NATIONAL COORDINATOR FOR AQUACULTURE NEW ANIMAL DRUG APPLICATIONS (NADAs)
EIGHTH ANNUAL REPORT OF ACTIVITIES
May 15, 2002 to May 14, 2003
Submitted by
Rosalie A. Schnick
National Aquaculture NADA Coordinator
Michigan State University
June 6, 2003
AQUI-S®
The U.S. Fish and Wildlife Service (FWS) National Investigational New Animal Drug Application (INAD) Office (NIO) submitted the following efficacy data to the Center for Veterinary Medicine (CVM): steelhead trout (submitted March 31, 2003), rainbow trout, lake trout, and mountain whitefish (submitted May 8, 2003), cutthroat trout (submitted May 9, 2003), bull trout (submitted May 14, 2003), and hybrid striped bass (submitted May 28, 2003).
CHLORAMINE-T (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 walleyes in flow-through systems)
On July 19, 2002, CVM declared that the marker residue of chloramine-T, para-toluenesulfonamide (p-TSA), is not genotoxic.
The Upper Midwest Environmental Sciences Center (UMESC) submitted to CVM (1) target animal safety data and a Freedom of Information (FOI) summary on several species of cool water and warm water fish (August 28, 2002), (2) validation studies for chemical dilution models using chloramine-T and Rhodamine WT (October 30, 2002) to support environmental assessment issues, (3) environmental summary that was developed on public literature and data will be made available to any chloramine-T sponsors in Public Master File Number 5637 (October 31, 2002), and (4) efficacy data on the control of mortalities associated with external columnaris disease on walleyes (January 28, 2003).
On September 13, 2002, CVM accepted as complete the target animal safety data package on salmonids from NIO.
On November 7, 2002, the sponsor, Axcentive bv, submitted additional proprietary mammalian safety data to CVM.
On January 15, 2003, CVM accepted as complete from UMESC the simple analytical procedure to replace HPLC for monitoring treatment concentrations of chloramine-T on fish culture facilities.
On February 4, 2003, CVM accepted the FOI summary of the safety and efficacy of chloramine-T on all freshwater-reared salmonids from an NIO submission.
On April 9, 2003, CVM informed Axcentive bv that its mammalian safety data submission provided adequate information for the agency to declare the safe concentration of p-TSA in edible tissue to be 1 ppm.
On April 24, 2003, CVM stated that the data submitted by UMESC demonstrate that the determinative analytical method is applicable for the analysis of p-TSA in multiple species and appears to meet the limit of quantitation and limit of detection guidance levels at 1 ppm.
On April 28, 2003, UMESC completed the development of a proprietary environmental assessment and sent it with the appropriate numbers of copies to Axcentive bv for its review. Axcentive bv will submit that package to CVM into its INAD #8086 after the company finishes its review.
On May 7, 2003, CVM responded to an October 30, 2002 submission from UMESC on validation studies for chemical dilution models using chloramine-T and Rhodamine WT. CVM accepted the second model that used specific points of time to estimate effluent concentrations at the pipe where the effluents meet the public waters. This model is a conservative "universal" model to validate the flow of effluents for waterborne drugs that is applicable to other hatchery facilities.
In 2003, CVM’s Office of Research developed a confirmatory method for p-TSA in fish tissue to satisfy an all fish label claim.
CLOVE OIL
CVM issued a Guidance for Industry Document #150 on June 11, 2002 on the use of clove oil and eugenol as anesthetics for fish. CVM reiterated that Generally Recognized as Safe (GRAS) status as a food additive does not justify use as an animal drug and clove oil and eugenol are considered as unapproved new animal drugs. Neither clove oil nor eugenol can be used for routine clinical use on laboratory animals.
COPPER SULFATE (one label claim close to completion: control of Ichthyophthirius on channel catfish in earthen ponds with no outflows)
CRUDE CARP PITUITARY (one label claim close to completion: spawning aid on all freshwater-reared finfish)
CVM accepted the effectiveness component as complete for use of crude carp pituitary as a spawning aid in female finfish reared in freshwater on July 17, 2002.
DIQUAT DIBROMIDE
The sponsor, Syngenta Crop Protection, Inc., UMESC, 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.
FLORFENICOL (three label claims close to completion: control of (1) furunculosis in salmonids, (2) coldwater disease in freshwater-reared salmonids, and (3) enteric septicemia in catfish)
NIO submitted the following efficacy data: control of mortalities associated with coldwater disease in steelhead trout (submitted September 9, 2002; accepted March 4, 2003) and cutthroat trout (submitted January 7, 2003), systemic columnaris disease in coho salmon (submitted November 18, 2002; accepted April 21, 2003), furunculosis in coho salmon (submitted September 30, 2002; no clinically sound conclusions declared on March 12, 2003), and streptococcal septicemia in hybrid striped bass (February 10, 2003). A final decision of the effectiveness of florfenicol to control mortalities caused by these diseases will be made following review of other studies submitted by NIO.
On October 4, 2002, CVM accepted as supportive efficacy data for control of mortalities caused by coldwater disease in cutthroat trout submitted by NIO on April 10, 2002.
On September 25, 2002, UMESC submitted to the sponsor, Schering-Plough Animal Health, the target animal safety study on channel catfish for its submittal to CVM. In January 2003, CVM accepted as complete the target animal safety data for channel catfish.
FORMALIN (one additional label claim close to completion: control of mortalities associated with saprolegniasis on all fish)
On November 25, 2002, CVM approved a supplemental NADA from Natchez Animal Supply Company for its formalin product, Formalin-F®, to control certain fungi on the eggs of all fish, certain external protozoa and monogenetic trematodes on all fish, and external protozoan parasites on penaeid shrimp. The amendment to the Code of Federal Regulations was announced in the Federal Register on February 4, 2003.
CVM Office of Research 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 saprolegniasis on salmonids and channel catfish.
HYDROGEN PEROXIDE (four label claims close to completion: control of mortalities from (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 and warmwater finfish)
On June 24, 2002, CVM provisionally accepted the environmental assessment submitted by UMESC but the agency required a 21-day daphnia study that is in progress, characterization of the product chemistry, and reformatting of the environmental assessment.
On June 28, 2002, the sponsor, Eka Chemicals Inc., submitted a revision to their product chemistry package. CVM responded that the agency needed clarification on several points.
On August 16, 2002, CVM accepted as complete the target animal safety data from UMESC for all finfish eggs.
On August 16, 2002, CVM accepted as complete the efficacy data from UMESC for control of saprolegniasis on coldwater and coolwater finfish eggs.
On September 26, 2002, CVM accepted as supportive efficacy data to control external protozoan parasites on all salmonids submitted by UMESC.
UMESC submitted to CVM (1) efficacy studies to control mortalities associated with external columnaris disease on walleye and channel catfish (November 22, 2002) and (2) additional efficacy data on warmwater finfish eggs (February 25, 2003).
On December 10, 2002 and February 7, 2003, the National Aquaculture NADA Coordinator revised the hydrogen peroxide label to reflect the latest thinking on the claims that can be supported.
On December 12, 2002, UMESC and the National Aquaculture NADA Coordinator met with CVM to discuss the final label claim requirements for approval of hydrogen peroxide.
On March 13, 2003, the sponsor, Eka Chemicals, Inc., and the National Aquaculture NADA Coordinator met with CVM to clarify points in the product chemistry submission. The sponsor was satisfied with the discussion and planned to submit the revised package in a timely manner.
UMESC is conducting pivotal efficacy studies to control mortalities associated with saprolegniasis on rainbow trout and channel catfish.
LUTEINIZING HORMONE-RELEASING HORMONE ANALOG (LHRHA)
In spring 2003, CVM granted Auburn University an INAD for Luteinizing Hormone-Releasing Hormone analog (LHRHa) to manage spawning of channel and blue catfish.
17 α-METHYLTESTOSTERONE (MT)
On November 14, 2002, the sponsor, Rangen Inc. (via telephone), Auburn University, and the National Aquaculture NADA Coordinator met with CVM to discuss the remaining data requirements for the product chemistry and environmental safety technical sections.
The National Aquaculture NADA Coordinator reviewed the proposed efficacy protocol for the development of MT for ornamental fish and sent out comments on November 29, 2002. She continued to work with the University of Florida in the winter and spring of 2003 to finalize the protocol and the request for an INAD. Those items were submitted to CVM by the University of Florida on May 22, 2003.
On February 8-9, 2003, the North Central Regional Aquaculture Center voted to provide funds to complete the product chemistry and environmental safety technical section and directed the National Aquaculture NADA Coordinator to clarify the analytical methods issues.
In February and March 2003, the National Aquaculture NADA Coordinator developed a draft announcement for the studies to be funded and a status paper on the requirements for each study. She worked with CVM on determining the analytical methods that will be appropriate for the studies and experts in the field to delineate the requirements.
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–ANTIBACTERIAL (two label claims close to completion: control of mortalities associated with (1) systemic columnaris disease in selected freshwater-reared salmonids and (2) systemic coldwater disease in all freshwater-reared salmonids)
On May 17, 2002, CVM accepted extrapolated withdrawal times in all sizes of salmonids based on residue depletion data submitted by UMESC.
On September 9, 2002, UMESC resubmitted the liquid chromatographic determination of OTC in edible tissues of six species of fish and validation of an HPLC method for OTC in coho salmon and northern pike.
UMESC submitted to CVM (1) efficacy of OTC immersion to control bacterial diseases on freshwater fish (October 28, 2002), (2) letter package addressing the antimicrobial resistance issues with human food safety (October 30, 2002), (3) electronic files for revised Standard Operating Procedures for determining OTC in edible tissue (January 27, 2003), and (4) target animal safety data on coolwater and scaled warmwater fish (February 19, 2003).
On April 1, 2003, CVM responded to UMESC on the microbial safety component of the Human Food Safety technical section. CVM is requiring a microbial food safety assessment as outlined in CVM’s Guidance to Industry #152 "Evaluating the safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern."
On April 8, 2003, CVM responded to 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.
UMESC is developing an amended environmental assessment to allow additional claims for OTC.
OXYTETRACYCLINE—MARKING AID (one label claim close to completion: marking of fry and fingerling finfish by immersion)
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 a NADA or supplemental NADA.
POTASSIUM PERMANGANATE
The sponsor, Carus Chemical Company, submitted additional information on the product chemistry to CVM in March 2002 and the agency asked for clarification on several points in April 2002. The sponsor is preparing a response.
FEDERAL-STATE AQUACULTURE DRUG APPROVAL PARTNERSHIP PROJECT (includes eight drugs: AQUI-S®, chloramine-T, copper sulfate, florfenicol, formalin, hydrogen peroxide, oxytetracycline, and potassium permanganate)
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 100th 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.
The DAWG held a meeting on March 25, 2003 in Winston-Salem, North Carolina. The National Aquaculture NADA Coordinator provided a report on (1) the status of the Project Completion Report, (2) status of the work plan for initial approvals of all eight Project drugs, and (3) future plans for expanding and extending existing label claims. Each research facility (i.e., FWS, UMESC, and HKD-SNARC) 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, and IAFWA) and requested guidance and comments from the agencies involved to include (1) follow-up work, (2) new drugs, (3) definition of roles and responsibilities, and (4) funding and status of the National Aquaculture NADA Coordinator.
SPECIAL ACTIVITIES
EPA issued its proposed rule for aquaculture effluents on September 12, 2002 and comments were sent January 9, 2003 (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 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 107th 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 National Coordinator for Aquaculture New Animal Drug Applications had two publications, presented 11 papers, and wrote 23 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 May 14, 2003 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. Kent Sea Tech submitted a Research and Development Plan to CVM files.
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 NIO; 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 walleyes in flow-through systems.
Progress on chloramine-T:
On May 29, 2002, UMESC submitted an addendum for a simple analytical method to replace HPLC for monitoring treatment concentrations of chloramine-T on fish cultural facilities.
On June 3, 2002 and October 22, 2002, Axcentive bv and its U.S. representative requested meetings with the National Aquaculture NADA Coordinator in Chicago, Illinois to discuss progress on mammalian safety and environmental safety issues. She also continued to work with the sponsor, its U.S. representative, and CVM to resolve both issues.
On June 10, 2002, CVM accepted the analytical verification of target dose in flow-through systems from a NIO submission.
On July 19, 2002, CVM declared that p-TSA is not genotoxic based on proprietary genotoxicity studies submitted by Axcentive bv.
In August 2002, the U.S. representative for Axcentive bv and the National Aquaculture NADA Coordinator prepared documents to refute the nomination of chloramine-T and p-TSA for study under the National Toxicology Program. NTP went ahead with the toxicology studies anyway.
On August 28, 2002, UMESC submitted target animal safety data and a FOI summary on several species of cool water and warm water fish to CVM.
On September 13, 2002, CVM accepted as complete the target animal safety data package on salmonids from NIO.
C On October 30, 2002, UMESC submitted to CVM validation studies for chemical dilution models using chloramine-T and Rhodamine WT.
C On October 31, 2002, UMESC submitted an environmental summary to CVM that was developed on public literature and data will be made available to any chloramine-T sponsors in Public Master File Number 5637.
On November 7, 2002, the sponsor, Axcentive bv, submitted additional proprietary mammalian safety data to CVM.
On December 12, 2002, UMESC, NIO, and the National Aquaculture NADA Coordinator met with CVM to discuss the final label claim requirements for approval of chloramine-T.
On January 15, 2003, CVM accepted as complete from UMESC the simple analytical procedure to replace HPLC for monitoring treatment concentrations of chloramine-T on fish culture facilities.
On January 28, 2003, UMESC submitted efficacy data on the control of mortalities associated with external columnaris disease on walleyes.
On February 4, 2003, CVM accepted the FOI summary of the safety and efficacy of chloramine-T on all freshwater-reared salmonids from a NIO submission.
On April 9, 2003, CVM informed Axcentive bv that its mammalian safety data submission provided adequate information for the agency to declare that the safe concentration of p-TSA in edible tissue to be 1 ppm.
On April 24, 2003, CVM stated that the data submitted by UMESC demonstrate that the determinative analytical method is applicable for the analysis of p-TSA in multiple species and appears to meet the limit of quantitation and the limit of detection guidance levels at 1 ppm.
On April 28, 2003, UMESC completed the development of a proprietary environmental assessment and sent it with the appropriate number of copies to Axcentive bv for its review. Axcentive bv will submit that package to CVM into its INAD #8086 after the company finishes its review.
On May 7, 2003, CVM responded to an October 30, 2002 submission from UMESC on validation studies for chemical dilution models using chloramine-T and Rhodamine WT. CVM accepted the second model that used specific points of time to estimate effluent concentrations at the pipe where the effluents meet the public waters. This model is a conservative "universal" model to validate the flow of effluents for waterborne drugs that is applicable to other hatchery facilities.
In 2003, CVM’s Office of Research completed a confirmatory method for detecting p-TSA in fish tissue and it is at CVM’s Division of Residue Chemistry for final review.
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 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 will be submitted by Axcentive bv to CVM into INAD #8086 after the company finishes its review.
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 NIO the target animal safety technical section on freshwater-reared salmonids (September 13, 2002). UMESC submitted target animal safety data on several species of cool water and warm water fish to CVM (August 28, 2002).
Efficacy—CVM accepted as complete from NIO the efficacy technical section for control of mortalities associated with bacterial gill disease on all freshwater-reared salmonids at 12 to 20 mg/L for one hour. UMESC submitted efficacy data on the control of mortalities associated with external columnaris disease on walleye (January 28, 2003).
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 the Harry K. Dupree Stuttgart National Aquaculture Research Center (HKD-SNARC); one label claim close to completion: control of Ichthyophthirius on channel catfish in earthen ponds with no outflows.
Progress on copper sulfate:
HKD-SNARC is working closely with CVM on the remaining technical sections for approval: target animal safety study on channel catfish and revision of the environmental assessment.
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 HKD-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 HKD-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—HKD-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. HKD-SNARC performed such a study on channel catfish and will submit it to CVM.
Efficacy—CVM accepted as complete from HKD-SNARC the efficacy technical section for control of Ichthyophthirius on all fish. HKD-SNARC also conducted pivotal efficacy studies to control fungi on catfish eggs.
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 U.S. 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 a sponsor can be gained and the antimicrobial resistance issue can be resolved.
Florfenicol (oral antibacterial)—Status: The sponsor, Schering-Plough Animal Health, gained florfenicol 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 (Schering-Plough Animal Health), UMESC, and NIO; three label claims close to completion: control of (1) furunculosis in salmonids, (2) coldwater disease in freshwater-reared salmonids and (3) enteric septicemia in catfish.
Progress on florfenicol:
Under the florfenicol INAD exemption (INAD 10-697), NIO submitted the following efficacy data: (1) control of mortalities associated with coldwater disease in steelhead trout (submitted September 9, 2002; accepted March 4, 2003) and cutthroat trout (submitted January 7, 2003), (2) systemic columnaris disease in coho salmon (submitted November 18, 2002; accepted April 21, 2003), (3) furunculosis in coho salmon (submitted September 30, 2002; no clinically sound conclusions declared CVM on March 12, 2003), and (4) streptococcal septicemia in hybrid striped bass (February 10, 2003). A final decision of the effectiveness of florfenicol to control mortalities caused by these diseases will be made following review of other studies submitted by NIO.
On October 4, 2002, CVM accepted as supportive efficacy data for control of mortalities caused by coldwater disease in cutthroat trout submitted by NIO on April 10, 2002.
On September 25, 2002, UMESC submitted to Schering-Plough Animal Health the target animal safety study on channel catfish for its submittal to CVM.
In January 2003, CVM accepted as complete the target animal safety data for channel catfish that were developed by UMESC and funded and submitted by Schering-Plough Animal Health.
Current status of technical sections on florfenicol:
Product Chemistry—Accepted by CVM.
Mammalian Safety—Accepted by CVM.
Environmental Safety—Proprietary status.
Human Food Safety—Proprietary status.
C Target Animal Safety—CVM accepted as complete from Schering-Plough Animal Health (and conducted by UMESC) the target animal safety technical section on channel catfish; proprietary status on salmonids.
Efficacy—Proprietary status for company studies; UMESC validated methods to analyze for florfenicol in finfish feeds to support efficacy studies at NIO; NIO submitted four efficacy studies to CVM on coldwater disease, 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 and certain external protozoa and monogenetic trematodes on all finfish; 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:
On November 25, 2002, CVM approved a supplemental NADA from Natchez Animal Supply Company for its formalin product, Formalin-F®, to control certain fungi on the eggs of all fish, certain external protozoa and monogenetic trematodes on all fish, external protozoan parasites on penaeid shrimp. The amendment to the Code of Federal Regulations was announced in the Federal Register on February 4, 2003.
CVM Office of Research 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 saprolegniasis on salmonids and 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 fungi on salmonids from FWS and UMESC efforts.
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 from (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 and warmwater finfish.
Progress on hydrogen peroxide:
On June 24, 2002, CVM provisionally accepted the environmental assessment submitted by UMESC but the agency required a 21-day daphnia study that is in progress, characterization of the product chemistry, and reformatting of the environmental assessment.
On June 28, 2002, the sponsor, Eka Chemicals Inc., submitted a revision to their product chemistry package. CVM responded that the agency needed clarification on several points.
On August 8, 2002, UMESC submitted additional target animal safety data on paddlefish and rainbow trout eggs to CVM for an all finfish label.
On August 16, 2002, CVM accepted as complete the target animal safety data from UMESC for all finfish eggs.
On August 16, 2002, CVM accepted as complete the efficacy data from UMESC for control of saprolegniasis on coldwater and coolwater finfish eggs.
On September 26, 2002, CVM accepted as supportive efficacy data to control external protozoan parasites on all salmonids submitted by UMESC.
On November 22, 2002, UMESC submitted efficacy studies to control mortalities associated with external columnaris disease on walleye and channel catfish.
On December 10, 2002 and February 7, 2003, the National Aquaculture NADA Coordinator revised the hydrogen peroxide label to reflect the latest thinking on the claims that can be supported.
On December 12, 2002, UMESC and the National Aquaculture NADA Coordinator met with CVM to discuss the final label claim requirements for approval of hydrogen peroxide.
On February 25, 2003, UMESC submitted additional efficacy data on warmwater finfish eggs.
On March 13, 2003, the sponsor, Eka Chemicals, Inc., and the National Aquaculture NADA Coordinator met with CVM to clarify points in the product chemistry submission. The sponsor was satisfied with the discussion and planned to submit the revised package in a timely manner.
UMESC is conducting pivotal efficacy studies to control mortalities associated with saprolegniasis on rainbow trout and channel catfish.
Current status of technical sections on hydrogen peroxide:
Product Chemistry—Sponsor, Eka Chemicals, Inc., submitted product chemistry technical section on July 12, 1999 and a revised package on June 28, 2002 that CVM asked for additional information; meeting with CVM on March 13, 2003 provided clarification of remaining issues.
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, characterization of the product chemistry, and reformatting of the environmental assessment.
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—CVM accepted as complete the target animal safety technical section on all finfish from UMESC and the target animal safety technical section for all finfish eggs from UMESC.
Efficacy—CVM accepted as complete from UMESC the efficacy technical sections for the control of mortalities associated with (1) saprolegniasis on all salmonid eggs by a 15-minute treatment at 500 mg/L of hydrogen peroxide, (2) saprolegniasis on all coldwater and coolwater finfish eggs, and (3) bacterial gill disease on all freshwater-reared salmonids by a 60-minute treatment at 50 mg/L or 30-minute treatment at 100 mg/L. CVM accepted from UMESC 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 on all salmonids. UMESC submitted efficacy reports on the control of (1) saprolegniasis on a variety of cool and warmwater fish eggs (August 8, 2002), (2) external columnaris disease on channel catfish and walleye (November 22, 2002), and (3) additional efficacy data on warmwater finfish eggs (February 25, 2003); UMESC is conducting pivotal efficacy studies to control mortalities associated with saprolegniasis on rainbow trout and channel catfish.
MelaFix™ (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; 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 NIO; two label claims close to completion: control of mortalities associated with (1) systemic columnaris disease in selected freshwater-reared salmonids and (2) systemic coldwater disease in all freshwater-reared salmonids.
Progress on oxytetracycline:
On May 17, 2002, CVM accepted extrapolated withdrawal times in all sizes of salmonids based on residue depletion data submitted by UMESC.
On September 9, 2002, UMESC resubmitted the liquid chromatographic determination of OTC in edible tissues of six species of fish and validation of an HPLC method for OTC in coho salmon and northern pike.
On October 28, 2002, UMESC submitted a summary report to CVM on the efficacy of OTC immersion to control bacterial diseases of freshwater fish.
On October 30, 2002, UMESC submitted a letter package addressing the antimicrobial resistance issues with human food safety.
On January 27, 2003, UMESC submitted electronic files to CVM for revised Standard Operating Procedures for determining OTC in edible tissue.
On February 19, 2003, UMESC submitted target animal safety data on coolwater and scaled warmwater fish.
On April 1, 2003, CVM responded to the October 30, 2002 submission from UMESC on the microbial safety component of the Human Food Safety technical section. CVM is requiring a microbial food safety assessment as outlined in CVM’s Guidance to Industry #152 "Evaluating the safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern."
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.
C UMESC is developing an amended environmental assessment to allow additional claims for OTC.
Current status of 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. 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, and (5) extrapolated withdrawal times for salmonids (May 17, 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 (1) the liquid chromatographic determination of OTC in edible tissues of six species of fish and validation of an HPLC method in coho salmon and northern pike (September 9, 2002) and (2) letter package addressing the antimicrobial resistance issues with human food safety; CVM replied that a microbial food safety assessment is required.
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 submitted them to CVM (February 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. CVM accepted as complete from NIO the efficacy technical section the use of OTC at 3.75 g/100 lbs 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 submitted efficacy summary on the use of OTC immersion to control bacterial diseases of freshwater fish (October 28, 2002) and CVM declared that the data might support future pivotal studies.
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 HKD-SNARC; label claim in progress: control of Ichthyophthirius on channel catfish in earthen ponds with no outflows
Progress on potassium permanganate:
The sponsor, Carus Chemical Company, submitted additional information on the product chemistry to CVM in March 2002 and the agency has asked for clarification on several points in April 2002. The sponsor is preparing a response.
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—Accepted by CVM.
Target Animal Safety—HKD-SNARC completed a target animal safety study on channel catfish.
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 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 U.S. but needs positive marketing information; has approval in several countries.
On January 27, 2003, the licensed agent for the potential sponsor contacted the National Aquaculture NADA Coordinator to discuss ways of moving forward toward approval.
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.
The National Aquaculture NADA Coordinator met with the sponsor of Romet-30® on December 4-5, 2002 to discuss developments on palatability and data requirements 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, 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 U.S. 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.
ANESTHETICS
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 NIO; label claim in progress: zero withdrawal anesthetic in salmonids.
Progress on AQUI-S®:
Under the AQUI-S® INAD exemption (INAD 10-541), NIO submitted the following efficacy data: steelhead trout (submitted March 31, 2003), rainbow trout, lake trout, and mountain whitefish (submitted May 8, 2003), cutthroat trout (submitted May 9, 2003), bull trout (submitted May 14, 2003), and hybrid striped bass (submitted May 28, 2003).
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.
On December 12, 2002, the sponsor, UMESC, NIO, and the National Aquaculture NADA Coordinator met with CVM to discuss the data requirements for efficacy, human food safety, and target animal 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 December 17, 2002, the sponsor, UMESC, NIO, and the National Aquaculture NADA Coordinator held a teleconference to discuss how to proceed on the isomer issue.
UMESC is working on the analytical methods to detect isoeugenol in rainbow trout and has completed a pilot total residue depletion study on rainbow trout.
On June 3, 2003, the sponsor, UMESC, and the National Aquaculture NADA Coordinator will meet with CVM to discuss the isomers in the AQUI-S® as they relate to product chemistry and residue chemistry issues.
The National Aquaculture NADA Coordinator is working with the sponsor to develop a Research and Development Plan for the approval of AQUI-S® in the United States. The plan should be in place by the summer of 2003.
Current status of 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 a public environmental summary.
Human Food Safety—UMESC is planning to conduct a total residue depletion study as soon as issues are resolved related to the isomer concentrations.
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 NIO. NIO will submit a protocol for these studies to CVM. The sponsor is preparing 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 NIO 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. NIO submitted five efficacy studies in 2003.
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.
Oil of Cloves—Status: Oil of cloves (eugenol) is considered 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 and eugenol as anesthetics for fish. CVM reiterated that GRAS status as a food additive does not justify use as an animal drug and clove oil and eugenol are considered as unapproved new animal drugs. Neither clove oil nor eugenol can be used for routine clinical use on laboratory animals.
MS-222—Status: Two approved NADAs for MS-222 as an anesthetic with a 21-day withdrawal time.
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 as spawning aid.
Progress on CCP:
On July 17, 2002, CVM accepted the effectiveness component as complete for use of CCP as a spawning aid in female finfish reared in freshwater.
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.
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 as complete CCP as a spawning aid in freshwater-reared female finfish (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.
Luteinizing Hormone-Releasing Hormone analog (LHRHa)—Status: Early development stage
The National Aquaculture NADA Coordinator worked with Auburn University to develop an efficacy study protocol and request for INAD for Luteinizing Hormone-Releasing Hormone analog (LHRHa) to manage spawning of channel and blue catfish. The protocol and INAD request was submitted to CVM in March 2003 and the INAD was approved by CVM for the spring spawning season.
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 MT:
On November 14, 2002, the sponsor (via telephone), Auburn University, and the National Aquaculture NADA Coordinator met with CVM to discuss the remaining data requirements for the product chemistry and environmental safety technical sections.
The National Aquaculture NADA Coordinator reviewed the proposed efficacy protocol for the development of MT for ornamental fish and sent out comment on November 29, 2002. She continued to work with the University of Florida in the winter and spring of 2003 to finalize the protocol and the request for an INAD. Those items were submitted to CVM by the University of Florida on May 22, 2003.
On February 8-9, 2003, the North Central Regional Aquaculture Center voted to provide funds to complete the product chemistry and environmental safety technical section.
In February and March 2003, the National Aquaculture NADA Coordinator developed a draft announcement for the studies to be funded and a status paper on the requirements for each study. She worked with CVM on determining the analytical methods that will be appropriate for the studies and experts in the field to delineate the requirements.
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 and a method with greater recoveries.
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 and a more sensitive method to detect MT in water.
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. At least one potential sponsor has submitted a supplemental NADA for this label claim.
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.
February 10-14, 2003, the National Aquaculture NADA Coordinator met with FWS officials in Shepherdstown, WV to help plan a training course on the proper use of piscicides.
On April 9, 2003, the National Aquaculture NADA Coordinator met with EPA to discuss the reregistration of antimycin for public and private aquaculture and fisheries uses. The road map for reregistration includes a Standard Operating Procedures manual, training course, and defined labels with controls.
PUBLIC INFORMATION, WORKSHOPS, AND PRESENTATIONS
Federal-State Aquaculture Drug Approval Partnership Project (IAFWA Project)–includes eight drugs: AQUI-S®, chloramine-T, copper sulfate, florfenicol, formalin, hydrogen peroxide, oxytetracycline, and potassium permanganate.
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-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 100th 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.
The National Aquaculture NADA Coordinator spearheaded the effort to finalize the Completion Report for the IAFWA Project on March 19, 2003. The report is dedicated to Dr. Guy Stehly to died unexpectedly on March 6, 2003. He had directed and developed a major portion of the human food safety data for a number of the IAFWA Project drugs. He will be sorely missed by all who knew him.
The DAWG held a meeting on March 25, 2003 in Winston-Salem, North Carolina. The National Aquaculture NADA Coordinator provided a report on (1) the status of the Project Completion Report, (2) status of the work plan for initial approvals of all eight Project drugs, and (3) future plans for expanding and extending existing label claims. Each research facility (i.e., FWS, UMESC, and HKD-SNARC) 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, and IAFWA) and requested guidance and comments from the agencies involved to include (follow-up work, (2) new drugs, (3) definition of roles and responsibilities, and (4) funding and status of the National Aquaculture NADA Coordinator.
Aquaculture America 2003, Louisville, Kentucky
The National Aquaculture NADA Coordinator chaired the JSA Quality Assurance in Aquaculture Production meeting on February 17, 2003 because neither of the co-Chairs could be present due to a severe snowstorm. The Five-Year Plan was discussed to include the development of a matrix for all the drugs under development for approval. These matrices would provide complete information on the status and key players for each drug.
The National Aquaculture NADA Coordinator attended the Effluents Session on February 18, 2003 as co-Chair of the Drugs, Chemicals, and Aquatic Pathogens Subgroup of the JSA Aquaculture Effluents Task Force. EPA presented the results of the responses and mentioned that drugs and chemicals for an area of concern.
The National Aquaculture NADA Coordinator organized and chaired a producer session entitled "Successes and Challenges to the Aquaculture Drug Approval Process" and presented a talk entitled "Highlights and progress toward aquaculture drug approvals" on February 20, 2003.
Joint National Aquaculture Program Planning Workshop, St. Louis, Missouri
The National Aquaculture NADA Coordinator participated in the Joint National Aquaculture Program Planning Workshop for the U.S. Department of Agriculture’s Agricultural Research Service and Cooperative State Research, Education and Extension Service on November 20-21, 2002. The National Aquaculture NADA Coordinator emphasized the need for ARS to help in the approval research for aquaculture drugs in breakout sessions.
Review of fish in research document for the American Fisheries Society
The National Aquaculture NADA Coordinator completed a review of a document that discusses the use of drugs on research fish on November 29, 2002.
Annual Funding Drive
The National Aquaculture NADA Coordinator sent out letters to prospective sources of funding on January 5-9, 2003 for Year 9 starting May 15, 2003. Funding was received to cover a major portion of the funding needs.
Changes in CVM Positions
Several persons with good understanding of aquaculture drug needs were promoted to significant positions within CVM. Dr. Steve Vaughn was named Director of the Office of New Animal Drug Evaluation (ONADE) on November 3, 2002 and Dr. Bernadette Dunham was named Deputy Director of ONADE on December 16, 2002. Dr. Joan Gotthardt was promoted to the Directorship of the Division of Therapeutic Drugs for Food Animals on January 7, 2003 and Dr. Don Prater replaced Joan as the Aquaculture Drugs Team on May 23, 2003.
Anesthetics
The National Aquaculture NADA Coordinator was asked by the Executive Director of the American Fisheries Society (AFS) to lead a dialogue on the use of anesthetics in fisheries. She will be working with the Aquaculture Chemicals Subcommittee of the AFS Task Force on Fishery Chemicals to provide the dialogue.
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 were 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. She compiled comments and provided her own into a response that was submitted to the AETF on January 9, 2003. EPA had one question regarding extra-label use the answer to which was provided on May 21, 2003.
Minor Use Minor Species legislation
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, and now in 2003. It was reintroduced in the U.S. Congress into the House as (HR-2079 and into the Senate on March 27, 2003 (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 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 107th 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 National Aquaculture NADA Coordinator sent letters on April 21, 2003 to her congressional delegation to urge them to co-sponsor the bill. Senator Herb Kohl promised to keep her views in mind when the bill is debated on the Senate floor.
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.
Schnick, R.A. 2003. Notes from "The Drug Lady." American Fisheries Society Fish Health Newsletter 31(2):16-18.
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 B 8th 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.
Schnick, R.A. 2003. Aquaculture drugs. North Central Regional Aquaculture Center 2003 Program Planning Meeting, East Lansing, Michigan, February 8, 2003.
Schnick, R.A. 2003. Goal 1—Review and status of priority aquaculture drugs. Goal 2—Status matrix of aquaculture drug approvals—IAFWA Project drugs. Goal 6—Funding and update on National Aquaculture NADA Coordinator position. JSA Working Group on Quality Assurance in Aquaculture Production Meeting, Aquaculture America 2003, Louisville, Kentucky, February 17, 2003.
Schnick, R.A. 2003. Highlights and progress toward aquaculture drug approvals. Producer Session: Successes and Challenges to the Aquaculture Drug Approval Process, Aquaculture America 2003, Louisville, Kentucky, February 20, 2003.
Schnick, R.A. 2003. Drugs for aquaculture. Advanced Fish Medicine Course, Orlando, Florida, March 22-24, 2003.
Schnick, R.A. 2003. Status of work plans for initial approvals of all eight IAFWA Project drugs. Drug Approval Working Group Meeting, Winston-Salem, North Carolina, March 25, 2003.
SPECIAL REPORTS
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 pp.
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 pp.
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.
Schnick, R.A. 2002. National Coordinator for Aquaculture New Animal Drug Applications (NADAs). Eighth midyear report of activities, May 15, 2002 to November 9, 2002. Submitted to Ted Batterson, North Central Regional Aquaculture Center, East Lansing, Michigan. December 8, 2002. 14 pp.
Schnick, R.A. 2003. E-mail addresses for researchers working on aquaculture drug approvals. Submitted to Gary Jensen, co-Chair, Working Group on Quality Assurance in Aquaculture Production. December 16, 2002. 2 pp.
Schnick, R.A. 2003. Summary of activity highlights for the National Coordinator For Aquaculture New Animal Drug Applications (NADA) (January To December 2002). Submitted to potential funding sources. January 5-9, 2003. 3 pp.
JSA-AETF Drugs and Chemicals and Aquatic Animal Pathogens Technical Subcommittee. 2003. Solicited comments on drug and chemical effluents. Submitted by R.A. Schnick, co-Chair, to Gary Jensen, Chair, JSA-AETF, to be forwarded to EPA. January 29, 2003. 36 pp.
Schnick, R.A. 2003. 2003 Midyear report to the Governing Board: Task Force on Fishery Chemicals. Submitted to Fred Harris, President, AFS. February 2, 2003. 6 pp.
Schnick, R.A. 2003. Completion of drug approvals for the Federal-State Aquaculture Drug Approval Partnership Project. Submitted to Drug Approval Working Group. February 6, 2003. 16 pp.
Schnick, R.A. 2003. Draft label claim for 35% hydrogen peroxide. Submitted to UMESC and Eka Chemicals, Inc. February 7, 2003. 3 pp.
Schnick, R.A. 2003. Call for Statements of Interest: Drug Approval Research on 17 α-methyltestosterone (draft). Submitted to Ted Batterson, North Central Regional Aquaculture Center. March 10, 2003. 3 pp.
Moffitt, C., and R.A. Schnick. 2003. Minutes to meeting of the Joint Subcommittee on Aquaculture (JSA) Working Group on Quality Assurance in Aquaculture Production. Submitted to co-Chair, Gary Jensen for distribution to the group. March 12, 2003. 5 pp.
Schnick, R.A. 2003. Status of drug approval for 17 α-methyltestosterone. Submitted to persons interested in approval of 17 α-methyltestosterone. March 12, 2003. 4 pp.
Schnick, R.A., W.H. Gingerich, G.R. Stehly (deceased), J.R. Meinertz, L.J. Schmidt, M.P. Gaikowski, J.J. Rach, J.A. Bernardy, C. Vue, T.M. Schreier, D.L. Straus, B.R. Griffin (retired), D. Erdahl, and J. Bowker. 2003. Completion Report: Federal-State Aquaculture Drug Approval Partnership Project. Submitted by R.A. Schnick to Drug Approval Working Group. March 19, 2003. 40 pp.
Schnick, R.A. 2003. Minutes to Drug Approval Working Group meeting, Winston-Salem, North Carolina, March 25, 2003. Submitted to Drug Approval Working Group. April 10, 2003. 28 pp.
JSA-AETF Drugs and Chemicals and Aquatic Animal Pathogens Technical Subcommittee. 2003. Response to EPA question on extra-label use. Submitted by R.A. Schnick, co-Chair, to Gary Jensen, Chair, JSA-AETF, to be forwarded to EPA. May 21, 2003. 2 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.