FDA Regulation of Food and Drug Biotechnology

Jennifer A. Thelen

Introduction

In its broadest sense, referring to the application of a biological process to provide a good or service, biotechnology has been affecting the human food supply for centuries In products such as beer and cheese. Similarly, since the shift from hunters and gatherers to farmers humans have been selecting and propagating certain varieties of organisms based on their genetic makeup. The discovery of DNA as the mediator of this heritable property forty years ago introduced a novel type of biotechnology based on the new science of molecular genetics. This biotechnological process of transferring DNA of one organism to another is commonly referred to as genetic engineering. Thus, genetic engineering can be seen as an extension of these age-old techniques to improve the food supply. However, it can also be seen as a completely novel technology with a great potential for abuse, therefore demanding a high level of regulatory supervision. The debate as to how the Food and Drug Administration should treat genetically engineered foods reflects these tensions precisely. This paper will consider the FDA. approach to regulating genetically engineered foods and drugs. A critique of this system will be presented centered around the issues of processed-based regulation, consumer labeling, and pre-market notification.

The Coordinated Framework.

The first instance in the United States of regulating genetic engineering was a voluntary measure taken by scientists engaged in genetically engineering to stringently control their own research until the safety of the new technology could be assured. This conference led to the formation of the National Institutes of Health Recombinant DNA Advisory Committee (NIH-RAC) as well as formal guidelines for

recombinant DNA (rDNA) research issued by the National Institute of Health.¹ As the amount of genetic engineering activity became too great for the regulatory resources of the NIH, the Reagan Administrations Domestic Policy Council, a group of representatives from 18 agencIes and executive offices, that produced the "Proposal for a Coordinated Framework for Regulation of Biotechnology" in the Federal Register on December 31, 1984. The proposal called for EPA, FDA, and USDA to apply their current regulatory authority to genetically engineered organisms. Also, it was recommended that a coordinated science review mechanism be established to promote consistency in agency risk analysis. This was later established as the Biotechnology Science Coordinating Committee "BSCC" on November 14, 1985. The Coordinated Framework became official as revised in the June 1986 Federal Register.²

Currently, the USDA, EPA, NIH, NSF, FDA, and NAS-NRC are all represented in the BSCC, the statutory interagency coordinating mechanism within the Office of Science and Technology Policy. The Coordinated Framework maintains that only those organisms that pose unreasonable risks' should be subject to oversight. Further, the method of assessing the risks of genetically modified organisms will be based primarily on their comparability, in terms of a specified set of characteristics, to previously released organisms. This method will then

¹ Bernard Davis. ed.. The Genetic Revolution: Scientific Prosvects and Public Perception . (Baltimore: John Hopkins University Press. 1991): 31.

² United States General Accounting Office. Biotechnology: Managing the Risks of field Testing Genetically Engineered Organisms (Washington. D.C.: General Printing Office, June 1988):12.

be used to choose the appropriate level of oversight. There are four foundation propositions:

1) Biotechnology regulation should focus on the product organism,

not the process by which it was created.

2) Biotechnology regulation should be risk-based; oversight should

be exercised at a given level of risk only to the extent a net social

benefit is realized.

3) The basis for biotechnology risk assessment should be an

organism's familiarity.

4) Principles 1-3 can be used to generate categories of organisms

exempt from federal oversight.³

The FDA Statement of Policy: Foods Derived from New Plant Varieties.

The FDA policy towards genetically engineered foods is framed by the policy statement FDA Issued simultaneously with the Coordinated Framework in 1986, holding that "foods derived from plant varieties developed by the new methods of modification are to be regulated within the existing framework of the Food, Drug and Cosmetic Act."⁴ Hence, the postmarket authority under ß402(aXl) would continue to be the primary legal tool for ensuring the safety of whole foods derived from genetically modified plants.⁵ Therefore, the FDA has adopted the product not process approach to regulation. FDA will compare genetically engineered foods to those already on the market in order to determine their suitability for entry into the food supply.

In arriving at this policy decision, FDA considered what types of genetically engineered foods it will be called upon to regulate. Because of

~ ³ Peter Mostow. "Reassessing the Scope of Federal Biotechnology Oversight." Pace Environmental Law Review. . vol. 10:1. Fall 1992, Pg. 227, 237.

~ ⁴ Coordinated Framework for the Regulation of Bitoechnology. 51 Fed. Reg. 23,302(1986)

⁵ Secondary Direct Food Additives Permitted in Food for Human Consumption. 59 Fed.

Reg. 26,700 (1994)

the limitations of current molecular genetics, most crops modified using genetic engineering techniques will involve the transfer of a single gene or trait, rather than engineering a novel "ideal food." The policy statement gives examples of enhanced agronomic characteristics such as traits for improved food processing, improved nutritional content, enhanced protection against adverse weather, or protection against viruses.⁶

Theoretically, under the coordinated framework several federal agencies could regulate a single bloengineered food product. A plant genetically engineered to contain a biopesticide could come under the authority of the EPA as a pesticide under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). It could also be considered a plant pest to be regulated by the Animal and Plant Health Inspection Service (APHIS) under the Federal Plant Pest Act. Then, as the product moved into the grocery stores, It could be regulated by the FDA through its authority under the Federal Food Drug and Cosmetic Act. Thus, there is the possibility that food products of biotechnology will be subject to vast amounts of regulatory authority. As such, it is essential to the biotechnology industry that there be a clear, consistent regulatory policy.

The FDA will use the existing tools of food additive amendments, GRAS (generally recognized as safe), and labeling standards in order to assess whether or not genetically engineered foods are fit for consumption. The regulation of the foods will largely depend on the use of the food. "Whole foods,^" such as fruits, vegetables, and cereals that have been improved via biotechnology will be regulated as such and not

⁶ "Statement of Policy: Foods Derived from New Plant Varieties." 57 Fed. Reg. 22986 (1992)

subjected to the stricter requirements for food additives.⁷ Hence, the FDA has chosen not to regulate the introduced DNA as an added substance. Rather, they consider the added DNA to be no different than the 'natural' DNA ingested in every food consumed.⁸ The focus will be on the product of the introduced DNA, i.e. if the introduced DNA codes for an enzyme that will kill aphids, that enzyme will be subject to safety tests and FDA regulatory analysis.

Under ß402(a)(a) of the FDCA, the food additives amendment provision, different standards are set for inherent natural constituents of foods and unintentionally added substances that are poisonous or deleterious.⁹ This is because based on the record of safe development of new varieties of plants, FDA has generally not found it necessary to conduct pre-market safety reviews of whole foods derived from.¹⁰ This Is not the case with food additives. For example, a naturally occurring substance, such as solanin in a potato, will be considered legally adulterated, and therefore subject to enforcement action, only If the quantity is enough to make it injurious to health. Substances that are unintentional contaminants, such as PCBs or lead, will cause a food to be legally adulterated if they ~y render a substance injurious to health.¹¹ Under this standard, the food is adulterated if, by virtue of the presence of the added substance, there is a "reasonable possibility" that consumption of the food will be injurious to health.¹² This, then, is the

~ ⁷ Karen Goldman Herman. Re~uiation of Bloengineered Foods . 7 High Technology Law Journal. 107. 123(1993).

⁸ Robert Bohrer. "Food Products Affected by Biotechnology." University of Pittsburgh Law Review . 653. 660 (1994)

⁹ 57 Fed. Reg. 23.311.

¹⁰ 57 Fed. Reg. at 22.984.

~ ¹¹ Herman. at 124.

¹² 57 Fed. Reg. at 22.984.

higher standard mandated by the Food Additives Amendment of 1958, establishing a premarket approval requirement for food additives.

A food additive must submit to a premarket clearance by the FDA unless it is GRAS. A food is GRAS if its safety was known from common use in foods prior to January 1, 1958 or if its safety has been proven by scientific studies. It is the responsibility of food producers to determine if their substance is GRAS. However, if they market the food believing it to be GRAS, the FDA can decide that it is not and force it off the market. Cautious companies, then, can at the outset request FDA's opinion by filing a GRAS affirmation petition. If the substance fails to meet GRAS standards, a company must submit a food additive petition.¹³

How will all these regulations apply to biotechnology? Clearly, no substances will attain GRAS status by being in common use prior to January 1, 1958! However, the FDA anticipates that typically the transferred genetic material will not be subject to food additive regulation. This is because in most cases the substances expected to become components of food as a result of genetic modification will be the same or substantially similar to substances commonly found in food. Primarily, these substances will be proteins, lipids, and carbohydrates.¹⁴ As the decision of whether or not to apply for a food additive or GRAS affirmation petition will rest with the producer, the Statement of Policy includes detailed flow charts describing the scientific considerations important in evaluating the safety and nutritional value of foods. Based on this decision tree method, the FDA outlines three possible outcomes

¹³ 57 Fed. Reg. at 23.313.

¹⁴ 57 Fed. Reg. at 22.988.

for genetically engineered food plants: no concern; consult FDA, (both informally and formally), and new variety not acceptable.¹⁵ Guidance to Industry

As stated above, it is the responsibility of the producer to evaluate the safety of the food and assure that the safety requirement of ß402(a)( 1) is met. The producer will also have the legal responsibility to determine if the transcription product of the transferred genetic material, i.e. the expressed protein or enzyme, is subject to the food additive regulation or if it is GRAS. When these proteins or substances produced by proteins, such as carbohydrates or lipids, are aiready present in currently consumed foods, there Is unlikely to be a need for formal review. If the expression product differs significantly from Its common correlate, the substance may not be GRAS. Rather, it will require regulation as a food additive.¹⁶

The FDA has provided a guidance section for industry to make its

own determinations if genetically engineered products are as safe and

nutritious as their parents. The assessment scheme focuses on

characteristics of the host and donor, nature of the genetic change, the

identity and function of the newly introduced species, and the

unexpected or unintended effects that may arise. The following are

considered:

• Toxicants characteristic of the host and donor species

• Potential that food allergens will transfer from one source to another

• Concentration and bioavallablity of Important nutrients

• Safety and nutritional value of newly introduced proteins

¹⁵ Boher. at 660.

¹⁶ 57 Fed. Reg. at 22.984.

• Identity, composition, and nutritional value of modified carbohydrates, fats, or oils.¹⁷

The FDA has developed this assessment procedure based on the information and established practices of traditional plant breeders. It is intended that as more is known about genetically engineered organisms and their use in the food supply, these charts will be modified.¹⁸ At this point, FDA estimates that it will require premarket approval only when the BT toxin is used to confer pest resistance, a potential for allergic reactions exists, a natural toxin level increases, nutrition levels are changed, or a substance is introduced that was not previously part of the food supply.¹⁹

It is in the best interest of a food producer for the substance to be approved as GRAS rather than as a food additive. Although in the end the outcome will be the same if the product is safe, the intermediate process can cost a food producer time and money. GRAS is a self-executing provision; the manufacturer performs the tests and makes the determination on her own. Further, GRAS determinations are generally broader than the very narrow uses permitted for food additives. Finally, even if the sponsor does not want to take the risk that the FDA will not agree with her determination and requests FDA affirmation of GRAS status, the FDA review process is quicker and less cumbersome.²⁰ A food additive petition can take as long as seven years.²¹

¹⁷ 57 Fed. Reg.at22.992.

¹⁸ 57 Fed. Reg. at 22,992.

¹⁹ Maher, at 133.

²⁰ Bohrer. at 658.

²¹ Herman. at 124.

Labeling

Section 403(i) of the FD&C Act requires that a producer of a food product describe the product by Its common or usual name and reveal all facts that are material in light of representations made or suggested by labeling or with respect to consequences which may result from use.²² The Statement of Policy calls for labeling "if a food derived from a new plant variety differs from it's traditional counterpart such that the common or usual name no longer applies to the new food, or if a safety or usage issue exists to which consumers must be alerted.^"23 For example, if a tomato has an introduced peanut protein, and that protein is of the type that triggers allergic reactions in certain consumers, and there is insufficient information to suggest that the protein would not cause a reaction, that Information would be a material fact. If it were omitted, the label of the tomato would be misleading under ß403(a) of the act.²⁴

However, FDA has determined that the process of genetically engineering food is not a material fact that requires disclosure in the labeling of food. Rather, the agency will determine on a case-by-case basis whether it will review the food additive status of the substances and work with the sponsor on a case-by-case basis to determine labeling requirements.²⁵ Although consumers submitted comments to the FDA that they had a right as well as a desire to know whether or not their foods had been derived from genetically engineered plants, the agency usually limits the materiality concept to information about the food

²² 21 U.S.C. 343(1); 21 U.S.C. 343(a); 21 U.S.C. 32 1(n).

²³ 57 Fed. Reg. at 22.984.

²⁴ 57 Fed. Reg. at 22.984

²⁵ The Blue Sheet. June 3. 1992.

itself and not details of the process. For example, in the past there was a clamor for labeling as to whether or not Irradiation was used in food processing. As there was no evidence that irradiation of an ingredient would affect the characteristics of the food, the agency held that it was not material information required to be on the label.²⁶ And while the FDA recognizes protein source information to be material to some consumers with respect to religious or cultural beliefs, this determination only applies in the contest of addition to food from things derived directly from animal or microbial sources, not biotechnology. "There is a scientific basis to conclude that such genetic alterations do not change the essential nature of the plant, nor do they confer 'animal-like' characteristics to the plant."²⁷

Eventually, the numbers of genetically engineered foods will be so great that the FDA will not be able to perform case-by-case reviews. As such, the FDA has requested data and information to further define what is a "genetically engineered" organism, under what circumstances labeling would be necessary, how foods derived by genetic engineering differ from other varieties developed by traditional methods of plant breeding, how could required labeling for food allergy be accomplished, and to specify how labeling would be accomplished as a practical matter. The FDA is considering proposals for both required and voluntary labeling. As such, the FDA is requesting information on any industry plans to satisI~' "niche" markets for consumers who want genetically

²⁶ Food Labeling: Food Derived From New Plant Varieties. 58 Fed. Reg. 25837, 25,838 (1993)

²⁷ 58 Fed. Reg. 25.839.

engineered foods labeled and the role FDA would play in regulating these markets.²⁸

Calgene: The Flaw Saw Tomato

On August 12, 1991 Calgene, a California-based biotechnology company, requested an advisory opinion from FDA as to whether or not Flavr Savr tomatoes are food and therefore subject to the same regulation as other tomatoes. The Flavr Savr tomato has been genetically engineered so that it can vine-ripen but still reach the consumer without rotting. Calgene has produced this tomato by introducing an 'anti-sense sequence for the gene that ordinarily produces the enzyme responsible for degrading the cell walls of ripened tomatoes. Anti-sense nucleotide sequences can be used to inhibit or reduce the levels of one of a plant's or animal's normal constituents. By slowing down the rate of expression of the "rotting" enzyme, polyglacturonase, the Calgene tomato rots at a slower rate. Therefore, this tomato will taste better than supermarket tomatoes that are picked green and ripened by exposure to ethylene gas.²⁹

Calgene maintains that the anti-sense polyglacturonase is not an additional substance. Rather, the Flavr Savr tomato differs from supermarket tomatoes only in its lower levels of the polyglacturonase enzyme. Thus, this tomato is like any other new variety developed by traditional plant breeding methods. However, in introducing the anti-sense sequence the scientists used a common research tool, the gene for kanamycin resistance. This gene is used to select the cells that have added the desired genetic sequence. This is done by linking the

²⁸ 58 Fed. Reg. 25.839.

²⁹ Bohrer. at 671.

kanamycin resistance gene to the anti-rotting gene. The cells are then grown in a kanamycin environment. Only the cells that have kanamycin resistance, and also the new sequence, will survive. The kanamycin gene does persist beyond the research stage in that low levels of both the kanamycin resistance gene and the enzyme it codes for, kanamycin phosphotransferace II, are expected to be present in the foods derived from such plants.³⁰

As there is currently concern over the widespread use of antibiotics in animal feed as well as human and animal medicines due to increased chances of resistance, the idea of introducing an antibiotic resistance gene into the environment has raised many eyebrows. Calgene, aware of these worries, submitted a request to the FDA requesting an advisory opinion on the safety of using a ka.namycin resistance gene in food plants for both human health and the environment. Using the flowcharts provided in the 1992 Statement, there are two questions that seem troublesome with respect to kanamycin resistance: (1) Does the biological function of the protein raise safety concerns? (2) Will the introduced gene be a macroconstituent in the human diet? With respect to the first question, while it is unlikely that the enzyme would survive intact the digestive process to counteract an orally administered antibiotic, this question needs to be further explored. As to the second question, antibiotic resistance is a widely used tool in genetic engineering. As such, one can except that most genetically engineered crops will be marked with the kanamycin resistance gene.³¹ It needs to be explored if, by granting the kanamycin resistance enzyme GRAS or a

³⁰ Bohrer. at 673.

³¹ Bohrer. at 674.

food additive amendment status, its widespread use will have a deleterious effect on either human health or the environment. It is noted that while Calgene has no doubt performed many of these tests, the company may not have been required to do so by the FDA.³²

On May 23, 1994 the FDA announced that the agency had concluded that FLAVR SAVR tomatoes have not been significantly altered when compared to varieties of tomatoes with a history of safe use. The FDA amended the agency's food additive regulations to provide for the safe use of axnlnoglycoside 3 minutes - phosphotransferase II ('APH' - the transcription product of the kanamycin resistance gene). The agency determined that the protein did not differ enough from other phosphorylating enzymes in the food supply to warrant concern, especially considering the low exposure levels and digestibility of APH.³³ As to the antibiotic resistance, the agency commented that the patient population likely to be exposed to axnlnoglycoside antibiotics are unlikely to be consuming tomatoes or other fresh fruits and vegetables.³⁴ Further, the FDA declined to deviate from it's practice of not treating as an ingredient a new constituent of a plant introduced by breeding or other agricultural techniques, hence neither the kanamycin resistance gene nor APH will be required to be listed as ingredients under ß403(1) of the act.³⁵ Based on these findings, the FDA amended the agency's food additive regulation to provide for the safe use of APH as a processing aid and declared that it had no plans to regulate the DNA itself as a food additive. And although the agency did not require labeling of the Flavr

³² Bohrer. at 674.

³³ 59 Fed. Reg. 26,702.

³⁴ 59 Fed. Reg. 26.703.

³⁵ 59 Fed. Reg. 26.708.

Savr tomato, Calgene has agreed to do so in response to the tremendous public outcry.

Bovine Growth Hormone

On November 5, 1993 the FDA approved a new animal drug application providing for the subcutaneous use of sterile recombinant bovine somatrophin 'r-BST', also known as bovine growth hormone.³⁶ In the late 1980s when plans to market the genetically engineered equivalent to the naturally occurring cow growth hormone became known, there was a great consumer uproar.³⁷ This concern led to an extraordinary six-year period of regulatory review.³⁸ During this period, technicians at the U.S. FDA Center for Veterinary Medicine found there were no adverse effects on human health from consuming milk and meat from cows injected with r-BST. Despite these conclusions, FDA delayed commercial marketing and requested a second opinion from NIH, who then determined that r-BST is "essentially the same" as milk from untreated animals.³⁹

Despite these extra efforts to ensure the safety of this new animal drug, in April of 1989 two dairy states, Wisconsin and Minnesota, passed laws prohibiting the sale or use of r-BST in daliy cows. Plans to sell rBST brought a temporary ban from the European Community. There was a call for further study of the potential hazards and impacts before sales could resume.⁴⁰ Consumer groups threatened to boycott the milk from cows treated with this new animal drug."' All this, despite the

³⁶ 58 Fed. Reg. 59.946.

³⁷ Hernian.at 113.

³⁸ Bohrer. at 653.

³⁹ The Blue Sheet . December 12. 1990.

⁴⁰ Linda Maher, "The Environment and the Domestic Regulatory Framework for Biotechnology.' 8 Journal of Environmental Law & Utigatlon . 133. (1993) 41 Hernian.at 112.

overwhelming evidence of the safety of the drug as well as the phenomenal increase in milk production. Clearly, this case study demonstrates how the decision as to the regulatory policy for genetically engineered foods must extend far beyond simply the scientific Issues at hand.

Critique of the FDA Policy and Recommendations

As addressed above, the budding biotechnology industry has called for clear rules that will not hamper economic development. Environmentalists have called for caution in light of the uneertainties surrounding the new science of molecular genetics. Consumers have called for better tasting and cheaper food products, yet are cautious about purchasing a product dubbed "genetically engineered." Has the new FDA policy satisfied all of these concerns? Has it satisfied any? Can it? There are three areas that criticism about the FDA policy is targeted: biotechnology as a process should be regulated; labeling of genetically engineered organisms should be required; and premarket notification should be mandatory.

Process over Product Based Regulation

Many argue that bloengineered foods do not fit into any existing regulatory categories.⁴² Prior to the development of genetic engineering techniques, interspecles breeding occurred only among closely related lines. For example, domesticated wheat would be crossed with a wild relative to confer a pest resistance trait. With the development of molecular genetics that same wheat plant can incorporate genes from a much wider spectrum of donors, including animals and bacteria. On the one hand, this leads to greater control over the final organism, as only

⁴² Herman. at 127.

15-

the chosen characteristics are introduced. However, there is still much that is not understood about molecular genetics. Researchers have found that the characteristics of genetically engineered organisms differ from those the researcher intended. This can be due to the fact that genetic engineers can not control where they insert genetic material in an organism's genome. Additionally, interactions among genes and the effect of the environment on gene expression are not well understood.⁴³ Hence, advocates for per se regulation of genetically engineered foods maintain that Just because no disasters or adverse side effects have yet occurred does not mean that the need for regulatory caution is any less. Therefore, in the face of uncertainty, error should be on the side of caution. Further, the burden of uncertainty should be borne by the biotechnology industry in the form of slower development to market times.

Advocates for biotechnology specific legislation argue that the current policies were designed for chemical substances, not living organisms that can mutate and change.⁴⁴ This also extends to an important basis for the risk assessment mechanism set up by the FDA, that the more familiar an organism is to its common or usual relative, the safer it is. The potential for unexpected consequences, such as activating pathways or effecting other enzymes can not always be predicted by the familiarity of an organism. Finally, while this group may concede that genetically organisms may not be per se risky, they maintain that they "might very well have characteristics that make the

~ ⁴⁴ Hopkins. D. Douglas. Rebecca Goldburg. Steven Hirsch. "A Mutable Feast." Enviommental Defense Fund. October 1. 1991. Pg. 56.

~⁴⁵ Herman. at 115.

risks they pose of a sort not easily regulated by the current regimes."⁴⁵ It can be argued that the product over process based regulation is a

concession to industry. After all, the multinational companies who have the money to pay for the costly research to develop these products have been regulating their pharmaceutical and processed food products with the FDA for years. The machinery to file for the food addition petition or GRAS affirmation is already in place. As the FDA has traditionally been in the position of regulating the industry for the protection of the consumer, one has to ask if the FDA has conceded to industry, with what is the consumer left?

In the end, the arguments for a product based, as opposed to a process based, regulatory policy are stronger. Primarily, any government wide biotechnology regulatory agency would be too broad to be effective given the wide range of applications of molecular genetics. Hence, it is unlikely that this basic tenet of the Coordinated Framework is going to change. A key component of the Coordinated Framework is interagency coordination. If the FDA were to decide not to comply with process-based regulation, it would be labeled a non-team player. In order to preserve its jurisdictional territory, the FDA must maintain positive relations with the EPA and USDA. Finally, any gaps in the regulations that emerge as a result of product based regulation can be bridged by a mandatory pre-market notification policy.

Labeling

The FDA requires, with few exemptions, that any food fabricated from two or more ingredients carry a label disclosing the ingredients by their common or usual name. The FDA has determined that the process

'~⁴⁵ Mostow, at 242.

of genetic engineering itself does not warrant inclusion on the label under the materiality threshold of ß201(n) nor 8403(a), however the agency has requested comments on the labeling of foods derived from new plant varieties.

Many consumer advocacy groups, such as Jeremy Rllkin's Foundation for Economic Trends, an anti-biotechnology organization, have demanded that foods be labeled as "genetically engineered."⁴⁶ In a report submitted to the FDA, the Environmental Defense Fund made a similar request, maintaining that such labeling was required under the FD&C Act. "An expression product of genetic material from another species, or of synthesized genetic material, should be considered a food ingredient and be labeled under existing FDA regulations."⁴⁷ The EDF claims that the ß403(1) ingredients labeling provision requires labeling if a food has genetically engineered components as "such substances are essentially fabricated from the substances."⁴⁸ In the past the FDA has required common or usual names to be used on ingredients to meet the needs of consumers with special dietary interests, as in the protein source rule mentioned above. This is simply an extension of this rule, i.e. that adding an introduced genetic sequence is a deliberately added ingredient that makes the final product have some greater value than the separate, uncombined ingredients.⁴⁹

Section 403(a) prohibits labeling that is "false or misleading in any particular."⁵⁰ FDA has interpreted the term misleading to include omission of information constituting a material fact. In 1986 FDA held

⁴⁶ The Blue Sheet. 6/3/92

⁴⁷ Douglas. at 9.

⁴⁸ Hopkins at 40.

⁴⁹ Hopkins at 43.

⁵⁰ 21 U.S.C. i343(a)

that it would determine what is material based on consumer perception:

"Whether information is material under 21 U.S.C. ß321(n) depends not on the abstract worth of the information but on whether consumers view such information as important and whether the omission of label information may mislead a consumer."⁵¹ In light of the uproar over both the Calgene tomato and bovine growth hormone, It is likely that a significant portion of the public feels this information Is material.

FDA has decided that this information is material based on it's own understanding of the scientific issues in question, i.e. inserting a gene from an animal to a plant does not confer animal-like characteristics nor is ingesting the interspecies DNA any different than ingesting intraspecles DNA. However, it is unlikely that this scientific information is meaningful to the majority of consumers. Rather, the public has a heightened awareness of environmental damage and health problems that manifest decades after being exposed to the causative agent.⁵² By relying on scientific propositions to determine meaningful, the FDA has detoured from it's policy of judging materiality based on consumer perception.

For the time being, at least, the FDA policy against mandatory labeling of genetically engineered foods is likely to be irrelevant in light of the consumer outcry over the release of r-BST and the Flavr Saw tomato. Although consumers may not be per se opposed to genetic engineering, they are fearful that "companies that bloengineer foods to enhance their flavor, texture, color, durability or shelf life may not have to disclose

~ ⁵¹ Final Rule: Irradiation in teh Production . Processing. and Handling of Food. 51 Fed.Reg. 13376. 13388(1986)

⁵² Herrnan,at 115.

that fact."⁵³ The growing demand for organic fruits and vegetables, as well as foods packaged without preservatives demonstrates that consumers want to know more about what they are consuming. Biotech companies are fearful of a scenario where tomatoes are stamped with a double helix, which consumers will equate with Frankenstein and the poison skull. However, this can be prevented through education, perhaps similar to nutrition labeling. Indeed, if biotechnology is to become an important factor in the American consumer's life, then the consumer deserves to understand what exactly this revolution is all about in order to be able to make informed decisions about what risks are acceptable.

Mandatory Pre-Market Notification

Under the current policy, producers are only required to consult the FDA if there are objective considerations, laid out in the flow charts, that raise safety questions. Theoretically, then, a food producer could market a genetically engineered food with out ever being subjected to FDA regulation. While it is likely that for the next few years, as the number of genetically engineered foods is minimal, producers will error on the side of caution and request advisory opinions, this is not likely to last once more genetically engineered organisms are on the market. The EDF has recommended to the FDA that producers of new genetically engineered foods analyze the composition of these foods and notify the FDA of the results of these tests before the foods are introduced or delivered into interstate commerce.⁵⁴ They argue that such a proeedure will increase the chances of discovering inadvertent changes that might

⁵³ Mlchaei Schrage. "Genetically Engineered Foods May Be Safe, but They Still Should be Labeled." The Washington Poet. June 5, 1992, pg. bi 1.

⁵⁴ Hopklns, at 56.

pose risks to consumers by 'double-checking' the tests it Is assumed producers will perform.⁵⁵ If the producers are not required to disclose this information, as under the current system, the FDA will not be in possession of the knowledge that will be essential to updating and revising the risk assessment policy as more and more genetically engineered products are brought to the marketplace.

By relying solely on the producer's evaluation of the risks laid out by the FDA, easily quantified risks that fit into the cost benefit framework are given precedence over harder to quanitify risks.⁵⁶ A producer, with a significant profit motive, is Ill equipped to make the significant value or political decisions that g1~g..the risks of biotechnology will entail. Federal regulators can not shy away from the fact that regulating the products of biotechnology necessarily means making value judgments. "Risk assessment holds out the promise of 'objective', scientific regulations, regulations that are easier to defend and which, because they tend to seem less directly political, are less likely to become embroiled in political controversy."⁵⁷ On the other hand, it is arguable whether FDA would ever engage Itself in this type of decision making. This is due to the limited resources of the FDA as well as bureaucratic hesitance to engage in outright political decision-making.

By building up it's own database of information on genetically engineered foods, the FDA could better serve as a watch-dog over producers as well as ensure that the "soft" or second-order risks that do not fit easily into quantitative analysis are considered in the risk

⁵⁵ Hopkins, at 56.

⁵⁶ Moetow. at 243.

~' ⁵⁷ Moetow. at 243.

assessment procedure. In situations where risk assessment leads to uncertainty, factors left out by quantitative risk assessment should be given more weight.⁵⁸ Although this would require more FDA resources than the current plan, the majority of the burden would still be passed on to industry by mandating that certain tests be performed. Further, gathering information now will lead to a better, more informed regulatory structure in the future. Hence, FDA can save itself and the biotechnology industry resources over the long run.

Conclusion

The biotechnology revolution has occurred in a society that, for the first time, is aware of the complexity of any introduction of technology and the possibility for unintended effects. Ozone depletion and climate change stand as constant reminders. We have become self-conscious of our ability to control technology. Necessarily, biotechnology regulation will not proceed in the same manner as the chemical and nuclear industries before it. Rather, the complexity and uncertainty of the genome should be recognized at every step of the way. The line must be drawn between these risks and the great societal and economic benefits to be gained by this powerful technology.

The FDA is necessarily the agency that must perform this baiancing act with respect to genetically engineered foods. This can best be done by carefully monitoring and compiling information on these foods as they enter the marketplace. Frequent re-evaluations of the risk assessment framework must be performed based on this information. The FDA must also ensure that consumers are informed and educated about the role of biotechnology in their food supply. The FDA entrusts

⁵⁸ Moetow. at 267.

⁵ *

*

~~~₄ owed.