Submitted by

Rosalie A. Schnick
National Aquaculture NADA Coordinator
Michigan State University
3039 Edgewater Lane
La Crosse, Wisconsin 54603-1088
Phone: (608) 781-2205
Fax: (608) 783-3507
E-mail: RozSchnick@centurytel.net
Website: http://aquanic.org/aquadrugs/index.htm

EIGHTH MIDYEAR SUMMARY OF ACTIVITY HIGHLIGHTS FOR THE NATIONAL COORDINATOR FOR AQUACULTURE NEW ANIMAL DRUG APPLICATIONS

(May 15, 2002 to November 9, 2002)

CHLORAMINE-T

On July 19, 2002, the Center for Veterinary Medicine (CVM) declared that the marker residue of chloramine-T, p-TSA, is not genotoxic.

CVM accepted the target animal safety data on chloramine-T for salmonids in September 2002.

The Upper Midwest Environmental Sciences Center (UMESC) submitted an environmental summary on chloramine-T and p-TSA to CVM on September 16, 2002.

UMESC submitted target animal safety data on several species of cool water and warm water fish to CVM on August 25, 2002.

CVM’s Office of Research developed a confirmatory method for p-TSA in fish tissue to satisfy an all fish label claim.

CRUDE CARP PITUITARY

CVM accepted the effectiveness component as complete for use of crude carp pituitary as a spawning aid in female finfish raised in freshwater on July 17, 2002.

DIQUAT DIBROMIDE

Syngenta Crop Protection, Inc. and the National Aquaculture NADA Coordinator met with CVM on August 28, 2002 to discuss the development of the Technical Sections for approval of their diquat product.

FORMALIN

CVM approved a supplemental NADA on November 25, 2002 for Natchez Animal Supply Company for its formalin product, Formalin-F®, to control certain fungi on the eggs of all fish and certain external protozoa and monogenetic trematodes on all fish.

HYDROGEN PEROXIDE

Eka Chemicals, Inc. submitted a revised Product Chemistry Technical Section on June 28, 2002.

CVM completed its review of the environmental assessment on hydrogen peroxide to support an all fish label claim on June 24, 2002 and required a 21-day chronic toxicity study on daphnia.

UMESC submitted efficacy reports on the control of saprolegniasis on a variety of cool and warm water fish eggs and on the control of columnaris on channel catfish and walleye to CVM on August 8, 2002.

17 %-METHYLTESTOSTERONE

The NADA sponsor (Rangen, Inc. on conference phone), INAD sponsor (Auburn University), and the National Aquaculture NADA Coordinator met with CVM on November 14, 2002 to clarify the data requirements for Product Chemistry and Environmental Safety Technical Sections.

 

 

OVAPLANT™ AND OVAPRIM™

Syndel International Inc. and the National Aquaculture NADA Coordinator met with CVM on June 5, 2002 to discuss the status of each Technical Section for approval.

OXYTETRACYCLINE

On May 21, 2002, CVM accepted the Public Master File for the use of oxytetracycline immersion for skeletal marking of fry and fingerling finfish. CVM published a notice in the Federal Register on July 15, 2002 that this use is approved and invited sponsors to apply for an NADA or supplemental NADA.

FEDERAL-STATE AQUACULTURE DRUG APPROVAL PARTNERSHIP PROJECT–SPECIAL PROJECTS

The Celebration Luncheon on September 18, 2002 at the Big Sky Resort, Montana for the Federal-State Aquaculture Drug Approval Project (known as the IAFWA Project) was a huge success. More than 80 persons attended and certificates and plaques were provided to those individuals, agencies, organizations, and companies that contributed to the successes.

The Drug Approval Working Group (DAWG) held a meeting at the 100^th anniversary celebration of the IAFWA at Big Sky Resort, Montana on September 19, 2002. The National Aquaculture NADA Coordinator gave a report on (1) general outline of what needs to be done and the cost, (2) what to do next to complete the label claims, and (3) how to systematically march to end points. The DAWG voted to have UMESC use the remaining Federal Aid funds for Year 8 Work Plan studies and to provide partial funding for the position of the National Aquaculture NADA Coordinator. The DAWG will remain in place for another year at least to direct the remaining studies.

SPECIAL ACTIVITIES

EPA issued its proposed rule for aquaculture effluents on September 12, 2002 and comments are due January 27, 2003. EPA hosted its first public meeting to discuss the proposed rule in the morning of October 30, 2002 in Washington, DC.

The Minor Use Minor Species legislation failed to pass in the 107^th Congress but it will be introduced in the 108^th Congress.

The National Coordinator for Aquaculture New Animal Drug Applications had one publication, presented six papers, and wrote nine reports.

PROJECT OBJECTIVES

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.

PROGRESS AND PRINCIPAL ACCOMPLISHMENTS

The National Aquaculture NADA Coordinator provided many information transfers from May 15, 2002 to November 9, 2002 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.

THERAPEUTANTS

Amoxicillin (oral antibacterial)—Status: Early development stage; antimicrobial resistance issue needs to be addressed.

Chloramine-T (external antibacterial)—Status: Sponsor (Axcentive bv; formerly Akzo Nobel Chemicals, Inc.) committed to INAD/NADA; one label claim close to approval.

Axcentive bv and its U.S. representative requested meetings with the National Aquaculture NADA Coordinator in Chicago, Illinois on June 3, 2002 and October 22, 2002 to discuss progress on mammalian safety and environmental safety issues.

Axcentive bv submitted genotoxicity studies and information to CVM on June 18, 2002 and CVM declared that p-TSA is not genotoxic on July 19, 2002.

The U.S. representative for Axcentive bv and the National Aquaculture NADA Coordinator prepared documents in August 2002 to refute the nomination of chloramine-T and p-TSA for study under the National Toxicology Program.

Progress on 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. Axcentive bv submitted genotoxicity studies and information to CVM on June 18, 2002 and CVM declared that p-TSA is not genotoxic on July 19, 2002.

Environmental Safety—UMESC submitted an environmental summary to CVM on September 16, 2002. The environmental summary developed on public literature and data will be made available to any chloramine-T sponsors in Public Master File Number 5637. UMESC also developed a proprietary environmental assessment that will be submitted by Axcentive bv to CVM into INAD #8086 after it finishes its review.

Human Food Safety—CVM accepted residue chemistry studies by UMESC for total residue depletion and metabolism of chloramine-T in several species of fish; para-toluene sulfonamide (p-TSA) was established as the major metabolite in fish and declared as a marker residue for chloramine-T in juvenile rainbow trout. CVM accepted simple colorimetric procedure by UMESC for use in efficacy studies for determining chloramine-T concentrations in treatment waters. UMESC completed research to bridge the proposed analytical method for p-TSA with an outdated, labor intensive method previously used to quantify p-TSA in fish tissue. Data developed with the proposed method for p-TSA were similar to analytical data developed with the outdated method indicating that the two methods were successfully bridged. 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 will write a final report describing validation of the confirmatory method and submit it to CVM by December 31, 2002.

Target Animal Safety—U.S. Fish and Wildlife Service (FWS) at Bozeman, Montana submitted a report to CVM on the toxicity of chloramine-T to salmonids and completed its submission of histopathology report on April 1, 2002; CVM accepted these data in September 2002. UMESC submitted target animal safety data on several species of cool water and warm water fish to CVM on August 25, 2002.

Efficacy—Efficacy data requirements are met for chloramine-T for control of mortalities associated with flavobacterial infections on gills of salmonids reared in freshwater at 12 to 20 mg/L for one hour. UMESC will submit any pivotal efficacy data on coolwater fish by December 31, 2002.

UMESC submitted FOI summaries on target animal safety (April 26, 2002) and on human food safety (April 23, 2002. The effectiveness FOI will be submitted by December 31, 2002.

Copper Sulfate (external microbicide)—Status: All submissions should soon be completed for control of Ichthyophthirius on catfish in ponds.

Progress on Technical Sections on copper sulfate:

Product Chemistry—Accepted by CVM from the sponsor, Phelps Dodge Refining Corporation.

Mammalian Safety—Accepted by CVM; a Freedom of Information (FOI) summary written by CVM on March 3, 2000.

Environmental Safety—The revised environmental safety technical section for all fish was reviewed by CVM in 2000 and CVM is requiring an additional study. A study at HKD-SNARC addressed the use of copper sulfate in ponds was completed and will be incorporated into a revised EA and submitted to CVM by December 31, 2002.

Human Food Safety—Accepted by CVM; 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—Additional target animal safety studies with a histopathology component are required for an all fish label claim. HKD-SNARC performed such a study on channel catfish and will submit it to CVM by December 31, 2002.

Efficacy—Accepted by CVM for control of Ichthyophthirius on all fish.

HKD-SNARC also conducted pivotal efficacy studies to control fungi on catfish eggs.

HKD-SNARC is preparing a Freedom of Information Summary (FOI) document on efficacy, target animal safety, and environmental safety for the control of Ichthyophthirius sp. on catfish in ponds by copper sulfate. The FOI will be submitted to CVM by December 31, 2002. When the target animal safety and environmental safety technical sections are accepted by CVM, the data requirements will be complete for control of Ichthyophthirius on catfish in ponds.

Cutrine-Plus™ (external microbicide)—Status: No interest by potential sponsor; early development stage, no recent activity.

Diquat Dibromide (external microbicide)—Status: Sponsor made commitment to develop INAD/NADA; early development stage.

Syngenta Crop Protection, Inc. and the National Aquaculture NADA Coordinator met with CVM on August 28, 2002 to discuss the development of the Technical Sections for approval of their diquat product.

Earth Tec Algicide/Bactericide™ (external microbicide)—Status: No recent activity by sponsor; early development stage.

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

Erythromycin (oral antibacterial)—Status: Sponsorship needs to be resolved; all technical sections except sponsor product chemistry submitted; risk assessment needed on potential for disease resistance in humans; near NADA approval for bacterial kidney disease in salmonids if can gain sponsor and resolve the antimicrobial resistance issue.

Florfenicol (oral antibacterial)—Status: Sponsor recently allowed the development of florfenicol for approval in U.S.; approved in Canada in August 1997 to control furunculosis in Atlantic salmon. Sponsor will continue to develop data for aquaculture approval for control of diseases in salmonids and catfish but the efforts by the IAFWA Project on florfenicol have been redirected by the IAFWA Drug Approval Working Group (DAWG) to other IAFWA Project drugs.

Under the florfenicol INAD exemption (INAD 10-697), FWS National INAD Office (NIO) completed 12 efficacy trials to control mortalities of salmonids, muskellunge, and hybrid striped bass infected with a variety of fish pathogens. Final reports on the effective studies will be submitted to CVM by December 31, 2002.

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 and certain external protozoa and monogenetic trematodes on all finfish. All submissions should soon be completed for control of mortalities associated with fungal infections on all fish.

Natchez Animal Supply Company submitted a supplemental NADA to CVM on June 5, 2001 for its formalin product, Formalin-F®, to control certain fungi on the eggs of all fish and certain external protozoa and monogenetic trematodes on all fish. The supplemental NADA was approved on November 25, 2002.

Progress on 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 fungi on salmonids from FWS and UMESC efforts.

CVM and UMESC found the disease model to be inconsistent so these facilities have been completing the fungal disease model development and are performing pivotal efficacy studies for control of fungi on salmonids and channel catfish.

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; three label claims nearing completion for approval.

Progress on Technical Sections on hydrogen peroxide:

Product Chemistry—Sponsor, Eka Chemicals, Inc., submitted product chemistry technical section on July 12, 1999. Eka Chemicals, Inc. submitted a revised Product Chemistry Technical Section on June 28, 2002.

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. UMESC will complete the study by December 31, 2002 and will submit the results to CVM by March 31, 2003.

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—Target animal safety technical section on all fish eggs submitted by UMESC to CVM was accepted for a dose range of 500–1,000 mg/L for northern pike, lake trout, and common carp. A target animal safety technical section on all fish from UMESC was accepted on October 4, 2001 by CVM.

Efficacy—CVM accepted pivotal efficacy data for treatment of salmonid eggs to control mortalities associated with saprolegniasis by a 15-minute treatment at 500 mg/L of hydrogen peroxide; and a 60-minute treatment at 50 mg/L or 30-minute treatment at 100 mg/L of hydrogen peroxide to control mortalities associated with bacterial gill disease on salmonids. CVM accepted the following as supporting data: (1) 60-minute treatments to control mortalities associated with external columnaris disease in yellow perch and (2) treatment of external parasitic infestations in fish. UMESC submitted efficacy reports on the control of saprolegniasis on a variety of cool and warmwater fish eggs and on the control of columnaris on channel catfish and walleye to CVM on August 8, 2002.

UMESC submitted several FOI summaries for efficacy on fish eggs and fish and additional documents summarizing data for the effectiveness section of the FOI will be submitted to CVM by December 31, 2002.

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

Neomycin sulfate (vibriosis control)—Status: No activity on this drug.

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. Almost all submissions are considered complete for control of mortalities associated with systemic columnaris disease in selected salmonids and systemic coldwater disease in all salmonids.

Progress on Technical Sections on OTC:

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

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 new EA for any new label claims. UMESC is in the process of writing the EA and will submit it to CVM by December 31, 2002. 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 in the spring of 2003 and the results will be submitted as an amendment to the environmental assessment report by June 30, 2003.

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 9E C 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, and (4) a study completed by UMESC bridging the HPLC OTC detection method to the official microbial assay method. 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. CVM sent a letter on September 9, 2002 concerning the analytical method in fish tissue to UMESC and a response is being prepared. This correspondence will not affect the pending label amendments. Efforts on this technical section are considered complete.

Target Animal Safety—Previously accepted by CVM for catfish, salmonids, and lobsters under original NADA from Pfizer, Inc. Target animal safety studies conducted according to Good Laboratory Practice regulations are required for cool water fish because there are no adequate pivotal and supporting efficacy studies on these additional species to demonstrate that OTC is safe. UMESC conducted these studies and is preparing a submission to CVM by December 31, 2002.

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. CVM accepted the use of OTC at 3.75 g/100 lb of fish for 10 days as effective in reducing mortalities from (1) systemic columnaris disease in steelhead trout and (2) systemic coldwater disease in fingerling coho salmon. The efficacy technical section developed by UMESC from a data call-in was accepted as supporting data for control of (1) Aeromonas sp. in cool water species, and (2) systemic columnaris disease in salmonids.

UMESC researchers collaborated with the state of Iowa in conducting a pivotal efficacy trial to control mortalities associated with systemic columnaris disease in walleye (Stizostedion vitreum). The results of the efficacy trial were forwarded to NIO for review.

The target animal safety section of the FOI will be submitted to CVM by December 31, 2002..

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: Sponsor is committed to revising a product chemistry technical section; several Technical Sections ready for submission

Progress on 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; additional data are still needed. The sponsor is in the process of providing the additional data.

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. Tier I studies will be submitted to CVM by December 31, 2002.

Human Food Safety—Accepted by CVM.

Target Animal Safety—HKD-SNARC completed a target animal safety study on channel catfish and will submit it by December 31, 2002. HKD-SNARC plans to conduct a target animal safety on rainbow trout.

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

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.

Quinine (internal microbicide—Status: Some interest on the part of potential sponsor in a NADA approval in the United States but needs positive marketing information.

Romet-30® (oral antibacterial)—Status: Romet-30® has limited approvals for catfish and salmonids. Early development stage for extensions and expansions.

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, 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.

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. These uses 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.

The SLN registration in California is in jeopardy because the state wants more data.

ANESTHETICS

AQUI-S™—Status: Sponsor (AQUI-S New Zealand LTD.) proceeding with worldwide drug approval.

Progress on Technical Sections on AQUI-S™:

Product Chemistry—Accepted elsewhere; no current activity for U.S.

Mammalian Safety—The sponsor (AQUI-S New Zealand LTD.) 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. 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 and has completed an environmental biodegradation study in freshwater and salt water that will soon be submitted to CVM for review. UMESC is performing a literature search that will result in an environmental assessment that will be submitted to CVM by December 31, 2002.

Human Food Safety—UMESC submitted a protocol for a total residue depletion study to CVM on July 3, 2002 and comments were received from CVM on August 8, 2002. UMESC plans to conduct a total residue depletion study and submit it by December 31, 2002.

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 at FWS. NIO will submit a protocol for these studies to CVM by December 31, 2002. The sponsor is ready to submit target animal safety and efficacy studies on salmonids completed in Canada to CVM.

Efficacy—Preliminary efficacy studies were completed at UMESC on a variety of fish species. Pivotal efficacy studies will be performed by FWS 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 efficacy studies on salmonids completed in Canada to CVM.

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.

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

Oil of Cloves—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 issued a Guidance for Industry Document #150 on June 11, 2002 on the use of clove oil as an anesthetic for fish. CVM reiterated that GRAS status as a food additive does not justify its use as an animal drug and clove oil is considered as an unapproved new animal drug. Clove oil also cannot be used for routine clinical use on laboratory animals.

SPAWNING AND GENDER MANIPULATION AIDS

Crude Carp Pituitary (CCP)—Status: Sponsor and interested parties proceeding toward NADA approval. All submissions should be completed soon for use on all fish.

Progress on 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

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. A researcher from Mississippi State University completed target animal safety studies on CCP and submitted them to CVM.

Efficacy—A literature review on efficacy 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. CVM accepted the effectiveness component as complete for use of CCP as a spawning aid in female finfish raised in freshwater on July 17, 2002.

17 β-estradiol (estrogen)—Status: Sponsor established INAD #10-673) and had a meeting with CVM to determine data requirements; early development stage.

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.

17 α-methyltestosterone (MT)—Status: Sponsor is developing NADA package; INAD sponsors actively pursuing a NADA approval; environmental assessment reviewed, revised, and resubmitted.

Progress on 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. CVM held a meeting on November 14, 2002 to clarify the data requirements.

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; met on November 14, 2002 to discuss how to meet the remaining data requirements for this Technical Section.

Human Food Safety—Accepted by CVM.

Target Animal Safety—CVM found a target animal safety study on percids by Southern Illinois University to be inadequate; literature review on other species completed by Auburn University.

Efficacy—Auburn University is coordinating a compassionate INAD on tilapia and is in the process of completing the final report for submission to CVM; North Central Regional Aquaculture Center representatives are coordinating a compassionate INAD on percids.

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

Syndel International Inc. and the National Aquaculture NADA Coordinator met with CVM on June 5, 2002 to discuss the status of each Technical Section for approval.

ReproBoost™ (Gonadotropin Releasing Hormone)—Status: Sponsor recently submitted INAD letter of intent; early development stage.

CHEMICAL MARKING AGENTS

Calcein—Status: Have sponsor; Early development stage.

Oxytetracycline—Status: Public Master File from NRSP-7 accepted by CVM

On May 21, 2002, CVM accepted the Public Master File for the use of oxytetracycline immersion for skeletal marking of fry and fingerling finfish. CVM published a notice in the Federal Register on July 15, 2002 that this use is approved and invited sponsors to apply for an NADA or supplemental NADA.

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 presented a paper on the feasibility of the reregistration of antimycin at the annual meeting of the American Fisheries Society on August 22, 2002.

Fish Management Chemicals Subcommittee (FMCS) met at the annual meeting of the American Fisheries Society on August 21-22, 2002 to discuss the next steps in the reregistration of antimycin, the development of a new rotenone use survey, and a training course on the use of piscicides.

PUBLIC INFORMATION, WORKSHOPS AND PRESENTATIONS

Federal-State Aquaculture Drug Approval Partnership Project (IAFWA Project)

The Drug Approval Working Group (DAWG) for the Federal-State Aquaculture Drug Approval Partnership Project (IAFWA Project) held a meeting in Bozeman, Montana on July 31 to August 2, 2002 to (1) discuss the progress being made on the IAFWA Project drugs and (2) the future of public drug approval efforts after 2002.

Celebration Steering Committee (Bob Miles, Doug Hanson, Roz Schnick, Dave Pederson, and Dave Erdahl) planned the celebration of the success of the IAFWA Project. The National Aquaculture NADA Coordinator prepared lists of invitees and awardees, wrote a brochure that was handed out at the Luncheon, arranged for a speaker, arranged for plaques for key participants, and contacted and secured sponsors for the event.

The Celebration Luncheon on September 18, 2002 at the Big Sky Resort, Montana for the Project was a huge success. More than 80 persons attended and certificates and plaques were provided to those individuals, agencies, organizations, and companies that contributed to the successes.

The DAWG held a meeting at the 100^th anniversary celebration of the IAFWA at Big Sky Resort, Montana on September 19, 2002. The National Aquaculture NADA Coordinator gave a report on (1) general outline of what needs to be done and the cost, (2) what to do next to complete the label claims, and (3) how to systematically march to end points. The DAWG voted to have UMESC use the remaining Federal Aid funds for Year 8 Work Plan studies and to provide partial funding for the position of the National Aquaculture NADA Coordinator. The DAWG will remain in place for another year at least to direct the remaining studies. Dr. Bill Gingerich provided the status of all submissions made to CVM since the Federal-State Aquaculture Drug Approval Partnership Project began.

Antimicrobial Resistance

The report on the American Academy of Microbiology’s colloquium entitled "The role of antimicrobials in agriculture: A critical scientific assessment" was presented to CVM in June 2002 that indicates a general lack of problems in aquaculture.

EPA Effluent Guidelines Plan

The Joint Subcommittee on Aquaculture formed the Aquaculture Effluents Task Force (AETF) 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. EPA issued its proposed rule for aquaculture effluents on September 12, 2002 and comments are due January 27, 2003. EPA hosted its first public meeting to discuss the proposed rule in the morning of October 30, 2002 in Washington, DC. The AETF combined two Technical Subgroups to form the Drugs and Chemicals and Aquatic Animal Pathogens Technical Subgroup at its afternoon meeting on October 30, 2002.

The National Aquaculture NADA Coordinator sent out requests for data and information to the Drugs and Chemicals and Aquatic Animal Pathogens Technical Subgroup on November 6 and 8, 2002 regarding the proposed rule and solicited comments by EPA.

Minor Use Minor Species legislation

A bill entitled "Minor Animal Species Health and Welfare Act of 2000" was introduced in the U.S. Congress into the House on June 27, 2000 (HR-4780) and into the Senate on October 5, 2000 (S-3169). 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.

A revised bill "Minor Use Minor Species Animal Health Act of 2001" was reintroduced into the House on May 24, 2001 (HR-1956) and into the Senate on August 2, 2001 (S-1346). The MUMS Coalition met on June 22, 2001 to coordinate the legislative effort on the bill, present information to legislative staff, and contact individual congressmen and senators for their support and sponsorship.

The MUMS bill was attached to the Bioterrorism Bill but it was removed from the bill shortly before its passage on May 22, 2002. The MUMS legislation did not pass in the 107^th congress because the Administration made it clear to all members of congress that they only wanted to deal with Homeland Security issues and a "clean" continuing resolution to keep the government going.

The MUMS Legislation will be reintroduced early in the 108th Congress by including it in the Animal Drug User Fee Act. The version to be introduced will be the one agreed upon following extensive technical assistance from the FDA but without the tax provisions. Since it looks like the 108th Congress will consider a tax bill, the coalition will explore the opportunities of having the tax provisions of the MUMS bill introduced separately.

PUBLICATIONS, MANUSCRIPTS, PAPERS PRESENTED, AND SPECIAL REPORTS

PUBLICATIONS

Finlayson, B.J., R.A. Schnick, R.L. Cailteux, L. DeMong, W.D. Horton, W. McClay, and C.W. Thompson. 2002. Potential of antimycin A use in fisheries and its potential for reregistration. Fisheries 27(6):10-17.

PAPERS PRESENTED

Schnick, R.A. 2002. Progress to achieve new animal drug approvals. National Association of State Aquaculture Coordinators, St. Pete Beach, Florida, May 28-31, 2002.

Schnick, R.A. 2002. Overview of progress toward aquaculture drug approvals. USFWS–8^th Annual INAD Coordination Workshop, Bozeman, Montana, July 31 to August 2, 2002.

Schnick, R.A. 2002. Update on Project activities/progress. Drug Approval Working Group Meeting, Big Sky, Montana, September 19, 2002.

Schnick, R.A. 2002. Update on aquaculture NADAs. NRSP-7 Fall Meeting, Rockville, Maryland, September 30, 2002.

Schnick, R.A. 2002. Comments on EPA proposed rule for drugs and chemicals. JSA Aquaculture Effluents Task Force Meeting, Washington, DC, October 30, 2002.

Schnick, R.A. 2002. Successes coming for aquaculture drug approvals. Joint Subcommittee on Aquaculture, Washington, DC. October 31, 2002. 6 pp.

SPECIAL REPORTS

Schnick, R.A. 2002. National Coordinator for Aquaculture New Animal Drug Applications (NADAs). Seventh annual report of activities, May 15, 2001 to May 14, 2002. Submitted to Ted Batterson, North Central Regional Aquaculture Center, East Lansing, Michigan. July 7, 2002. 20 pp.

Schnick, R.A. 2002. 2002 annual report of the AFS Task Force on Fishery Chemicals. Submitted to the Governing Board and AFS President, Ken Beal, Bethesda, Maryland. July 12, 2002. 6 pp.

Schnick, R.A. 2002. Substances nominated to the NTP for toxicological studies and testing recommendations made by the NTP Interagency Committee for Chemical Evaluation and Coordination (ICCEC) on April 17, 2002: Chloramine-T [127-65-1] and p-Toluenesulfonamide [70-55-3]. Submitted to Dr. Scott A. Masten, Office of Chemical Nomination and Selection, NIEHS/NTP on August 12, 2002. 3 pages.

Schnick, R.A. 2002. Draft minutes to scoping meeting on diquat with the Center for Veterinary Medicine and Syngenta Crop Protection, Inc., August 28, 2002. Submitted to Syngenta Crop Protection, Inc. on September 13, 2002. 5 pages.

Schnick, R.A. 2002. Final status of the Federal-State Aquaculture Drug Approval Partnership Project and future direction of drug approvals of importance to public aquaculture. Submitted to IAFWA Drug Approval Working Group on September 18, 2002. 9 pages.

Schnick, R.A., W.H. Gingerich, B.R. Griffin, and D. Erdahl. 2002. Final Federal Aid Report: Federal-State Aquaculture Drug Approval Partnership Project. Submitted to David Pederson, Federal Aid Coordinator, Twin Cities, Minnesota for distribution to all parties interested in this Project. September 13, 2002. 22 pp.

Gingerich, W.H., G.R. Stehly, J.R. Meinertz, J.A. Bernardy, M.P. Gaikowski,, J.J. Rach, L.J. Schmidt, C. Vue, R.A. Schnick, B.R. Griffin, D. Erdahl, J. Bowker, and D. Carty. 2002. Approval of Drugs for Public Fish Production: Eighth annual report of progress [performance period: July 1, 2001 to June 30, 2002]. Biological Resources Division, USGS, Upper Midwest Environmental Sciences Center, La Crosse, Wisconsin. September 25, 2002. 27 pp.

Schnick, R.A. 2002. Reaching our goals of drug approvals of importance to aquaculture. Submitted to Drug Approval Working Group. September 27, 3003. 17 pp.

Schnick, R.A. 2002. Minutes to Drug Approval Working Group Meeting, Big Sky, Montana, September 19, 2002. Submitted to Drug Approval Working Group. October 25, 2002. 14 pp.

 The National Coordinator for Aquaculture New Animal Drug Applications is attempting to carry out these goals and objectives through this web site. Please use the e-mail address, RozSchnick@centurytel.net  , to contact her for input and questions.

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