Report

Issues in the Regulation of Genetically Engineered Plants and Animals

Quick Summary

A range of options exists to enhance the regulatory review process to address new challenges future products of agricultural biotechnology are likely to present, although opinions vary about the need for change, according to Issues in the Regulation of Genetically Engineered Plants and Animals, a report by the Pew Initiative on Food and Biotechnology.

Introduction

Over the last quarter century, the rapid development of modern biotechnology (see Figure 1.1) has led to the creation of new varieties of plants and animals containing novel traits that would be difficult or impossible to achieve through traditional breeding. Biotechnology is a powerful tool that has the potential to deliver many benefits. Products have been developed or are being developed that can improve the agronomic performance of food crops (such as delivering higher yields or increased disease resistance), provide new consumer benefits (such as healthier oils and vegetables with longer shelf lives), provide new ways to make valuable industrial and pharmaceutical chemicals in plants and animals, and deliver environmental benefits (such as a reduction in the use of pesticides). Regarding fish and livestock, biotechnology has the potential to improve animal health, reduce the costs of production, and improve the quality of food derived from these animals.

Scientific reviews have generally found that the risks posed by biotechnology products do not differ in kind from the risks posed by their conventionally produced counterparts (GAO 2002; NRC 1987). In some ways, genetic engineering is more precise than conventional breeding, because scientists know what genetic material is being introduced and generally understand the functions of the expressed proteins. However, genetic engineering greatly expands the range of genetic material available for modifying plants and animals. Genetic engineering can introduce substances into food that have never been in the food supply before, and can give plants and animals new traits that have not previously been introduced into specific environments.

Concerns have therefore been raised about the potential of genetic engineering to introduce new toxins and allergens into food and to reduce essential nutrients (FDA 1992). Concerns have also been raised about potential adverse effects on the environment from the introduction of novel genetic traits, which could inadvertently be passed on to related wild plants or animals, reducing biological diversity and disrupting ecological systems (NRC 2002b). Plants that have been engineered to express substances to repel pests have raised concerns due to their possible impact on organisms other than the targeted plant pests and the possibility that the pests may become resistant to the pesticidal substances over time (NRC 2000).

The question of how best to regulate genetically engineered (GE) food and other products of agricultural biotechnology has been debated for nearly as long as the technology has existed. Since 1986, biotechnology products have been regulated under a Coordinated Framework of laws administered primarily by three agencies—the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the U.S. Department of Agriculture (USDA).1 The central premise of the Coordinated Framework was that the process of biotechnology itself poses no unique risks and that products engineered by biotechnology should therefore be regulated under the same laws as conventionally produced products with similar compositions and intended uses. A second and no less important conclusion was that existing laws were adequate to meet regulatory needs.

Under the Coordinated Framework and related agency regulations, the first generation of genetically engineered crops has been introduced and commercialized. Today, a significant percentage of the corn, cotton, and soybeans in the United States is grown from genetically engineered varieties.2 For the most part, this first generation of agricultural biotechnology products consists of single-gene, single-trait modifications made for agronomic purposes, primarily to make crops pest resistant or herbicide tolerant. The adequacy of the Coordinated Framework has been a matter of disagreement from the beginning. Some have criticized the regulatory system in general (McGarity and Hansen 2001; Alliance for Bio-Integrity et al. v. Shalala, 116 F. Supp.2d 166 (D.D.C. 2000); Hansen 1999; Hopkins, Goldburg, and Hirsch 1991; Krimsky et al. 1989). Specific risk assessments and product approvals made by the agencies have also been the subject of criticism (NRC 2000, 120-125; UCS 1994). Others have argued that the regulatory system has worked well; they point to the absence of any evident food safety or environmental problems (NRC 2002b; Chassy et al. 2001; NRC 2000; Smith 2000) and the general scientific consensus that GE products are no riskier than their conventionally produced counterparts. Still others have argued that GE foods are over-regulated under the Coordinated Framework and should be afforded no greater review than conventional foods (Miller and Conko 2003).

The introduction of the first generation of GE crops did not occur without controversy. In Europe, the food safety crisis caused by “mad cow disease,” while unrelated to GE food, raised broad concerns among EU consumers about the safety of the food supply and the competence of government regulators, contributing to widespread consumer wariness about GE food (Pringle 2003, 103). The resulting rejection of GE crops and market demand for non-GE varieties has become a major challenge for farmers, grain processors, grain shippers, food manufacturers, and others in industry (Shadid 2001; Shoemaker et al. 2001). Incidents in the United States have also illustrated the challenge of managing GE crops. In 2000, traces of StarLink, a GE variety of corn not approved for food use, were discovered in numerous food products. While the highly publicized incident caused no documented harm to human health, product recalls and trade disruptions cost industry hundreds of millions
of dollars (Lueck 2000).

Today, biotechnology developers are poised to bring the next generation of agricultural biotechnology products to market (Monsanto 2003; PIFB 2001). (See Figure 1.2) While some new crop varieties will continue to deliver benefits primarily to farmers in the form of increased pest resistance or herbicide tolerance, others will represent a significant departure from the first generation. The next generation of GE crop varieties will likely include a wider range of desirable agronomic traits, including drought tolerance. Food crops may be modified with traits to improve freshness, taste, and nutrition. Plants could also be modified for nonfood purposes, such as the manufacture of pharmaceutical or industrial chemicals.

The next generation of agricultural biotechnology also includes animals. In some cases, transgenic animals could be modified to include traits that improve the production offood; examples include faster-growing fish and disease-resistant cattle. In other cases, animals will be modified to produce industrial or pharmaceutical products, and even to grow organs for human transplantation. Many of these genetic modifications will be substantially more complex than the singlegene, single-trait modifications of the first generation of GE crops. The new products are expected to enter into the regulatory review process in the next two to ten years and could pose novel issues for the regulatory agencies.

When the federal agencies first proposed the Coordinated Framework nearly 20 years ago, they acknowledged the need to periodically reassess the regulatory system to ensure that it is keeping pace with the rapid development of the technology (OSTP 1984).3 The impending introduction of the next generation of agricultural biotechnology products has led to a renewed interest in examining the adequacy of the current regulatory system for such future products.

In evaluating the adequacy of a regulatory system, the purposes of the system must initially be considered. The primary purpose of any regulatory system is to protect againstharm by assessing and managing the risks of potentially harmful products and activities. At the same time, a regulatory system should provide a clear pathway to the market for safe and useful products. Over the years, Congress has passed numerous laws to ensure the safety of food, drugs, pesticides, chemicals, and other substances that could pose risks to health or the environment. While the primary goal of a regulatory system is to prevent harm, the public trust generated by an effective and credible regulatory system also has considerable importance for commerce. Regulation can provide assurance to consumers that they can rely upon the agency's independent expertise and purchase products without concern. These commercial benefits can be lost, however, if consumers lack confidence in the integrity and competence of the regulatory system. For this reason, many interested parties, including the biotechnology industry, have consistently acknowledged the importance that a credible, rigorous regulatory system has in ensuring the market acceptance of its products.4

Read Full Section: Introduction (PDF)

Report

Regulating Genetically Engineered Plants for Environmental Protection

Two federal agencies are responsible for assessing and managing environmental risks concerning genetically engineered (GE) plants: the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture (USDA), and the Environmental Protection Agency (EPA). To date, more than 50 GE products have been reviewed by these agencies and received sanction for commercial use.1 These products have been limited in scope; most are crops that have been rendered either insect resistant (through the insertion of Bacillus thuringiensis (Bt) genes, which have pesticidal properties) or herbicide tolerant. Their use has become widespread in the United States.2

The regulatory and scientific environment in which APHIS and the EPA operate is dynamic and has been rapidly evolving. In a recent report, the National Research Council (NRC) of the National Academy of Sciences stated:

The committee finds that APHIS and other regulatory agencies charged with assessing the safety of transgenic plants face a daunting task. This is so in part because environmental risk assessment of transgenic plants is new and in part because the social context in which regulatory decisions about transgenic organisms must now be made is dramatically different from the one in which these agencies have been accustomed to working (NRC 2002b).

This chapter describes and analyzes a variety of issues relating to the regulatory system governing GE crops and environmental protection. It contains four main sections. The first provides a summary of the key issues in play. The second describes in detail the existing regulatory system involved in managing the environmental impacts of GE plants and microorganisms. The third section delves further into the key issues and concerns regarding the existing system. And the fourth and final section offers several possible means for addressing those issues and concerns, if policy makers determine that changes are needed.

Read Full Section: Regulating Genetically Engineered Plants for Environmental Protection (PDF)

Regulating Genetically Engineered Crops and Foods for Food Safety

Scientific reviews have generally found that the use of genetic engineering to modify food crops is unlikely to raise any unique food safety concerns that could not also be posed by conventional breeding techniques (NRC 1987 and 2000). While the nature of the risks is not unique, however, genetic engineering does enable plant breeders to use genes from virtually any other organism, dramatically expanding the genetic palette available. In some cases, the genetic material and its expressed proteins may not previously have been found in food. This wide range of genetic material, and the relative lack of experience with novel genes and their proteins, are the principal justifications that federal regulatory agencies use for their increased oversight of genetically engineered (GE) crops and foods (FDA 1992).

The Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) share responsibility for the safety of food derived from GE crops. The FDA has general responsibility for food safety issues that might be posed by food derived from GE crops (OSTP 1986). The EPA has responsibility for food safety regarding pesticidal substances produced by some GE crops to resist insects (40 CFR Parts 152 and 174).

This chapter reviews the federal regulatory system governing food safety, as it applies to GE crops and foods. It contains four sections. The first is a brief summary of some of the key issues under debate regarding the safety of food products derived from GE crops. The second describes the FDA's and the EPA's existing regulatory systems regarding food safety, and how those systems apply to GE products. The third section describes in detail the key issues and concerns regarding the existing regulatory system. And the fourth section outlines possible approaches—both administrative and legislative—for addressing those issues and concerns, should policy makers decide that reforms are needed.

Read Full Section: Regulating Genetically Engineered Crops and Foods for Food Safety (PDF)

Regulating Genetically Engineered Animals

Numerous genetically engineered (GE) animals and products derived from those animals are currently under development in laboratories around the United States (NRC 2002a and 2004).1 Only one, a transgenic ornamental aquarium fish, has been commercialized (Weiss 2003); no other GE animals nor products derived from them have yet been marketed. The first GE food animal to be commercialized may be a type of salmon that contains an introduced growth hormone (Martin 2003). Other GE animals under development include animals that:

  • produce pharmaceuticals for animal or human use,
  • contain other substances that can be processed into commercial products,
  • are disease-resistant or have other desirable production attributes, or
  • contain organs or tissues that can be transplanted into humans.

 

Some of these animals may be intended to enter the food supply (e.g., the faster-growing salmon), while others are intended for nonfood uses and may need to be kept out of the food supply (e.g., cows that produce human drugs in their milk).

No new laws have been codified to specifically address the regulation of GE animals. And, because GE animals are so new and are still largely being used only in research, the agencies likely to oversee them have not yet established clear overall or product-specific policies for regulating them under existing laws. Regulators, researchers, developers, and potential consumers are thus currently navigating in uncertain waters, and the discussion of regulatory policies in this chapter is necessarily somewhat speculative.

The Food and Drug Administration (FDA) may regulate GE animals under the new animal drug provisions of the federal Food, Drug, and Cosmetic Act (FDCA; 21 USC § 360b; CEQ and OSTP 2001). Nonetheless, it remains unclear exactly how this law would be applied to GE animals, and it is possible that other agencies, with other statutory authorities, may also play a role.

This chapter provides an analysis of the regulatory and policy issues regarding GE animals. The chapter contains four main sections. The first is an overview of some of the key issues under debate regarding GE animals. The second section describes the FDA's regulatory systems for new animal drugs and food safety and explains how these could apply to GE animals. The section also describes the animal and plant quarantine, animal welfare, and meat safety regulatory systems of the U.S. Department of Agriculture (USDA) and the potential roles each may play in creating a regulatory framework for GE animals. The third section describes in detail the key issues and concerns regarding the regulatory system for GE animals. And the fourth section outlines possible approaches—both administrative and legislative—for addressing those issues and concerns, should policy makers determine that change is needed.2

Read Full Section: Regulating Genetically Engineered Animals (PDF)

Regulatory Coordination for Genetically Engineered Crops

While the previous chapters each focused on the regulatory systems of one or two federal agencies, this chapter is centered on the issue of coordination among the various agencies. In particular, it addresses possible approaches for improving coordination among the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Environmental Protection Agency (EPA)—the three agencies with primary responsibility for genetically engineered (GE) plants, animals, and products under the 1986 Coordinated Framework (OSTP 1986). One possible approach for coordinating the regulatory systems governing GE plants is described in detail.

At present, the Coordinated Framework is expected to serve as a regulatory safety net under which all plant-based products are subject to pre-market oversight by at least one federal agency, and sometimes by two or three agencies (OSTP 1986). For example, for plants that produce pesticidal substances (called “plant-incorporated protectants,” or PIPs), three agencies are typically involved.

  1. The USDA's Animal and Plant Health Inspection Service (APHIS) reviews plants for their potential effects on agriculture and the environment under the Federal Plant Pest Act (formerly 7 USC § 150aa et seq.), now subsumed by the Plant Protection Act (PPA; 7 USC § 7701 et seq.), and also under the National Environmental Policy Act (NEPA; 42 USC § 4321 et seq.).
  2. The EPA reviews the potential effects on human health and the environment of pesticidal substances produced by plants, under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA; 7 USC § 136 et seq.) and the pesticide residue provisions of the federal Food, Drug, and Cosmetic Act (FDCA; 21 USC § 346a).
  3. The FDA reviews the food and feed safety and nutritional aspects of whole foods, and any other nonpesticidal substances that might be added to plants through genetic alteration, under the food safety provisions of the FDCA (21 USC § 301 et seq.).

While agencies have worked to increase cooperation and coordination, issues remain. In particular, the system can present challenges for small companies and public researchers, who often face multi-agency reviews with little or no comprehensive guidance on who must be talked to and when. Also, the interested public is left largely in the dark about how any given GE product is proceeding through the regulatory review process, particularly given that some agency guidance is unclear or lacking and some key decisions are made via informal, private consultations. Due to this lack of transparency, it is nearly impossible to track a GE product from the initial phases of regulation (e.g., a field trial) through to commercialization (e.g., a GE food set to enter the food supply) via the information provided by the agencies on their respective web sites. Product characterizations and the timing and substance of posted data vary widely. And there is no single, authoritative source of information about specific products undergoing regulatory review. Also, technology developers often claim confidentiality for large portions of submissions, making it difficult for third parties to make independent assessments, particularly prior to commercialization (NRC 2000, 177-178; 2002b, 178).

The regulatory system can also appear to be unpredictable. Many procedures for product review and safety assessment are not spelled out in formal regulations, policies, or guidelines. Given the diversity of products under development and the rapidly advancing state of the science, the agencies have elected to develop their review procedures largely through case-by-case assessments of individual submissions. For those not directly involved in the process, attempting to determine what was done and why, or whether a similar process will be followed in the future, can be difficult. In the case of APHIS and the FDA, it is not clear how newer products that incorporate pharmaceuticals and vaccines into crops are being reviewed. Moreover, it is not clear that like reviews are conducted in the same manner or with comparable rigor by different agencies (e.g., ecological risk assessments by APHIS and the EPA (NRC 2000, 165-166, 170-171; 2002b, 178) and allergenicity assessments by the
FDA and the EPA complement one another (NRC 2000, 168-169)).

In general, the agencies appear to have avoided overlapping reviews and responsibilities through understandings reached in the development of the Framework and through interagency memoranda of understanding (USDA and EPA, no date). The substance of these understandings is not readily available to the public, however, and the possibility of redundancies exists, particularly in the review of PIPs by the EPA and APHIS. This chapter reviews options for achieving greater coordination among the agencies that regulate GE plants and GE plant products, should policy makers decide that such change is needed.

Read Full Section: Regulatory Coordination for Genetically Engineered Crops (PDF)

Appendices

We at the Pew Initiative on Food and Biotechnology (PIFB) would like to thank the individuals listed below for contributing to our understanding of the regulatory issues surrounding agricultural biotechnology. These individuals include members of the Stakeholder Forum on Agricultural Biotechnology: Nearly 100 outside legal, scientific, and policy experts provided assistance to the Forum's efforts through briefings, presentations, research, analysis, and informal discussions; and those who took part in a joint meeting with the National Research Council. We would also like to give special notice to Jennifer Thomas-Larmer, whose wordsmithing abilities and understanding of regulatory issuesmade her the ideal editor of this report.

Read Full Section: Appendices (PDF)

References

AAP (American Academy of Pediatrics) Committee on Nutrition. 2002. New infant formula additives approved by FDA. AAP News 20 (5): 209. http://aapnews.aappublications.org/cgi/content/full/20/5/209
AP (Associated Press). 2003.
 More regulations for biotech products aren't necessary, FDA says. June 18.
APHIS (Animal and Plant Health Inspection Service, U.S. Department of Agriculture). 1985. Policy statement on the protection of privileged or confidential business information.
 Federal Register 50: 38561. September 23.
———. 1993. Genetically engineered organisms and products: Notification procedures for the introduction of certain regulated articles, and petition for nonregulated status.
 Federal Register 58: 17044. March 31.
———. 1995.
 Discussion of the review and evaluation procedures associated with the permitting process for a proposed introduction of a transgenic arthropod. Riverdale, MD: APHIS. http://www.aphis.usda.gov/brs/arthropod/tgendisc.html
———. 1996.
 Guide for preparing and submitting a petition for genetically engineered plants. November. Riverdale, MD: APHIS. http://www.aphis.usda.gov/brs/pdf/usergen8.pdf
———. 1997. Genetically engineered organisms and products: Simplification of requirements and procedures for genetically engineered organisms.
 Federal Register 62: 23945. May 2.
———. 2001.
 What you as a producer need to know about the new scrapie eradication program. Riverdale, MD: APHIS. http://www.aphis.usda.gov/vs/nahps/scrapie/eradicate.html 
———. 2002a.
 Annual highlights report FY 2002: Animal Health Protection Act. Riverdale, MD: APHIS. http://www.aphis.usda.gov/vs/highlights/section2/section2-3.html
———. 2002b. Notice of intent: Environmental impact statement, genetically engineered pink bollworm.
 Federal Register 67: 5086-5087. February 4.
———. 2003a.
 Compliance and enforcement (press release). October 17. Riverdale, MD: APHIS. http://www.aphis.usda.gov/brs/compliance.html
———. 2003b. Interim rule and request for comments: Introduction of plants genetically engineered to produce industrial compounds.
 Federal Register 68: 46434. August 6.
———. 2003c. Proposed rule: Field testing of plants engineered to produce pharmaceutical and industrial compounds.
 Federal Register 68: 11337. March 10.
———. 2003d.
 USDA to require permits for all industrial biotech plants (press release). August 5. Riverdale, MD: APHIS. http://www.aphis.usda.gov/lpa/news/2003/08/bioplants_brs.html
———. 2004. Environmental impact statement: Introduction of genetically engineered organisms.
 Federal Register 69: 3271. January 23.
BIO (Biotechnology Industry Organization). 2000.
 Comments to the Food and Drug Administration on biotechnology for the year 2000 and beyond. January 11. Washington, DC: BIO. http://www/bio.org/food&ag/011300statement.asp
———. 2003.
 Biotechnology: A new link to hope. (Editors' and reporters' guide, 2003-2004.) Washington, DC: BIO. http://www.bio.org/er/industrial.asp
Bucchini, Luca, and Lynn Goldman. 2002.
 A snapshot of federal research on food allergies: Implications for genetically modified food. Washington, DC: Pew Initiative on Food and Biotechnology.
CDC (Centers for Disease Control and Prevention). 1999. Infant metabolic alkalosis and soy-based formula—United States.
 Morbidity and Mortality Weekly Report 28: 121-123. March 3. http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/lmrk121.htm
CEQ and OSTP (Council on Environmental Quality and Office of Science and Technology Policy, The White House). 2001.
 CEQ and OSTP assessment: Case studies of environmental regulations for biotechnology. Washington, DC: OSTP. http://www.ostp.gov/html/012201.html
Caplan, Richard. 2001.
 Raising risk: Field testing of genetically engineered crops in the United States. June. Washington, DC: U.S. Public Interest Research Group. http://pirg.org/ge/reports/RaisingRisk.pdf
———. 2003.
 Raising risk: Field testing of genetically engineered crops in the United States. June. Washington, DC: U.S. Public Interest Research Group. http://www.uspirg.org/reports/RaisingRisk2003.pdf
Carpenter, Janet E. 2001.
 Case studies in benefits and risks of agricultural biotechnology: Roundup Ready soybeans and Bt field corn. January. Washington, DC: National Center for Food and Agricultural Policy. http://www.ncfap.org/reports/biotech/benefitsandrisks.pdf
Chassy, Bruce M., et al. 2001.
 Evaluation of the U.S. regulatory process for crops developed through biotechnology: Issue paper 19. Washington, DC: Council for Agricultural Science and Technology.
ChemAlliance. 2001.
 Background: TSCA. http://www.chemalliance.org/Handbook/background/back-tsca.asp
Codex Task Force (Codex
 ad hoc Intergovernmental Task Force on Foods Derived from Biotechnology, Codex Alumentarius Commission). 2002. Draft principles for the risk analysis of foods derived from modern biotechnology. March. Yokohama, Japan: Codex Task Force. ftp://ftp.fao.org/codex/alinorm03/Al03_34e.pdf
CRS (Congressional Research Service). 1999.
 Summaries of environmental laws administeredby the EPA (#RL30022). January 2. Washington, DC: CRS. http://www.ncseonline.org/NLE/CRSreports/BriefingBooks/Laws/index.cfm?&CFID=11039391&CFTOKEN=36780160
CSPI (Center for Science in the Public Interest). 2001.
 Comments on docket number 00N-1396: Premarket notice concerning bioengineered foods. May 10. Washington, DC: CSPI. http://www.cspinet.org/biotech/pbn_rule.html
CTIC (Conservation Technology Information Center, Purdue University). 2002.
 Conservation tillage and plant biotechnology: How new technologies can improve the environment by reducing the need to plow. W. Lafayette, IN: CTIC. http://www.ctic.purdue.edu/CTIC/BiotechPaper.pdf
CVM (Center for Veterinary Medicine, Food and Drug Administration, U.S. Department of Health and Human Services). 1992.
 CVM guideline 41: Draft guideline for formatting, assembling, and submitting new animal drug applications. Rockville, MD: CVM.
———. 1994.
 CVM guideline 3: General principals for evaluating the safety of compounds used in food-producing animals. Rockville, MD: CVM.
———. 1996.
 CVM update: Caution urged on use of Warbex. October 4. Rockville, MD: CVM.
———. 1997a.
 CVM guideline 58: Good target animal study practices: Clinical investigators and monitors. May. Rockville, MD: CVM.
———. 1997b.
 CVM program policy and procedures manual: Guide 1240.3500, general review and enforcement policies, new animal drug determination. Rockville, MD: CVM. (Originally published July 24, 1989; published with minor changes September 5, 1997.)
———. 2002.
 The administrative new animal drug application process. Rockville, MD: CVM.
———. 2003a.
 CVM update: Transcript available for VMAC meeting on animal cloning. December 5. Rockville, MD: CVM. http://www.fda.gov/cvm/index/updates/VMACTran.htm
———. 2003b.
 RE: Recent incident at the University of Illinois. Letter from Dr. Stephen Sundlof, Director of CVM, to various scientists. May 13. Rockville, MD: CVM. http://www.fda.gov/cvm/biotechnology/landgrantltr.htm
Eastham, Katie, and Jeremy Sweet. 2002.
 Genetically modified organisms (GMOs): The significance of gene flow through pollen transfer. Environmental issue report No. 28.
Copenhagen: European Environment Agency. http://reports.eea.eu.int/environmentalissue_report_2002_28/en/GMOs%20for%20www.pdf
EPA (Environmental Protection Agency). 1993.
 EPA's biotechnology oversight program under the Toxic Substances Control Act. Washington, DC: EPA. http://www.nal.usda.gov/bic/Federal_Biotech/epatosca.doc.html
———. 1994. Plant-pesticides subject to the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act: Proposed policy.
 Federal Register 59: 60496. November 23.
———. 1997. Microbial products of biotechnology: Final regulations under the Toxic Substances Control Act.
 Federal Register 62: 17910. April 11.
———. 1999.
 Status report: TSCA biotechnology submissions. Washington, DC: EPA. http://www.epa.gov/opptintr/biotech/pdf/bistat99.pdf
———. 2001a.
 Biopesticides registration action document: Bacillus thuringiensis plant-incorporated protectants. October 16. Washington, DC: EPA. http://www.epa.gov/pesticides/biopesticides/pips/bt_brad.htm
———. 2001b. Bt
 cotton refuge requirements for the 2001 growing season. Washington, DC: EPA. http://www.epa.gov/pesticides/biopesticides/pips/bt_cotton_refuge_2001.htm
———. 2002.
 EPA's Regulation of Bacillus thuringiensis (Bt) crops. May. Washington, DC: EPA. http://www.epa.gov/pesticides/biopesticides/pips/regofbtcrops.htm
———. 2003.
 Notifications: FY98 to present. Washington, DC: EPA. http://www.epa.gov/opptintr/biotech/submiss.htm
EPA FIFRA SAP. (Environmental Protection Agency, Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel). 2002.
 SAP meeting minutes no. 2002-05: A set of scientific issues being considered by the Environmental Protection Agency regarding: corn rootworm plant-incorporated protectant non-target insect and insect resistance management plans. Arlington, VA. August 27-29. http://www.epa.gov/oscpmont/sap/2002/august/august2002final.pdf
Fabi, Randy. 2002. Japan finds StarLink in U.S. corn cargo—U.S. exporters. Reuters. December 27. FDA (Food and Drug Administration, U.S. Department of Health and Human Services). 1986. Letter from John M. Taylor, Acting Associate Commissioner for Regulatory Affairs, to Edward L. Rogers, Esq. September 29. Rockville, MD: FDA.
———. 1992. Statement of policy: Foods derived from new plant varieties.
 Federal Register 57: 22984. May 29.
———. 1997a.
 Guidance on consultation procedures: Foods derived from new plant varieties. October. Rockville, MD: FDA. http://vm.cfsan.fda.gov/~lrd/consulpr.html
———. 1997b. Proposed rule: Substances generally recognized as safe.
 Federal Register 62: 18938. April 17.
———. 1998. Draft guidance for industry: Use of antibiotic resistance marker genes in transgenic plants.
 Federal Register 63: 47505. September 8.
———. 2000.
 Action levels for poisonous or deleterious substances in human food and animal feed: Industry activities staff booklet. August. Rockville, MD: FDA. http://www.cfsan.fda.gov/~lrd/fdaact.html
———. 2001a. Proposed rule: Premarket notice concerning bioengineered foods.
 Federal Register 66: 4706. January 18.
———. 2001b. Voluntary labeling indicating whether foods have or have not been developed using biotechnology: Draft guidance for industry.
 Federal Register 66: 4839. January 18.
———. 2002a. Drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals: Draft guidance for industry.
 Federal Register 67: 57828. September 12.
———. 2002b.
 List of completed consultations on bioengineered foods. Rockville, MD: FDA. http://www.cfsan.fda.gov/~lrd/biocon.html
———. 2003a.
 FDA statement regarding Glofish. December 9. Rockville, MD: FDA. http://www.fda.gov/bbs/topics/news/2003/new00994.html
———. 2003b. Records and reports concerning experience with approved new animal drugs.
 Federal Register 68: 15355. March 31.
FAO (Food and Agriculture Organization, The United Nations) and WHO (World Health Organization). 2001.
 Evaluation of allergenicity in genetically modified foods. Rome, Italy: FAO. http://www.fao.org/es/ESN/food/pdf/allergygm.pdf
Foreman, Carol Tucker. 2004. Can U.S. public support for food biotechnology be salvaged?
 American Enterprise. March. FSIS (Food Safety and Inspection Service, U.S. Department of Agriculture). 1997a. Decision criteria for the evaluation of nontransgenic animals from transgenic animal research. Washington, DC: FSIS. (Originally issued in March 1994 and revised in June 1997.)
———. 1997b.
 Points to consider in the food safety evaluation of transgenic animals from transgenic animal research. Washington, DC: FSIS. (Originally issued in September 1990 and revised most recently in June 1997.)
———. 2001.
 Protecting the public from foodborne illness: The Food Safety and Inspection Service. Washington, DC: FSIS. http://www.fsis.usda.gov/oa/background/fsisgeneral.htm 
GAO (General Accounting Office). 2002.
 Genetically modified foods: Experts view regimen of safety tests as adequate, but FDA's evaluation process could be enhanced. GAO-02-566. Washington, DC: GAO.
Gillis, Justin. 2004. Biotech limits found lacking.
 Washington Post. January 21. E1.
GMA (Grocery Manufacturers of America). 1999.
 Groups call attack on safety review of biotech foods “beyond reason” (press release). October 6. Washington, DC: GMA. http://www.gmabrands.com/news/docs/NewsRelease.cfm?DocID=433
Hansen, Michael. 1999. A regulatory patchwork – with big holes.
 Environmental Forum. http://www.consumersunion.org/food/forumcpi799.htm
Hopkins, D. Douglas, Rebecca Goldburg, and Steven A. Hirsch. 1991.
 A mutable feast: Assuring food safety in the era of genetic engineering. New York: Environmental Defense Fund. http://www.environmentaldefense.org/documents/1727_MutableFeast.pdf
IFT (Institute of Food Technologists). 1996.
 Appropriate oversight for plants with inherited traits for resistance to pests: A report for eleven professional scientific societies. Chicago: IFT.
Jaffe, Gregory. 2003a.
 Planting trouble: Are farmers squandering Bt corn technology? An analysis of USDA data showing significant noncompliance with EPA's refuge requirements. June. Washington, DC: Center for Science in the Public Interest. http://cspinet.org/new/pdf/bt_corn_report.pdf
———. 2003b. Planting trouble update. September. Washington, DC: Center for Science in the Public Interest. http://cspinet.org/new/pdf/planting_trouble_update1.pdf
James, C. 2002.
 Global status of commercialized transgenic crops: 2002. ISAAA Brief No 27. Ithaca, NY: ISAAA.
Korwek, Edward L., and Peter L. de la Cruz 1985. Regulation of Environmental Releases of Genetically Manipulated Microorganisms.
 Rutgers Computer and Technology Law Journal 11: 301.
Krimsky, Sheldon, et al. 1989. Controlling the risk in biotech.
 Technology Review 92: 62. July. Lueck, Sarah. 2000. Corn-recall cost could reach into the hundreds of millions. Wall Street Journal. November 3.
Martin, Andrew. 2003. One fish, two fish, genetically new fish.
 Chicago Tribune. November 12. A1.
Maryanski, J.H. 1995.
 CFSAN handout: FDA's policy for foods developed by biotechnology. Rockville, MD: Center for Food Safety and Applied Nutrition, FDA. http://www.cfsan.fda.gov/~lrd/biopolcy.html
McGarity, Thomas O., and Karl O. Bayer. 1983. Federal regulation of emerging genetic technologies.
 Vanderbilt Law Review 36: 461.
McGarity, Thomas O., and Patricia I. Hansen. 2001.
 Breeding distrust: An assessment and recommendations for improving the regulation of plant derived genetically modified foods. Washington, DC: Consumer Federation of America Foundation.
Miller, Henry I., and Gregory Conko. 2003. Children as policy pawns.
 Washington Times. October 5.
Monsanto. 2003.
 Progress in the product pipeline. St. Louis: Monsanto. http://www.monsanto.com/monsanto/layout/sci_tech/prod_pipeline/productpipeline.asp
NASS (National Agricultural Statistics Service, U.S. Department of Agriculture). 2002.
 Biotechnology varieties: Acreage. June. Washington, DC: NASS.
———. 2003.
 Corn and biotechnology special analysis. July 11. Washington, DC: NASS. http://www.usda.gov/nass/pubs/bioc0703.pdf
NCGA (National Corn Growers Association). 2003a.
 NCGA, USGC pleased U.S. pursuing case against EU moratorium (press release). May 13. Washington, DC: NCGA. http://www.ncga.com/news/releases/2003/may/news051303.htm
———. 2003b.
 Survey shows corn growers good stewards of Bt technology (press release). November 13. Washington, DC: NCGA.
NFPA (National Food Processors Association). 2003.
 USDA action to require permits for industrial biotech plants a good step forward, but more oversight and containment controls are needed (press release). August 6. Washington, DC: NFPA. http://www.nfpa-food.org/News_Release/NFPANewsRelease080603.htm
NIH (National Institutes of Health). 1994. Guidelines for research involving recombinant DNA molecules.
 Federal Register 59: 34496. July 5.
Noah, Lars, and Richard A. Merrill. 1998. Starting from scratch?: Reinventing the food additive approval process.
 Boston University Law Review 78: 329.
NRC (National Research Council, National Academy of Sciences). 1987.
 Introduction of recombinant DNA-engineered organisms into the environment: Key issues. Washington, DC: National Academy Press.
———. 1998.
 Ensuring safe food: From production to consumption. Washington, DC: National Academy Press.
———. 2000.
 Genetically modified pest-protected plants: Science and regulation. Washington, DC: National Academy Press.
———. 2002a.
 Animal biotechnology: Science-based concerns. Washington, DC: National Academy Press.
———. 2002b.
 Environmental effects of transgenic plants: The scope and adequacy of regulation. Washington, DC: National Academy Press.
———. 2004.
 Biological confinement of genetically engineered organisms. Washington, DC: National Academy Press.
OSTP (Office of Science and Technology Policy, The White House). 1984. Proposed coordinated framework for regulation of biotechnology.
 Federal Register 49: 50858. December 31.
———. 1986. Announcement of policy and notice for public comment: Coordinated framework for regulation of biotechnology.
 Federal Register 51: 23302. June 26.
———. 1990. Announcement of policy: Exercise of federal oversight within scope of statutory authority: Planned introductions of biotechnology products into the environment.
 Federal Register 55: 31118. July 31.
———. 1992. Announcement of policy: Exercise of federal oversight within scope of statutory authority: Planned introductions of biotechnology products into the environment.
 Federal Register 57: 6753. February 27.
———. 2002. Notice: Proposed federal actions to update field test requirements for biotechnology derived plants and to establish early food safety assessments for new proteins produced by such plants.
 Federal Register 67: 50578. August 2.
PIFB (Pew Initiative on Food and Biotechnology). 2001.
 Guide to U.S. regulation of genetically modified food and agricultural biotechnology products. Washington, DC: PIFB. http://pewagbiotech.org/resources/issuebriefs/1-regguide.pdf
———. 2002.
 Three years later: Genetically engineered corn and the monarch butterfly controversy. Washington, DC: PIFB. http://pewagbiotech.org/resources/issuebriefs/monarch.pdf
———. 2003.
 Public sentiments about genetically modified food: September 2003 update. Washington, DC: PIFB. http://pewagbiotech.org/research/2003update/
———. 2004.
 Bugs in the system? Issues in the science and regulation of genetically modified insects. Washington, DC: PIFB. http//:pewagbiotech.org/research/bugs/bugs.pdf
Pollack, Andrew. 2000. Safeway recalls taco shells after test questions corn origin.
 New York Times. October 12. C2.
Pringle, Peter. 2003.
 Food, Inc. New York: Simon & Shuster.
Ritchie, James D. 2003. Curtains for corn rootworm.
 The Corn and Soybean Digest. April.
Shadid, Anthony. 2001. Agricultural business may face overhaul: Report says segregating biotech crops could cost billions, take years.
 Boston Globe. March 22. E1.
Shoemaker, Robbin, et al. 2001.
 Economic issues in agricultural biotechnology. ERS agriculture information bulletin no. 762. Washington, DC: Economic Research Service, U.S. Department of Agriculture.
Smith, Nick. 2000.
 Seeds of opportunity: An assessment of the benefits, safety, and oversight of plant genomics and agricultural biotechnology. Report of the Chairman of the Subcommittee on Basic Research, House Committee on Science. 106th Cong., 2nd Session. Committee Print 106-B. April.
Stakeholder Forum on Agricultural Biotechnology. 2003.
 An overview of the process. Washington, DC: Pew Initiative on Food and Biotechnology. http://pewagbiotech.org/consensus/FinalReport.pdf
Taylor, Michael R., and Jody S. Tick. 2001.
 StarLink: Issues for the future. Washington, DC: Pew Initiative on Food and Biotechnology and Resources for the Future.
———. 2003.
 Post market oversight of biotech foods: Is the system prepared?. Washington, DC: Pew Initiative on Food and Biotechnology and Resources for the Future.
Treibwasser, Keith, and Ron Olson. 2003. Presentation to the USDA Advisory Committee on Biotechnology and 21
st Century Agriculture. Washington, DC. September 16. http://www.usda.gov/agencies/biotech/ac21/meetings/mtg_sept03/USDA%20trieb-olson%209-16.ppt
UBA (Umweltbundesamt (Germany's Federal Environmental Agency)). No date.
 A guide to environmental institutions in Germany. Berlin, Germany: UBA. http://www.umweltdaten.de/medien-e/guide-env-inst.pdf
UCS (Union of Concerned Scientists). 1994.
 Comments to the USDA on an environmental assessment and finding of no significant impact of genetically engineered virus-resistantsquash. July. Washington, DC: UCS. http://www.ucsusa.org/documents/squash.pdf
USDA (U.S. Department of Agriculture). 2001. Declaration of emergency because of infectious salmon anemia.
 Federal Register 66: 65679. December 20.
———. 2002.
 USDA announces actions regarding Plant Protection Act violations involving Prodigene, Inc. (press release). December 6. Washington, DC: USDA. http://www.usda.gov/news/releases/2002/12/0498.htm
———. 2003.
 Veneman announces additional protection measures to guard against BSE (press release). December 30. Washington, DC: USDA. http://www.usda.gov/news/releases/2003/12/0449.htm
USDA (U.S. Department of Agriculture) and EPA (Environmental Protection Agency). No date.
 Memorandum of understanding: EPA/OPP and USDA/APHIS process for sharing information on herbicide-tolerant crops. Washington, DC: USDA. http://www.aphis.usda.gov/brs/mou1.html
U.S. House of Representatives, Committee on Agriculture, Subcommittee on Conservation, Credit, Rural Development, and Research. 2003.
 Review of biotechnology in agriculture. Hearing. June 17. 108th Congress, 1st Session. Washington, DC.
Weise, Elizabeth. 2003. Many biotech farms ignore planting rules.
 USA Today. September 11. D5.
Weiss, Kenneth. 2003. In reversal, FDA says it will not regulate bioengineered fish.
 Los Angeles Times. December 10. 31.
Williams, Frances. 2003. U.S. fires first shot at EU biotech policy.
 Financial Times. August 19. 7.

Personal Communications Cited
James V. Aidala, former Assistant Administrator, Office of Prevention, Pesticides, and Toxic Substances, Environmental Protection Agency. September 16, 2003.
Thomas Bundy, Deputy Assistant General Counsel (Retired), Regulatory Division, Office of General Counsel, U.S. Department of Agriculture. November 30, 2003.