How did the Food and Drug Administration (FDA) get involved in Aquatic Animal Medicine?

Food, Drug and Cosmetic Act provides for the regulation of drugs for all animals. The Bureau of Veterinary Medicine regulates the marketing of all drugs for animals other than man. This includes aquatic mammals and fish. We have a historic problem in terminology in this area of medicine. I noticed when I first wrote this down I differentiated between aquatic animals and fish, which is just not the case, as the term aquatic animals is all-inclusive.

There are certain drugs that have been traditionally used with aquatic animals and are considered by many to be "not new animal drugs". However, as defined in the Food, Drug and Cosmetic Act, the majority of drugs used in aquatic mammals and fish are new animal drugs. The Act defines a new animal drug as any drug not generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended or suggested in the labeling.

The courts have ruled that general recognition of safety and efficacy must be based upon data from adequate and well controlled studies, not from the opinion of "experts." However, in reviewing basic information on the safety and efficacy of some of these drugs, there were no data per se to support this.

There are few approved drugs for fish and none for aquatic mammals, and most drugs used for treatment of diseases in species such as aquatic animals are considered minor use drugs by FDA. The cost of research and development of minor use drugs is often greater than the profits which can be obtained from sale of aquatic animal drugs. For this reason, not many companies are willing to sponsor new animal drug applications for aquatic animal medicine. There just isn't enough demand for the product.As there are few approved drugs for application to aquatic animal disease problems, there is high usage of unapproved drugs.

The use of approved products in non-food animals seldom creates a public health problem, but they may be neither safe nor effective for the subject being treated. The user of the drug is basing his application on his own or another's judgment that it is probably safe and effective. "Safe and effective drugs," as determined by use experience, is often based on small samples involving uncontrolled studies in which the treated animal did not die, or show any apparent toxic reactions, and appeared to get well or improve.

The requirements of the Act are very stringent and have made research expensive and apparently prohibitive. The term fish includes so many species that testing for all species is virtually impossible. For example, five fish species were proposed as models to demonstrate safety of specific drugs for all fish species. An attempt was made to select the most sensitive species. It is, however, very presumptuous to say that the safety of a drug for these five species is such a good model that we can apply this across the board. When tests are proposed, many questions arise, such as:

• what environment should the fish be placed in?
• should the water be hard or soft water?
• is pH important?
• is it safe in both oviparous and viviparous?
• is it usable in both salt water and fresh water?
• what is the effect of temperature?

Application of drugs to food fish raises new problems. There are additional requirements on food fish. It must be demonstrated that when using the product there is no residue of the drug in the edible tissues of the animal (fish) at the time it is intended to be used, or that the level of the drug (residue) is, in fact, safe for man. To further complicate matters, this requirement applies to the major metabolites of the drug also. If the data is to be species specific, then the generation of data and its analysis become a more difficult problem in the generation of data.

Due to such problems, we have developed a Minor Drug Policy in the Bureau of Veterinary Medicine. The policy says that data generated in closely related species and other animal models may be extrapolated to the target species in drug application. This may allow for greater flexibility; if the metabolites are the same in "x" numbers of species, then there won't be any need of further demonstration of the safety of that metabolite when it is used in target species.

In the FDA the human drug residue question is controlled within the Bureau of Foods (BF). Although the apparent dual jurisdiction can cause some problems, they (BF) have the ability to determine if the safety level of tissue derived from food fish would be safe for man. The cost of data gathering here too is also high.

Because of these problems, there is a need to share data. Aquaculture groups such as yours, for example, could sponsor a "new animal drug application," and pool data. This would decrease the expenditure of resources for a single sponsor and still allow for generation of significant data.

At a future time, if you desire to obtain approval for a new animal drug, I strongly recommend that you consult with the Bureau of Veterinary Medicine before initiating any studies that will involve the expenditure of significant resources. We can and will review any protocols submitted to us. Through the cooperative efforts of groups like yours, the drug industry and the federal government, I only hope that more safe and effective drugs will be available for aquatic animal medicine.

If you have a question relative to the new animal drug status of a particular product, you are invited to write to the:
Bureau of Veterinary Medicine Food and Drug Administration 
5600 Fishers LaneRockville, Md. 20857