The Aquatic Animal Drug Approval Partnership (AADAP) program works with the Association of Fish and Wildlife Agencies’ Drug Approval Working Group (AFWA/DAWG) to obtain U.S. Food and Drug Administration (FDA) approval of drugs for use in aquaculture and fisheries management programs throughout the U.S. Although a number of new aquaculture drugs have been added to the collective fisheries “medicine chest” in the past 10-15 years, the number of FDA-approved drugs for aquatic animals is still very limited. As certain priority drugs have been approved for specific uses, the collaborative research efforts of AADAP, the DAWG, and associated entities have shifted to reflect new priorities, including generating data to support new approvals, identifying emerging disease issues with limited or non-existent treatment options, and seeking approval for non-therapeutic drugs (e.g., for use in skeletal marking, spawning, or sedation). As such, AADAP and the DAWG proposed to assess the current and future unmet drug needs of hatchery personnel, fish health professionals, and fisheries management biologists. A survey was constructed to canvass the aquaculture community across the country. The survey was meant to determine fish drug needs related to: 1) freshwater diseases/pathogens of concern to fisheries professionals, 2) non-therapeutic freshwater purposes (spawning, marking, sedation, sex reversal, etc.), and 3) culture and/or management of marine fish species in seawater environments. The intention was to use the survey results to: 1) better incorporate national drug needs within the DAWG priorities and direction of effort, 2) engage with current drug sponsors or find new sponsors as needed, and 3) prioritize the generation of data to support new approvals or new expanded claims for drugs that are currently approved.
The survey was first distributed to state agencies via the DAWG in the summer of 2017, then to all managers/project leaders at the U.S. Fish and Wildlife Service’s National Fish Hatcheries, Fish & Wildlife Conservation Offices, Fish Health Centers, and Fish Technology Centers via AADAP in the winter of 2018. The survey was then expanded to include input from private fish farmers via the National Aquaculture Association in the summer of 2018. The document was prefaced by a brief description of its purpose and included a list of all currently available FDA-approved drugs, as well as drugs available under an Investigational New Animal Drug (INAD) exemption.
Once received from each organization, survey results were entered into a Microsoft Access database and exported to a Microsoft Excel spreadsheet, where needs were filtered, counted, and ranked. Needs were ranked first by how often they were suggested, and then by how many respondents made the suggestion. Initial analysis of the survey results showed a number of suggestions for drugs and use patterns that are considered to have Low Regulatory Priority (LRP) or Deferred Regulatory Status (DRS) by the FDA. These categories include use patterns for drugs that are considered to be of little risk to aquatic organisms, humans, or the environment, and are therefore unlikely to be regulated as long as certain conditions are met. Initial analysis also showed suggestions for drugs and use patterns that are already FDA-approved. Therefore, all of these suggestions were removed from the dataset in order to capture true, unmet drug needs in the U.S., and the resulting rankings include only new indications and those available under an INAD exemption.
A total of 107 surveys were completed and returned to AADAP for compilation: 38 from federal facilities, 54 from state facilities, and 15 from private facilities.
Top disease concerns and drugs suggested for approval
Eighty-two of the 107 respondents included a disease concern for which they would like to see an effective FDA-approved drug. The top five disease concerns for all organization types combined (federal, state, and private) were, in order of level of concern: 1) columnaris, 2) external protozoans, 3) saprolegniasis/other fungus, 4) copepods, and 5) bacterial gill disease. When determining the top disease concerns by organization type, federal facilities indicated saprolegniasis was the main concern, while state facilities indicated external protozoans were the main concern, and private facilities indicated copepods were the main concern.
Seventy-nine of the 107 respondents included a suggestion for a drug they would like to see approved for a therapeutic use. The top five drugs suggested for approval by all organization types combined were 1) hydrogen peroxide/35% PEROX-AID®, 2) formalin, 3) emamectin benzoate (SLICE®), 4) potassium permanganate, and 5) florfenicol (Aquaflor®). When determining the top suggested drug for approval by organization type, federal and state facilities suggested hydrogen peroxide/35% PEROX-AID® and private facilities suggested emamectin benzoate (SLICE®).
Emerging disease concerns
Thirty-one of the 107 respondents noted a concern about an emerging disease for which there are no FDA-approved drugs or drugs in the approval pipeline. A total of 36 emerging diseases were mentioned. When these diseases were categorized by type, the leading emerging concern for all respondents was parasites, followed by viruses, and then bacteria. When broken down by organization type, federal and state facilities were most concerned about emerging parasite problems, while private facilities were most concerned about emerging viral problems.
Looking at all emerging diseases individually, the top five were 1) whirling disease, 2) trematodes, 3) iridovirus, 4) enteric redmouth disease (ERM), and 5) Flavobacterium. By organization type, the top emerging disease concern was ERM for federal facilities, whirling disease for state facilities, and iridovirus for private facilities.
Looking at emerging disease concerns by species type, the majority of concern was for freshwater fish instead of marine fish. In addition, concern for non-salmonid diseases was slightly higher than concern for salmonid diseases. Of non-salmonid species, there was slightly more concern for warm/cool water species than for ornamental species.
Non-therapeutic drug needs
Seventy of the 107 returned surveys included a suggestion for a non-therapeutic drug need. Most suggestions fell into one of the following categories: sedation/anesthesia, gender manipulation, skeletal marking, and spawning aids. Sedation was by far the top non-therapeutic drug need for all respondents, followed by gender manipulation, skeletal marking, and spawning aids.
This survey was useful in identifying some of the current and future unmet drug needs of public and private aquaculture across the U.S. However, it is important to note that the number of surveys returned to us represents a relatively small subset of the entire aquaculture community and as such, survey results may not be as comprehensive as originally anticipated. Because the process to obtain new FDA-approved drugs for use in aquatic species is long, arduous, and expensive, it is imperative that our efforts are focused and prioritized. Results from this survey are currently being used to re-evaluate AADAP and DAWG priorities and the collective direction of effort, as well as to further engage current and new drug sponsors, and to direct research towards generating data to support new approvals or new, expanded claims for drugs that are already approved.