History of the AADAP Research Program (updated 19 July 2011)...
The U.S. Fish and Wildlife Service’s (FWS) Investigational New Animal Drug (INAD) Program was established in 1994. At that time, our office consisted of a Coordinator (Dr. Dave Erdahl), an Assistant Coordinator (Mr. Jim Bowker), and a part-time Administrative Assistant (Ms. Robyn Barkley). Initially, we stayed busy establishing and administering FWS's Investigational New Animal Drug (INAD) exemptions. Such exemptions, which are granted by the U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM), allow legal access to experimental aquaculture drugs while data required for full FDA/CVM approval are generated. However, it soon became clear that not only were the many public and private entities working towards aquaculture drug approvals being overwhelmed by FDA/CVM’s data requirements, but also that INAD-generated efficacy data, while useful, would not fulfill all efficacy technical section requirements . Consequently, we began to expand our scope of work to include aquaculture drug efficacy research. For example, we conducted several studies to evaluate the effectiveness of hydrogen peroxide to control fungal infections on salmonid eggs. Ultimately, in 1996, we established a full-fledged aquaculture drug efficacy research program with support from the FWS’s Washington, D.C., Office.
Becoming involved in bona fide aquaculture drug approval research dictated a “shift in focus” from academic science-based research to regulatory science-based research. Both types of research seek to understand and explain complex natural relationships; however, the goals of academic science-based research differ from those of regulatory science-based research (http://sciencepolicy.colorado.edu/klamathbasin/science_policy/regulatory_vs_academic.html). Consequently, the manner in which academic science-based studies are designed and conducted can be quite different from that in which regulatory science-based studies are designed and conducted. After several false starts, we became intimately familiar with FDA/CVM Guidance for Industry documents and their value in developing and writing research study protocols.
In 1996, we wrote our first research protocol which was developed to evaluate the effectiveness of chloramine-T (CLT) to control mortality, caused by bacterial gill disease, in a variety of salmonids. When FDA/CVM accepted the protocol, we then began a “grass-roots” effort to find partners (public and private) who would allow us to conduct relatively short-term CLT efficacy studies at their hatcheries and with their fish. What followed was a rapid introduction to the biological and logistical challenges associated with finding suitable study locations and getting staff and equipment on-site before fish became too sick to treat effectively. We conducted our first field efficacy study in March 1997 at the FWS's Neosho National Fish Hatchery, with support from the hatchery crew. During the next few years, we wrote research study protocols to evaluate the effectiveness of several other experimental aquaculture drugs, and we traveled to numerous public and private hatcheries to conduct studies in support of aquaculture drug approvals. From early on, the success of our program has been dependent on the willingness of our partners — hatchery administrators, managers, and their staffs; fish health experts (veterinarians and fish health biologists); aquaculture drug companies; and fish-feed manufacturers — to commit time, people, products, and money to our research efforts. We’re thankful for the opportunities we’ve had to work with many excellent fisheries and veterinary professionals.
In 1998, we expanded our scope of work to include target animal safety (TAS) research. Target animal safety studies are conducted under federal Good Laboratory Practice (GLP) guidelines for nonclinical laboratory studies and designed to empirically estimate what FDA/CVM describes as a “margin of safety”—a multiple of a proposed maximum treatment concentration and/or treatment duration. Typically, an experimental aquaculture drug is administered to healthy target animals at up to 5 times (5X) the proposed maximum treatment concentration for 3 times (3X) the proposed treatment duration and 1 times (1X) the proposed treatment frequency. Data generated (e.g., mortality, gross pathology, histopathology, behavior, and dose-verification) are submitted to FDA/CVM for review. The FDA/CVM rules if the data adequately demonstrate the safety of the product for its proposed use on the target animal(s). The outcome of such a review affects the final decision by FDA/CVM to approve (or not) a new or expanded New Animal Drug Application. With the help of USGS-BRD, Upper Midwest Environmental Sciences Center and USDA-ARS, Stuttgart National Aquaculture Research Center, we established a GLP program and instilled a GLP-attitude among the research staff. In 1999, we conducted our first series of TAS studies, which focused on evaluating the safety of CLT to rainbow trout.
The AADAP program currently has seven employees, four of which work full-time in efficacy and target animal safety research. To date, we have conducted efficacy studies with 10 drugs, conducted or coordinated TAS studies with five drugs, and “passed” two FDA inspections of our GLP program. We continue to prioritize our work activities based on recommendations from our partners, especially the Association of Fish and Wildlife Agencies Drug Approval Working Group. We welcome the challenges associated with conducting efficacy and TAS research and always look forward to working with our partners in pursuit of aquaculture drug approvals.