The FDA has authority under the act to ensure the safety of most domestic and imported foods in the U.S. market, except meat and poultry which are regulated by the Department of Agriculture. Pesticides are regulated primarily by the Environmental Protection Agency (EPA), which reviews safety and sets tolerances (or establishes exemptions from tolerance) for pesticides. FDA monitors foods to enforce the tolerances set by EPA for pesticides.
Bioengineered foods and food ingredients (including food additives) must comply with the same standards of safety under the act that apply to other food products. This means that these products must be as safe as the products in our grocery stores today. The FDA has broad authority to initiate regulatory action if a product fails to meet the safety standards under the act.
This year is also significant for U.S. agricultural biotechnology. It will be th e first year that bioengineered food crops will be a significant part of the total U.S. production of food crops, even though the total acreage of bioengineered crops will be a fraction of the production of commodity products such as soybean and corn. These bioengineered varieties include soybeans, corn, canola, tomato, squash, cotton, and potato. The plants and the foods and feeds derived from them have been tested extensively in the U.S. for environmental safety and for consumption as human food and feed for animals. Several firms have completed all necessary regulatory requirements for commercial distribution of these crops in the U.S. These bioengineered crops are the second major category of bioengineered food products in the U.S. that follows the earlier food processing enzymes such as chymosin (rennet) that was first approved in the U.S. in 1990.2
The FDA relies primarily on two sections of the act to ensure the safety of foods and food ingredients. The first is the adulteration provisions of section 402(a)(1). Generally, whole foods, such as fruits, vegetables, and grains, are not subject to premarket approval. The act places a legal duty on developers to ensure that the foods they market to consumers are safe and comply with all legal requirements. The FDA has authority to remove a food from the market if it poses a risk to public health. This is the primary legal tool that the FDA intends to rely on to ensure the safety of bioengineered foods.
The second section of the act that the FDA relies on is the food additive provision (section 409). Under this section, substances that are intentionally added to food are food additives, unless the substance is generally recognized as safe (GRAS) or is otherwise exempt (e.g., a pesticide). Food additives are subject to review and approval by the FDA before they may be used in food. The FDA also reviews and affirms the GRAS status of food ingredients when there is a question regarding the regulatory status of a substance intended for use in food. The legal basis of the FDA's policy may be found in the 1992 policy.
The centerpiece of our 1992 policy is a comprehensive "guidance to industry" section that discusses scientific issues regarding safety and identifies circumstances when firms should consult with the FDA. The agency's guidance to industry establishes a "standard of care" for developers. The scientific principles of the FDA's policy have been published in Science magazine4 and are consistent with the principles for safety assessment discussed by the U.S. National Research Council,5,6 the World Health Organization and the Food and Agriculture Organization of the United Nations,7 and the Organization of Economic Cooperation and Development.8
In one case published recently, a developer, following the FDA's guidance, demonstrated that a protein transferred from Brazil nut to soybean caused an allergic reaction (via skin-prick test) in individuals who are sensitive to Brazil nut.9 Consequently, development of this modified soybean has been discontinued.
Many genes introduced into plants are obtained from sources that are less frequently or are not known to be associated with allergic reactions. There is no test that will predict potential allergenicity for proteins derived from sources that are not known to cause allergic reactions. However, steps can be taken to reduce the possibility that a newly introduced protein will be an allergen. The protein's structure can be compared to the reported structures for allergenic proteins, and, if similarity is found and if sera from sensitive individuals are available, an analysis of possible cross reaction can be conducted. Many proteins in bioengineered foods have been derived from microbial sources, and developers have demonstrated that these proteins do not have characteristics associated with food allergens, i.e. they do not share structural similarity to allergens and they are not resistant to digestive enzymes and acid.
For food ingredients produced via fermentation using microorganisms that contain antibiotic resistance marker genes, such as chymosin, manufacturing and purification steps must inactivate viable organisms and produce a finished product that is free of transforming DNA.
The issues regarding the use of antibiotic resistance marker genes in food crops are more complex and to some extent hypothetical because there is no known mechanism for transfer of a plant gene to a microorganism. Calgene, Inc. requested that the FDA review the use of kanamycin resistance (kanr) the development of several crops including tomato. The firm also requested that the FDA regulate the enzyme expressed by kanr, aminoglycoside 3'phosphotransferase II (APH3'II), as a food additive in order to demonstrate that the only newly added substance in the Flavr SavrTM tomato meet the stringent standard for food additives. Calgene submitted extensive data and information to the FDA to support the safe use of kanr in tomato, cot canola. FDA concluded that the use of kanr in these crops was safe.10
Subsequently, the FDA established an informal process by which firms can inform the FDA that they have completed a food and feed safety assessment. The FDA requests that firms submit a summary of their assessment to the agency. The FDA does not request the original data and, therefore, does not conduct a scientific review of the firm's decision. This informal process has worked well to date and permits the FDA to identify any unresolved safety or regulatory issues before products reach the market.
As summarized in our paper in Science, "FDA's science-based approach for ensuring the safety of foods from new plant varieties focuses safety evaluation on the objective characteristics of the food: The safety of any newly introduced substances and any unintended increased concentrations of toxicants beyond the range known to be safe in food or alterations of important nutrients that may occur as a result of genetic modification. Substances that have a safe history of use in food and substances that are substantially similar to such substances generally would not require extensive premarket safety testing. Substances that raise safety concerns would be subjected to closer inquiry. This approach is both scientifically and legally sound and should be adequate to fully protect public health while not inhibiting innovation" (see reference 4).
Presented at the BioJapan '96 Symposium held on July 24-27, 1996 in Tokyo, Japan.