May 15, 1999 to November 9, 1999

A major effort is being made to develop legislation to facilitate the minor use/minor species (MUMS) drug approval process. The legislative bill will be called Minor Animal Species Health and Welfare Act of 2000.

In May 1999, Dr. Joan Gotthardt replaced Dr. Tom Bell at CVM for reviewing aquaculture drug submissions. On September 27, 1999, CVM hired a second technical reviewer for efficacy and target animal safety data submissions for aquaculture drugs.

Phelps Dodge Refining Corporation obtained acceptance of the product chemistry technical section for copper sulfate from the Center for Veterinary Medicine (CVM) on May 4, 1999.

Revisions to the target animal safety and ecological risk assessment for copper sulfate were submitted the Stuttgart National Aquaculture Research Center (SNARC) to CVM in October and June, respectively. When these two technical sections are accepted by CVM, all the technical sections needed for approval of copper sulfate to control Ich infections will be completed.

Eka Chemicals Inc. submitted the product chemistry technical section for hydrogen peroxide to CVM on July 12, 1999.

Stoller Fisheries submitted the product chemistry technical section for common carp pituitary to CVM on September 21, 1999.

The National NADA Coordinator organized, chaired, and gave the keynote address at a session on international harmonization of antibacterial approvals and sensitivity testing at the European Association of Fish Pathologists (EAFP) 9th International Conference, September 19-24, 1999 in Rhodes, Greece.

Schering-Plough Animal Health submitted a major data package to CVM for florfenicol to control furunculosis in salmonids on September 30, 1999.

The NADA Coordinator had one publication, three manuscripts in review, presented three papers and talks, and wrote 19 reports.

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.

The National NADA Coordinator provided many information transfers from May 15, 1999 to November 9, 1999 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 is working with GB Research and Kent Seafarms to gain a new United States representative for the development of its amoxicillin product.

Chloramine-T (external antibacterial)--Status: Sponsor has committed to INAD/NADA; major effort for NADA approval under the International Association of Fish and Wildlife Agencies (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 National NADA Coordinator met with representatives of Akzo Nobel Functional Chemicals on June 8, 1999 in La Crosse, Wisconsin to discuss the remaining data requirements for chloramine-T, develop a timetable to complete these requirements, and determine the market potential for all its uses.

The National NADA Coordinator is working with Akzo and CVM to finalize the protocols for the genotoxicity studies on the marker residue of chloramine so that Akzo can complete the remaining mammalian safety data requirements.

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.

The sponsor of copper sulfate, Phelps Dodge Refining Corporation, obtained acceptance of the product chemistry technical section from CVM on May 4, 1999.

The revised Ecological Risk Assessment (ERA) for the use of copper sulfate to control certain waterborne fish diseases was submitted by SNARC to CVM on June 29, 1999. SNARC submitted the revised target animal safety studies to CVM on October 29, 1999.

The National NADA Coordinator prepared draft letters on July 14, 1999 that were submitted by Phelps Dodge Refining Corporation to CVM concerning a request for exclusivity and for the writing of the human food safety portion of the Freedom of Information summary for copper sulfate.

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 sponsor gained.

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 of mortalities associated with susceptible systemic bacterial diseases on all fish.

The National NADA Coordinator met with a representative of Schering-Plough Animal Health during World Aquaculture ‘99 to discuss the potential for drug approval of florfenicol in Chile and worldwide.

The U.S. Fish and Wildlife Service (FWS) has developed a draft protocol that the sponsor reviewed for a new, limited INAD to be initiated in early 2000. FWS developed a list of facilities that have a proven track record of doing good efficacy studies that was given to Schering-Plough Animal Health for their review and acceptance. The sponsor expects to tightly oversee the development of florfenicol for aquaculture use in the United States.

A meeting was held on July 20-21, 1999 with Schering-Plough Animal Health, FWS, the Upper Midwest Environmental Sciences Center (UMESC), and the National NADA Coordinator to discuss the details in initiating the efficacy studies through a FWS-INAD and in conducting the residue chemistry studies.

Discussions on the development of florfenicol were held with CVM at the FWS-INAD Coordination meeting in Bozeman, Montana on August 4-5, 1999.

Schering-Plough Animal Health submitted a data package to CVM containing product chemistry, residue chemistry, target animal safety, and efficacy for florfenicol to control furunculosis in salmonids on September 30, 1999. The environmental assessment will follow.

Schering-Plough Animal Health reviewed the quality assurance and Good Laboratory Practices procedures at UMESC on October 5-6, 1999.

Schering-Plough Animal Health recently gained an approval in the United Kingdom for the use of florfenicol to control furunculosis in Atlantic salmon in marine netpens.

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 2000 for control or prevention of mortalities associated with fungal infections on salmonids and for control or prevention of mortalities associated with fungal infections on all fish.

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 a 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 prevention of mortalities associated with fungal infections on all fish eggs in the United States if data from Canada are acceptable, in 2000 for control or prevention of 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.

In 1999, UMESC was 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.

The sponsor (Eka Chemicals Inc.) has completed the negotiations with Syndel International Inc. to do the marketing of hydrogen peroxide (Perox-Aid™) for fisheries use in Canada.

The sponsor submitted the product chemistry technical section for hydrogen peroxide on July 12, 1999.

A series of meetings were held in July, August, October, and November 1999 at UMESC with the National NADA Coordinator to discuss the development of the remaining data requirements to complete the submission of all the technical sections needed for approval of hydrogen peroxide. Supporting efficacy data will be collected in 2000 at public and private hatcheries under the Eka Chemicals Inc. INAD.

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.

The National NADA Coordinator is discussing the development of data to add tilapia to the OTC label with SNARC and the Northeastern region of the National Research Support Program Number Seven (NRSP-7).

Potassium Permanganate (external microbicide)--Status: Sponsor recently submitted an INAD/NADA letter of intent, product chemistry, and a request for categorical exclusion for environmental safety; major effort for NADA approval under IAFWA Project. BOTTOM LINE: All submissions should be completed in 2001 for control or prevention of 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.

The sponsor of potassium permanganate submitted to CVM the product chemistry technical section on December 8, 1998 and environmental safety technical section on February 23, 1998. CVM has requested more information on the environmental safety of potassium permanganate.

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.

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 a unanimous vote of the IAFWA Project stakeholders.

Sea Lice Control (various drugs and pesticides)--Status: Various drugs and pesticides (azamethiphos or Salmosan™, cypermethrin or Excis™) are being pursued by the United States and Canada and are at various stages of registration and approval.

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 sponsor of AQUI-S™ completed a Cooperative Research and Development Agreement with the U.S. Geological Survey on July 7, 1999 to provide funding for a residue chemistry study.

The National NADA Coordinator met with representatives of the company that developed AQUI-S™ in Sydney, Australia during World Aquaculture ‘99 and in Nelson, New Zealand on May 11, 1999 to discuss the strategies for the development of the drug for the United States market and worldwide.

The sponsor has recent information from a National Toxicology Program (NTP) study at the University of Arizona that the major ingredient in AQUI-S™ is not a carcinogen. However, NTP continued to pursue studies on the safety of the main ingredient so that CVM was not able to grant a compassionate INAD until this issue is resolved.

The plan by FWS to have a compassionate INAD exemption in place on AQUI-S™ by the end of July 1999 has been put on hold until agreement can be obtained from CVM that the mammalian toxicology studies show no potential for being a carcinogen.

CVM is planning a meeting for November 18, 1999 to discuss the mammalian safety of the main ingredient in AQUI-S™ with the sponsor and the National NADA Coordinator.

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-22 as an anesthetic with a 21-day withdrawal time.

Oil of Cloves--Status: Oil of cloves (eugenol) is considered Generally Recognized as Safe 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.

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 on efficacy and 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.

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

With the help of the National NADA Coordinator, the sponsor, Stoller Fisheries, submitted the product chemistry technical section for CCP to CVM on September 21, 1999.

17 -estradiol (estrogen). Status: Sponsor and interested parties working on the development of an INAD; early development stage.

The National NADA Coordinator began in June 1999 to work with the potential INAD sponsor for the development of estrogen to gender manipulate American eels to all female populations. A draft letter was written by the National NADA Coordinator for submission to CVM by the sponsor. Draft protocols were reviewed and procedures delineated for gaining an approval.

Human Chorionic Gonadotropin (hCG)--Status: September 1999 NADA approval in the United States.

Chorulon® (human chorionic gonadotropin, hCG) 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 approval since 1986 when formalin was first approved for fish and because it was approved for all fish.

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

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; environmental assessment reviewed, revised, and resubmitted. BOTTOM LINE: All technical section submissions should be into CVM by the end of 2000.

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, Montana on August 4-5, 1999. Discussions centered particularly on the status of chloramine-T, AQUI-S™, and florfenicol and the general progress of the IAFWA Project.

The Drug Approval Oversight Subcommittee (DAOS) formed to aid the federal-state aquaculture drug approval partnership program (IAFWA Project) to achieve its goal of obtaining drug approvals for U.S. public aquaculture held a meeting in Killington, Vermont on September 16-17, 1999 to discuss the progress being made on the IAFWA Project drugs and to support the extension of the IAFWA Project until at least 2002.

Status of the crop grouping research: Ohio State University is completing work on the model waterborne drug, benzocaine. Classical compartmental pharmacokinetic models are being developed in five phylogenetically diverse species. Physiologically based pharmacokinetic (PBPK) 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.

A website was established for the National NADA Coordinator on April 12, 1999 at http://ag.ansc.purdue.edu/aquanic/jsa/Aquadrugs/index.htm. Major items were added to the website in August 1999.

In May 1999, Dr. Joan Gotthardt replaced Dr. Tom Bell at CVM for reviewing aquaculture drug submissions.

The National NADA Coordinator attended a meeting at the American Farm Bureau Association on June 29, 1999 to bring stakeholders interested in forming a coalition to institute various provisions in the MUMS document. The intent was to reach an agreement on the priority provisions, develop specific strategies for implementing priority items, identify collective and individual actions, and develop an appropriate communication network.

The National NADA Coordinator attended the American Fisheries Society annual meeting in Charlotte, North Carolina on August 28-31, 1999 to finalize a manual on the administrative and technical procedures for the use of rotenone in public and private waters. Rotenone is used by resource agencies and private aquaculture facilities to control undesirable fish.

In its meeting on September 8, 1999, the MUMS Coalition asked CVM a series of questions and supplied a list of provisions it supports in general. CVM was very supportive of all the provisions and answered all the questions raised by the MUMS Coalition.

On September 9, 1999 the MUMS Coalition met to discuss the development of legislation to be called the Minor Animal Species Health and Welfare Act of 2000 and the strategies for getting the legislation through Congress.

The National NADA Coordinator organized, chaired, and gave 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.

On September 27, 1999, CVM hired a second technical reviewer for efficacy and target animal safety data submissions for aquaculture drugs.

The U.S. Food and Drug Administration (FDA) has requested comment on a draft provision in Compliance Policy Guide (CPG) entitled "Use of medicated feeds for minor species." The purpose of the draft CPG would be to provide guidance to FDA’s field offices concerning the Agency’s exercise of regulatory discretion with regard to the extra-label use of medicated feeds for minor species. Comments are due November 23, 1999.

Special Reports

Schnick, R.A. 1999. Dates for all submissions for label claims [Caveat: Needed are adequate efficacy data, timely sponsor submissions, and full funding]. Submitted to the DAOS Chair, Mike Gibson, Hot Springs, Arkansas. April 9, 1999. 1 pp

Schnick, R.A. 1999. National Coordinator for Aquaculture New Animal Drug Applications (NADAs). Fourth annual report of activities, May 15, 1998 to May 14, 1999. Submitted to Ted Batterson, North Central Regional Aquaculture Center, East Lansing, Michigan. April 23, 1999. 15 pp.

Schnick, R.A. 1999. Annual report for Contract #97-106. Submitted to the Center for Tropical and Subtropical Aquaculture, Waimanalo, Hawaii. April 23, 1999. 8 pp.

Schnick, R.A. 1999. The bottom line (March 1999). Submitted to the DAOS Chair, Mike Gibson, Hot Springs, Arkansas. April 23, 1999. 2 pp.

Gingerich, W.H., G.R. Stehly, J.A. Bernardy, V.K. Dawson, M.P. Gaikowski, J.R. Meinertz, R.A. Schnick, and B.R. Griffin. 1999. Approval of drugs for public fish production, a federal aid report of progress for IAFWA Project years one through five. Biological Resources Division, USGS, Upper Midwest Environmental Sciences Center, La Crosse, Wisconsin. May 1999. 32 pp.

Schnick, R.A. 1999. Proposed Project Area III: National Coordinator for Aquaculture New Animal Drug Applications - Year Five. Submitted to the Center for Tropical and Subtropical Aquaculture, Waimanalo, Hawaii. June 2, 1999 (revised October 6, 1999). 26 pp.

Schnick, R.A. 1999. 1999 annual report of the AFS Task Force on Fishery Chemicals. Submitted to the Governing Board and AFS President, Bob Carline, Bethesda, Maryland. June 23, 1999. 6 pp.

Schnick, R.A. 1999. Progress toward technical section submissions for IAFWA Project drug approvals (July 1994 to 1999). Submitted to Bob Miles, IAFWA, Washington, DC. July 7, 1999. 8 pp.

Schnick, R.A. 1999. Quarterly report for Contract #98-113 (April 1, 1999 to June 30, 1999). Submitted to the Center for Tropical and Subtropical Aquaculture, Waimanalo, Hawaii. July 7, 1999. 1 pp.

Schnick, R.A. 1999. National issue: Need for drug approvals for the whole aquaculture industry. Submitted to Gale Peek, National Aquaculture Workshop, sponsored by National Oceanic and Atmospheric Administration, August 11-13, 1999 in Silver Spring, Maryland. July 16, 1999. 4 pp.

Schnick, R.A. 1999. Status of IAFWA Project drugs in August 1999. Submitted to Mike Gibson, Chair, IAFWA Drug Approval Oversight Subcommittee, Hot Springs, Arkansas. August 10, 1999. 2 pp.

Schnick, R.A. 1999. Status of the aquaculture drug approval process in August 1999. Submitted to Website. August 19, 1999. 5 pp.

Schnick, R.A. 1999. List of drugs, sponsors, INAD/NADA numbers, and dates (August 24, 1999). Submitted to Website. August 24, 1999. 3 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 annual report of progress [performance period: July 1, 1998 to June 30, 1999]. Biological Resources Division, USGS, Upper Midwest Environmental Sciences Center, La Crosse, Wisconsin. August 29, 1999. 45 pp.

Schnick, R.A. 1999. Minutes to the MUMS Meeting with CVM, September 8, 1999. Submitted to Randy MacMillan, Chair of the MUMS Coalition, Buhl, Idaho, for transmission to the attendees and CVM for comment. September 13, 1999. 6 pp.

Schnick, R.A. 1999. MUMS provisions summary as of September 9, 1999. Submitted to Mike Gibson, Chair, IAFWA Drug Approval Oversight Subcommittee, Hot Springs, Arkansas. September 15, 1999. 2 pp.

Schnick, R.A. 1999. Antimicrobial resistance issues and aquaculture drugs. Submitted to Randy MacMillan, Chair of the white paper on antimicrobial resistance, Buhl, Idaho. September 16, 1999. 10 pp.

Schnick, R.A. 1999. Quarterly report for Contract #98-113 (July 1, 1999 to September 30, 1999). Submitted to the Center for Tropical and Subtropical Aquaculture, Waimanalo, Hawaii. October 7, 1999. 1 pp.

Schnick, R.A. 1999. National Aquaculture INAD/NADA Coordinator. Progress report for the period September 1, 1992 to August 31, 1999. Submitted to North Central Regional Aquaculture Center, East Lansing, Michigan. October 29, 1999. 24 pp.

Schnick, R.A. 1999. Overview of NADA Coordinator activities. USFWS - INAD Coordination Workshop, Bozeman, Montana, August 4-5, 1999.

Schnick, R.A. 1999. Aquaculture NADA Coordinator update. Meeting of the JSA Working Group on Quality Assurance in Aquaculture Production, Washington, DC, September 9, 1999.