Q. Who regulates animal biotechnology products?

A. The FDA Center for Veterinary Medicine (CVM) regulates, in whole or in part, diverse animal biotechnology products.

Q. Has FDA approved transgenic animals to enter the food supply?

A. No. Most transgenic animals under development are regulated by one or more FDA Centers. There are procedures to request approval to enter transgenic animals into the food or feed supply. No approvals have been granted for entry into the human food supply.

The procedures for biopharm animals (producing drugs or biologics) are described in the 1995 Points to Consider in the Manufacture and Testing of Therapeutic Products for Human Use Derived from Transgenic Animals. For these types of animals, as well as others generated by biomedical research, the Center for Veterinary Medicine (CVM) serves as a consulting group to the other FDA Centers in the food and feed safety evaluation.

Gene-based modifications of animals for production or therapeutic claims fall under CVM regulation as new animal drugs. Investigational applications are filed for these modifications where, with a showing of adequate safety data, the sponsor may request disposition of animals by slaughter for food or for processing into animal feed components.

To date, no transgenic animals have been approved for use as human food. A very limited number have been approved for rendering into animal feed components.

Q. How far along is the development of animal biotech products?

A. Non-heritable modifications (gene therapy) are still in early stages of development for animals, although this is a very active area in human medicine. These products are anticipated to be individual animal injections that would modify only some of the cells of the body to express a protein, protein hormone or enzyme. For example, individual steers could be modified to produce more muscle mass without having to modify the breeding herd, where additional muscle mass could cause calving difficulties.

Heritable modifications or germ-line transgenic animals with agronomic traits are most advanced for fish, and have already begun to receive public attention in the U.S. and abroad. Most of the modifications currently relate to improving animal productivity.

Are there any biotech products currently in use?

A. Yes. CVM's first recombinant DNA product - recombinant bovine somatotropin (BST) for dairy cows.

Q. How will these products be regulated?

A. Most, but probably not all, gene-based modifications of animals for production or therapeutic claims fall under CVM regulation as new animal drugs. As strange as it may seem at first, many of the modifications being investigated involve the addition of new animal drug substances. For example, adding growth hormone to a cow can be accomplished through use of BST injections, through gene therapies to create BST-producing regions in the body of the cow, or through germ-line modification, making a transgenic variety that contains extra BST-coding genes in every cell of the body, including reproductive cells. It all amounts to adding an animal drug, but the conditions are different - dose, areas of the body where the drug is released, opportunity for a withdrawal time, etc. The substances being added are for the purpose of improving animal health or productivity.

Q. Are there specific regulations for transgenic animals?

A. The animal drug provisions of the Federal Food, Drug, and Cosmetic Act best fit transgenic animals that have agronomic traits now being investigated and developed. Other transgenics will no doubt come along that could be viewed as containing food additives, color additives, and vaccines. Development of site-specific gene insertion techniques and animal genome projects could change the scope of potential genetic modifications to yield a wider variety of products than are currently being investigated.

Q. Have any transgenic fish been approved in the U.S.?

A. Transgenic fish of various species of salmon, tilapia, channel catfish and others are being actively investigated worldwide as possible new food-producing varieties. Technology developed for using transgenic fish as laboratory models to study developmental biology is being applied to food fish species with the aim of adding agronomically important traits, like improved growth rates and disease resistance.

No transgenic fish have been approved for producing food in the U.S., although a variety of transgenic fish species can be found in laboratories around the world. As there is active investigation of transgenic fish abroad, as well as in the U.S., the public and the research community are occasionally exposed to predictions of the imminent commercial release of transgenic fish into the food supply. This should not occur without the pre-market approval from CVM, for those fish that have an added gene-based animal drug.

Q. What limitations does current technology have on the production of transgenic fish?

A. The current technology has limitations that affect what types of transgenics can be developed. The "transgenes" are limited to short gene constructs and are inserted randomly and in variable numbers of copies in each individual. This creates difficulty in stabilizing genetic modifications in a breeding population. There may be uncontrolled expression of the transgene. It may be expressed all the time; it cannot be turned off. Insertion sites for the transgenes may inadvertently affect the expression of other genes by disabling them or turning them on at an inappropriate time. The incidental insertion of drug resistance genes from bacterial plasmids introduces further uncertainties as to food safety. The technology for creating transgenic animals is constantly improving and will soon begin to reduce the limitations of the current approaches and improve the competitive balance with other approaches to breed improvement.

Q. What about biocontainment concerns?

A. Breeding programs are needed to stabilize the transgenes in a patentable variety and to produce numbers necessary for regulatory approvals and for marketing. Biocontainment strategies, both from an engineering and biological point of view, are necessary to prevent escape of the transgene into wild fish populations and to provide a means of control over the unlicensed breeding of the patented variety. These features add to the costs of development and affect competitiveness of the approach versus other, more traditional, breeding approaches. Biocontainment needs are specific for each species and the location where it would be reared.

Q. Are there environmental concerns?

A. The primary environmental concerns about releases of transgenic fish, for example, include competition with wild populations, movement of the transgene into the wild gene pool, and ecological disruptions due to changes in prey and other niche requirements in the transgenic variety versus the wild populations. For example, transgenic tilapia (with cold tolerance similar to the unmodified species) might require little containment in the northern tier of the U.S., but might be excluded from the Gulf States altogether, where tilapia may be a serious exotic invader of freshwater streams and ponds. These site-specific concerns may make it necessary to control the sites where transgenic fish are reared and the level of biocontainment required might differ from site to site. Any biocontainment other than absolute containment will have to be assessed for specific proposed sites.

Q. How will the public accept foods derived from transgenic animals?

A. Germ-line transgenic modifications of animals, including fish and shellfish, have already begun to receive public attention in the U.S. and abroad. Public acceptance of foods derived from transgenic animals will be important to the success of any transgenic variety introduction. Approval by FDA or a food regulatory group in another country does not guarantee public acceptance. Labeling of food from transgenic animals will likely be even more important to consumers desiring a choice than has been observed for milk derived from BST-treated dairy cows or for transgenic plant varieties. Ethical concerns among the public over the appropriate use of animals are issues, not evident with transgenic plants, that may affect public acceptance of transgenic animals as food sources. There is also expected to be variation among the citizens of different countries as to their acceptance of transgenic animals. Development of a world market for a transgenic animal variety is currently fraught with difficulties owing to the varying cultural views and governments.