An amended New Animal Drug Application (NADA) was approved by the Center for Veterinary Medicine (CVM) on June 18, 1998 for the expansion of formalin use to control or prevent fungus on all fish eggs and external parasites on all fish.

All technical sections for an approval of copper sulfate have been submitted to CVM for review or have been reviewed. Preliminary indications are that the label will only cover the control of Ichthyopthirius but for all fish.

Summary reports for the data call-in for the efficacy data on chloramine-T to control or prevent mortalities from bacterial gill disease were submitted to CVM on July 30, 1998 as technical sections for review. At a January 25, 1999 meeting, CVM discussed the outstanding data requirements for chloramine-T and responded to the Inherent Withdrawal Time proposal made by the National NADA Coordinator. CVM proposed two mammalian safety studies that would allow use of chloramine-T in both public and private aquaculture instead of accepting the Inherent Withdrawal Time proposal that would have limited the use of chloramine-T to only public aquaculture facilities. The requirements for mammalian toxicology testing are substantially less than what the agency had originally requested in November 1997.

A meeting with CVM and the sponsor of hydrogen peroxide was held on June 18, 1998 to discuss the remaining data requirements, the mechanisms for transferring the Canadian dossier to CVM, and setting up a Public Master File. Enough data may exist for an early approval in the United States. CVM determined that the human food safety data requirements are met. The efficacy technical section was submitted to CVM on September 18, 1998 for the use of hydrogen peroxide to control or prevent mortalities associated with saprolegniasis on all fish.

A summary data package containing product chemistry, mammalian toxicology, human food safety, environmental assessment, efficacy, and target animal safety was submitted to CVM on September 3, 1998 by the sponsor of Pyceze™ for its use to control or prevent saprolegniasis on fish eggs.

A coordination meeting was held in La Crosse, Wisconsin on March 17-18, 1999 to discuss plans for implementation of a general U.S. Fish and Wildlife Service (FWS) investigational new animal drug (INAD) exemption for florfenicol..

The National NADA Coordinator submitted a request to Pfizer, Inc. to petition CVM to recalculate the current withdrawal time for all fish treated with oxytetracycline (OTC) based on a recent UMESC submission to CVM documenting the loss of OTC residues in salmon below 9 C and the new OTC tolerance in animal tissues.

The sponsor of potassium permanganate submitted the environmental assessment to CVM on February 23, 1998 and the product chemistry technical section on December 8, 1998.

Comments were submitted to the U.S. Food and Drug Administration on August 21, 1998 regarding the FDA Modernization Act of 1997. The FDA was urged to increase the number of aquaculture reviewers and submit to Congress the document "Proposals to increase the availability of approved animal drugs for minor species and minor uses."

The Drug Approval Oversight Subcommittee (DAOS) formed to aid the Federal-State Aquaculture Drug Approval Partnership program (a project of the International Association of Fish and Wildlife agencies=IAFWA Project) to achieve its goal of obtaining drug approvals for U.S. public aquaculture held a series of meetings (September 11, 1998 in Savannah, Georgia; January 11, 1999 in Arlington, Virginia; and March 26-27 in San Francisco, California) to discuss progress, issues, and extend the IAFWA Project another three years to June 2002. A work planning meeting was held November 19-20, 1998 in La Crosse, Wisconsin.

The FWS Bozeman National INAD Office expanded its scope in January 1999 to include other entities (other public agencies and private producers) under their INAD exemptions.

The document "Proposals to increase the availability of approved animal drugs for minor use and minor species" (MUMS) was released to Congress and the public by CVM on October 29, 1998. MUMS is critical to gaining approvals of aquaculture drugs.

The National NADA Coordinator gave an overview presentation on international aspects of antibiotic sensitivity determination and the need for harmonization in aquaculture medicines at the Workshop on minimum inhibitory concentration methodologies used in aquaculture, November 24-27, 1998, Weymouth, UK. These tests will allow the aquaculture community to defend its attempts to gain approval and use of oral antimicrobials in the aquatic environment, an area under attack by the Centers for Disease Control and Prevention (CDC). CDC has stated that the environmental application of antibiotics in aquaculture should be banned.

The National NADA Coordinator volunteered to be on two National Aquaculture Association committees--pursuing the Minor Use/Minor Species provisions and developing a white paper on antimicrobial resistance. She prepared a document entitled "Minor use/minor species (MUMS) document provisions to benefit the aquaculture industry on February 18, 1999.

The National NADA Coordinator organized, chaired, and gave the keynote address at a session on worldwide cooperation toward aquaculture drug approvals at the World Aquaculture ‘99, April 26 to May 2, 1999 in Sydney, Australia.

The National NADA Coordinator pursued and obtained enough funding for this position for Year 5 (May 15, 1999 to May 14, 2000) to continue on a full-time basis. Over 50 letters were sent out requesting Year 5 funding.

A website was established for the National NADA Coordinator on April 12, 1999 at http://ag.ansc.purdue.edu/aquanic/jsa/Aquadrugs.htm.

The NADA Coordinator had two manuscripts in press, presented 16 papers and talks, and wrote 32 reports.

PROJECT OBJECTIVES

The overall goal of this project is for the National Coordinator for Aquaculture New Animal Drug Applications (National 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 NADA Coordinator provided many information transfers this year 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 community.

Amoxicillin (oral antibacterial)--Status: Two sponsors have submitted INAD/NADA letters of intent; early development stage

The National NADA Coordinator met on October 19, 1998 with CVM and GB Research Inc.(a sponsor of amoxicillin) for a pre-submission conference regarding the development of data that will lead to an approved NADA for amoxicillin trihydrate. GB Research Inc. presented a plan for funding the necessary research and CVM provided insight on the technical sections needed for completion of a NADA submission.

The US representative sent out the funding plan to INAD holders through individual mailings, the USDA mailgroup, and the National NADA Coordinator in January 1999.

The National NADA Coordinator requested and was able to establish a Public Master File on amoxicillin at CVM.

Chloramine-T (external antibacterial)--Status: Sponsor has committed to INAD/NADA; major effort for NADA approval under the IAFWA Project and compassionate INADs. BOTTOM LINE: All submissions should be completed in 2000 for control of mortalities associated with bacterial gill disease on salmonids, in 2001 for control of mortalities associated with bacterial gill disease on cool- and warmwater fish and external flavobacteriosis on salmonids, and in 2002 for control of mortalities associated with external flavobacteriosis on cool- and warmwater fish.

The Upper Midwest Environmental Sciences Center (UMESC, formerly the Upper Mississippi Science Center), under the federal-state drug approval partnership program [International Association of Fish and Wildlife agencies= (IAFWA) Project], issued a data call-in on November 14, 1997 for all the efficacy data on chloramine-T that can support a label claim to control or prevent mortalities related to external flavobacterial infections in cultured freshwater fish. Data were received January 15, 1998, organized in March 1998, evaluated in April 1998, and summary reports prepared to address efficacy technical sections to both prevent and control bacterial gill disease in selected species were submitted to the Center for Veterinary Medicine (CVM) on July 30, 1998.

IAFWA Project coordinators, representatives of the drug sponsor, and IAFWA representatives met on January 25, 1999 with Center For Veterinary Medicine staff to discuss outstanding data requirements for Chloramine-T and learn of CVM’s response to the Inherent Withdrawal Time proposal made by the National NADA Coordinator on October 24, 1998. CVM proposed two mammalian safety studies that would allow use of chloramine-T in both public and private aquaculture instead of accepting the Inherent Withdrawal Time proposal that would have limited the use of chloramine-T to only public aquaculture facilities and early life stages. The requirements for mammalian toxicology testing are substantially less than what the agency had originally requested in November 1997. The Agency furthered clarified requirements to address technical guidelines in human food safety, environmental safety, efficacy and target animal safety.

A regulatory analytical method for para-toluenesulfonamide in fish tissue to support residue depletion studies was submitted on May 15, 1998 to CVM for review.

Akzo Nobel Chemicals, Inc. informed the National NADA Coordinator on March 24, 1999 that the company will not fund any additional studies to support the approval for chloramine-T, including the additional genotoxicity work that is required to establish a tolerance for chloramine-T in fish tissues. The company will continue to act as a sponsor for their product in the United States and to provide any existing materials such as protocols, environmental safety data, and product chemistry information. Because of this change, UMESC has opted to spend Akzo contributed funds being held at UMESC on the required genotoxicity studies. Formerly, UMESC was recommending that these funds be used to support target animal safety studies in salmonids. Instead, the work on salmonids will be completed by Bozeman Fish Technology Center and UMESC will conduct target animal safety studies on representative cool- and warmwater species with public funds.

The National NADA Coordinator developed a fact sheet on March 29, 1999 entitled "What is needed to gain an approval of chloramine-T for salmonids?" in an attempt to answer questions concerning the drug’s status.

Copper Sulfate (external microbicide)--Status: Sponsor submitted INAD/NADA letter of intent and product chemistry technical section; major effort for approval under the IAFWA Project and compassionate INADs. BOTTOM LINE: All submissions should be completed in 1999 for control Ichthyopthirius on all fish. The claims for control or prevention of other external microbes on all fish would be based on efficacy studies that would be completed in 2001 if stakeholders are interested.

Phelps Dodge Refining Corporation (El Paso, Texas) submitted an application for an INAD/NADA (INAD #10-046) on April 3, 1997, a request for two labels on the same package on October 24, 1997, and the product chemistry data on March 12, 1998. The product chemistry technical section was reviewed by CVM on April 15, 1998 and October 15, 1998 and the sponsor responded to the items on July 31, 1998 October 30, 1998.

Efficacy and target animal safety data and the environmental assessment have been submitted to CVM by the Stuttgart National Aquaculture Research Center. All the data needed for an approval of copper sulfate have been submitted as of early 1998 and all the technical section packages are under review by CVM.

Cutrine-Plus™ (external microbicide)--Status: Some interest by potential sponsor; early development stage

Diquat Dibromide (external microbicide)--Status: No commitment by potential sponsor; early development stage

Earth Tec Algicide/Bactericide™ (external microbicide)--Status: Sponsor recently submitted INAD/NADA letter of intent; early development stage

Enrofloxacin (oral antibacterial)--Status: INADs inactive in the United States because of fluoroquinolone 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; near NADA approval for bacterial kidney disease in salmonids if gain sponsor

Florfenicol (oral antibacterial)--Status: Sponsor recently allowed the development of florfenicol for approval in United States; approved in Canada in August 1997 to control furunculosis in Atlantic salmon; IAFWA Project drug. BOTTOM LINE: All submissions should be completed in 1999 for control of mortalities associated with furunculosis in Atlantic salmon and in 2002 for control mortalities associated with susceptible systemic bacterial diseases on all fish.

A meeting was held on August 26, 1998 between CVM and Schering-Plough Animal Health regarding the development of florfenicol ( a broad spectrum antibacterial) for aquaculture in light of CVM’s new policy on disease resistance issues. CVM indicated this issue affects all animal drugs including any drugs developed for aquaculture uses.

Scientists from UMESC, the Stuttgart National Aquaculture Research Center, the FWS Bozeman INAD Office, the FWS Olympia Fish Health Laboratory, and State of Iowa Rathburn Hatchery, met with the National NADA Coordinator in La Crosse, Wisconsin on March 17-18, 1999 to discuss plans for implementation of a general FWS INAD for florfenicol. Questions raised at the meeting were sent to Schering-Plough Animal Health to answer on March 19, 1999 by the National NADA Coordinator.

The National NADA Coordinator developed draft letters of request for INADs on florfenicol for UMESC and FWS on February 26, 1999 and March 19, 1999, respectively.

Formalin (external microbicide)--Status: IAFWA Project drug; Supplemental NADA approved on June 18, 1998 for control of certain fungi on the eggs of all finfish and certain external protozoa and monogenetic trematodes on all finfish. BOTTOM LINE: All submissions should be completed in 1999 for control or prevention of mortalities associated with fungal infections on salmonids and in 2000 for control or prevention of mortalities associated with fungal infections on all fish.

An amended NADA was approved by CVM on June 18, 1998 for the expansion of formalin use to control or prevent fungus on all fish eggs and external parasites on all fish.

At the Work Planning/Coordination Meeting of the IAFWA Project held November 19-20, 1998 in La Crosse, Wisconsin, CVM reviewers indicated that a broad label of all fish to treat external fungal infections was not possible because of the lack of information for cool- and warmwater fish. IAFWA members attending the meeting voted to have UMESC proceed immediately to perform pivotal efficacy studies on cool- and warmwater fish to support an amended NADA and to delay pivotal efficacy studies at UMESC on potassium permanganate and AQUI-S™.

A study protocol was developed at UMESC to determine the efficacy of formalin for treating saprolegniasis in channel catfish and laboratory testing began in early 1999.

Fumagillin (microsporidiosis control)--Status: Sponsor recently submitted INAD/NADA letter of intent; 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; one U.S. sponsor is interested in gaining an NADA approval; IAFWA Project drug; efficacy (eggs and fish) and target animal safety technical section on eggs submitted; human food safety data requirements are met. BOTTOM LINE: All submissions should be completed in 1999 for control or prevent mortalities associated with fungal infections on all fish eggs in the United States if data from Canada are acceptable, in 2000 for control or prevent mortalities associated with fungal infections on all fish, and in 2001 for external flavobacteriosis and bacterial gill disease on all fish and to control parasitic infestations on all fish.

A meeting with CVM and the sponsor of hydrogen peroxide was held on June 18, 1998 to discuss the remaining data requirements for hydrogen peroxide. Discussions centered on the mechanisms for transferring the Canadian dossier to CVM and for setting up a Public Master File. Enough data may exist for an early approval in the United States. CVM determined that the human food safety data requirements are met.

UMSC submitted efficacy and target animal safety data to CVM September 18, 1998 for review and comment to support an NADA for the use of hydrogen peroxide to control and/or prevent mortalities associated with saprolegniasis on all cultured freshwater fish.

UMSC is in the process of completing experiments in collaboration with state hatcheries to determine the efficacy of hydrogen peroxide to control external parasitic infestations and to control mortalities associated with external flavobacterial infections on representative cultured freshwater fish.

FWS is modifying the protocol for hydrogen peroxide and plans to initiate an INAD in early 1999 through the National Research Support Program Number Seven (NRSP-7) for its use to control or prevent mortalities associated with external bacterial infections and control external parasitic infestations.

The sponsor is negotiating with a company to do the marketing of hydrogen peroxide for fisheries use in Canada.

Neomycin sulfate (vibriosis control)--Status: Currently no activity on this drug

Oxytetracycline (OTC, oral antibacterial)--Status: Currently approved for control of certain bacterial diseases in catfish, salmonids, and lobsters and as a marking agent in Pacific salmon; IAFWA Project drug; near-term approval as marking aid on all cultured freshwater fish and as a control for bacterial diseases on shrimp. BOTTOM LINE: All submissions should be completed in 1999 for control of Aeromonas sp. in esocids, in 2000 for systemic flavobacteriosis in salmonids, and in 2001 for control of mortalities associated with systemic columnaris disease in cool- and warmwater fish.

A call-in of efficacy data initiated in October 1997 for any and all efficacy data on OTC that can support the extension and expansion of the NADA was evaluated beginning in May 1998, and the summary report was submitted to CVM on January 25, 1999. Assessment by UMESC scientists suggest that the data from the call-in support extending the label to include treatment of Aeromonas hydrophila in esocids.

An analytical method to analyze for oxytetracycline in fish feeds in support of INAD pivotal efficacy testing at participating INAD hatcheries was accepted by CVM on July 29, 1998.

An oxytetracycline residue depletion study was recently completed at low temperatures at the Quilcene National Fish Hatchery. The data should allow treatment of yearling salmonids below 9 C. The report was submitted to CVM in February 1999.

The National NADA Coordinator submitted a request to Pfizer, Inc. to petition CVM to recalculate the current withdrawal time for all fish treated with OTC based on a recent UMESC submission to CVM documenting the loss of OTC residues in fry/fingerling coho salmon below 9 C and the new OTC tolerance in tissues of 2 g/gm.

Potassium Permanganate (external microbicide)--Status: Sponsor recently submitted an INAD/NADA letter of intent; major effort for NADA approval under IAFWA Project. BOTTOM LINE: All submissions should be completed in 2001 for control or prevent mortalities associated with external fungal infections on all fish and in 2002 for control or prevention of mortalities associated with external flavobacteriosis and bacterial gill disease and control of parasitic infestations on all fish

A residue chemistry technical section was submitted to CVM for review in early summer 1998. The sponsor has agreed to prepare and submit the environmental assessment after a positive meeting with CVM on January 28, 1998.

The sponsor submitted the environmental assessment to CVM on February 23, 1998 and product chemistry technical section on December 8, 1998 and has not received a response.

Pet Fish Therapeutants (various drugs and pesticides)--Status: Major effort to resolve non-food fish issue for these drugs by private consultant

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

Pyceze™ (external microbicide)--Status: Sponsor recently submitted an INAD/NADA letter of intent and summary of all major technical sections; early development stage

A summary data package containing product chemistry, mammalian toxicology, human food safety, environmental assessment, efficacy, and target animal safety was submitted to CVM on September 3, 1998 by the sponsor of Pyceze™ for its use to control or prevent saprolegniasis on fish eggs.

Quinine (internal microbicide)--Status: Some interest on the part of potential sponsor in a U.S. NADA approval if market is large enough

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. Recently, the Centers for Disease Control and Prevention have presented concerns about the use of all fluoroquinolones in animal health because of the 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 an 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

Trichlorfon (external parasite control)--Status: Some interest on the part of potential sponsor in a U.S. NADA approval; has approvals in several countries; Special Local Need registrations granted in 1998

Aqui-S™/Aqui-S Plus™--Status: Sponsor proceeding with worldwide drug approval; drug being assessed by the IAFWA Project. BOTTOM LINE: All submissions should be completed in 2000 for zero or low withdrawal time anesthetic for Atlantic salmon and in 2002 for all fish.

The FWS is initiating an INAD on Aqui-S™ to cover all public and private facilities in early 1999.

A study protocol was developed to determine the target animal safety of AQUI-S^TM treatments to various cultured freshwater fishes and laboratory testing has begun at UMESC.

The sponsor (1) submitted an environmental assessment of AQUI-S™ to the Center for Veterinary Medicine (CVM) on November 13, 1998, (2) has recent information from a National Toxicology Program study at the University of Arizona that the major ingredient in AQUI-S™ is not a carcinogen, (3) is close to submitting the product chemistry technical section for AQUI-S™, and (4) will provide funding for a residue chemistry study in AQUI-S™ at UMESC.

A cooperative research and development agreement is being developed between UMESC and the sponsor of AQUI-S™ to cover cooperative efforts on the development of AQUI-S™ as a short withdrawal time anesthetic.

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

The National NADA Coordinator responded to several requests for information on the regulatory status of oil of cloves in 1998 because of a recent article on its apparent regulatory allowance by CVM.

Common Carp Pituitary (CCP)-- Status: Sponsor and interested parties proceeding toward NADA approval. BOTTOM LINE: All submissions should be completed in 2000 for use on all fish.

A literature review was completed on the efficacy and target animal safety of common carp pituitary and presented on August 5, 1998 in Bozeman, Montana at the FWS-INAD Coordination Workshop. Plans are being made to prepare the document for submission to CVM in late 1998.

The National NADA Coordinator is working with a researcher from Mississippi State University to complete the needed target animal safety studies.

Gonadotropin Releasing Hormone (GnRH)--Status: Sponsor recently submitted INAD letter of intent; early development stage

Human Chorionic Gonadotropin (hCG)--Status: Near-term NADA approval in the United States

The National NADA Coordinator contacted CVM to determine the status of hCG in the review process--hCG continues to be under review and is a high priority.

The 1996 interim regulatory policy on the use of hCG was revised so that producers could use the drug under a veterinarian’s prescription along with notification of CVM. This policy was renewed in 1998 and will continue until hCG gains approval.

Ovaprim™--Status: Sponsor recently submitted INAD letter of intent; early development stage

17 -methyltestosterone (MT)--Status: Sponsor is developing NADA package; INAD sponsors actively pursuing a NADA approval; NADA approval anticipated when environmental and product chemistry requirements have been reviewed by CVM and all requirements are met

On June 9, 1998, CVM responded to the environmental assessment that was submitted by Auburn University on November 7 and 26, 1997. A response including revisions to the calculations and assumptions made in the original submission was prepared and submitted to CVM on October 30, 1998.

The sponsor (Rangen, Inc.) is working on the product chemistry section of the NADA.

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

Major advances were made toward communication and coordination of INAD/NADAs of high priority drugs important to public fish production at a workshop held by the FWS in Bozeman, MT on August 4-5, 1998. Discussions centered on the situation regarding chloramine-T and the progress of the IAFWA Project.

The Drug Approval Oversight Subcommittee (DAOS) formed to aid the federal-state aquaculture drug approval partnership program (a project of the International Association of Fish and Wildlife agencies=IAFWA Project) to achieve its goal of obtaining drug approvals for U.S. public aquaculture held a meeting on September 11, 1998 in Savannah, Georgia to discuss progress, issues, and extend the IAFWA Project another three years to June 2002.

A Work Planning/Coordination Meeting of the IAFWA Project held November 19-20, 1998 in La Crosse, Wisconsin, evaluated the progress being made on the technical sections for each work plan and made amendments to the existing work plan where necessary. DAOS members voted to have UMESC proceed immediately to perform pivotal efficacy studies on cool- and warmwater fish to support a formalin amended NADA and to delay pivotal efficacy studies on potassium permanganate and AQUI-S™. The group supported the direction and schedules of the rest of the work plans as outlined by the principal investigators. CVM urged the IAFWA Project to aid sponsors in dealing with antimicrobial resistance and environmental safety issues that recently became major concerns for gaining any animal drug approvals.

The federal portion of the IAFWA Project has been secured until June 30, 2002 and efforts are being made to add to the 28 states who currently support the extension.

A meeting was held at the FWS in Arlington, Virginia on January 11, 1999 to brief Project stakeholders and participants on the status of the IAFWA Project. Project issues were discussed, clarifications in work plans were presented and definitions of the Project objectives were made.

As a result of the January 11, 1999 meeting, DAOS Chair Mike Gibson asked that brief progress reports be prepared for submission to all state resource agencies requesting participation for an additional three years. In response, the National NADA Coordinator and Dr. William Gingerich prepared documents that were sent to the Chair to brief DAOS members and state partners. Single page tables and two page summaries of all accomplishments and current status of each project drug were prepared.

The DAOS held a meeting at the North American Wildlife and Natural Resources Conference in San Francisco, California on March 26-27, 1999. Dr. William Gingerich and the National NADA Coordinator met with DAOS and the IAFWA Inland Fisheries Committee and presented information on the progress and various issues related to the IAFWA Project. The DAOS offered to address the issues raised at the meeting.

Status of the crop grouping research: Ohio State University is completing work on the model water borne drug, benzocaine. Classical compartmental pharmacokinetic models are being developed in five phylogenetically diverse species. Physiologically based pharmacokinetic models have been developed in channel catfish and rainbow trout. UMESC will use these PBPK models to support their work on florfenicol. Work on florfenicol will continue until the end of the IAFWA project. When completed, CVM will have a comprehensive data set from which to make a decision on crop grouping.

Meetings and Special Activities

The Bozeman National INAD Office expanded its scope in May 1998 to include other entities (other public agencies and private producers) under their INAD exemptions that had been in the Western Regional INAD Project. By January 1999, FWS included all states and the private sector under their INADs.

Comments were submitted by the National NADA Coordinator to the U.S. Food and Drug Administration on August 21, 1998 regarding the FDA Modernization Act of 1997. The FDA was urged to increase the number of aquaculture reviewers and submit to Congress the document "Proposals to increase the availability of approved animal drugs for minor species and minor uses."

The National NADA Coordinator was asked and accepted the lead editor position to the subject area "Drug/Pesticide Usage/Labeling" in the National Catfish Information Database (NCID) on September 3, 1998.

The document "Proposals to increase the availability of approved animal drugs for minor use and minor species" (MUMS) was released to Congress and the public by CVM on October 29, 1998. MUMS is critical to gaining approvals of aquaculture drugs.

The National NADA Coordinator reviewed the "Proposals to increase the availability of approved animal drugs for minor species and minor uses" (MUMS document) and presented analysis of the proposal to the Animal Health Institute on November 9, 1998. To fully implement the MUMS document, the following will be required: (1) six amendments to the Food, Drug and Cosmetic Act, (2) one amendment to the Internal Revenue code, (3) increased or new congressional appropriations for budgets of minor use programs and CVM, and (4) numerous changes to federal regulations, policies, and administration of FDA, CVM, and USDA.

The National NADA Coordinator gave an overview presentation on international aspects of antibiotic sensitivity determination and the need for harmonization in aquaculture medicines at the Workshop on minimum inhibitory concentration methodologies used in aquaculture, November 24-27, 1998, Weymouth, UK. These tests will allow the aquaculture community to defend its attempts to gain approval and use of oral antimicrobials in the aquatic environment, an area under attack by the Centers for Disease Control and Prevention (CDC). CDC has stated that the environmental application of antibiotics in aquaculture should be banned.

The National NADA Coordinator organized and chaired a producers session on compassionate INADs at Aquaculture America‘99, Tampa, Florida, January 27-30, 1999.

The National NADA Coordinator prepared a draft letter for the National Aquaculture Association for additional CVM funding and reviewers for aquaculture drugs on February 16, 1999 to alleviate the backlog in aquaculture drug reviews.

The National NADA Coordinator volunteered to be on two National Aquaculture Association committees--pursuing the Minor Use/Minor Species provisions and developing a white paper on antimicrobial resistance. She prepared a document entitled "Minor use/minor species (MUMS) document provisions to benefit the aquaculture industry on February 18, 1999.

The National NADA Coordinator organized, chaired, and gave the keynote address at a session on worldwide cooperation toward aquaculture drug approvals at the World Aquaculture ‘99, April 26 to May 2, 1999 in Sydney, Australia.

The National NADA Coordinator is organizing, chairing, and giving the keynote address at a session on international harmonization of antibacterial approvals and sensitivity testing at the EAFP 9th International Conference, September 19-24, 1999 in Rhodes, Greece.

The National NADA Coordinator sent out 50 letters for funding and obtained enough funding for this position for Year 5 (May 15, 1999 to May 14, 2000) to continue on a full-time basis.

The National NADA Coordinator participated in the strategic planning sessions held at the annual meeting of the North Central Regional Aquaculture Center, Columbia, Missouri, February 26-28, 1999.

A website was established for the National NADA Coordinator on April 12, 1999 by the U.S. Department of Agriculture. The website address is http://ag.ansc.purdue.edu/aquanic/jsa/Aquadrugs.htm.

Publications

Schnick, R.A. 1998. Approval of drugs and chemicals for use by the aquaculture industry. Veterinary and Human Toxicology 40(Supplement 2): 9-17.

Manuscripts

Schnick, R.A. (In press). Use of chemicals in fish management and fish culture: past and future. In D.J. Smith, W.H. Gingerich, and M. Beconi-Barker, editors. Xenobiotic Metabolism in Fish. Plenum Publishing Corporation, New York.

Schnick, R.A. (In review). International harmonization of antibacterial sensitivity determination for aquaculture drugs. Aquaculture.

Special Reports

Schnick, R.A. 1998. Package on extension of the IAFWA Federal-State Aquaculture Drug Approval Partnership Project. Submitted to Mike Gibson, Chair, IAFWA Drug Approval Oversight Subcommittee, Hot Springs, Arkansas. May 18, 1998. 8 pp.

Schnick, R.A. 1998. Minutes to the hydrogen peroxide meeting (April 11, 1997). Submitted to the Center for Veterinary Medicine, Rockville, Maryland. May 20, 1998. 2 pp.

Schnick, R.A., W.H. Gingerich, and B.R. Griffin. 1998. Approval of Drugs for Public Fish Production: Year 4 Progress to Date (July 1, 1997 to May 15, 1998) and Year 5 projected work (July 1, 1998 to June 30, 1999). Biological Resources Division, Upper Mississippi Science Center, La Crosse, Wisconsin. May 22, 1998. 15 pp

Schnick, R.A. 1998. Worldwide aquaculture drug approvals through partnerships in the United States. Submitted to Dow Agrosciences LLC, Indianapolis, Indiana. June 9, 1998. 10 pp.

Schnick, R.A. 1998. Year 12 Proposed Project Area IV: National Coordinator for Aquaculture New Animal Drug Applications - Year 4. Submitted to CTSA Administrative Center, Waimanalo, Hawaii for funding. July 10, 1998. 15 pp. (Revised September 4, 1998; October 8, 1998).

Schnick, R.A. 1998. 1998 annual report of the AFS Task Force on Fishery Chemicals. Submitted to AFS President, Bill Taylor. July 23, 1998. 5 pp.

Schnick, R.A. 1998. Response to FDA objectives on the FDA Modernization Act of 1997 (Docket No. 98N-0339). Submitted to the U.S. Food and Drug Administration, Washington, DC. August 21, 1998. 8 pp.

Gingerich, W.H., G.R. Stehly, V.K. Dawson, M.P. Gaikowski, G.E. Howe, J.R. Meinertz, J.J. Rach, R.A. Schnick, and B.R. Griffin. 1998. Approval of Drugs for Public Fish Production: Fourth annual report of progress [performance period: July 1, 1997 to June 30, 1998]. Biological Resources Division, Upper Mississippi Science Center, La Crosse, Wisconsin. August 27, 1998. 47 pp.

Schnick, R.A. 1998. Aquaculture drug approval progress in the United States in September 1998. Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. September 3, 1998. 3 pp.

Schnick, R.A. 1998. Report to the Working Group on Quality Assurance in Aquaculture Production. Submitted to the Working Group on Quality Assurance in Aquaculture Production, Washington, DC. September 4, 1998. 5 pp.

Gingerich, W.H., and R.A. Schnick. 1998. Approval of Drugs for Public Fish Production: Year 5 Project Work Plan and updates of Project status. Submitted to the IAFWA Drug Approval Oversight Subcommittee (DAOS), Savannah, Georgia. Biological Resources Division, Upper Mississippi Science Center, La Crosse, Wisconsin. September 11, 1998. 9 pp.

Schnick, R.A. 1998. Quarterly report for Contract No. #97-106 (National Coordinator for Aquaculture New Animal Drug Applications: reporting period, April 1, 1998 to September 30, 1998. Submitted to Center for Tropical and Subtropical Aquaculture, The Oceanic Institute, Waimanalo, Hawaii. September 30, 1998. 1 pp.

Schnick, R.A. 1998. Status of the aquaculture drug approvals in the United States (as of October 7, 1998). Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. October 7, 1998. 3 pp.

Schnick, R.A. 1998. Status of the IAFWA Project Study Plans (as of October 7, 1998). Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. October 7, 1998. 53 pp.

Schnick, R.A. 1998. Semi-annual report for Contract No. #97-106 (National Coordinator for Aquaculture New Animal Drug Applications): reporting period, April 1, 1998 through September 30, 1998. Submitted to Center for Tropical and Subtropical Aquaculture, The Oceanic Institute, Waimanalo, Hawaii. October 10, 1998. 7 pp.

Schnick, R.A. 1998. Minutes to Hydrogen Peroxide Meeting with the Center for Veterinary Medicine (June 18, 1997). Submitted to Eka Chemicals for transmittal to the Center for Veterinary Medicine, Rockville, Maryland. October 14, 1998. 3 pp.

Schnick, R.A. 1998. Aquaculture drugs (INADs/NADAs): Progress report for the period, September 1, 1992 to August 31, 1998. Submitted to North Central Regional Aquaculture Center, Michigan State University, East Lansing, Michigan. October 23, 1998. 18 pp.

Schnick, R.A. 1998. Minutes to the pre-submission conference on amoxicillin with CVM, GB Research Inc. and the National NADA Coordinator (October 19, 1998). Submitted to the Center for Veterinary Medicine, Rockville, Maryland. October 24, 1998. 3 pp.

Schnick, R.A. 1998. Draft proposal to gain aquaculture drug approval of chloramine-T under the early life stage policy. Submitted to the Center for Veterinary Medicine, Rockville, Maryland. October 24, 1998. 20 pp.

Schnick, R.A. 1998. National Coordinator for Aquaculture New Animal Drug Applications (NADAs): Mid-year report of activities, May 15, 1998 to November 9, 1998. Submitted to North Central Regional Aquaculture Center, Michigan State University, East Lansing, Michigan. October 30, 1998. 9 pp.

Schnick, R.A. 1998. Status of IAFWA Project study plans. Submitted to IAFWA Project shareholders, La Crosse, Wisconsin. November 19, 1998. 6 pp.

Schnick, R.A. 1998. Minutes to the Work Planning/Coordination Meeting for IAFWA Aquaculture Drug Approval Project. Submitted to attendees of the meeting. December 17, 1998. 18 pp.

Schnick, R.A. 1998. Worldwide efforts to gain approvals of gender manipulation aids. Submitted to G.P. Satyanarayana Rao, Bangalore, India. December 17, 1998. 3 pp.

Schnick, R.A. 1999. Quarterly report for Contract No. #97-106 (National Coordinator for Aquaculture New Animal Drug Applications: reporting period, October 1, 1998 to December 31, 1998. Submitted to Center for Tropical and Subtropical Aquaculture, The Oceanic Institute, Waimanalo, Hawaii. January 13, 1999. 1 pp.

Schnick, R.A. 1999. List of actual and potential sponsors for aquaculture drugs (as of January 1999). Submitted to the Working Group on Quality Assurance in Aquaculture Production. January 27, 1999. 4 pp.

Gingerich, W.H., G.R. Stehly, V.K. Dawson, M.P. Gaikowski, G.E. Howe, J.R. Meinertz, J.J. Rach, R.A. Schnick, and B.R. Griffin. 1999. Approval of Drugs for Public Fish Production: Fifth midyear report of progress [performance period: July 1, 1998 to December 31, 1998]. Biological Resources Division, Upper Mississippi Science Center, La Crosse, Wisconsin. January 29, 1999. 35 pp.

Schnick, R.A. 1999. Status of the aquaculture drug approvals in the United States in January 1999. Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. February 1, 1999. 4 pp.

Schnick, R.A. 1999. Minutes to the Chloramine-T Meeting, January 25, 1999. Submitted to the attendees and the Center for Veterinary Medicine. February 11, 1999. 2 pp.

Schnick, R.A. 1999. 1999 midyear report of the AFS Task Force on Fishery Chemicals. Submitted to AFS President, Bob Carline. February 12, 1999. 5 pp.

Schnick, R.A. 1999. Efficacy studies needed for aquaculture drugs. Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. February 23, 1999. 1 pp.

Schnick, R.A. 1999. List of drugs, sponsors, INAD/NADA numbers, and dates. Office of the NADA Coordinator, Michigan State University, La Crosse, Wisconsin. February 26, 1999. 3 pp.

Schnick, R.A. 1999. Minutes to the IAFWA Drug Approval Oversight Subcommittee Meeting at the 64th North American Wildlife and Natural Resources Conference. Submitted to the DAOS Chair, Mike Gibson, Hot Springs, Arkansas. April 1, 1999. 8 pp.

PRESENTATIONS

Schnick, R.A. 1998. Overview of NADA Coordinator activities. Presented at the FWS-INAD Coordination Workshop, Bozeman, Montana, August 4-5, 1998.

Schnick, R.A. 1998. NADA Coordinator update. Presented via speaker phone at the meeting of the JSA Working Group on Quality Assurance in Aquaculture Production, Washington, D.C., September 4, 1998.

Schnick, R.A. 1998. Overview of the activities of the National Coordinator for Aquaculture New Animal Drug Applications and suggestions for enhancing dialogue with the Minor Use Animal Drug Program. Presented at the meeting of the Minor Use Animal Drug Program Technical Committee for NRSP-7, Rockville, Maryland, September 22, 1998.

Schnick, R.A. 1998. The effect of the Animal Drug Availability Act of 1996 and the FDA Modernization Act of 1997 on approvals of animal health products for minor species/minor uses. Presented at the 1998 Animal Health Institute Joint Meeting, San Diego, California, November 9, 1998.

Schnick, R.A. 1998. Overview of IAFWA Project status. Presented at the Coordination meeting for IAFWA Aquaculture Drug Approval Project, La Crosse, Wisconsin, November 19-20, 1998.

Schnick, R.A. 1998. Overview of the international aspects of antimicrobial sensitivity determination and the need for harmonization in aquaculture drugs. Presented at the Workshop on MIC Methodology (EU Concerted Action - Fair-CT97-3760, Weymouth, England, November 24-27, 1998.

Schnick, R.A. 1999. National NADA Office aquaculture drug approval activities. Presented at the Aquaculture Drugs and Chemicals Approval Update - 1999, Arlington, Virginia, January 11, 1999.

Schnick, R.A. 1999. Introduction and discussion of INADs and new NADAs. Presented at the session "Aquaculture drug approvals through producer INADs" at Aquaculture America ‘99, Tampa, Florida, January 27-30, 1999.

Schnick, R.A. 1999. Update on activities of the National Coordinator for Aquaculture New Animal Drug Applications. Presented at the meeting of the Joint Subcommittee on Aquaculture, Working Group on Quality Assurance in Aquaculture Production at Aquaculture America ‘99, Tampa, Florida, January 27-30, 1999.

Schnick, R.A. 1999. Update on the IAFWA drug approval process. Presented at the 1999 Mid-Continent Fish Culture Workshop, North Kansas City, Missouri, February 2-3, 1999.

Schnick, R.A. 1999. Aquaculture drug approval progress for the catfish industry. Presented at the Annual Meeting of the Catfish Farmers of America, New Orleans, Louisiana, February 18-20, 1999.

Schnick, R.A. 1999. Advances in fishery chemicals. Presented at the 1999 Colorado/Wyoming AFS Meeting "Reeling in the next millennium", Cheyenne, Wyoming, March 1-3, 1999.

Schnick, R.A. 1999. Overview of florfenicol approval process. Presented at the Coordination meeting for florfenicol efficacy studies, La Crosse, Wisconsin, March 17-18, 1999.

Schnick, R.A. 1999. Progress and issues related to the Federal-State Aquaculture Drug Approval Partnership. Presented at the meeting of the IAFWA Drug Approval Oversight Subcommittee, San Francisco, California, March 25-28, 1999.

Schnick, R.A. 1999. Keynote address: International cooperation toward aquaculture drug approvals. Presented at World Aquaculture ‘99, Sydney, Australia, April 25-30, 1999.

Schnick, R.A. 1999. USA programs related to aquaculture drug approval development and issues. Presented to the Australian Department of Agriculture, Fisheries and Forestry, Canberra, Australia, May 3, 1999.