Biotechnology Project
Center for Science in the Public Interest
 How to Approach the Regulatory Conundrum?

By Gregory A. Jaffe, Director, Biotechnology Project
presented at the National Agricultural Biotechnology Council's Foods for Health conference — May 19, 2002.

Today, farmers and the environment benefit from the first generation of agricultural biotechnology crops. The biotechnology industry and academics trumpet the next generation of genetically engineered ("GE") crops, such as more nutritious foods and plants used to produce pharmaceuticals, antibodies and industrial enzymes. If those crops are commercialized, is the current regulatory structure in the United States up to the task of ensuring that those products are safe for humans and the environment? This paper analyzes the ability of the regulatory system to adequately regulate the next generation of agricultural biotechnology products. It concludes that without additional legal authority and stronger oversight, the US regulatory system cannot ensure that only agricultural biotechnology products that are safe for humans and the environment are commercialized.

I.  What the Future Holds?

Virtually every week there is media coverage about new applications for agricultural biotechnology. Some applications add new genes to crops to make food more nutritious. For example, in the past year, the press has reported on the following potential products:

  • Scientists have inserted two genes from a daffodil and one from a bacterium into rice plants to create golden rice. That rice produces beta-carotene, which the human body turns into vitamin A.

  • At University of California at Davis, scientists have modified rice plants to carry a human gene for a milk enzyme called lactoferrin. Rice containing that human breast milk protein may be helpful in fighting infections.

  • In Australia, one of the four primary protein genes present in cows has been inserted into calves to enable production of high protein milk. Those cows may produce more nutritious milk.

  • Researchers are trying to increase the anti-oxidant properties of tomatoes by engineering them with more lycopene and increased levels of lutein (known to help fight eye disease).

Research is also being conducted so that agricultural crops can be employed as factories to produce biological molecules in a cost-efficient and renewable manner. For example:

  • Prodigene has engineered corn plants to produce avidin and trypsin. Avidin, which is usually found in egg whites, is used in medical and biochemical diagnostics. Trypsin is an industrial enzyme used to produce drugs.

  • Epicyte is currently engineering plants to produce antibodies, such as a topically applied antibody that prevents the transmission of herpes simplex virus.

  • Hiridin, an anticoagulant, has been produced in transgenic canola and is available commercially in Canada. That human protein is used to treat blood clots.

  • In April, a company announced that it has produced a genetically engineered corn that contains a protein on the surface of HIV, the virus that causes AIDS. The next step for that edible vaccine is animal studies to see if ingestion of the corn elicits an immune response. Other crops, such as bananas and carrots, are also being engineered to produce vaccines.

Those potential products and many others provide some hope that the next generation of products may benefit consumers, both in developed and developing countries. If those products are commercialized, fruits, vegetables, and grains will become vehicles that provide consumers with more nutritious and healthful foods and biological factories that produce useful medical and industrial molecules.

II.  Is the Regulatory Structure Up to the Task of Regulating New Uses of Agricultural Biotechnology?

Currently, agricultural biotechnology is regulated to protect human health and the environment. Is the current federal regulatory system up to the task of thoroughly assessing the safety to humans and the environment of the next generation of GE crops? A review of the regulatory system's treatment of the first generation of biotech crops identifies both weaknesses and gaps in the current system and problems that will arise when regulating future crops. New statutory authority and stronger oversight is needed to ensure that only commercial products that are safe for humans and the environment are marketed.(1)

III.  Ensuring that GE crops are Safe to Eat

Consumers want assurance that the foods they eat are safe to consume. Thus, the Food and Drug Administration ("FDA") should ensure the safety of biotech foods before they are marketed to them. FDA's current regulatory system, however, does not adequately ensure that only safe GE crops are marketed.

A.  Current Regulation of Biotech Foods

Currently, FDA does not formally approve any GE crops as safe to eat. FDA has the authority to approve new food additives, but says that the GE crops developed so far do not fall within that authority. Instead, FDA has determined that GE crops are similar to conventionally bred crops and should typically fall into the category of "generally recognized as safe" ("GRAS") foods. FDA's policy does allow a GE crop to be treated as a food additive requiring mandatory approval if that crop raises a food-safety concern. However, to date, FDA has not determined that any GE crop should be considered a food additive and it is unclear if any future crop will fall into that category. Both FDA and the biotechnology industry will strongly resist putting biotech foods through the food additive process, since that process is perceived as time-consuming and burdensome.

To oversee any potential food-safety concerns that might exist for a GE crop, FDA adopted a voluntary consultation process to review safety data provided by companies to ensure compliance with existing laws. In that process, the biotechnology company provides summary information about the food-safety of its product to FDA and FDA provides informal advice about the adequacy of the tests conducted by the company. In conducting its scientific safety assessment, the company provides information to show that its biotech variety is "substantially equivalent" or as safe as its conventionally bred counterpart. To date, almost all commercialized GE crops have proceeded through the voluntary consultation process before marketing.

B.  Problems with FDA Current Biotechnology Policy

There are numerous problems with FDA's current policy for GE crops. First, the consultation process is voluntary. There is no legal obligation that requires that companies provide a safety assessment to FDA and no consequences to a company if they do not voluntarily consult. Second, the consultation process is developer-driven instead of FDA-driven. The biotechnology company decides what safety tests to conduct and what data to submit to FDA because the company's obligation is to satisfy itself that the product is safe rather than prove safety to FDA. The voluntary process provides FDA with limited ability to require specific tests or mandate specific data. Third, FDA's food-safety analysis is not comprehensive. FDA guidance states that the consultation process is "not a comprehensive scientific review of the data generated by the developer." Fourth, and most importantly, FDA does not determine if the product is safe. The voluntary consultation process culminates with FDA stating that it has "no further questions . . . at this time" regarding the food instead of a statement that the product is safe to eat.

Although no human health problems with GE crops have been detected, the voluntary consultation process is not the most effective way to protect human health and engender public confidence. As the next generation of GE crops are marketed in the coming years, the scientific safety issues raised by those more complex GE crops (such as nutritionally enhanced crops or plants engineered with new metabolic pathways) cannot be adequately assessed with this industry-driven process.

C.  FDA's Recently Proposed Mandatory Notification Rule

In January 2001, FDA proposed regulations that would mandate notification before a GE food is marketed. Although that proposal improves upon the current process by mandating agency review and increasing transparency, it does not change the agency's scientific review nor will it result in an official safety determination. Under the mandatory notification, FDA still does not respond with an affirmation that the food is safe to eat. Also, if a developer markets a biotech food without notifying FDA, FDA still must prove the food is adulterated before it can be removed from commerce.

D.  How Will the Current System Treat the Second Generation of Biotech Foods?

As products such as golden rice or high lycopene tomatoes make their way to the marketplace, will FDA's current regulatory policy treat them any differently than the first generation of herbicide-resistant and pesticide-producing crops? The answer is no. It is unlikely that FDA will treat the second generation of GE food crops as products that contain food additives since the gene products in high lycopene tomatoes or rice engineered to contain a human breast milk protein are substances normally found in the human diet. Thus, the only food-safety assessment those products will receive is the less-than-comprehensive voluntary consultation process. Those products would have to abide by the mandatory notification process, but only if FDA finalizes that proposed rule. FDA has stated that it will not make a decision on its proposed rule before sometime in fiscal year 2003 and no one knows what form the final rule will take if promulgated.

E.  A Proposal for a Mandatory Approval Process

FDA should establish a new mandatory approval process, unrelated to the current food additive process, for GE crops. FDA should promulgate regulations that establish testing and data requirements based on advice from a National Academy of Sciences panel of scientists charged with determining what scientific information is needed to assess the food-safety concerns of such crops. The approval process should have time limits so that each submitted application receives a determination from FDA in a reasonable period of time. In addition, the mandatory approval process should ban any biotech food with a new allergen as well as prohibit approvals for crops intended for animal feed but not human consumption. If new legislation is needed so that FDA can implement an approval process, Congress should pass such legislation.

A mandatory pre-market approval process at FDA for biotech foods would have numerous advantages over the current system. First, an approval by FDA would provide an independent check on industry's safety determination. FDA would share responsibility for the safety determination and would help prevent food-safety mistakes. Second, it eliminates the gap in the U.S. regulatory system which allows some biotech foods, but not others, from being marketed without pre-approval. Currently transgenic animals require pre-market approval by FDA and pesticidal plants require pre-market approval by the Environmental Protection Agency, yet non-pesticidal transgenic plants only need go through FDA's voluntary consultation process. Third, an approval process would not be more burdensome to applicants than the current voluntary process. The industry states that it already conducts all reasonable and necessary tests to ensure safe products, so there is little likelihood that FDA would require significant new testing. Fourth, a mandatory approval process would conform the US regulatory system to similar systems in Canada and Europe, which affirmatively approve biotech foods before marketing. Finally, a food-safety determination by FDA would go a long way to improving consumer confidence and public perception of the safety and acceptability of biotech foods. Consumers are much more comfortable with FDA determining a food is safe to eat that relying on Monsanto or Dupont's own safety determination.

In conclusion, the benefits of a properly constructed mandatory approval process at FDA are tremendous and the burdens to industry need not be much greater than the current voluntary consultation process. It is unclear why industry is against a process which would provide an independent verification of their product's safety and sway skeptical consumers. Therefore, producers of new GE crops should embrace sensible legislation to require a mandatory approval of GE crops, such as Senator Durbin's Genetically Engineered Foods Act.

IV. Environmental Issues Surrounding GE Crops

The second major regulatory issue for new GE crops is ensuring that those crops do not cause environmental problems. For the federal regulatory system to adequately carry out that function, the system must:

  1. Ensure that all biotech products get a thorough environmental assessment by a competent government agency before release into the environment; and

  2. Ensure that if products are approved with conditions to manage possible environmental risks, those conditions are adhered to (through compliance assurance and enforcement measures).

Unfortunately, the current federal regulatory system for GE crops at the U.S. Department of Agriculture ("USDA") falls short on both accounts.(2)

A. The Current Regulatory System at USDA

Under the authority of the Plant Pest Act, USDA has established a regulatory system for genetically engineered plants that could become plant pests. Crops subject to those regulations include (1) any crop that is a listed plant pest, and (2) any crop that has introduced DNA from a listed plant pest or an organism whose plant pest status is undetermined. For example, the regulations capture any genetically engineered crop that uses agrobactium DNA as part of its genetic construct to insert a new gene into a plant. The regulations do not include crops engineered using a gene gun, unless the inserted DNA comes from a listed plant pest or an organism whose plant pest status is undetermined.

Any plant covered by USDA's regulation must submit to one of three oversight processes before release into the environment. The first of those processes is a notification, in which the applicant provides USDA with details about its proposed release and USDA has thirty days to respond to the notification. USDA has established criteria to determine which products are eligible for the notification process and guidelines that must be met to minimize environmental effects from the release. Notification is currently used to regulate virtually all of the field tests for GE crops under USDA's jurisdiction and even for some crops that are grown commercially.

The second process is permitting, which requires a more detailed application and a longer review time at USDA before the release is authorized. Genetically engineered plants that must be permitted (instead of a notification) include crops producing pharmaceuticals and those that could affect non-target organisms. Permitting is not used as commonly as the notification process, although hundreds of permits have been issued since USDA began regulating GE crops.

The third process at USDA is a petition for non-regulated status. A petition is a request that USDA determine that there is no plant pest risk associated with the crop and that the crop no longer needs to be regulated. A petition for non-regulated status has been the primary pathway to commercialize GE crops. Before a petition is granted, USDA conducts an environmental assessment of the crop and seeks public input through a formal public comment period.

B. Inadequacies with USDA's Current System

There are numerous inadequacies with USDA's current regulation of GE crops. First, the regulatory system only captures GE crops that could become plant pests, leaving a gap in USDA's authority so that some GE crops, such as those made with a gene gun and corn DNA, do not require even a notification before release into the environment.

Second, for GE crops covered by USDA's regulations, those regulations do not require that a thorough environmental assessment occur prior to the plant's release into the environment. Crops released through either the notification or the permitting process almost never receive an individual environmental assessment, yet some of those crops might have significant environmental impacts. A recent National Research Council ("NRC") report determined that "With few exceptions, the environmental risks that might accompany future novel plants cannot be predicted. Therefore, they should be evaluated on a case-by-case basis." Yet, the notification and permitting process does not evaluate environmental risks on a case-by-case basis since no environmental assessment is conducted for most individual applications processed using those procedures.

Third, for those crops that do receive a thorough environmental assessment from USDA (consisting primarily of crops that seek nonregulated status), those environmental assessments are inadequate. According to the NRC report: "Currently, APHIS environmental assessments focus on the simplest ecological scale.... APHIS should includeany impact on regional farming practice or systems in its deregulation assessments." Thus, USDA's environmental assessments do not address all relevant environmental concerns.

Fourth, it is unclear whether USDA has the legal authority to adequately address environmental issues that arise in an environmental assessment. USDA has regulatory authority to address plant pest risks but does not have authority to prevent a crop's release if it may cause ecological harms unrelated to agriculture.

Fifth, most large-scale releases occur after the GE crop has obtained nonregulated status. Although the petition process for nonregulated status is transparent, open for public comment, and involves an environmental assessment, the process results in a crop that is no longer regulated by USDA. That prevents USDA from requiring post-release monitoring for environmental effects and from addressing environmental issues that might occur. Therefore, for the vast majority of crops, USDA has extremely limited ability to address environmental issues that might arise after commercialization.

Finally, the process at USDA involves no food-safety analysis of the crop before it is released into the environment. For open-pollinating crops such as corn, a release could result in the gene product entering the food chain. USDA's process makes no assessment whether that gene product will be harmful to humans if it does enter the food supply.

C. Preventing Contamination of Other Crops and the Food Supply from Experimental GE Crops and/or GE Crops Producing Non-food Products.

When USDA regulates a GE plant under either the notification or the permitting process, one of USDA's goals is "to minimize persistence in the environment and inadvertant mixing with ... products which are used for food or feed." This is accomplished, in part, by using containment and/or segregation procedures. Those procedures may limit contamination but do not eliminate it, since eliminating all contamination is impossible.

The ability of the regulatory system to adequately contain GE plants producing products that might harm the environment or humans is extremely important, whether it is a corn plant producing a pharmaceutical or a sunflower plant producing an industrial chemical. USDA and FDA have stated they are working on a guidance that will address contamination issues surrounding pharmaceutical plants but that guidance currently is not publicly available. Yet, numerous field trials and commercial planting of pharmaceutical crops have occurred without uniform standards to minimize contamination. Consumers will lose confidence in agricultural biotechnology and the safety of the food supply if they find out that some food they are eating contains a pharmaceutical or industrial chemical that has not been found safe to ingest. Thus, strong regulatory structures that minimize contamination are important.

1. Containment Procedures

The first way to minimize the effects of GE crops on non-GE crops and the food supply is through containment procedures. Those procedures attempt to limit gene flow of the introduced gene. Containment procedures include reproductive isolation measures, such as distance restrictions for planting GE crops from non-GE crops, guard rows between GE and non-GE crops, the use of male sterile lines that don't shed pollen, harvesting prior to flowering, netting or bagging of pollen prior to flowering, and the staggering of flowering times for adjacent crops.

For example, USDA recently sent a letter to companies planning on planting pharmaceutical corn crops in 2002 that set forth distance restrictions that ranged from 1/4 mile to 5 miles (the latter being the distance from seed corn) and planting times for the GE corn that were either 14 or 21 days before or after adjacent non-GE corn crops. The letter, however, contained no scientific justification for the distances or planting times chosen nor set forth how effective those restrictions would be in reducing or eliminating contamination of non-GE crops. It is unclear whether those distances and planting times will reduce the chances of gene flow by 50%, 90%, or 99%. Thus, although reproductive isolation is necessary and needs to be established, there should be a public explanation why certain procedures are required and what is the expected benefit of those procedures.

The second type of containment procedures that minimize persistence of the GE crop in the environment are post-harvest restrictions. Post-harvest restrictions include limiting the use of land for a period of time following the planting, monitoring the land and neighboring fields for volunteer plants of the GE crop, and destroying the crop after harvest using specific procedures. Those post-harvest restrictions are important to prevent GE crops from persisting in the environment after the field trial or commercial planting. It is unclear, however, how effective those activities are in preventing gene transfer.

2. Segregation

In addition to containment procedures, segregation is usually employed to ensure that experimental GE-crops and GE-crops producing non-food products do not mix withe crops (both GE and conventional) that are grown for food purposes. Segregation has generally involved dedicated machinery and vehicles to harvest, store and transport certain GE-crops.

Is segregation effective in preventing contamination? When farmers planted the GE corn called StarLink that had been only approved for feed uses, Aventis (the developer of StarLink) agreed that the crop would be segregated from corn used for human consumption. StarLink corn, however, did end up in the food supply, either because no segregation system was actually put in place or because the system that was put in place was ineffective. Many experts now question whether any segregation system can effectively separate out one type of corn from another. Thus, it is an open question how effective segregation can be at eliminating contamination of the food supply. If properly set up, segregation can minimize contamination, but may never be able to completely eliminate it.

D. Enforcement

When a GE crop has been approved to be released into the environment, frequently the approval sets forth conditions to minimize or eliminate environmental and/or food-safety risks. It is imperative that developers and growers comply with those conditions and it is USDA's job to make sure those conditions are being adhered to. Is USDA doing a good job enforcing its conditional approvals? The answer is no.

USDA has conducted some inspection of field trials and commercial releases that have permits or submitted notifications, although the level of effort is small compared to the universe of GE crops. To date, there have been over 9,000 permitted releases or notifications for GE crops, yet only a very small fraction of those releases have been inspected by USDA. The inspections USDA has conducted have resulted in approximately 60 enforcement actions, primarily letters explaining improper conduct and requesting that restrictions be adhered to.

When USDA does inspect a permitted release, however, it is unclear whether those inspections are as comprehensive as needed to safeguard the environment. In particular, USDA does not check to see if the containment or segregation procedures are working. For example, inspectors do not check neighboring fields to see if pollen has drifted and caused gene flow to non-GE crops. Also, they do not test grains on the farm or neighboring farms to ensure that the crop has been properly segregated. Thus, USDA should not just inspect to see if the conditions imposed on a GE-crop have been met, but whether those conditions result in the containment and segregation expected from the proper implementation of those conditions.

E. Conclusions About USDA's Regulation of GE Crops

USDA's regulations do not adequately protect the environment and humans from current GE crops and will not adequately protect the environment and humans from the next generation of crops, such as those producing pharmaceutical plants. In particular, the USDA regulatory system has the following deficiencies:

  • It does not capture all GE crops;

  • It does not result in a thorough environmental assessment for all GE crops;

  • It does not have a mechanism for the monitoring of environmental problems that might arise after a crop has obtained nonregulated status, nor a means of enforcement if a problem occurs; and

  • It does not conduct inspections to identify whether containment procedures to minimize gene flow from GE crops and segregation requirements to minimize food contamination from certain GE crops are effective.

Until those deficiencies are eliminated, the federal government will not be adequately ensuring that the only GE crops released into the environment are safe to humans and the environment.

V. What to Do About GE Crops that are not Intended to be Food but Might End Up in the Food Supply?

As discussed earlier, the next generation of biotech crops will use food crops to produce non-food products, such as pharmaceutical plants or plants engineered to produce medical diagnostic proteins. What happens if those crops accidentally end up in the food supply due to gene flow from pollen, contamination of seed stock, or a breakdown in an identity-preserved segregation system? Will they be safe to consume? Will they be safe to consume only at certain exposure levels? Is there any authority for FDA to review and approve those products as safe to eat in case they enter the food supply? Those are all questions that need to be addressed. Containment and segregation will not be 100% effective, so it is only a matter of time before one or more of the non-food GE crops ends up in our food supply.

The Federal Food Drug and Cosmetic Act ("FFDCA") regulates anything that is intended to be used as food or feed. A pharmaceutical corn plant or a corn plant producing avidin, however, is not intended by the developer to be used as food or feed. Thus, those products are neither food additives, nor would they be subject to FDA's voluntary notification process (or FDA' s proposed mandatory notification rule). FDA has limited authority over those products unless they show up in food. At that stage, FDA could consider foods containing the pharmaceutical drug or industrial chemical adulterated and remove them from the market. The burden would be on FDA, however, to prove they are adulterated.

The current system is not the best way to ensure a safe food supply, when contamination by non-food GE crops is inevitable. A possible solution to this problem would be for the proposed mandatory FDA approval process to apply to non-food GE crops. Under that approval system, FDA could set tolerances for non-food GE crops. Then, if that GE crop entered the food supply, eating the engineered substance would be safe as long as the substance was below the tolerance level. No consumers would need to fear that they were eating food with unsafe substances in it. In addition, the rigor of the food-safety assessment conducted by FDA could be proportionate to the physical and biological confinement of the crop. If the pharmaceutical plant was grown in a cave or a location far from other corn plants, only a limited food-safety assessment might be required because the likelihood of contamination would be extremely small. If the pharmaceutical plant was grown in Iowa, however, then a complete food-safety analysis might be warranted.

VI. Conclusion

Although agricultural biotechnology may allow us to produce more nutritious foods and useful medical products, the current federal regulatory structure is not up to the task of safeguarding those products. With new legal authority and better regulations, a strong, but not stifling, system can be established that independently reviews and approves products that are safe for consumers and the environment. Such a system is essential if consumers are to have confidence in biotechnology and accept biotechnology products in the marketplace.

1 Although the next generation of biotechnology crops includes the production of drugs and the delivery of vaccines, the drugs and vaccines produced will be regulated similarly to conventionally produced drugs and vaccines. Therefore, this presentation will not include a discussion of those regulatory issues.

2 This presentation will focus on the USDA regulatory process for biotech crops and does not discuss EPA's regulatory structure for plants engineered to contain a pesticide.

Frequently-Asked Questions Articles and Speeches Regulatory Actions Reports and Reviews Take Action!