1National Coordinator for Aquaculture New Animal Drug Applications, Michigan State University, 3033 Edgewater Lane, La Crosse, WIS 54603-1088, USA ² CEFAS Fish Diseases Laboratory, The Nothe, Barrack Road, Weymouth, Dorset, DT4 SUB, United Kingdom ³Salmon Health, 20th Floor, 45 O’Connor, Ottawa, Ontario K1P 1A4, Canada ⁴STERMOR-Aquaculture Health Consulting, Keerfahler, 56760 Penestin, France ⁵Animal Health Products & OTC Products, Products Development Division, Tanabe Seiyaku Co. Ltd., 2-10 Dosho-matchi 3-Chome, Chuo-ku, Osaka, Japan ⁶Fish Health Section, Southeast Asian Fisheries Development Center, 5021 Tigbauan, Iloilo, Philippines ⁷Coordinator, Working Group on Aquaculture Drug Registration, 329 Allens Rivulet Road, Allens Rivulet, Tasmania, Australia 7150

It is time for world-wide co-operation to gain approvals of drugs and licensure of biologics for aquaculture. At the Workshop on International Harmonization for Aquaculture Drugs and Biologics held in February 1997, a start was made toward that goal. One of the five committees set up to help this process was the one to identify priority drugs and vaccines. A Workshop and Round table were held on this topic at the EAFP Eighth International Conference on Diseases of Fish and Shellfish, Edinburgh, Scotland, September 14-19, 1997. The Workshop, "Models of Partnership for Registration of Drugs and Vaccines", and the Round table, "Progress with Registration of Drugs and Vaccines for Aquaculture", identified (1) what aquaculture drugs are approved and what vaccines are licensed in each country or continent; (2) the top priority drug and vaccine needs for approval and licensure in each country or continent; (3) certain guidelines and regulations for approval or licensure; (4) the researchers and the institutions that are performing the needed research or that have the capability and expertise to perform this research; and (5) existing partnerships throughout the world that have worked together to gain legal products for aquaculture.

This Workshop and Round table did not completely identify the standards and guidelines required in each country but a determination was made on which ones are the most important to harmonize. Pharmaceutical, chemical, and vaccine companies provided great insight into this area. The Workshop and Round table helped the communications process by setting up mechanisms to keep all countries informed of the progress in this area. This communication network then can help to educate persons about the processes and to advocate for co-operation.

Aquaculture Drug Approvals in Each Country or Continent

The drug approval process varies in each country and continent. A brief summary follows for each continent along with tables that list the approved drugs and licensed vaccines. These tables do not indicate the diseases and species for which they are indicated.

AFRICA--Some of the 50 countries in Africa have aqua-culture industries but most countries do not have any regulations regarding the use of drugs or vaccines.

ASIA--The control of aquaculture drugs in the region varies among countries from no regulation to restrictive regulations. In countries where regulation is in effect, the process for approval of drug for food animals including those used in aquaculture is complicated, time consuming, and expensive. Most often, the standards and requirements used for human and veterinary drugs set by the Ministries of Health and Agriculture are adopted and used. Data needed includes information on efficacy against target organisms, toxicity to non-target organisms, residues in food animals, human safety, and environmental safety.

In Japan, drugs for domestic animals including those for fisheries are controlled by the "Pharmaceutical Affairs Law". Guidelines are available for the quality, safety, and efficacy criteria for the data. Data are submitted to the Central Pharmaceutical Affairs Council for review and then to the Subcommittee on Drugs for Fisheries, Subcommittee on Residues, Special Committee on Veterinary Medicinal Products, and finally to the Executive Committee. If the application is successfully reviewed by these committees, it is finally approved by the Ministry of Agriculture, Forestry and Fisheries. The approval of drugs is regulated under Good Manufacturing Practices (1991), Good Laboratory Practices (1987), Good Clinical Practices (1997), and Good Post-Market Surveillance Practices (1997). Japan estimates that its annual losses from diseases are $125 million with 70% of these losses from saltwater fish. The most common infections occur on yellowtails. Generally, it takes one year from application to approval. See Table 1 for the drugs approved for use in Japan.

In the Philippines, evaluation and control of veterinary drugs and related products are enforced by the Department of Agriculture through the Bureau of Animal Industry and the Department of Health through the Bureau of Food and Drugs. The Fertilizer and Pesticide Authority of the Department of Agriculture is responsible for registration and classification of pesticides, fertilizers, soil conditioners, and microbial inoculants. In Thailand, drugs are controlled by the Department of Fisheries. In China, imported drugs are approved for use by the Animal Drugs Examination Commission, Ministry of Agriculture.

AUSTRALIA--Applications can be submitted to the National Registration Authority to seek exemptions from the need for registration for a number of chemicals used by the aquaculture industry. A formal exemption means that the aquaculture industry can legally use a particular drug or chemical for certain specified uses without the need to get it formally registered or permitted. The following chemicals have been granted exemptions from the need for registration as a result of this process: calcium carbonate, calcium hydroxide, calcium oxide, calcium/magnesium carbonate, calcium sulfate, zeolite, aluminum sulfate, ferric chloride, inorganic fertilizers, and organic fertilizers.

A Minor Use Permit (MUP) is a short term permit given for approximately 12 months on the basis that not enough information or resources are available to sustain a full application for registration and the quantities used are relatively small. Several drugs fall in this category. After enough data are generated, the drug is approved (see Table 1 for approvals).

EUROPE--Because the definition of a Veterinary Medicinal Product (VMP) is wide and in practice covers all the health and hygiene products that are to be used on animals, most of the very old and well known compounds that have been used over decades in aquaculture had to be reviewed, at least for the Maximum Residue Limit (MRL) assessment (Council Regulation EEC/2377/90). Old and new substances have to be defended by a sponsor who should complete the required studies, and submit a dossier to the European Commission (EC). All the existing substances which had not been given an MRL were supposed to be banned from animal usage after January 1, 1998. In fact, the EC has extended that deadline until December 1999 for those substances for which dossiers were submitted before January 1, 1996 (Council Regulation, March 1997 NE 434/97).

The result of the MRL assessment is the classification of substances into four annexes, Annex 1 when the MRL is fixed; Annex II when the substance does not need to be subjected to an MRL (e. g., VMPs only intended of use on pets or considered as safe in general); Annex III when a temporarily MRL is fixed; and Annex IV, when no MRL can be fixed. This latter classification results in a complete ban of the substance from the animal health usage.

The corresponding world-wide regulation relates to the Codex Alimentarius (WHO and FAO jurisdiction). Very similar files to those prepared for the European evaluation have to be submitted. Ultimately, when a food animal substance is finally approved by the Codex Alimentarius, it should provide a world-wide guarantee of its innocuity and safety.

The MRL status is also the first step to Marketing Authorizations (MAs) applicable to VMPs in each Member State. In fact, at present, no new MA application will be evaluated by the national regulatory authorities prior to the publication of the corresponding MRL. Furthermore, the question is now discussed to allow field clinical trials on a future VMP only after an MRL is published on the active ingredient. The MA authorization is given for a finished VMP, by a national regulatory authority after the review of a file that contains an additional package of information on the product, on target animal safety tests, the Environmental Risk Assessment (ERA), and the efficacy of the product (Council Directives 81/851, 81/852, 92/18). It also states the withdrawal times for the product.

Over the past years, there has been now an increasing concern on the innocuity of VMPs towards the environment. A note for guidance (EMEA/CVMP/055/96-Final) was recently issued to define the specific requirements for VMPs. This will result in a significant additional cost to the data package of all VMPs. This ERA now represents the first priority for drug registration issues in Europe, since good progress has been made on MRLs.

Fish oral drugs, external antibacterial and antiparasitic compounds, can be considered as full VMPs. In accordance with the CVMP guideline (EMEA/CVMP/153a/97), Salmonidae are being considered as a major animal food producing species which implies that a full MRL dossier should be submitted.

The MRL regulations created a big concern over the past years in the aquaculture industry, particularly when some widely used drugs were banned such as the nitrofurans and chloramphenicol and placed in Annex IV. Meetings and workshops were organized with various regulatory authorities, national and European, producers, scientists, veterinarians, and the pharmaceutical industry to discuss the future availability and non-availability of drugs for the aquaculture industry.

Today, the fish MRL situation does not look as critical as it once was, although several compounds have not received their final MRL. The CVMP has recently proposed a pragmatic approach for the establishment of fish MRLs in Europe (EMEA/CVMP/153b/97-Final) that was just approved (September 11, 1997). No additional metabolism studies should be required on fish if they have been already carried out on major food animal species. Only cold residue depletion studies would then have to completed. Furthermore, if an MRL is given on Salmonidae, it should also apply for the other fish species raised in Europe. When this proposal enters into application, some of the molecules will be given an MRL on fish very soon (see Table 1 for approvals).

NORTH AMERICA (UNITED STATES AND CANADA)--The U.S. Food and Drug Administration’s Center for Veterinary Medicine (CVM) regulates the manufacture, distribution, and use of animal drugs. CVM is responsible for ensuring that drugs used in food-producing animals are safe and effective and that food products derived from treated animals are free from potentially harmful residues. CVM establishes tolerances and withdrawal times as needed for all drugs approved for use in food-producing animals. CVM reviews New Animal Drug Application data generated through an Investigational New Animal Drug (INAD) exemption. See Table 1 for approved drugs in the United States. CVM allows other than pharmaceutical firms to be sponsors of INADs under a compassionate policy.

The U.S. drug approval process is analogous to that in Canada, requiring approval of manufacturing, human food and target species safety and efficacy sections. There are specific differences between the requirements; in particular, the United States has a specific requirement for an environmental assessment and CVM will accept product data packages in phases. The Canadian Bureau of Veterinary Drugs requires that a submission be complete before it can be reviewed and has recently introduced cost recovery fees.

The CVM understands the need to work with the aquaculture industry to resolve the drug availability situation. Over the last few years, CVM has developed several programs that clarified data requirements and created flexibility in the approval process. One of the major programs initiated by CVM was a formal low regulatory priority (LRP) status for certain drugs. Currently, 18 unapproved drugs have been designated as low regulatory priority for enforcement purposes. These drugs include acetic acid, calcium chloride, calcium oxide, carbon dioxide gas, Fuller’s earth, garlic, hydrogen peroxide, ice, magnesium sulfate, onion, papain, potassium chloride, providone iodine compounds, sodium bicarbonate, sodium chloride, sodium sulfite, urea and tannic acid. The CVM considers the available information on their safety to humans and the environment, when the drugs are used under defined conditions, to be an adequate basis for deferring any regulatory action against their use. CVM views LRP drug status as a tenuous situation because they are still unapproved drugs. As a result, CVM advocates that LRP drugs go through the approval process to become legal products.

*Currently not being distributed **New Zealand ***Limited registration

ASIA--Several vaccines are used in Asia (excluding Japan) but only three are commercially available--Vibrio parahaemolyticus vaccine (Vibrogen-S) for shrimp, Penaeid multivalent bacterin (P.M.B. vaccine) for shrimp, and Vibrio anguillarum bacterin for fish. Japan has three licensed vaccines. See Table 2 for details.

AUSTRALIA--There is only one licensed vaccine in Australia and that is through the Department of Primary Industry and Fisheries in Tasmania for Atlantic salmon and rainbow trout.

EUROPE--A critical situation has been created on fish vaccine availability in Europe. New vaccines have to meet the requirements which are defined in the Council Directive 92/18 (1992). In addition, all vaccine applications which were previously accepted in each Member State have to be reviewed in the scope of this new 92/18 format. Meeting the requirement of quality standards for vaccine manufacturing (Good Manufacturing Practices) has become one major priority of vaccine manufacturers.

Most fish vaccines are available in UK for salmon through a complete licence (MA) or an Animal Test Certificate (ATC), and meeting the major needs of the farming industry. For the other farmed fish in Europe, the availability in vaccines remains very low. These markets are much less attractive to vaccine manufacturers. New valences and new application methods are to be developed. To compensate this shortage of licensed fish vaccines in some EU countries, autogenous vaccines have been widely used.

NORTH AMERICA (UNITED STATES)--The Animal and Plant Inspection Service (APHIS) of the U.S. Department of Agriculture regulates all veterinary biologics produced in, shipped into, or exported from the United States.

ASIA--Many drugs need to be approved in the Asian countries other than Japan. Japan needs just a few drugs to complete their medicine chest (see Table 3 for details).

AUSTRALIA--Minor Use Permits have been issued for seven antibacterials, four antiparasitics, four antifungals, two anaesthetics, three spawning aids, one immunostimulant, and one piscicide (not listed in Table 3 because it is not a drug). See Table 3 for details for drug needs.

NORTH AMERICA (CANADA)--The status of approved therapeutants in Canada was very limited prior to the implementation of the Salmon Health project. Industry needs were assessed through a national survey that identified five national priorities that are listed in Table 3. Working with manufacturers and regulators, several milestones were met in a relatively brief period of time. The list of four licensed compounds was expanded to seven with temporary registration for an additional three compounds which were under investigation (Table 3). Presently data is being reviewed or developed, in co-operation with the sponsors, for new drug submissions for remaining priorities

NORTH AMERICA (UNITED STATES)--Major progress was made under various partnerships and compassionate Investigational New Animal Drug (INAD) exemptions toward gaining at least 20 new or amended New Animal Drug Applications (NADA) within at least the next three years. In addition, there are drugs that are of interest that may gain approvals beyond three years. See Table 3 for details on both categories.

Priority Vaccine Needs in Each Country

Researchers, Facilities, and Partnerships for Drug Approvals

ASIA--There are several groups involved in drug research and approval process for aquaculture species. In many countries in the region, the Ministry of Health and the Ministry of Agriculture is most often the approving authorities. Research institutes and universities conduct research on toxicity studies, drug screening, efficacy trials, and human safety trials. The country and the institution(s) involved are as follows:

1. Bangladesh--Ministry of Livestock and Fisheries

2. Cambodia--Department of Fisheries

3. India--Ministry of Agriculture; Indian Council of Agricultural Research, Central Institute of Freshwater Aquaculture; Central Institute of Brackish water Aquaculture; Central Marine Fisheries Research Institute; College of Fisheries, University of Agricultural Sciences; Cochin University of Science and Technology; University of Madras; and Andhra University

4. Indonesia--Drugs and Food Control, Ministry of Health; Veterinary Drugs Control Division, Directorate of Animal Health, Ministry of Agriculture; Department of Fisheries, Ministry of Agriculture; Research Institute for Freshwater Fisheries

5. Korea--Animal Health Division, Ministry of Agriculture, Forestry and Fisheries

6. Malaysia--Ministry of Health; Ministry of Agriculture; Veterinary Research Institute; Fisheries Research Institute, Department of Fisheries; University Putra Malaysia (Faculty of Applied Science & Technology, Faculty of Veterinary Medicine and Animal Science); Universiti Sains Malaysia (Faculty of Zoology)

7. People's Republic of China--Surveillance Institute of Food Hygiene, Ministry of Public Health; Bureau of Fisheries, Ministry of Agriculture; Institute of Hydrobiology, Academia Sinica

8. Philippines--Bureau of Food and Animal Drugs, Department of Health; Bureau of Animal Industry, Department of Agriculture; Fertiliser and Pesticide Authority, Department of Agriculture; Southeast Asian Fisheries Development Center, Aquaculture Department (SEAFDEC/AQD); Bureau of Fisheries and Aquatic Resources (BFAR); University of the Philippines (College of Fisheries, Institute of Biology, Institute of Marine Science, College of Veterinary Medicine); Central Luzon State University (College of Fisheries); Mindanao State University (College of Fisheries)

9. Singapore--Ministry of Health; Primary Production Department, Ministry of National Development; Veterinary Public Health Laboratory; National University of Singapore

10. Sri Lanka--Veterinary Drug Control Authority, Ministry of Livestock and Animal Production; University of Peradeniya (Fac. of Veterinary Medicine)

11. Taiwan--Feed and Drug Division, Animal Industry Department, Council of Agriculture; Taiwan Fisheries Research Institute; National Taiwan University (Faculty of Zoology)

12. Thailand--Ministry of Public Health; Ministry of Agriculture and Cooperatives; Department of Fisheries; Aquatic Animal Health Research Institute (AAHRI); National Institute of Coastal Aquaculture (NICA); Feed Quality Control and Development Division; Kasetsart University (Faculty of Fisheries, Fac. of Veterinary Medicine); Chulalongkorn University (Fac. Veterinary Medicine, Fac. of Marine Science); Mahidol Medical University

13. Vietnam--Invention and Discovery Department, Ministry of Health; National Evaluation Council; Research Institute for Aquaculture; Nhatrang Fisheries University; Thuduc Agriculture University; Cantho Agriculture University

EUROPE--European funding is available through grants as (1) the SME-SMI (Craft) which associate private European SME or SMI and scientific teams. The SME-SMI are fish producers, fish vaccine or drug manufacturers, fish feed producers, and (2) the other European grants, AIR, FAR, who are mainly associating different scientific teams, but can also include a private partner.

The goals of these partnerships are not directly the development and registration of drugs and vaccines, but they certainly contribute to put the pharmaceutical firm on the right track if one firm is included. The fact that many of the studies conducted under these European grants would not meet the quality standards that are required for a registration (GLP, GCP) may limit their use in a registration file.

In France, such collaborations are often done under public funds, national or local, and private funds (farmers, fish feed manufacturers, and/or the pharmaceutical industry). For example, the pharmacokinetics of oxolinic acid on turbot was studied under such an arrangement.

In order to get a fruitful collaboration, each of the associated partners must understand that the first aim of these funded projects is to get a product registered. This means that a fish vaccine or drug firm should be associated to the project. This partner will co-ordinate the whole project as it has a direct interest in it, carry out the registration steps onwards, and deal with regulatory authorities. To get a clear interest of the pharmaceutical industry in these partnerships, it is then crucial that it has the ownership of the results, the rights to use them for registration and commercial purposes.

The scientific community has a direct interest on these projects only if they can publish in agreement with the sponsors, which may not be the case. Furthermore, this work has to be carried out under GLP or GCP, which fact results in a significant study cost increase, and implies that the studies could only be carried out in fully GLP certified contract research facilities. At present, only a limited number of these facilities exist for fish work in Europe, mainly in Norway and in UK.

NORTH AMERICA (CANADA)--Salmon Health was developed to assist pharmaceutical companies to compile data submission dossiers to meet the requirements of regulatory and licensing agencies. Salmon Health is a self-funding program of the Canadian Aquaculture Industry Alliance working to ensure that aquaculturists have access to safe and effective fish health management tools in an appropriate regulatory environment. The goal of Salmon Health is to bring the needs of producers to manufacturers and regulators, bringing the latter two together in way that meets the needs of all three. Funding for the Salmon Health project comes from direct contributions from supporters who share the same objectives as Salmon Health. These supporters come from the aquaculture sector, manufacturing sectors (pharmaceutical and feed) and government agencies. Funding from all of the supporters is channelled into the following efforts: (1) determining therapeutant priorities, (2) identifying candidate compounds that meet these priorities, (3) documenting therapeutant market potential, (4) collating available information from a world wide body of scientific knowledge, and (5) working with pharmaceutical companies to draft plans for new drug submissions.

While development of safe and efficacious therapeutants remains the primary goal, increasing emphasis is placed on ensuring that the regulatory framework is in place to meet the prime directive. One issue that relates to this is the international harmonisation of drug submission requirements between countries for both therapeutants and vaccines and vaccine quality assurance requirements. In many instances these requirements are very similar, yet different enough that manufacturers have to duplicate efforts which further detracts from financial incentives to bring products to the market. Where residues are concerned, equivalence of maximum residue levels (MRL) facilitates movement of products across borders by ensuring similar therapeutant standards are developed and used. A lack of appropriate and accurate fish pharmacokinetic models exacerbates issues relating to setting minimum MRLs. Concurrent with the harmonisation of MRLs is the development of HACCP based processing and production protocols which are becoming internationally recognised food processing safety standards.

The Salmon Health model has been successful, largely due to the partnerships developed between industry, manufacturers and government agencies. In fact Salmon Health receives support from producer associations that represent 90% of North American farmed salmon production by volume, value and number of species. In the span of approximately five years the number of approved therapeutants for salmon farmers in Canada has increased from three to six, with temporary registration of three additional compounds. In the first three years of the program, many of the objectives were met in providing therapeutants to meet priorities set by the industry. As the program evolves, new priorities are being established with increasing focus on vaccine development and therapeutant regulatory and fish health management issues.

NORTH AMERICA (UNITED STATES)--Public and private aquaculture organisations are forming coalitions and appointing regional INAD co-ordinators. These new coalitions are facilitating the approval process by consolidating and disclosing compassionate INADs, developing new compassionate INADs, helping to define food/non-food fish, life stages, and crop grouping for drug-specific applications, seeking Low Regulatory Priority status for numerous drugs and chemicals, and exploring strategies for funding drug approval research.

UMSC. The Upper Mississippi Science Center (UMSC), la Crosse, Wisconsin is one of two federal laboratories involved in the IAFWA Project. UMSC has the combination of uniquely designed laboratory facilities for specialised fishery drug and chemical research, a balanced blend of highly trained professional staff, state-of-the-art instrumentation, laboratory capabilities to test a diverse range of aquatic organisms, an established and recognised quality assurance program, and a proven record to develop approval and registration information for aquaculture drugs and fishery pesticides.

BPA/FWS Erythromycin Registration Project. In 1989, the Bonneville Power Administration (BPA) provided funding for the first comprehensive, publicly funded drug registration project to conduct the necessary research and assemble drug registration packages for use of erythromycin as a feed additive and injectable treatment in salmonid fish culture. In 1992, at the request of the Pacific Northwest Fish Health Protection Committee, this drug registration effort was expanded so that field trials with erythromycin could be conducted at salmonid culture facilities throughout the Pacific Northwest. The University of Idaho conducted all of the laboratory studies needed for approval and has searched for a pharmaceutical sponsor.

U.S Fish and Wildlife Service--The U.S. Fish and Wildlife Service (FWS) established a national Investigational New Animal Drug (INAD) office in Bozeman, MT in 1994 that is co-ordinating all FWS-INAD related activities (e.g., protocol development, data collection and analysis). These activities involve 12 individual INAD exemptions, 90 facilities, and approximately 300 INAD units.

Western Regional INAD Project--In November 1993, the Western Regional INAD Project was established as a government-private sector partnership to sponsor and manage clinical field trials for three therapeutants (oxytetracycline, chloramine-T, and formalin) at 218 facilities operated by six state conservation agencies, three tribal groups, and 24 private fish producers in Alaska, California, Idaho, Montana, Oregon and Washington. The project terminates on December 31, 1997 and there is hope that these INADs will be extended by other sponsors.

States--Twenty states have 61 individual INAD exemptions for eight therapeutants, one anaesthetic, and three spawning aids. Many states have offered to consolidate their INADs with other states, and in some cases, with the private sector.

Veterinarians--Veterinarians have increased their involvement in aquaculture and have teamed up with fish health professionals working for state and Federal agencies. This process has been aided by an Aquaculture and Seafood Advisory Committee established by the American Veterinary Medical Association (AVMA) and by discussions with the American Fisheries Society’s Fish Health Section.

CVM. The Center for Veterinary Medicine (CVM) understands the need to work with the aquaculture industry to resolve the drug availability situation. Over the last few years, CVM has developed several programs that clarified data requirements and created flexibility in the approval process. The major programs are formal compassionate investigational new animal drug (INAD) exemptions, formal low regulatory status for certain drugs, flexible labelling, innovative approaches to efficacy and target animal safety studies, encouragement of crop grouping research, and encouragement of disclosure and consolidation of INADs.

The Joint Canadian-United States Workshop on Jurisdiction of Sea Lice Treatment and Control established a joint Canada and United States Aquaculture Working Group to institute international harmonisation activities. This means that data could be shared and certain requirements for all drugs could be harmonised so that there could be joint submissions leading to approvals being granted simultaneously in both countries.

The International Harmonization Workshop for Aquaculture Drugs/Biologics, held in Seattle, Washington on February 24, 1997, created an educational forum to exchange information and identified issues between public and private sectors and international organisations with the goal of initiating follow-up strategies to advance harmonisation of drug maximum residue levels, aquaculture drug approval standards, and biological licensure.

Two major animal drug laws and follow up regulations were recently implemented in the United States that have an impact on the approval of aquaculture drugs: The Animal Drug Availability Act of 1996 and the recently finalised regulations for the Animal Medicinal Drug Use Clarification Act of 1994. The former codifies the efforts by CVM to facilitate minor use drug approvals and the latter clarifies extra-label use in aquaculture.

ROUND TABLE DISCUSSION

Another area of discussion centred on the development of advocacy groups, communication mechanisms, and educational programs. The topics included the need to (1) encourage producers to buy only licensed products, (2) encourage groups to develop and use quality assurance programs, (3) develop integrated fish health management programs, (4) work with feed manufacturers on aquaculture feed issues, and (5) consider post-approval monitoring for environmental effects, presence of residues, and disease resistance. The group agreed that communication mechanisms need to be in place to keep all players informed on drug approval and vaccine license issues. They agreed that the information presented at this workshop needed to be available in a publication and presented at the 1998 International Harmonisation Workshop on Aquaculture Drugs and Biologics to be held in Las Vegas, Nevada (USA) in February 1998. Mail groups need to be set up via e-mail to provide for a forum for information exchange and advocacy. Web sites need to be set up to help in the transfer of information.

CONCLUSIONS