NATIONAL COORDINATOR FOR AQUACULTURE NEW ANIMAL DRUG APPLICATIONS (NADAs)

NINTH ANNUAL SUMMARY OF ACTIVITY HIGHLIGHTS FOR THE NATIONAL COORDINATOR FOR AQUACULTURE NEW ANIMAL DRUG APPLICATIONS (NATIONAL AQUACULTURE NADA COORDINATOR)

(May 15, 2003 to May 14, 2004)

AMOXICILLIN—ORAL ANTIBACTERIAL (one initial label claim in progress: control of mortalities associated with Streptococcus infections in hybrid striped bass)

On November 11, 2003, the U.S. representative of the sponsor, GB Research, Inc., submitted an efficacy study to the Center for Veterinary Medicine (CVM) on amoxicillin to control Streptococcus infections in hybrid striped bass to the sponsor’s Investigational New Animal Drug (INAD) exemption file. The study had been performed at the Harry K. Dupree National Aquaculture Research Center (SNARC).

AQUI-S®—ANESTHETIC (one initial label claim in progress: zero withdrawal anesthetic for all salmonids)

On June 3, 2003, the sponsor, AQUI-S New Zealand Ltd. and its U.S. representative along with the Upper Midwest Environmental Sciences Center (UMESC) and the National Aquaculture NADA Coordinator met with CVM to discuss the data requirements for product chemistry and human food safety of AQUI-S®.

On July 29, 2003, the U.S. representative of the sponsor of AQUI-S® along with UMESC, the U.S. Fish and Wildlife Service (FWS) Aquatic Animal Drug Approval Partnership Program (AADAPP), and the National Aquaculture NADA Coordinator met in Bozeman, Montana to discuss the potential need for a large amount of radiolabeled material and how to fund the purchase of the material.

AADAPP submitted the following pivotal efficacy data on AQUI-S® to CVM (1) shortnose sturgeon (September 4, 2003), (2) Chinook salmon (October 2, 2003), (3) largemouth bass (October 21, 2003), (4) hybrid striped bass (November 14, 2003), (5) rainbow trout (January 20, 2004), and (6) channel catfish (February 6, 2004). On December 15, 2003, AADAPP submitted supportive efficacy data on AQUI-S® to CVM on (1) hybrid striped bass, (2) tilapia, and (3) hybrid carp/goldfish.

The sponsor submitted to CVM (1) a full biological activity report to CVM for Product Chemistry data (October 2003) and (2) two biodegradation studies for the Environmental Safety Technical Section (November 24, 2003).

On January 29, 2004, CVM accepted as supportive from AADAPP the efficacy studies for steelhead trout, lake trout, mountain whitefish, rainbow trout, cutthroat trout, bull trout, and hybrid striped bass.

The National Aquaculture NADA Coordinator obtained funding through the North Central Regional Aquaculture Center (NCRAC) for the radiolabeled material needed for the total residue depletion study to be conducted by UMESC.

The National Aquaculture NADA Coordinator worked with the sponsor to develop a Research and Development Plan for the approval of AQUI-S® in the United States that was submitted to CVM by the sponsor in April 2004.

On May 19, 2004, the National Aquaculture NADA Coordinator and the sponsor met with CVM to discuss the status of the company’s data requirements and how to proceed to meet those requirements.

CHLORAMINE-T—EXTERNAL ANTIBACTERIAL (two label claims close to completion: control of mortalities associated with (1) bacterial gill disease on all freshwater-reared salmonids and (2) external columnaris disease on walleye)

On July 16, 2003, the sponsor, Axcentive bv, submitted the proprietary environmental assessment (EA) on chloramine-T to CVM. UMESC developed the EA for the sponsor with funds from the company.

On July 11, 2003, CVM reinstated the slaughter authorization for the use of chloramine-T under FWS’s INAD. The CVM decision was based on the acceptance of mammalian safety data from Axcentive bv.

CVM accepted as complete the (1) Efficacy Technical Section for control of external columnaris disease on walleye from UMESC (January 30, 2004) and (2) Target Animal Safety Technical Section for all coolwater and warmwater fish from UMESC (March 11, 2004).

The sponsor, Stoller Fisheries, has decided not to pursue a response to CVM request for a revision of its product chemistry technical section.

On October 2, 2003, the sponsor, Syngenta Crop Protection, Inc., declared that the senior management could not support the development of their diquat product for aquaculture use because of the requirement to manufacture their product under Good Manufacturing Practices.

FLORFENICOL—ORAL ANTIBACTERIAL (four label claims close to completion: control of mortalities associated with (1) furunculosis in freshwater-reared salmonids, (2) coldwater disease in freshwater-reared salmonids, (3) systemic columnaris disease in freshwater-reared salmonids and catfish, and (4) enteric septicemia in catfish)

On August 7, 2003, CVM accepted as complete the AADAPP efficacy data for the control of coldwater disease in all freshwater-reared salmonids.

In the fall 2003, CVM accepted as complete the sponsor’s (Schering-Plough Animal Health) (1) Target Animal Safety Technical Section on freshwater-reared salmonids and (2) Human Food Safety Technical Section on freshwater-reared salmonids.

Since June 2003, Schering-Plough Animal Health submitted (1) final Product Chemistry Technical Section, (2) final Environmental Safety Technical Sections for pond and flow-through systems, and (3) final Human Food Safety Technical Section for freshwater-reared salmonids.

On April 23, 2004, UMESC submitted a project completion report to the International Association of Fish and Wildlife Agencies on the analytical support of pivotal efficacy studies for florfenicol used in public fisheries.

FORMALIN—EXTERNAL MICROBICIDE (one additional label claim close to completion: control of mortalities associated with saprolegniasis on all fish)

On October 22, 2003, UMESC submitted to CVM the Efficacy Technical Section for the control of saprolegniasis on channel catfish.

HYDROGEN PEROXIDE—EXTERNAL MICROBICIDE (four label claims close to completion: control of mortalities associated with (1) saprolegniasis on all finfish eggs, (2) saprolegniasis on all finfish, (3) bacterial gill disease on all freshwater-reared salmonids, and (4) external columnaris disease on all coolwater fish and channel catfish)

CVM accepted as complete from UMESC the (1) Efficacy Technical Section for the control of mortalities associated with external columnaris disease on coolwater fish and channel catfish (November 21, 2003), (2) Target Animal Safety Technical Section for all finfish eggs (November 26, 2003), (3) Efficacy Technical Section for the control of mortalities associated with saprolegniasis on all finfish eggs (February 9, 2004).

On January 14, 2004, UMESC submitted an Efficacy Technical Section for hydrogen peroxide to control mortalities associated with saprolegniasis on channel catfish.

On February 11, 2004, CVM accepted as complete the Product Chemistry Technical Section from the sponsor, Eka Chemicals, Inc.

17α-METHYLTESTOSTERONE (MT)—GENDER MANIPULATION AID (one label claim close to completion: gender manipulation aid for tilapia)

On August 1, 2003, Cornell University submitted to CVM two final reports: (1) use of MT for sex reversal (masculinization) of early life stage tilapia and (2) animal safety.

The National Aquaculture NADA Coordinator worked with the University of Florida to gain a MT INAD for ornamentals in the fall of 2003.

In December 2003, Auburn University submitted to CVM a final report on the efficacy of MT in tilapia.

On January 28, 2004, CVM extended the MT INAD for tilapia under Auburn University for six months.

The National Aquaculture NADA Coordinator obtained support from NCRAC on February 7, 2004 to fund a MT target animal safety study on tilapia because CVM recently determined that one was needed.

On February 26, 2004, AADAPP submitted a request to CVM to sponsor an INAD for MT.

On February 7, 2004, NCRAC selected the University of Wisconsin at Madison to conduct biodegradation and stability studies on MT.

OXYTETRACYCLINE—ORAL ANTIBACTERIAL (two label claims close to completion: control of mortalities associated with (1) systemic columnaris disease in steelhead trout and (2) systemic coldwater disease in all freshwater-reared salmonids)

On December 19, 2004, CVM accepted as complete the Target Animal Safety Technical Section from UMESC for all coolwater and scaled warmwater fish.

On April 27, 2004, the National Aquaculture NADA Coordinator and the sponsor met with CVM to discuss (1) requirements for changes in the formulation and (2) remaining data requirements (especially environmental safety) to add new salmonid label claims to the NADA.

OXYTETRACYCLINE—IMMERSION ANTIBACTERIAL AND MARKING AID (one label claim approved=marking all fish and three label claims close to completion: control of mortalities associated with (1) bacterial gill disease, (2) external columnaris disease, and (3) systemic columnaris disease on coolwater and warmwater fish)

On December 24, 2003, CVM approved the supplemental NADA for Alpharma Animal Health’s oxytetracycline product (OXYMarine™) as an otolith marking aid for all finfish.

ROMET®—ORAL ANTIBACTERIAL (previously approved for control of enteric septicemia in catfish and furunculosis in salmonids)

The sponsor, Alpharma Animal Health, resolved the palatability problems with Romet-TC® Type B medicated feed and submitted the information to CVM. In late November 2003, CVM declared that no supplemental NADA would be required to use as indicated.

EFFLUENTS. EPA signed the final rule for national effluent limitation guidelines and standards on June 30, 2004. Among others, the rule will apply to the use, storage, and reporting requirements of drugs and chemicals at selected facilities where the water is released into public waters.

MUMS. A bill entitled "Minor Use Minor Species Animal Health Act" (MUMS) passed the full Senate on March 8, 2004 and the House Energy and Commerce Committee on June 24, 2004. The bill goes before the full House sometime after July 4, 2004.

ADUFA. The Animal Drug User Fee Act (ADUFA) of 2003 (Public Law 108-130) was passed by U.S. Congress in late December 2003 and authorized FDA to collect user fees for certain drug approval applications. All sponsors had to respond to letter from FDA but sponsors of drugs for minor species or minor uses will not have to pay any fees.

The National Coordinator for Aquaculture New Animal Drug Applications had one publication in press, presented 19 papers, and wrote 34 special reports.

The overall goal of this project is for the National Coordinator for Aquaculture New Animal Drug Applications (National Aquaculture NADA Coordinator) to coordinate activities for investigational new animal drug exemptions (INADs) and new animal drug applications (NADAs) to expedite approval for the use of various drugs in aquaculture. Specific objectives related to that goal are to:

Serve as an information conduit between INAD/NADA applicants and the U.S. Food and Drug Administration’s Center for Veterinary Medicine (CVM);

Identify and encourage prospective INAD participants to become involved in specific investigational studies and NADA approval-related research;

Seek the support and participation of pharmaceutical sponsors for INAD studies and NADAs and coordinate with INAD/NADA sponsors to achieve CVM approval more quickly;

Guide prospective and current INAD holders on the format for INAD exemption requests and related submissions to CVM;

Identify existing data and remaining data requirements for NADA approvals;

Review, record, and provide information on the status of INADs and NADAs;

Provide liaison and coordination among all the federal agencies involved in the INAD/NADA process; and

Provide public education related to training and guidance in obtaining INAD exemptions and pursuing NADA approval.

 

The National Aquaculture NADA Coordinator provided many information transfers from May 15, 2003 to May 14, 2004 and worked to obtain INADs, NADAs, and approvals for a number of drugs that are considered to be of high priority for approval by the public and private aquaculture communities.

Amoxicillin (oral antibacterial)—Status: Early development stage; antimicrobial resistance issue needs to be addressed. Kent Sea Tech Corporation, the U.S. representative for the sponsor, GB Research, submitted a Research and Development Plan to CVM files. Initial label claim in progress: control of mortalities associated with Streptococcus infections in hybrid striped bass.

On November 11, 2003, Kent Sea Tech Corporation submitted to CVM an efficacy study on amoxicillin to control Streptococcus infections in hybrid striped bass. The study had been performed at the Harry K. Dupree National Aquaculture Research Center (SNARC).

The National Aquaculture NADA Coordinator helped in March 2004 with the letter requesting a one-year extension of the INAD exemption for amoxicillin. The extension was granted in the spring 2004.

Chloramine-T (external antibacterial)—Status: Was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (Axcentive bv; formerly Akzo Nobel Chemicals, Inc.), UMESC, and AADAPP; two label claims close to completion: control of mortalities associated with (1) bacterial gill disease on all freshwater-reared salmonids and (2) external columnaris disease on walleye.

Progress on chloramine-T (May 15, 2003 TO May 14, 2004):

On May 14, 2003, the National Aquaculture NADA Coordinator provided the sponsor, Axcentive bv, with information on recent efficacy studies and the current status of the approval process for chloramine-T.

On July 16, 2003, the sponsor submitted the proprietary environmental assessment (EA) on chloramine-T to CVM. The Upper Midwest Environmental Sciences Center (UMESC) developed the EA for the sponsor with funds from the company. The National Aquaculture NADA Coordinator helped the sponsor with the submission.

On July 11, 2003, CVM reinstated the slaughter authorization for the use of chloramine-T under the U.S. Fish and Wildlife Service’s (FWS) Investigational New Animal Drug (INAD) exemption. The CVM decision was based on the acceptance of mammalian safety data from Axcentive bv.

On January 30, 2004, CVM accepted as complete from UMESC the efficacy technical section for controlling external columnaris disease on walleye by chloramine-T.

On March 11, 2004, CVM accepted as complete from UMESC the target animal safety technical Section on coolwater & warmwater fish for chloramine-T.

Current status of technical sections on chloramine-T:

Product Chemistry—The sponsor, Axcentive bv (a 100% daughter company of PNP Holding bv, Barneveld, The Netherlands) is committed to developing the product chemistry technical section and submitting it to CVM into INAD #8086.

Mammalian Safety—The sponsor is addressing this technical section. CVM declared that p-TSA is not genotoxic based on proprietary data submitted by Axcentive bv (July 19, 2002). CVM accepted additional proprietary mammalian safety data from Axcentive bv; based on those data, CVM declared that the safe concentration of p-TSA in edible tissue of fish is 1 ppm (April 9, 2003).

Environmental Safety—CVM accepted a dilution model to detect effluents from waterborne drugs at the outlet pipe (May 7, 2003). UMESC submitted an environmental summary to CVM into Public Master File Number 5637 (October 31, 2002); these data are available to any chloramine-T sponsors. UMESC also developed a proprietary environmental assessment that was submitted by Axcentive bv on July 16, 2003 to CVM under INAD #8086.

Human Food Safety—CVM accepted (1) residue chemistry studies by UMESC for total residue depletion and metabolism of chloramine-T in several species of fish; p-TSA was established as the major metabolite in fish and declared as a marker residue for chloramine-T in juvenile rainbow trout, (2) simple colorimetric procedure by UMESC for use in efficacy studies for determining chloramine-T concentrations in treatment waters, (3) research by UMESC that bridges the proposed HPLC analytical method for p-TSA with an outdated, labor intensive method previously used to quantify p-TSA in fish tissue (January 13, 2003), and (4) determinative method in multiple species (April 24, 2003). Through an interagency agreement with UMESC, CVM’s Office of Research developed a confirmatory method for p-TSA in fish tissue to satisfy an all fish label claim. UMESC submitted a FOI summary on human food safety to CVM. CVM declared that the safe concentration of p-TSA in edible tissue of fish is 1 ppm (April 9, 2003).

Target Animal Safety—CVM accepted as complete from (1) the Aquatic Animal Drug Approval Partnership Program (AADAPP) the target animal safety technical section on freshwater-reared salmonids (September 13, 2002) and (2) UMESC the target animal safety technical section on coolwater and warmwater fish (March 11, 2004).

Efficacy—CVM accepted as complete from (1) AADAPP the efficacy technical section for control of mortalities associated with bacterial gill disease on all freshwater-reared salmonids and (2) UMESC the efficacy technical section for controlling external columnaris disease on walleye (January 30, 2004).

Copper Sulfate (external microbicide)—Status: Was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (Phelps Dodge Refining Corporation) and SNARC; one label claim close to completion: control of Ichthyophthirius on channel catfish in earthen ponds with no outflows.

Progress on copper sulfate (May 15, 2003 to May 14, 2004):

The representative for Phelps Dodge Refining Corporation is now David Fisher.

SNARC had the data audit completed on the target animal safety study on channel catfish and is in the process of developing the final report for submission to CVM through Phelps Dodge Refining Corporation.

Current status of technical sections on copper sulfate:

Product Chemistry—CVM accepted as complete from the sponsor, Phelps Dodge Refining Corporation.

Mammalian Safety—CVM accepted as complete from the sponsor, Phelps Dodge Refining Corporation; FOI summary written by CVM on March 3, 2000.

Environmental Safety—The revised environmental safety technical section for use in earthen ponds with no outflows was reviewed by CVM in 2000 and CVM is requiring an additional study. A study at SNARC addressed the use of copper sulfate in ponds was completed and will be incorporated into a revised EA and submitted to CVM.

Human Food Safety—CVM accepted as complete from SNARC the human food safety technical section; FOI written by CVM on March 3, 2000--no tolerances, regulatory methods, or withdrawal times are needed for finfish treated with copper sulfate.

Target Animal Safety—SNARC submitted literature on target animal safety studies and additional target animal safety studies with a histopathology component are requested by CVM for an all fish label claim. SNARC performed such a study on channel catfish and will submit it to CVM.

Efficacy—CVM accepted as complete from SNARC the efficacy technical section for control of Ichthyophthirius on all fish. SNARC also conducted pivotal efficacy studies to control fungi on catfish eggs.

Diquat Dibromide (external microbicide)—Status: No sponsor is available to complete the approval process.

On September 2, 2003, the sponsor, Syngenta Crop Protection, Inc., held a conference call with NRSP-7 and the to discuss the product chemistry issues and potential ways of resolving them.

On October 2, 2003, Syngenta Crop Protection, Inc. declared that the senior management could not support the development of their diquat product for aquaculture use because of the requirement to manufacture its product under Good Manufacturing Practices.

Enrofloxacin (oral antibacterial)—Status: INADs inactive in the United States because of fluoroquinolone and antimicrobial resistance issues; no sponsor interest.

Erythromycin (oral antibacterial)—Status: A sponsor is available for erythromycin—Bimeda Inc.; most technical sections submitted except sponsor product chemistry; risk assessment needed on potential for disease resistance in humans and hazard in the environment (to complete the Environmental Safety and Human Food Safety Technical Sections); near NADA approval for bacterial kidney disease in salmonids if can resolve the antimicrobial resistance issue.

Recently, Bimeda Inc. agreed to become the NADA sponsor of erythromycin when the data packages are accepted by CVM.

Studies are underway at the University of Idaho to (1) understand the extent of erythromycin resistant microflora in the GI tract of fish following treatment with erythromycin and (2) address the fate of erythromycin in sediment ponds with a history of erythromycin treatment. A risk assessment document will follow these studies.

Florfenicol (oral antibacterial)—Status: The sponsor, Schering-Plough Animal Health, gained florfenicol (Aquaflor®) approval in Canada in August 1997 to control furunculosis in Atlantic salmon; sponsor is developing data for aquaculture approval for control of diseases in salmonids and catfish; was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor, UMESC, and AADAPP; four label claims close to completion: control of mortalities associated with (1) enteric septicemia in catfish, (2) coldwater disease in freshwater-reared salmonids, (3) furunculosis in freshwater-reared salmonids, and (4) systemic columnaris disease in freshwater-reared salmonids and catfish.

Progress on florfenicol (May 15, 2003 to May 14, 2004):

On August 7, 2003, CVM accepted as complete the AADAPP efficacy data for the control of coldwater disease in all freshwater-reared salmonids.

In the fall 2003, CVM accepted as complete the sponsor’s target animal safety technical section on freshwater-reared salmonids.

In the fall 2003, CVM accepted as complete the sponsor’s human food safety technical section on freshwater-reared salmonids.

On November 8, 2003, the National Aquaculture NADA Coordinator provided the sponsor with information on veterinarians who could prescribe Aquaflor® when it gains approval as a Veterinary Feed Directive drug for its use to control enteric septicemia in catfish.

On January 16, 2004, the sponsor submitted to CVM the final package for the product chemistry technical section.

In January and February 2004, the sponsor submitted to CVM the final packages for the environmental safety technical section.

On April 23, 2004, UMESC submitted a project completion report to the International Association of Fish and Wildlife Agencies on the analytical support of pivotal efficacy studies for florfenicol used in public fisheries.

Current status of technical sections on florfenicol:

Product Chemistry—Submitted by sponsor—final package.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Submitted by sponsor—final package.

Human Food Safety—Accepted by CVM: Residue chemistry for catfish and for freshwater-reared salmonids and microbial food safety for all fish.

Target Animal Safety—Accepted by CVM: channel catfish and freshwater-reared salmonids.

Efficacy—Accepted by CVM: enteric septicemia in catfish; coldwater disease in salmonids. UMESC validated methods to analyze for florfenicol in finfish feeds to support efficacy studies at AADAPP; AADAPP submitted efficacy studies to CVM on systemic columnaris disease and furunculosis in salmonids and streptococcal septicemia in hybrid striped bass.

Formalin (external microbicide)—Status: Supplemental NADAs approved on June 18, 1998 and November 25, 2002 for control of certain fungi on the eggs of all finfish, certain external protozoa and monogenetic trematodes on all finfish, and certain external protozoa on penaeid shrimp; was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsors (Natchez Animal Supply Company, Western Chemical Inc. and Argent Chemical Laboratories), UMESC, and CVM’s Office of Research; one additional label claim close to completion: control of mortalities associated with saprolegniasis on all fish.

Progress on formalin (May 15, 2003 to May 14, 2004):

Recently both the CVM Office of Research and UMESC completed pivotal efficacy studies for control of saprolegniasis on salmonids and channel catfish. Final reports to CVM that have or will request an "all fish" label claim.

The National Aquaculture NADA Coordinator worked extensively with a sponsor on a manufacturer for formalin.

On October 22, 2003, UMESC submitted to CVM a final report on the pivotal efficacy studies on the control of saprolegniasis on channel catfish

Current status of technical sections on formalin:

Product Chemistry—Accepted by CVM.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Accepted by CVM.

Human Food Safety—Accepted by CVM.

Target Animal Safety—Accepted by CVM.

Efficacy—CVM informally accepted supporting efficacy for control of saprolegniasis on salmonids from FWS and UMESC efforts. UMESC submitted pivotal efficacy studies on the control of saprolegniasis on channel catfish (October 22, 2003).

Fumagillin (microsporidiosis control)—Status: No recent sponsor activity; several efforts to collect efficacy data in public and private sector; early development stage.

Hydrogen peroxide (external microbicide)—Status: Currently considered as a low regulatory priority drug for use as a fungicide on fish and fish eggs but CVM has encouraged the development of a NADA; was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (Eka Chemicals Inc.) and UMESC; four label claims close to completion: control of mortalities associated with (1) saprolegniasis on all finfish eggs, (2) saprolegniasis on all finfish, (3) bacterial gill disease on all freshwater-reared salmonids, and (4) external columnaris disease on all freshwater-reared coolwater finfish and channel catfish.

Progress on hydrogen peroxide (May 15, 2003 to May 14, 2004):

On June 25, 2003, the National Aquaculture NADA Coordinator revised the hydrogen peroxide label to reflect the latest thinking on the label claims that can be supported and submitted it to the sponsor.

On June 30, 2003, Eka Chemicals, Inc. submitted a revised product chemistry package to CVM to answer the remaining questions on manufacture of hydrogen peroxide. On February 11, 2004, CVM accepted as complete from the sponsor the product chemistry technical section

On November 21, 2003, CVM accepted as complete the efficacy data from UMESC for the control of mortalities associated with external columnaris disease on coolwater fish and channel catfish.

UMESC recently completed pivotal efficacy studies to control mortalities associated with saprolegniasis on rainbow trout and channel catfish and is in the process of writing up the final reports.

UMESC is conducting the pivotal 21-day Daphnia study requested by CVM to complete the Environmental Safety Technical Section.

On November 26, 2003, CVM accepted as complete from UMESC the target animal safety technical section for all fish eggs.

On January 14, 2004, UMESC submitted pivotal efficacy technical section on the control of saprolegniasis on catfish.

On February 9, 2004, CVM accepted as complete from UMESC the efficacy technical section for saprolegniasis on all fish eggs.

Current status of technical sections on hydrogen peroxide:

Product Chemistry—Accepted by CVM (February 11, 2004).

Mammalian Safety—Accepted by CVM. The FOI summary was written by CVM on March 22, 2000.

Environmental Safety—A model was developed by UMESC to estimate discharged environmental concentrations based on UMESC hatchery survey and a point source dilution model from the U.S. Geological Survey. UMESC wrote an environmental assessment to support an all fish label claim and submitted it to CVM on March 14, 2000 and the final review by CVM was completed on June 24, 2002. CVM required a 21-day chronic toxicity study on daphnia and reformatting of the environmental assessment that are in progress.

Human Food Safety—Accepted by CVM. The FOI summary was written by CVM on March 22, 2000--no tolerances, regulatory methods, or withdrawal times are needed for finfish and their eggs treated with hydrogen peroxide.

Target Animal Safety—Accepted by CVM: all finfish from UMESC and all finfish eggs from UMESC (November 26, 2003).

Efficacy—Accepted by CVM: control of mortalities associated with (1) saprolegniasis on all salmonid eggs, (2) saprolegniasis on all finfish eggs, (3) bacterial gill disease on all freshwater-reared salmonids, (4) external columnaris disease on all coldwater fish, and (5) external columnaris disease on channel catfish. CVM accepted from UMESC the following as supporting data: treatment of external parasitic infestations on all salmonids. UMESC submitted pivotal efficacy technical section on the control of saprolegniasis on catfish (January 14, 2004) and completed pivotal efficacy studies to control mortalities associated with saprolegniasis on rainbow trout.

MelaFix™ (external microbicide)—Status: Have sponsor; early development stage

Oxytetracycline (OTC, oral antibacterial)—Status: Currently approved for control of certain systemic bacterial diseases in catfish, salmonids, and lobsters and as an oral marking agent in Pacific salmon; was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (Phibro Animal Health, formerly Pfizer, Inc.), UMESC, and AADAPP; two label claims close to completion: control of mortalities associated with (1) systemic columnaris disease in steelhead trout and (2) systemic coldwater disease in all freshwater-reared salmonids.

Progress on oral oxytetracycline (May 15, 2003 to May 14, 2004):

In October 2003, CVM accepted as complete from AADAPP the FOI for the control by oral OTC of coldwater disease in all freshwater-reared salmonids.

On December 19, 2003, CVM accepted as complete from UMESC the target animal safety technical section for coolwater and scaled warmwater fish.

On April 27, 2004, the National Aquaculture NADA Coordinator, the sponsor, and UMESC met with CVM to discuss (1) requirements for changes in the formulation and (2) remaining data requirements (especially environmental safety) to add new salmonid label claims to the NADA. UMESC wrote a revised EA that is out for peer review before it is submitted to CVM.

Current status of technical sections on oral oxytetracycline:

Product Chemistry—Previously accepted by CVM under original NADA from Pfizer, Inc. (now owned by Phibro Animal Health). The sponsor is working on changing the formulation.

Mammalian Safety—Previously accepted by CVM under original NADA from Pfizer, Inc. (now owned by Phibro Animal Health).

Environmental Safety—Previously accepted by CVM under original NADA from Pfizer, Inc. (now owned by Phibro Animal Health). CVM is requiring a revised EA for any new label claims. UMESC wrote a revised EA that is out for peer review before it is submitted to CVM. UMESC is preparing under contract with the University of Wisconsin-Madison a model to describe the fate of oxytetracycline released into the environment from aquaculture facilities. Validation of the estimated model concentrations will be conducted at an aquaculture facility and the results will be submitted as an amendment to the environmental assessment report.

Human Food Safety—Previously accepted by CVM for certain label claims under original NADA from Pfizer, Inc. for OTC for cold water species above 9EC and warm water species above 16EC. Recently, CVM accepted (1) residue chemistry studies submitted by UMESC for use of OTC below the label claim limit of 9EC which established a withdrawal time of three days for juvenile salmonids, (2) residue depletion studies submitted by UMESC for the use of OTC in juvenile cool water species with a zero withdrawal time, (3) an HPLC method developed by UMESC to detect OTC in feed and fish tissue, (4) a study completed by UMESC bridging the HPLC OTC detection method to the official microbial assay method, (5) extrapolated withdrawal times for salmonids (May 17, 2002), (6) liquid chromatographic determination of OTC in edible tissues of six species of fish (September 9, 2002), and (7) validation of an HPLC method in coho salmon and northern pike (September 9, 2002). UMESC petitioned CVM to shorten the withdrawal time for OTC in all freshwater fish species based on its residue depletion data and the new tolerance of 2 ppm. UMESC submitted a letter package addressing the antimicrobial resistance issues with human food safety; CVM replied that a microbial food safety assessment is required. Efforts by the National Aquaculture NADA Coordinator and the sponsor are underway to address this issue.

Target Animal Safety—Previously accepted by CVM for catfish, salmonids, and lobsters under original NADA from Pfizer, Inc. Accepted by CVM: coolwater and scaled warmwater fish from UMESC (December 19, 2003).

Efficacy—Previously accepted by CVM under original NADA from Pfizer, Inc. for OTC use on catfish, salmonids and lobsters to control certain systemic bacterial diseases. Accepted by CVM: control of mortalities associated with (1) systemic columnaris disease in steelhead trout from AADAPP and (2) systemic coldwater disease in all freshwater-reared salmonids from AADAPP. The efficacy technical section developed by UMESC from a data call-in was accepted as supporting data for control of (1) Aeromonas sp. in coolwater species, and (2) systemic columnaris disease in salmonids.

Oxytetracycline (OTC, immersion antibacterial)—Status: No current sponsor for antibacterial use; three label claims close to completion: control of mortalities associated with (1) bacterial gill disease, (2) external columnaris disease, and (3) systemic columnaris disease on coolwater and warmwater fish.

Progress on immersion otc (May 15, 2003 to May 14, 2004):

UMESC is conducting pivotal efficacy studies on coolwater and warmwater fish for control of mortalities associated with (1) bacterial gill disease, (2) external columnaris disease, and (3) systemic columnaris disease.

On December 10, 2003, UMESC submitted to CVM data to verify the dose for pivotal efficacy studies.

Current status of technical sections on immersion OTC:

Product Chemistry—Accepted by CVM.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Accepted by CVM for marking by immersion from NRSP-7.

Human Food Safety—Accepted for all fish by CVM for marking by immersion from NRSP-7.

Target Animal Safety—Accepted for all fish by CVM for marking by immersion from NRSP-7.

Efficacy—On April 8, 2003, CVM responded to an October 28, 2002 submission from UMESC on the efficacy of OTC immersion treatment of bacterial diseases in and on coolwater fish. CVM commented that OTC immersion may be effective against bacterial diseases in a variety of species and the efficacy data may support future pivotal data. Pivotal efficacy studies underway by UMESC on coolwater and warmwater fish for control of (1) bacterial gill disease, (2) external columnaris disease, and (3) systemic columnaris disease.

Pet Fish Therapeutants (various drugs and pesticides)—Status: Major effort to resolve non-food fish issues for these drugs through Minor Use Minor Species legislation.

Potassium Permanganate (external microbicide)—Status: Was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (Carus Chemical Company) and SNARC; label claim in progress: control of Ichthyophthirius on channel catfish in earthen ponds with no outflows

Progress on potassium permanganate (May 15, 2003 to May 14, 2004):

The National Aquaculture NADA Coordinator worked with the sponsor on the product chemistry revision.

Current status of technical sections on potassium permanganate:

Product Chemistry—The sponsor, Carus Chemical Company, submitted product chemistry technical section for all fish to CVM on December 8, 1998; CVM asked for additional data; the sponsor provided additional data (March 2002) and CVM is asking for clarification (April 2002).

Mammalian Safety—Accepted by CVM.

Environmental Safety—The sponsor submitted a request for a categorical exclusion from an environmental assessment for all fish to CVM on February 23, 1998; CVM is requiring an environmental assessment. Efforts at Arkansas State University began in January 2002 on environmental fate and effects studies with funding from the Multi-State Conservation Grant Program.

Human Food Safety—CVM accepted as complete from SNARC the human food safety technical section.

Target Animal Safety—SNARC completed a target animal safety study on channel catfish.

Efficacy—SNARC completed pivotal efficacy studies that demonstrate efficacy to prevent Ichthyophthirius on channel catfish and tilapia. SNARC completed controlled efficacy studies for control of Ichthyophthirius on channel catfish and tilapia. A pivotal efficacy study is planned when seasonal water temperatures are optimal for control of Ichthyophthirius on channel catfish.

Praziquantel (trematode and cestode control)—Status: Some interest on the part of potential sponsor in a NADA approval in the United States but needs positive marketing information; has approval in several countries.

Pyceze® (external microbicide)—Status: Sponsor submitted an INAD/NADA letter of intent and summary of all major technical sections; met with CVM on development of data; early development stage.

Romet® (oral antibacterial)—Status: Romet-30® has approvals for control of enteric septicemia in catfish and furunculosis in salmonids; early development stage for extensions and expansions; sponsor resolved palatability for Romet-TC® (new label name for Type B medicated feed; previously called Romet-B®).

Progress on Romet® (May 15, 2003 to May 14, 2004):

Romet® TC is approved for Type B medicated feeds and its status was clarified and concurred with by CVM in late November 2003: Recent controlled studies by Alpharma Animal Health show that fish will eat feeds containing Romet® TC (16.7% sulfadimethoxine and 3.34% ormetoprim) as readily as they will consume non-medicated control diets. Use Directions for Romet® TC call for preparation of a liquid slurry that is then used to coat fish feeds. This can be accomplished by placing pellets in a cement mixer or by spreading them on a plastic or smooth surface for the coating process. The coated pellets should be allowed to air dry for several hours prior to use. These Use Directions are consistent with the approved drug label (ROMET-30® Type A Medicated Article) and the approved Blue Bird labels for medicated feeds. Although no additional pre-marketing approval is required for Type B Medicated Feeds, Alpharma consulted CVM and received their concurrence. No feed mill license is required to use Romet® TC to make medicated fish feeds.

The National Aquaculture NADA Coordinator worked extensively with the sponsor and CVM to help in the process of gaining acceptance by CVM of the resolution of the palatability problems with Romet-TC®.

Current status of technical sections on Romet®:

Product Chemistry—Accepted by CVM.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Accepted by CVM.

Human Food Safety—Accepted for catfish and salmonids by CVM.

Target Animal Safety—Accepted for catfish and salmonids by CVM.

Efficacy—Accepted for control of enteric septicemia in catfish and furunculosis in salmonids by CVM; palatability problems resolved by sponsor.

Sarafloxacin (oral antibacterial)—Status: Previously, most of the NADA technical sections were submitted by Abbott Laboratories and accepted by CVM for control of enteric septicemia in catfish with sarafloxacin. However, the Centers for Disease Control and Prevention (CDC) presented concerns about the use of all fluoroquinolones in animal health because of the perceived potential for developing pathogen resistance to drugs used in humans. It is doubtful that a new NADA on sarafloxacin or any fluoroquinolone will be allowed for aquaculture uses by CVM. Sarafloxacin was replaced by florfenicol as the oral antibacterial and model drug for crop grouping research in January 1998 by a unanimous vote of the IAFWA Project stakeholders.

Sea Lice Control (various drugs and pesticides)—Status: Various drugs and pesticides (azamethiphos or Salmosan™, cypermethrin or Excis™) are being pursued by the United States and Canada and are at various stages of registration and approval. Uses of several drugs and pesticides are being challenged on the East coast, particularly in Maine. An INAD for Slice™ (emamectin benzoate) was allowed by CVM as a result of great need for a control that could not be challenged to the extent that the others have been.

Trichlorfon (external parasite control)—Status: Some interest on the part of potential sponsor in a NADA approval in the United States; has approvals in several countries; several Special Local Need registrations obtained in 1998 for control of predaceous insects.

AQUI-S®—Status: Was a Federal-State Aquaculture Drug Approval Partnership Project drug and now under development by the sponsor (AQUI-S New Zealand LTD.), UMESC, and AADAPP; label claim in progress: zero withdrawal anesthetic in all salmonids for short-exposure handling (rested harvest, spawning, marking, tagging, measuring, and sexing)

Progress on Aqui-S® (May 15, 2003 to May 14, 2004):

From May 29 to June 3, 2003, the National Aquaculture NADA Coordinator hosted a representative from AQUI-S New Zealand prior to the meeting with CVM and discussed strategies for approval. Both saw a presentation by UMESC on the status of the residue chemistry studies on AQUI-S®.

On June 3, 2003, the sponsor and its U.S. representative along with UMESC and the National Aquaculture NADA Coordinator met with CVM to discuss the data requirements for product chemistry and human food safety of AQUI-S®. A major topic of discussion was the need to clarify the ratio of isomers in the formulation before any human food safety studies begin.

On July 29, 2003, the U.S. representative of the sponsor, UMESC, AADAPP, and the National Aquaculture NADA Coordinator met in Bozeman, Montana to discuss the potential need for a large amount of radiolabeled material and how to fund the purchase of the material. UMESC is conducting a series of pilot studies to further delineate the design of the total residue depletion study so that the exact amount of radiolabeled material needed for the study is known.

AADAPP submitted efficacy studies on AQUI-S® for the following species: (1) shortnose sturgeon as pivotal on September 4, 2003, (2) Chinook salmon as pivotal on October 2, 2003, (3) largemouth bass as pivotal on October 21, 2003, (4) hybrid striped bass as pivotal on November 14, 2003, (5) hybrid striped bass, tilapia, and hybrid carp/goldfish as supportive on December 15, 2003, (6) rainbow trout as pivotal on January 20, 2004, and (7) channel catfish as pivotal on February 6, 2004.

In October 2003, the sponsor submitted to CVM information and studies on the activity of AQUI-S® that is needed for decisions on product chemistry and efficacy.

On November 24, 2003, the sponsor submitted to CVM two biodegradation studies (freshwater & saltwater).

The National Aquaculture NADA Coordinator and UMESC collaborated on a preliminary proposal that was submitted to the Sea Grant Program in November 2003 for funding the radiolabeled material for the total residue depletion study on rainbow trout, a surrogate for all salmonids. This proposal did not receive funding.

In December 2003, the sponsor selected Tom Goodrich to be the U.S. representative.

On January 12, 2004, AADAPP submitted to CVM a protocol for a target animal safety study on rainbow trout.

On January 29, 2004, CVM accepted from AADAPP four efficacy studies on salmonids (steelhead trout, lake trout, mountain whitefish, rainbow trout, cutthroat trout, and bull trout) and one on hybrid striped bass as supportive.

Prior to February 7, 2004, the National Aquaculture NADA Coordinator was able to get a commitment from the sponsor to provide part of the funding (up to $50,000) for the radiolabeled material.

On February 7, 2004, the National Aquaculture NADA Coordinator was able to get a commitment from the North Central Regional Aquaculture Center=NCRAC) to provide part of the funding (up to $60,000) for the radiolabeled material. The request was based on a white paper written by the National Aquaculture NADA Coordinator. The National Aquaculture NADA Coordinator prepared a problem statement on this issue that was submitted to NCRAC and that statement was integrated into a proposal that was submitted to the U.S. Department of Agriculture (USDA) for funding on April 9, 2004. USDA agreed to fund the radiolabeled material through NCRAC.

The National Aquaculture NADA Coordinator met with the sponsor of AQUI-S® and other key participants in the approval process in Seattle, Washington on March 16, 2004 to discuss (1) communication structure among the various groups working on the drug’s approval, (2) resources available to complete the technical sections, (3) regulatory status of technical sections and targets for completion, (4) potential label claims, and (5) any impediments to completion.

The National Aquaculture NADA Coordinator worked with the sponsor to develop a Research and Development Plan for the approval of AQUI-S® in the United States. The sponsor submitted the plan to CVM in April 2004.

On May 19, 2004, the National Aquaculture NADA Coordinator and the sponsor met with CVM to discuss the status of the company’s data requirements and how to proceed to meet those requirements.

The National Aquaculture NADA Coordinator prepared a white paper on AQUI-S® that was sent to all Drug Approval Working Group members on May 24, 2004 for gaining support for funding the remaining data requirements.

On May 25, 2004, the National Aquaculture NADA Coordinator worked with the sponsor to provide comments to CVM’s Memorandum of Conference on the June 4, 2003 meeting.

Current status of technical sections on Aqui-S®:

Product Chemistry—The sponsor (AQUI-S New Zealand LTD.) submitted studies on activity of AQUI-S® to CVM (October 2003).

Mammalian Safety—The sponsor conducted a review of the mammalian safety literature to determine whether to continue with the original active ingredient in light of National Toxicology Program (NTP) studies to test for its potential carcinogenicity. A 90-day feeding study demonstrated no carcinogenicity but NTP decided to proceed with a two-year study that was completed in Spring 2004. The sponsor concluded that the active ingredient is safe and presented these conclusions to CVM on November 18, 1999 and decided to proceed with the drug approval in the U.S. for original active ingredient based on their assessment of scientific data that the active ingredient is not a carcinogen.

Environmental Safety—The sponsor submitted a summary to CVM in the late 1990s and environmental biodegradation studies in freshwater and saltwater (November 24, 2003).

Human Food Safety— UMESC conducted a series of pilot studies to delineate the design of the total residue depletion study so that the exact amount of radiolabeled material needed for the study is known. UMESC is planning to conduct a pivotal total residue depletion study after the pilot studies are completed and radiolabeled material has been obtained. The National Aquaculture NADA Coordinator obtained partial funding from NCRAC (February 7, 2004) for the radiolabeled material that is needed to the total residue depletion study on rainbow trout, a surrogate for all salmonids.

Target Animal Safety—Preliminary toxicity studies have been completed at UMESC on a variety of fish species but UMESC will not perform any other studies because funds were diverted to fulfill the need for human food safety studies. Pivotal target animal safety studies on salmonids will be performed by AADAPP. AADAPP submitted a protocol for these studies to CVM (January 12, 2004). The sponsor is preparing to submit to CVM target animal safety and efficacy studies on Atlantic salmon completed in Canada.

Efficacy—Preliminary efficacy studies were completed at UMESC on a variety of fish species. Pivotal efficacy studies will be performed by AADAPP on a variety of fish species but UMESC will not perform any other studies because funds were diverted to fulfill the need for human food safety studies. The sponsor is ready to submit to CVM pivotal efficacy studies on Atlantic salmon completed in Canada. CVM accepted as supportive four efficacy studies on salmonids and one on hybrid striped bass (January 29, 2004). AADAPP submitted additional efficacy studies on a variety of species from September 2003 to February 2004.

Benzocaine—Status: Major effort by IAFWA Project for NADA approval terminated because of decision by IAFWA Project stakeholders to select AQUI-S® as the candidate anesthetic in the U.S. public aquaculture sector; no known drug approval activities underway.

Clove oil—Status: Oil of cloves (eugenol) is considered Generally Recognized as Safe (GRAS) when used as a direct food additive (21CFR184.1257); however, to use eugenol as an anesthetic on fish, it must be approved by CVM for that purpose. A sponsor is required to proceed toward approval and no sponsor has come forward; no known drug approval activities underway. CVM provided guidance on the use of clove oil in Guidance for Industry #150: Status of Clove Oil and Eugenol for Anesthesia of Fish.

The National Aquaculture NADA Coordinator has provided CVM with information from the literature regarding detailed composition of clove oil (May and June 2004).

MS-222—Status: Two approved NADAs for MS-222 as an anesthetic with a 21-day withdrawal time.

Crude Carp Pituitary (CCP)—Status: Interested parties proceeding toward NADA approval but sponsor, Stoller Fisheries, has decided not to pursue a response to CVM request for a revision of its product chemistry technical section.

Progress on CCP (May 15, 2003 to May 14, 2004):

The sponsor has not decided to pursue a response to CVM request for a revision of its product chemistry technical section on CCP.

Current status of technical sections on CCP:

Product Chemistry—The sponsor submitted the product chemistry technical section for CCP to CVM on September 21, 1999. The sponsor received a response on November 22, 1999 from CVM that asked for more information. The sponsor has not decided to pursue a response.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Accepted by CVM.

Human Food Safety—Accepted by CVM.

Target Animal Safety—A literature review on target animal safety of CCP was completed, presented on August 5, 1998 in Bozeman, Montana and submitted to CVM in summer 1999 by the Southeastern region of NRSP-7. Mississippi State University completed target animal safety studies on CCP and is in the process of submitting them to CVM.

Efficacy—Accepted as complete from NRSP-7 by CVM as a spawning aid in freshwater-reared female finfish (July 17, 2002).

Human Chorionic Gonadotropin (hCG)—Status: September 1999 NADA approval in the United States. Chorulon® (human chorionic gonadotropin) was approved on September 7, 1999 by CVM as a spawning aid by intramuscular injection for all fish and requires a prescription under the direction of a veterinarian. This approval is significant because it is the first original NADA approval since 1986 when formalin was first approved for fish and because it was approved for all fish.

Luteinizing Hormone-Releasing Hormone analog (LHRHa)—Status: Auburn University gained an INAD for LHRHa in the Spring 2003; early development stage.

17 α-methyltestosterone (MT)—Status: Sponsor, Rangen, Inc., is developing NADA package; INAD sponsors actively pursuing a NADA approval; one label claim close to completion: gender manipulation aid for tilapia

Progress on MT (May 15, 2003 to May 14, 2004):

The National Aquaculture NADA Coordinator developed the announcement for biodegradation and stability studies to be funded by the North Central Regional Aquaculture Center (NCRAC) that was sent to prospective contractors on August 29, 2003. The University of Wisconsin-Madison was selected as the contractor and is in the process of developing the protocols for the studies to be submitted to CVM for review.

On August 1, 2003, Cornell University submitted to CVM two final reports on MT: (1) use of MT for sex reversal (masculinization) of early life stage tilapia and (2) animal safety of MT to tilapia.

The National Aquaculture NADA Coordinator worked with the University of Florida to gain a MT INAD for ornamentals in the fall of 2003.

In December 2003, Auburn University submitted a final report to CVM on the efficacy data on tilapia generated under the INAD.

On January 28, 2004, CVM extended the INAD for tilapia under Auburn University for six months.

The National Aquaculture NADA Coordinator obtained support from NCRAC on February 7, 2004 to fund a target animal safety study on tilapia because CVM recently determined that one was needed. She developed the Call for Statement of Interest in bidding on this study.

On February 26, 2004, AADAPP submitted a request to CVM to sponsor an INAD for MT.

A prospective contractor has been selected to perform the target animal safety study on tilapia and is in the process of developing the protocol.

Current status of technical sections on MT:

Product Chemistry—The sponsor, Rangen, Inc., submitted a product chemistry technical section on 17 α-methyltestosterone to CVM on November 8, 2000. CVM is requiring more information, stability studies, and an analytical method with greater recoveries. The University of Wisconsin-Madison was selected as the contractor to complete these requirements and is in the process of developing the protocols for the studies to be submitted to CVM for review.

Mammalian Safety—Accepted by CVM.

Environmental Safety—Auburn University received a response from CVM on November 8, 1999 regarding the revised environmental assessment for MT that requested additional information, a biodegradation study, and a more sensitive method to detect MT in water. The University of Wisconsin-Madison was selected as the contractor to complete these requirements and is in the process of developing the protocols for the studies to be submitted to CVM for review.

Human Food Safety—Accepted by CVM.

Target Animal Safety— Cornell University submitted to CVM an animal safety study on tilapia; CVM found a target animal safety study on percids by Southern Illinois University to be inadequate; literature review on other species completed and submitted by Auburn University. CVM recently determined that a target animal safety study on tilapia was needed and NCRAC has agreed to fund this study; a prospective contractor has been selected to perform the target animal safety study on tilapia and is in the process of developing the protocol.

Efficacy— Cornell University submitted to CVM a final report on the efficacy of MT to tilapia; Auburn University is coordinating a compassionate INAD on tilapia and completed and submitted the final report to CVM in December 2003; North Central Regional Aquaculture Center representatives are coordinating a compassionate INAD on percids. AADAPP submitted a request for an INAD on MT.

Ovaplant™ and Ovaprim™—Status: Sponsor recently submitted INAD letter of intent; early development stage.

Calcein—Status: Have sponsor (Western Chemicals Inc.); early development stage.

Oxytetracycline (immersion)—Status: APPROVED: marking aid by immersion for all fish.

On December 24, 2003, CVM approved OxyMarine®--Alpharma Animal Health became the sponsor of a supplemental NADA for marking aid by immersion for all fish.

Strontium Chloride—Status: Western Chemical Inc. is the sponsor; some work completed in Alaska; some efficacy studies underway under Western NRSP-7.

PISCICIDES--Both rotenone and antimycin are used by hatcheries in resource agencies and private aquaculture facilities to control diseases in cultured fish and undesirable fish in ponds.

The National Aquaculture NADA Coordinator hosted a meeting of the American Fisheries Society’s Fish Management Chemicals Subcommittee (FMCS) on July 23-27, 2003 to discuss (1) a training course on the use of piscicides, (2) Standard Operating Procedures manual for antimycin.

FMCS members provided a training course on the use of piscicides on October 27-31, 2003 in West Virginia and in April 2004 in Arizona. Another training course will be given in October 2004 in West Virginia.

The National Aquaculture NADA Coordinator communicated by phone with FMCS and FWS representatives who met in Washington, DC on January 30, 2004 to discuss a plan for the reregistration of antimycin.

The National Aquaculture NADA Coordinator met with a FMCS representative and the Rotenone Task Force on May 7, 2004 in New York City, New York to discuss the registration of a new formulation of rotenone that does not use a petroleum hydrocarbon solvent system.

Federal-State Aquaculture Drug Approval Partnership Project; known as the IAFWA Project (includes eight drugs: AQUI-S®, chloramine-T, copper sulfate, florfenicol, formalin, hydrogen peroxide, oxytetracycline, and potassium permanganate)

AADAPP hosted the 9^th Annual INAD Workshop on July 30-31, 2003 that centered on the progress being made on the drugs in the Federal-State Aquaculture Drug Approval Partnership Project (a project under the auspices of the International Association of Fish and Wildlife Agencies=IAFWA; project known as the IAFWA Project). The presentations included (1) progress being made on the IAFWA Project drugs, (2) public fish production database availability, (3) overviews of activities by AADAPP, SNARC, USDA’s Agriculture Research Service (ARS), UMESC, CVM’s Office of Research, CVM’s Aquaculture Drugs Team, Washington offices for FWS, USGS/BRD, ARS, (4) other drugs under development including erythromycin, calcein, N-Halamine, Romet®, Pyceze®, MinnCare®, diquat, and (5) update on the Minor Use Minor Species (MUMS) legislation. As a result of the meeting, the public fish production database was made available on the website for the National Aquaculture NADA Coordinator (http://ag.ansc.purdue.edu/aquanic/jsa/aquadrugs/index.htm).

The IAFWA Drug Approval Working Group (DAWG) held a meeting on September 10, 2003 in Madison, Wisconsin. The National Aquaculture NADA Coordinator provided a report on (1) the status of IAFWA Project drugs toward initial approval, (2) funding needs for the position, and (3) future plans for expanding and extending existing label claims. Each research facility (i.e., AADAPP and UMESC) provided a status report for the current research year. CVM reported that, from the agency’s perspective, great progress has been made on the IAFWA Project drugs. The USGS prepared a draft Memorandum of Understanding for the IAFWA Project agencies (USGS, ARS, FWS, IAFWA, and Michigan State University). In a post-DAWG meeting, the group discussed the (1) format of future DAWG meetings, (2) funding needs for AQUI-S®, (3) funding the public sector activities of the National Aquaculture NADA Coordinator, and (4) future research efforts.

The DAWG also held a meeting on March 17, 2004 in Spokane, Washington. The format of the meeting was changed to allow for greater time to discuss issues and pursue action items. Thus, the National Aquaculture NADA Coordinator provided documents before the meeting on the technical progress toward drug approvals and at the meeting, presented a brief overview of recent efforts toward initial approvals of project drugs. Detailed discussions centered on AQUI-S®, copper sulfate, Animal Drug User Fee Act (ADUFA), proposed Memorandum of Understanding for IAFWA Project agencies, and funding sources for drug approvals. At the Pre-DAWG meeting on March 17, 2004, the group had the major discussions that centered on AQUI-S®, status of initial label claims, and ADUFA.

When Bob Miles retired as IAFWA Resources Director in July 2003, Eric Schwaab replaced him.

The National Aquaculture NADA Coordinator finalized a white paper on the funding needs for this position. The paper includes (1) the justification for funding from the public aquaculture sector, (2) a two-year budget, (3) scheduled activities, and (4) potential products for the period of October 1, 2003 to September 30, 2006. The National Aquaculture NADA Coordinator went from full-time to three-quarter time due to lack of funds starting October 1, 2003 and then went 35 hours per week on May 15, 2004 because her appeal to adequately support this position was heard.

The Aquaculture Effluents Task Force (AETF) was formed to coordinate and facilitate input of science-based information to assist in the development of national effluent limitation guidelines and standards for aquaculture facilities by EPA. AETF, in this time period, (1) provided EPA with documents of the judicious use of drugs and chemicals and (2) held a teleconference with EPA and the different subgroups on May 27, 2003 to discuss remaining issues and set a course of action on effluents. EPA officials met with CVM to work toward a Memorandum of Agreement to distinguish their respective legal authorities and establish an effective mechanism to address the discharge of drugs. The Drugs and Chemicals and Aquatic Animal Pathogens Technical Subgroup (1) responded to EPA questions on drugs on May 21, 2003 and (2) provided EPA on July 10, 2003 with actual volume figures for antibiotic sales in the US in 2001 and 2002 to counteract the impression that tons of antibiotics are used in US aquaculture [Note: The National Aquaculture NADA Coordinator was one of the authors].

EPA developed a draft Notice of Data Availability (NODA) and distributed copies to federal agencies in September 2003 and published it in the Federal Register on December 29, 2003 and EPA signed the final rule on June 30, 2004. The rule will apply to the use, storage, and reporting requirements of drugs and chemicals at selected facilities where the water is released into public waters.

AETF provided comments on the draft NODA on February 13, 2004 that included responses to questions regarding drugs and chemicals. AETF met for the last time at Aquaculture 2004 to discuss the final rule with EPA and get clarification of the current thinking of EPA.

A bill originally entitled "Minor Animal Species Health and Welfare Act of 2000" was renamed and reintroduced into Congress as "Minor Use Minor Species Animal Health Act" in 2001, 2002, 2003, and 2004. It was reintroduced in the U.S. Congress into the House as (HR-2079 and into the Senate (S-741). The MUMS Act will facilitate and accelerate the approvals of aquaculture drugs. The bill includes provisions for early life stages that should help expedite the approvals of aquaculture drugs that are of interest to public and private fish production.

The National Aquaculture NADA Coordinator sent e-mails to state fish chiefs on July 3, 2003 to urge them to support the MUMS legislation and counteract the misinformation being transmitted by opponents to the bill.

MUMS legislation passed the Senate HELP Committee in November 2003, the full Senate on March 8, 2004, and the House Energy and Commerce Committee on June 24, 2004. The bill goes before the full House sometime after July 4, 2004.

The Animal Drug User Fee Act of 2003 (Public Law 108-130) was passed by U.S. Congress in late December 2003 and authorizes FDA to collect user fees for certain drug approval applications. All sponsors will have to respond but sponsors of minor species or minor uses will not have to pay fees. CVM sent letters to all holders of INADs and NADAs on February 25, 2004 to gain information on any errors or omissions in the listing of products or establishments. The National Aquaculture NADA Coordinator sent information to all known INAD and NADA sponsors on March 11, 2004 on a guidance document to be posted on CVM’s website on Monday, March 15, 2004 that will direct them on how to apply for a waiver from any fees since their drug product involves minor species only.

On October 22, 2003, the National Aquaculture NADA Coordinator met with CVM’s Aquaculture Drugs Team to (1) provide historical background to the efforts to gaining approval of drugs for aquaculture and (2) provide the status of drug approvals from the industries’ perspective. The new CVM reviewer, Ruth Barratt, attended the meeting.

On December 2-4, 2003, the National Aquaculture NADA Coordinator met with CVM’s Aquaculture Drugs Team to (1) determine the course of action on several drugs nearing approval—hydrogen peroxide, oxytetracycline, and chloramine-T and (2) discuss data requirements for microbial food safety.

On April 26 and May 18, 2004, the National Aquaculture NADA Coordinator met with CVM’s Aquaculture Drugs Team to discuss the next day’s meetings on oxytetracycline and AQUI-S®, respectively.

The National Aquaculture NADA Coordinator was reappointed for another three-year term to the Technical Committee/Research of the North Central Regional Aquaculture Center.

MacMillan, J.R., R.A. Schnick, and G. Fornshell. 2003. U.S. aquaculture. Alliance for the Prudent Use of Antibiotics, Facts about Antibiotics in Animals and their Impact on Resistance (FAAIR) Project. Perspectives in Veterinary Medicine.

Schnick, R.A. 2003. Progress toward aquaculture drug approvals. National Association of State Aquaculture Coordinators, Seattle, Washington, June 11 to 14, 2003.

Schnick, R.A. 2003. Overview of progress toward aquaculture drug approvals. USFWS 9^th Annual INAD Coordination Workshop, Bozeman, Montana, July 30 to 31, 2003.

Schnick, R.A. 2003. Initial or supplemental New Animal Drug Application (NADA) approvals for Federal-State Aquaculture Drug Approval Partnership Project. USFWS 9^th Annual INAD Coordination Workshop, Bozeman, Montana, July 30 to 31, 2003.

Schnick, R.A. 2003. Chemical and drug use in aquaculture. International Association for Food Protection, New Orleans, Louisiana, August 10-13, 2003.

Schnick, R.A. 2003. Overview of progress toward aquaculture drug approvals. American Veterinary Medical Association Aquaculture and Seafood Advisory Committee, Chicago, Illinois, September 5 to 6, 2003.

Schnick, R.A. 2003. Status of each IAFWA Project drug toward initial approval. Drug Approval Working Group Meeting, Madison, Wisconsin, September 10, 2003.

Schnick, R.A. 2003. Possible future label claim needs. Drug Approval Working Group Meeting, Madison, Wisconsin, September 10, 2003.

Schnick, R.A. 2003. Future activities and funding needs for the National Coordinator for Aquaculture New Animal Drug Applications. Drug Approval Working Group Meeting, Madison, Wisconsin, September 10, 2003.

Schnick, R.A. 2003. Progress toward aquaculture drug approvals. NRSP-7 Fall Meeting, Rockville, Maryland, September 15 to 16, 2003.

Schnick, R.A. 2003. Historical efforts to gain drug approvals. Aquaculture Drugs Team, Center for Veterinary Medicine, Rockville, Maryland, October 22, 2003.

Schnick, R.A. 2003. Overview Federal-State Aquaculture Drug Approval Partnership Project. Joint Subcommittee on Aquaculture, Silver Spring, Maryland, October 23, 2003.

Schnick, R.A. 2003. Tracking aquaculture drug development. JSA Working Group on Quality Assurance in Aquaculture Production, Washington, DC, December 3-4, 2003.

Schnick, R.A. 2003. Matrices for tracking aquaculture drug development. JSA Working Group on Quality Assurance in Aquaculture Production, Washington, DC, December 3-4, 2003.

Schnick, R.A. 2004. Aquaculture drugs. North Central Regional Aquaculture Center Board of Directors and 2004 Planning Meeting, Milwaukee, Wisconsin, February 6-8, 2004.

Schnick, R.A. 2004. Matrices for tracking data gaps in aquaculture drug development. JSA Working Group on Quality Assurance in Aquaculture Production, Honolulu, Hawaii, March 1, 2004.

Schnick, R.A. 2004. Highlights and progress toward aquaculture drug approvals. Producer Session "Successes in Drug Approvals," Aquaculture 2004, Honolulu, Hawaii, March 3, 2004.

Schnick, R.A. 2004. Food fish industry—background & needs. NRSP-7 Spring Meeting, April 26, 2004, Rockville, Maryland.

Schnick, R.A. 2004. Highlights of recent efforts for initial IAFWA project drug approvals. IAFWA Drug Approval Working Group Meeting, Spokane, Washington, March 17, 2004.

Schnick, R.A. 2004. Aquaculture drugs—update. National Association of State Aquaculture Coordinators, Louisville, Kentucky, June 2-5, 2004. [Presented by Debra Sloan]

Schnick, R.A. 2003. National Coordinator for Aquaculture New Animal Drug Applications (NADAs). Eighth annual report of activities, May 15, 2002 to May 14, 2003. Submitted to Ted Batterson, North Central Regional Aquaculture Center, East Lansing, Michigan. June 6, 2003. 22 pp.

Schnick, R.A. 2003. Draft label claim for 35% hydrogen peroxide (Perox-Aid®). Submitted to Eka Chemicals Inc. June 25, 2003. 5 pp.

MacMillan, J.R., R.A. Schnick, and G. Fornshell. 2003. Volume of antibiotics sold (2001 and 2002) in US domestic aquaculture industry. Submitted to Gary Jensen for forwarding to EPA. July 10, 2003. 6 pp.

Schnick, R.A. 2003. 2003 annual report of the AFS Task Force on Fishery Chemicals. Submitted to the Governing Board and AFS President, Fred Harris, Bethesda, Maryland. July 13, 2003. 9 pp.

Schnick, R.A. 2003. Call for Statements of Interest: Drug Approval Research on 17α-methyltestosterone. Submitted to Ted Batterson, North Central Regional Aquaculture Center for distribution to potential contractors. August 29, 2003. 4 pp.

Schnick, R.A. 2003. Minutes to Drug Approval Working Group Meeting, Madison, Wisconsin, September 10, 2003. Submitted to Drug Approval Working Group. October 15, 2003. 13 pp.

Schnick, R.A. 2003. Status of drug approval for 17α-methyltestosterone. Forwarded to interested parties. October 2, 2003. 4 pp.

Schnick, R.A. 2003. Initial or supplemental New Animal Drug Application (NADA) approvals for Federal-State Aquaculture Drug Approval Partnership Project. Handout to selected CVM staff. October 31, 2003. 10 pp.

Gingerich, W.H. and R.A. Schnick. 2003. National Marine Aquaculture Initiative—Human food safety data for AQUI-S®, potential zero withdrawal anesthetic for all salmonids. A preliminary proposal submitted to the National Sea Grant College Program. November 25, 2003. 3 pp.

Schnick, R.A. 2003. Ninth midyear report of activities—National Coordinator for Aquaculture New Animal Drug Applications (May 15, 2003 to November 9, 2003). Submitted to Ted Batterson, North Central Regional Aquaculture Center for distribution to contributors to this position. December 6, 2003. 18 pp.

Schnick, R.A. 2003. Total annual public fish production (in millions) and funding of the IAFWA Project. Provided to IAFWA and states. December 17, 2003. 2 pp.

Schnick, R.A. 2004. Drug and chemical comments to EPA. Gary Jensen, Chairman, Aquaculture Effluents Task Force for forwarding to EPA. February 5, 2004. 2 pp.

Schnick, R.A. 2004. Radiolabeled materials for drug approval research on AQUI-S® (problem statement). Submitted to the North Central Regional Aquaculture Center. February 18, 2004. 2 pp.

Schnick, R.A. 2004. National Coordinator for Aquaculture New Animal Drug Applications (problem statement). Submitted to the U.S. Department of Agriculture. February 18, 2004. 2 pp.

Schnick, R.A. 2004. Status of drug approval for 17α-methyltestosterone (update). Submitted to North Central Regional Aquaculture Center. February 19, 2004. 4 pp.

Schnick, R.A. 2004. 2004 midyear report to the Governing Board. Submitted to Ira Adelman, President, American Fisheries Society. February 21, 2004. 8 pp.

Schnick, R.A. 2004. Call for Statements of Interest: Drug approval research on 17α-methyltestosterone. Submitted to Ted Batterson, North Central Regional Aquaculture Center for distribution to potential contractors. March 9, 2004. 3 pp.

Schnick, R.A. 2004. Summary of activity highlights for the National Coordinator for Aquaculture New Animal Drug Applications (May 15, 2003 to March 12, 2004). Submitted to the American Veterinary Medical Association. March 12, 2004. 6 pp.

Schnick, R.A. and T. Batterson. 2004. Total residue depletion study for AQUI-S® (proposal). Submitted to the U.S. Department of Agriculture. April 9, 2004. 6 pp.

AQUI-S New Zealand, Ltd. and R.A. Schnick. 2004. Research and Development Plan for AQUI-S® (INAD number 9731). Submitted to the Center for Veterinary Medicine. April 23, 2004. 6 pp.

Schnick, R.A. 2004. Initial or supplemental new animal drug application (NADA) approvals for the Federal-State Aquaculture Drug Approval Partnership Project. Submitted to Drug Approval Working Group members. April 23, 2004. 19 pp.

Schnick, R.A. 2004. Draft label claims for salmonids—oral oxytetracycline. Submitted to the Center for Veterinary Medicine. April 27, 2004. 1 pp.

Schnick, R.A. 2004. Draft label claim for 35% hydrogen peroxide (Perox-Aid®). Submitted to Eka Nobel Chemicals, Inc. May 3, 2004. 5 pp.

Schnick, R.A. 2004. Proprietary notes from Center for Veterinary Medicine (CVM) meeting with Phibro Animal Health, April 27, 2004. Submitted to Phibro Animal Health. May 11, 2004. 4 pp.

Schnick, R.A. 2004. Minutes to Drug Approval Working Group meeting, Spokane, Washington, March 17, 2004. Submitted to Drug Approval Working Group members. May 17, 2004. 12 pp.

Schnick, R.A. 2004. Potential supplemental new animal drug application (NADA) approvals for oxytetracycline. Submitted to the Center for Veterinary Medicine. May 17, 2004. 6 pp.

Schnick, R.A. 2004. Public notes from Center for Veterinary Medicine (CVM) meeting with Phibro Animal Health, April 27, 2004. Submitted to attendees and Drug Approval Working Group members. May 17, 2004. 3 pp.

Schnick, R.A. 2004. Initial new animal drug application (NADA) approval for AQUI-S®, zero withdrawal anesthetic, for (1) short-exposure handling for all freshwater- and saltwater-reared salmonids, and supplemental NADA approvals for AQUI-S® for (1) short-exposure handling for all cool and warm freshwater fish, (2) long-exposure handling for all fish, and (3) surgical anesthesia for all fish. Submitted to Drug Approval Working Group members. May 24, 2004. 6 pp.

Schnick, R.A. 2004. AQUI-®, a potential zero withdrawal anesthetic for all freshwater fish (white paper). Submitted to Drug Approval Working Group members. May 24, 2004. 7 pp.

Schnick, R.A. and J. Holland. 2004. Proprietary notes from the Center for Veterinary Medicine (CVM) meeting with AQUI-S New Zealand, LTD, May 19, 2004. Submitted to AQUI-S New Zealand, LTD. May 25, 2004. 5 pp.

Schnick, R.A. and J. Holland. 2004. Comments on CVM Memorandum of Conference on June 4, 2003 meeting. Submitted to the Center for Veterinary Medicine. May 25, 2004. 2 pp.

Schnick, R.A. 2004. Letter in support of NIST Technology Program proposal. Submitted to Jim Carlberg, Kent Sea Tech Corporation. June 4, 2004. 2 pp.

Schnick, R.A. 2004. State fish chiefs. Submitted to American Fisheries Society. June 11, 2004. 4 pp.

Schnick, R.A. 2004. AADAP newsletter. Submitted to Tom Bell. June 11, 2004. 1 pp.

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