implant with dextran adjuvant (DD), or implant with Quil A adjuvant (DQ).   8. Preparation of antigens from three different strains of Corynebacterium pseudotuberculosis: 8.1 Progress Study has been completed. Sheep were immunized 3X with each of the antigen preparations and subsequently bled for antibody production. A challenge model in mice has been evaluated at two different dosages and one strain was especially virulent, one strain produced grossly visible lesions but no obvious clinical signs and the third strain produced neither lesions nor clinical signs.   9. Target animal safety study for AQUI-S®20E: 9.1 Overview This represents one of our newest NIFA studies.   9.2 Methods A target animal safety study will be conducted for the AQUI-S®20E sedative in striped bass and pompano as model species.   Estimating Funding Needs for MUADP <ol start="4"> <li> In conjunction with NIFA and stakeholders, identify a stable funding source to work with the FDA/CVM to facilitate their approval of animal health products and provide information for the safe and efficacious use of these materials in specialty animal species.</li> </ol> To identify a stable funding source, it is necessary to accurately ascertain the current costs of performing Efficacy, Target Animal Safety and Human Food Safety studies under Good Laboratory Practices (21 CFR 58) and Good Clinical Practices. These estimates were performed over the past year using historical costs along with estimates from three commercial histopathology laboratories. All studies were assumed to be conducted under Good Laboratory practices. From required study length, total animal-days were calculated to estimate in life phase costs of each study. Post study estimate of residue analyses was based on one or two edible tissues per species. Gross and histopathology evaluations were based on 38 tissues required by FDA/CVM. Total direct costs thus estimated were $700,000 per species per drug and would require a research period of five years. Adding the costing of the Environmental Impact Assessment and one full time associate, the amount needed per operational unit is approximately $1 MM for the completion of one abbreviated animal drug approval (ANADA) within five years. Various structures are currently under examination to address stakeholder expectations and support. Grant Applications Description: USDA-NIFA-AFRI-Funding Opportunity Number 007052 in the animal health program area under “Therapeutic interventions for disease reduction or treatment.” Institution: Researchers within the Cornell University Aquatic Animal Health Program and USFWS Aquatic Animal Drug Approval Partnership (AADAP) program are proposing to continue a collaboration to conduct studies to increase the number of safe and effective drugs that can be used to benefit the U.S. aquaculture community. Scope of Work: Trials will be conducted with Florfenicol (AQUAFLOR®), Oxytetracycline (TM200), and Hydrogen peroxide (Perox-Aid®), which are used to treat diseases and parasites of fish. Budget: $200,000 for one year including $60,000 indirect costs

Publications

Smith, J.S., Mochel, J.P., Seo, Y.J., Ahrens, A.P. and Griffith, R.W. 2020 Preliminary evaluation of a repeated administration Pasteurella multocida respiratory disease induction method for goats. Comparative Medicine (In Press) Yaeger, M. J., Mochel, J. P., Wu, Z., Plummer, P.. Sahin, O., Beyi, A.F., Xu, C., Zhang, Q., and Griffith, R. 2020. Pharmacokinetics of Tulathromycin in Pregnant Ewes Challenged with Campylobacter jejuni. Frontiers in Veterinary Science, section Veterinary Pharmacology and Toxicology (Submitted). Yaeger, M. J., Mochel, J. P., Wu, Z., Plummer, P.. Sahin, O., Beyi, A.F., Xu, C., Zhang, Q., and Griffith, R. 2019 Pharmacokinetics of Tulathromycin in infected vs uninfected goats. ACVIM meeting (Phoenix, AZ) Getchell, Rodman G., D.M. Scott, B.M. Chambers, N. Wandelear, P.R. Bowser, P. Baneux, D. Kirby, H. Marquis, and M. Blair. 2020. The Safety of AQUI-S® 20E (10% Eugenol) as a sedative on marine fish. Aquaculture America 2020, February 9-12, 2020, Honolulu, HI. Getchell, Rodman G., Danielle M. Scott, Brian M. Chambers, Niccole Wandelear, Paul R. Bowser, Philippe Baneux, Drew Kirby, Hélène Marquis, and Marilyn Blair.  2019.  The safety of AQUI-S® 20E (10% Eugenol) as a sedative on a marine finfish. Aquatic Animal Drug Approval Partnership (AADAP) Program U.S. Fish and Wildlife Service,August 31, 2019 Bozeman, MT

Impact Statements

CVM determined that the Target Animal Safety technical section for strontium chloride hexahydrate immersion for the skeletal marking of freshwater salmonid fry and fingerlings was complete for this indication.