Statement on Biotechnology Issues by James H. Maryanski, Ph.D
Biotechnology Coordinator, Center for Food Safety and Aplied Nutrition
Food and Drug Administration
Before the Senate Committee on Agriculture, Nutrition and Forestry October 7, 1999
Mr. Chairman and members of the Committee, thank you for giving the Food and Drug Administration (FDA or the Agency) the opportunity to testify today on its regulatory program for foods derived from new plant varieties, including genetically engineered varieties. I am Dr. James Maryanski, Biotechnology Coordinator, in FDA’s Center for Food Safety and Applied Nutrition (CFSAN).
FDA believes it is very important for the public to understand how government is overseeing the new foods being introduced into the marketplace and to have confidence in that process. To that end the Agency appreciates this opportunity to describe its processes and procedures to the Committee and to the public, and to clarify what bioengineered food products are and how FDA regulates them.
For almost two decades FDA has been studying genetic modification techniques for drug-biologic development, as well as the development of new foods, and the Agency has carefully developed policies to accommodate the changing and evolving world of biotechnology. The evidence shows that we are meeting our goal of ensuring that these new products meet the same safety standards as traditional foods.
Mr. Chairman, you asked us to describe our legal authority and the regulatory procedures that industry follows to market a bioengineered food product. Before addressing those topics specifically, I would like to provide some background on food biotechnology.
First, let me explain what we mean when we refer to food biotechnology or genetically engineered foods. Many of the foods that are already common in our diet are obtained from plant varieties that were developed using conventional genetic techniques of breeding and selection. Hybrid corn, nectarines (which are genetically altered peaches), and tangelos (which are a genetic hybrid of a tangerine and grapefruit) are all examples of such breeding and selection. Food products produced through modern methods of biotechnology such as recombinant DNA techniques and cell fusion are emerging from research and development into the marketplace. It is these products that many people refer to as “genetically engineered foods.” The European Commission refers to these foods as Genetically Modified Organisms. The United States uses the term genetic modification to refer to all forms of breeding, both modern, i.e. genetic engineering, and conventional.
The new gene splicing techniques are being used to achieve many of the same goals and improvements that plant breeders have sought through conventional methods. Today’s techniques are different from their predecessors in two significant ways. First, they can be used with greater precision and allow for more complete characterization and, therefore, greater predictability about the qualities of the new variety. These techniques give scientists the ability to isolate genes and to introduce new traits into foods without simultaneously introducing many other undesirable traits, as may occur with traditional breeding. This is an important improvement over traditional breeding.
Second, today’s techniques give breeders the power to cross biological boundaries that could not be crossed by traditional breeding. For example, they enable the transfer of traits from bacteria or animals into plants.
In conducting its safety evaluations of genetically engineered foods, FDA considers not only the final product but also the techniques used to create it. Although study of the final product ultimately holds the answer to whether or not a product is safe to eat, knowing the techniques used to create the product helps in understanding what questions to ask in reviewing the product’s safety. That is the way FDA regulates both traditional food products and products derived through biotechnology.
Turning now to your first question on FDA’s legal authority over genetically engineered foods, FDA has authority under the Federal Food, Drug, and Cosmetic (FD&C or the Act) Act to ensure the safety of all domestic and imported foods for man or other animals in the United States market, except meat, poultry and egg products which are regulated by the United States Department of Agriculture (USDA). 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 adhere to the same standards of safety under the Act that apply to their conventional counterparts. This means that these products must be as safe as the traditional foods in the market. FDA has broad authority to initiate regulatory action if a product fails to meet the safety standards of the Act.
FDA relies primarily on two sections of the Act to ensure the safety of foods and food ingredients:
(1) The adulteration provisions of section 402(a)(1). Under this postmarket authority, FDA has the power to remove a food from the market (or sanction those marketing the food) if the food poses a risk to public health. It is important to note that 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.
(2) The food additive provisions (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, the safety of which is overseen by EPA).
The FD&C Act requires premarket approval of any food additive — regardless of the technique used to add it to food. Thus, substances introduced into food are either (1) new food additives that require premarket approval by FDA or (2) GRAS, and are exempt from the requirement for premarket review because, for example, there is a long history of safe use in food. Generally, whole foods, such as fruits, vegetables, and grains, are not subject to premarket approval because they have been used for food for lengthy periods of time.
Under FDA policy on foods derived from new plant varieties, a substance that would be a food additive if it were added during traditional food manufacture is also treated as a food additive if it is introduced into food through genetic modification of a food crop. For example, a novel sweetener bioengineered into food would likely require premarket approval. Generally, under Agency policy, substances intentionally introduced into food that would be reviewed as food additives include those that have unusual chemical functions, have unknown toxicity, or would be new major dietary components of the food.
In our experience to date, we have not seen substances of that type. The substances intentionally added to food via biotechnology to date have been well-characterized proteins, fats, and carbohydrates, and are functionally very similar to other proteins, fats, and carbohydrates that are commonly and safely consumed in the diet and so will be presumptively generally recognized as safe. Importantly, our authority under section 409 permits us to require premarket approval of any food additive and thus, to require premarket review of any substances intentionally introduced via bioengineering that are not generally recognized as safe.
FDA’s authority under current law, both pre- and postmarket provisions, is sufficient to ensure the safety in the marketplace of foods derived from new plant varieties.
SYSTEM OF REGULATIONS
Because FDA determined that bioengineered foods should be regulated like their conventional counterparts, FDA has not to date established any regulations specific to bioengineered food. In 1992 FDA published its “regulatory roadmap” policy document, the “Statement of Policy: Foods Derived from New Plant Varieties.” The statement explains FDA’s views about regulating human foods and animal feeds produced from new plant varieties, including crops developed by the newest methods of molecular and cell biology (such as recombinant DNA methods and somaclonal variation) and those developed using traditional techniques. The policy focuses on the traits and characteristics of the foods, and applies to all new varieties of food crops, no matter which techniques are used to develop them.
This science-based policy was developed through careful consideration of new developments in biotechnology. FDA scientists had carefully followed the developments in research over the previous several years to determine the types of commercial foods and food ingredients likely to be developed by recombinant DNA techniques. We also considered scientific principles for assessing safety that had been developed and agreed upon by several prestigious scientific groups, including the National Academy of Sciences (NAS), the Food and Agriculture Organization (FAO), the World Health Organization (WHO), and the Organization for Economic Cooperation and Development (OECD) in developing FDA’s policy.
In formulating FDA policy, we reviewed new foods under development through biotechnology, and found they shared certain common characteristics: (1) Recombinant DNA techniques are being used to introduce copies of one or a limited number of well-characterized genes into a desired food crop. The introduced gene or genes then become integrated in the plant and are passed to successive generations of plants by the natural laws of genetics; (2) In most cases, these genes produce proteins, or proteins that modify fatty acids or carbohydrates in the plant, in other words, common food substances; (3) The proteins, fatty acids, and carbohydrates introduced into food crops are well characterized and not known to be toxic and they would be digested to normal metabolites in the same manner that the body handles the thousands of different proteins, fat and carbohydrates that make up our diet today.
Since newly introduced substances in foods derived using recombinant DNA techniques would be proteins, fats or carbohydrates, we then examined the safety questions that should be addressed before products reach the market. We identified four broad safety issues that should be evaluated: (1) the need to ensure that new substances, that is, newly introduced proteins, fats, or carbohydrates are safe for consumption; (2) the need to ensure that the changes in the food, such as the level of natural toxins in the food, if any, stay within normal safe levels; (3) the need to ensure that significant nutrients stay within normal range; and (4) the need to analyze the potential for introduced proteins to cause allergic reactions. We incorporated these and other issues into a comprehensive guidance to industry that is central to our policy.
The guidance in our policy statement provides a “standard of care” to help plant developers ensure that the products they develop meet the safety standards of the FD&C Act. It also provides guidance to industry on those situations in which developers should specifically consult with FDA on issues such as labeling, design of appropriate test protocols, and whether a food additive petition would be required.
I would like to highlight some activities that we have engaged in following publication of our 1992 policy. In response to comments we have received regarding potential allergenicity of foods derived from bioengineered plants, we hosted a “Conference on Scientific Issues Related to Potential Allergenicity in Transgenic Food Crops” in 1994. We hosted this conference in cooperation with the EPA, and USDA. The goal of the Conference was to foster a dialogue among scientists on food allergy and new varieties of food crops developed by gene transfer to assess current information regarding what makes a substance such as a protein a food allergen and what means are available to assess allergenic potential. FDA has gained valuable insights on these issues from this conference.
Also in response to comments we received to the 1992 policy, FDA sought to develop sound scientific principles regarding the safety of the use of antibiotic resistance marker genes in the development of bioengineered plants intended for food use so as to provide sound scientific guidance to crop developers regarding the safe use of antibiotic resistance marker genes. We consulted with outside experts having expertise in relevant fields including gene transfer and antibiotic resistance. The purpose of the consultations was to determine whether circumstances exist under which FDA should recommend that a given antibiotic resistance gene not be used in crops intended for food use, and if so, to delineate the nature of those circumstances. Based on these consultations, FDA issued in September 1998, guidance on the use of antibiotic resistance marker genes in bioengineered plants intended for food use and requested comments on that guidance.
Finally, we should point out that the 1992 policy is not static. The policy was based on our research with respect to products that were in the development pipeline at the time. Since the statement was developed, we have not seen any products we did not anticipate, but it is important to point out that we are keeping abreast of new developments in this rapidly evolving technology and will modify the policy if necessary.
GETTING A BIOTECH PRODUCT TO MARKET
Finally you asked us to describe the procedures industry follows to get a biotech food product to market. In 1994, for the first bioengineered product planned for introduction into the market, FDA moved deliberately, following the 1992 policy. We conducted a comprehensive scientific review of Calgene’s data on the Flavr SavrTM tomato and the use of kanamycin resistance marker gene, and also held a public meeting of our Food Advisory Committee (the Committee) to examine applicability of the 1992 policy to products such as the Flavr SavrTM tomato. The Committee members agreed with FDA that the scientific approach presented in the 1992 policy was sound and that questions regarding the Flavr SavrTM had been addressed. The Committee members also suggested that we develop a more expedited process for FDA and the industry to reach decisions on the marketing of other bioengineered foods that do not raise substantive scientific issues.
Subsequently, FDA established an informal process by which firms can inform the Agency that they have completed a food or feed safety assessment. FDA requests that firms submit a summary of their assessment to the Agency. It is our expectation and experience that all firms have complied with this request for all plant varieties that have been commercialized to date. This process has worked well to date and permits the Agency to identify and resolve any safety or regulatory issues before products reach the market.
The goal of FDA’s evaluation is to ensure that human food and animal feed safety issues or other regulatory issues (e.g. labeling) have been addressed prior to commercial distribution. Agency scientists evaluate the available information to determine whether any unresolved issues exist, regarding the food variety that would necessitate legal action by the Agency if the product were introduced into commerce. Examples of such issues may include the potential for significantly increased levels of plant toxicants or anti-nutrients, reduction of important nutrients, new allergens, or the presence in the food of an unapproved food additive. FDA considers a consultation to be complete when all safety and regulatory issues are resolved. In 1994, FDA discussed this consultation process during a joint public meeting of the Agency’s Food Advisory Committee and its Veterinary Medicine Advisory Committee. The Committee members agreed with FDA that, based on the types of bioengineered foods and feeds under development, the consultation procedures provide an appropriate level of government oversight.
The Agency encourages developers to consult early in the development phase of their products, and as often as necessary. When a firm has accumulated the information that it believes is adequate to ensure that the product complies with the relevant provisions of the FD&C Act, the Agency recommends that the developer inform FDA about the bioengineered foods intended to be introduced into commercial distribution by providing a summary of the company’s safety and nutritional assessment which Agency scientists review for unresolved safety or regulatory issues.
The safety and nutritional assessment summary should normally contain sufficient information for Agency scientists to understand the approach the firm has followed in identifying and addressing relevant issues. Some examples of this information would include:
- The name of the food and the crop from which it is derived;
- The uses of the food, including both human food and animal feed uses;
- The sources, identities, and functions of introduced genetic material;
- The purpose or intended technical effect of the modification, and its expected effect on the composition or characteristic properties of the food or feed;
- The identity and function of any new products encoded by the introduced genetic material, including an estimate of its concentration;
Comparison of the composition or characteristics of the bioengineered food to that of food derived from the parental variety or other commonly consumed varieties with special emphasis on important nutrients, anti-nutrients, and toxicants that occur naturally in the food;
Information on whether the genetic modification altered the potential for the bioengineered food to induce an allergic response; and,
Other information relevant to the safety and nutritional assessment of the bioengineered food.
I would like to briefly go back to one of the items I just mentioned that we consider, and one that is a frequently raised concern about bioengineered food – – food allergens.
As we have described in our policy, foods derived from new plant varieties are regulated by FDA under the existing framework of the FD&C Act. Labeling, by law, is limited to identifying significant changes in a food’s composition, and it must not mislead consumers. Thus, for example, if a tomato had a soybean gene introduced into it, labeling would be needed to alert consumers to the presence of the potential allergen, unless it could be demonstrated scientifically that the soybean allergen was not present. It is also possible that if the Agency concluded that labeling alone would not adequately protect consumers, FDA would object to the marketing of the product.
Similarly, if a copy of a new gene introduced into a carrot produces a protein that significantly changes the composition of the vegetable, the name “carrot” may no longer accurately describe the product and a new name would be required.
In conclusion, Mr. Chairman, FDA takes seriously its mandate to protect consumers in the United States and to ensure that the United States ’ food supply continues to be one of the safest in the world. FDA’s process for evaluating bioengineered foods is one in which the public can have confidence that food biotechnology products must meet the law’s safety standards. FDA’s 1992 policy statement and our guidance documents make clear that premarket clearance is required if there is scientific uncertainty about the safety of food derived from bioengineered plants. The policy also makes clear that labeling will be required if the composition of the genetically modified food differs significantly from what is expected for that food, or if the genetically modified food contains potential allergens.
Mr. Chairman, we are confident that our approach is appropriate. It allows us to ensure the safety of new food products and also allow the use of safe, new biotechnology techniques that give manufacturers the ability to produce better products and provide consumers additional choices.
I would be happy to answer any questions the Committee may have.