U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
FDA Education/Compliance Program: 1995

FDA'S Policy for Foods Developed by Biotechnology

Emerging Technologies -- Biotechnology


Biotechnological methods of genetic engineering are relatively new techniques that plant breeders have to make direct modifications of DNA, a living thing's genetic materials. Scientists make copies to genes for desired traits and introduce the gene copy into an organism such as a food crop. The new gene is usually a single gene whose function is well understood. These new techniques avoid one of the major problems encountered by plant breeders who use cross hybridization - no unwanted or undesirable genes are introduced with the desired gene. In addition, scientists can make copies of genes from any organism - plant, animal, or microbe - that may yield a desired trait and introduce that gene into a food crop. This greatly expands the pool of potentially useful traits available to plant breeders to improve food crops.

Once a desired gene has been introduced into a crop via genetic engineering, the gene is usually crossed into other crop lines that have desired commercial traits. Such crossing also permits the breeder to evaluate the genetic stability of the new gene. Overall, genetic engineering allows breeders to develop new varieties more rapidly, but at this stage of the technology, the new methods are used in conjunction with other methods of plant breeding, such as cross-hybridization.

The time required to evaluate new varieties and the number of field trials will vary depending on the need to confirm performance, to evaluate characteristics of the food, to evaluate environmental effects, and to produce the required amount of seed before the new plant variety can be grown commercially by farmers.

Genetic engineering is used to achieve the same goals of agronomic and quality characteristics as traditional techniques and allows the breeder to make some modifications that would not be possible through other methods of plant breeding. Genetically engineered food crops have been developed to:


FDA evaluated the safety data and information developed by Calgene, Inc. regarding the FLAVR SAVRTM tomato, the first food derived from a plant modified via recombinant DNA techniques to be evaluated by the agency. In May, 1994, FDA and the FDA Food Advisory Committee agreed with Calgene that the FLAVR SAVRTM tomato was as safe as other commercial varieties of tomato.

In response to a petition by Calgene, FDA also issued a food additive regulation for the use of the selectable marker gene, kanamycin resistance, to develop via recombinant DNA techniques new varieties of tomato, including the FLAVR SAVRTM tomato, cotton, and oilseed rape (canola) plants.

In November, 1994, FDA reviewed the process for the FDA Food Advisory Committee (FAC) by which firms are informing the agency that they have completed their safety and nutritional assessment of foods derived from new plant varieties developed through recombinant DNA techniques. The agency also presented to the FAC the summary of the safety and nutritional assessment provided to FDA on seven new products. These included the following:

The FAC agreed with FDA that there are no outstanding food safety issues associated with these products.

These examples of foods derived from new plant varieties modified via recombinant DNA techniques, including the FLAVR SAVRTM tomato, were evaluated by the developers using safety and nutritional assessments consistent with the standard to care contained in FDA's 1992 policy.


In 1992, FDA published a policy statement that explains how foods- fruits, vegetables, grains, and their by products such as vegetable oils - are regulated under the FD&C Act. This policy applies to foods and food ingredients, including animal feeds, derived from plants modified through all methods of plant breeding, including genetic engineering.

Highlights of some of the important factors included in FDA's guidance to industry are the following:

  2. The introduced genetic materials should be well-characterized to ensure that any introduced genes do not encode harmful substances and should be stably inserted in the plant genome to minimize the chance for subsequent undesired genetic rearrangements.

  4. Plants are known to produce toxicants and antinutritional factors, such as protease inhibitors, hemolytic agents, and alkaloids which often protect the plant against pests and disease. Many of these toxicants are present in today's crops at levels that do not cause acute toxicity or do not affect humans or animals when the food is properly prepared. New plant varieties should not contain levels of such toxicants that are above the range that exists in today's crops.

  6. Another unintended consequence of genetic modification of the plant may be an alteration (relative to the total diet) in levels of important nutrients and bioavailability of a nutrient due to changes in the form of the nutrient or of other constituents that effect absorption or metabolism of nutrients.

  8. In some cases using genetic engineering, plant breeders may introduce genes into food crops that encode substances that differ substantially in structure and function from substances currently found in food. Based on current developments, such substances would be expected to be proteins or protein enzymes that modify carbohydrates and fatty acids in the food. In some cases, such substances will require premarket approval as food additives; in other cases, the food may require new labeling to properly inform consumers of the new attributes of the food. However, in most cases to date, the substances that occur in food as a result of gene transfer have been safely consumed as food previously or are substantially similar to food substances and would not require premarket review by FDA.

  10. There are thousands of different proteins in our food supply, and only a few cause food allergy reactions. However, because genetic engineering can result in the introduction of genetic material from essentially any source (plant, animal, or microbe) into food, there is a possibility that a protein encoded by the newly introduced genetic material will be an allergen and produce an allergic response in some members of the population. FDA has raised this issue in its guidance to industry, especially in cases where the transferred genetic material is derived from a source that is known to be commonly allergenic. Examples of such foods that affect the U.S. population include milk, eggs, fish crustacea, mollusks, tree nuts, wheat, and legumes (particularly peanuts and soybeans). FDA believes that proteins derived from commonly allergenic sources should be presumed to be allergens and special labeling would be required, unless scientific evidence demonstrates otherwise.

    In cases where a protein is derived from a source that is not known to be allergenic, it is not possible to definitively predict allergenic potential. While it is unlikely that a new protein that occurs in very low concentrations in food will be an allergen (as is the case for most proteins introduced via genetic engineering at this time), developers have taken steps to minimize the likelihood that a new protein will be an allergen by evaluating whether the new proteins exhibit characteristics typical of allergenic proteins (such as stability to heat, acid, and enzyme degradation).

    FDA encourages developers to discuss questions regarding allergenicity with agency scientists.

  12. In experiments involving genetic engineering, only a few plants cells take up the desired new gene. Developers use selectablemarker genes during gene transfer experiments to improve their chances of selecting plants that have successfully incorporated the desired gene. The most widely used marker is kanamycin resistance gene that produces the enzyme, aminoglycoside 3'-phosphotransferase II (also referred to as APH(3')II and neomycin phosphotransferase II). Plant cells are normally killed by antibiotics. APH3'II inactivates the antibiotics kanamycin and neomycin and permits plant cells to grow in culture that have incorporated gene and express the APH(3')II enzyme.

    Once the desired plant variety has been selected, the marker gene serves no useful purpose in the new plant, but it does continue to produce the gene product, APH(3')II in the case of kanamycin resistance. This enzyme is present at very low concentrations in food.

    The use of marker genes that encode resistance to clinically important antibiotics raises questions regarding whether the enzyme in the food could inactivate oral doses of the antibioticor whether the gene present in the plant DNA could betransferredto pathogenic microbes in the GI tract or in soil rendering themresistant to treatment with the antibiotic. FDA evaluated thesequestions for the use of kanamycin resistance in tomato, cotton, canola.

    FDA found that kanamycin and neomycin are very toxic antibiotics and as such have very limited oral clinical use and are used onlyin situations where patients are not consuming food. There is also too little of the essential cofactor, ATP, present in food for the enzyme to degrade a significant amount of antibiotic.

    There is no known mechanism by which a gene can be transferred from a plant chromosome to a microbe. Thus, the possibility of that such transfer would generate new resistant organisms is very small, especially when compared to the high rate of spread ofresistance through known mechanisms of microbe to microbe transfer to antibiotic resistance. FDA believes that the use of marker genes that encode resistance to other clinically useful antibiotics can be evaluated by similar criteria that were usedfor kanamycin resistance.

  14. Feeds developed for animals raised as food sources must be meet the same safety standards as human food under the FD&C Act. In contrast to the human diet, an animal feed derived from a singleplant may make up over half of the animal's diet. Further,animals consume plants and plant parts that are not part of the human diet. Nutrient composition and availability of nutrients are important considerations for animal health.

  16. The FD&C Act defines the information that must be disclosed in labeling (including the food label). The Act requires that all labeling be truthful and not misleading. The Act does not require disclosure in labeling of information solely on the basis of consumer desire to know. The Act does require that a food be given a common or usual name, and that the label disclose information that is material to representations made or suggested about the product and consequences that may arise from the use of the product.

    FDA will require special labeling if the composition of a food developed through genetic engineering differs significantly from its conventional counterpart. For example, if a food contained a major new sweetener as a result of genetic modification, new common or usual name or other labeling may be required. Similarly, if a new food contains an allergen that consumers would not expect in that food, labeling would be necessary to alert sensitive consumer. However, if a protein commonly produces very serious allergic reactions (e.g. peanut protein) and is transferred to another food, FDA would need to evaluate whether labeling would provide sufficient consumer protection.

    To date, FDA is not aware of information that would distinguish genetically engineered foods as a class from foods developed through other methods of plant breeding and, thus, require such foods to be specially labeled to disclose the method of development. The agency has not required labeling for other methods of plant breeding such as chemical - or radiation-induced not required to be labeled "hybrid sweet corn" because it wasdeveloped through cross-hybridization.

    FDA is reviewing public comments on labeling issues. One issue that is particularly difficult is the question of whether special labeling should be required for a food derived from a plant that has been modified to express a gene derived from an animal and whether the presence of such a gene or its product affects certain ethical or religious beliefs. Currently, no foods areapproaching the market that raise this issue. However, the issue is very complex, and FDA believes that further discussion is warranted.


FDA has provided guidance for developers that establishes a standard to care to ensure that foods derived from new plant varieties are safe and wholesome. Irrespective of the method by which a food is produced, all foods must meet the same stringent safety standards and be properly labeled in accordance with the FD&C Act.


  1. Statement of Policy: Foods Derived from new Plant Varieties, Federal Register, May 29, 1992, Vol. 57, pages 22984-23005.

  2. Food Labeling; Foods Derived from New Varieties, Federal Register, April 28, 1993, Vol. 58 pages 25837-25841.

  3. Memorandum, Summary of Consultation with Calgene, Inc. Concerning FLAVR SAVRTM Tomatoes, May 17, 1994, HFS-206 to HFS-200.

  4. Secondary Direct Food Additives Permitted in Food for Human Consumption; Food Additives Permitted in Feed and Drinking Water of Animals; Aminoglycoside 3'-Phosphotransferase II, Federal Register, May 23, 1994, Vol. 59, pages 26700-26711.

  5. Procedures of Industry-FDA Interaction Prior to Commercial Distribution of Foods Derived from New Plant Varieties Developed Using Recombinant DNA Techniques and Memoranda of Conference on Seven Genetically Engineered Crops.

Hypertext updated by dms, 07/03/97