By Sally L. McCammon, Science Advisor
to the Animal and Plant Health Inspection Service,
U.S. Department of Agriculture
"Advances in biotechnology -- being able to determine what has actually happened at the molecular and biochemical levels -- have increased the ability of regulators to scrutinize product safety and the effect of product modification upon safety," says Sally McCammon. In this article, she discusses the science-based approach to evaluating products derived from biotechnology, especially agricultural biotechnology, and the role U.S. government agencies play in the detailed and often complex process.
If genetically engineered organisms are to gain greater acceptance, decisions that address concerns associated with the application of biotechnology to agriculture must be science based. Science also must be the base by which regulatory officials can assure and build upon credibility, remain current, and assure a rational basis for decision-making. In this way, science and the legal processes are inextricably linked for regulations that evaluate biological products. This article outlines how U.S. regulatory authorities examine biotechnology products and coordinate their evaluation procedures to assure the highest degree of safety.
A SCIENCE-BASED REGULATORY APPROACH
To say that an assessment is science-based means that the review of any particular product is done using scientific criteria relevant to that product. Advances in biotechnology -- being able to determine what has actually happened at the molecular and biochemical levels -- have increased the ability of regulators to scrutinize product safety and the effect of product modification upon safety. The scrutiny of certain products and the rigor by which evaluations are performed have also increased due to biotechnology. The approach to review is constantly evolving due to new types of products and the availability of new scientific information.
The current regulatory approach in the United States is based on a determination in 1987 by the U.S. National Academy of Sciences (NAS) that "the risks associated with the introduction of rDNA-engineered organisms are the same in kind as those associated with the introduction into the environment of unmodified organisms and organisms modified by other genetic techniques." In 1989, NAS articulated the Concept of Familiarity, saying "familiar does not necessarily mean safe. Rather, to be familiar with the elements of an introduction [into the environment] means to have enough information to be able to judge the introduction's safety or risk." The familiarity criterion is central to a framework for evaluation of genetically modified plants and microorganisms. For plants, familiarity comes from comparison with the parent line or crop species with similar traits, as well as from actual field tests. With genetically modified plants, the standard of comparison is the unmodified plant.
Approaches to review were developed in the United States by the NAS and, among industrialized countries, by the Organization for Economic Cooperation and Development (OECD). In 1993, the OECD published principles for reviewing large-scale plantings of transgenic crop plants. That organization identified and discussed the general safety issues associated with new plant lines and crop cultivars, as well as risk management. These safety issues, including gene transfer, weediness, and effects on non-target organisms, are now generally accepted globally as the basis for evaluating transgenic plants. The OECD elaborated on the Concept of Familiarity, identifying familiarity with the crop plant, the trait, the environment, and the interaction of these three factors as being critical in the evaluation of transgenic plants.
THE U.S. DECISION-MAKING PROCESS
Since the White House Office of Science and Technology Policy published the "Coordinated Framework for the Regulation of Products of Biotechnology" in 1986, the United States has gained 13 years' experience in evaluating the products of biotechnology for safety. The Coordinated Framework established a strong federal commitment to the safe development of the products of biotechnology from the laboratory, through field-testing and development, and into the marketplace. The underlying assumption of the Coordinated Framework is that any risks from the products of biotechnology are the same in kind as those of similar products -- risks to agriculture, the environment, and human health. Thus, the existing statutes for addressing these risks have been deemed adequate to address any risks posed by product development using biotechnology, and no new "gene law" has been considered necessary.
Regulations, developed to implement statutes, establish procedures and criteria by which specific types of products are evaluated, including those produced using biotechnology such as vaccines, plant varieties, pesticides, animal products, and pharmaceuticals. In the United States, the agencies that examine plants and plant products are the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services, and the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture.
Under the U.S. regulatory system, a new genetically engineered plant could be reviewed by one or all three regulatory agencies, depending on the plant and the trait engineered into it. For instance, a Bt gene in a food crop would be reviewed by APHIS, EPA, and FDA; a plant with modified oil content for food would be reviewed by FDA and APHIS; modified flower color in a horticultural crop would be reviewed by APHIS alone. It usually takes at least five years of field testing, under APHIS oversight, for the developer of a new plant variety to evaluate the new line and to collect the data needed to pass through the regulatory system. Another two years may be needed for APHIS, EPA, and/or FDA (depending on the plant variety) to complete their reviews. The U.S. regulatory structure is based upon risk rather than process to assure safety, and its success is due to the fact that regulatory agencies with established credibility and expertise have been designated to evaluate the products of biotechnology.
THE REGULATORS' ROLES
APHIS regulates the development and field testing of genetically engineered plants, microorganisms, and certain other organisms under the authority of the Federal Plant Pest Act and the Plant Quarantine Act. APHIS regulations provide procedures for obtaining a permit or for providing notification of the intent to field test, prior to importation, interstate movement, or release into the United States. Authority is based on the use of plant pests to engineer plants so as to supply the genes inserted, to allow those genes to be expressed in plants, or to transfer the genes into plants. The APHIS review process evaluates agricultural and environmental safety issues.
APHIS has been reviewing applications for permits and notifications by industry, academia, and nonprofit organizations of field tests of transgenic crop plants since 1986, when it proposed the first regulation for these products. After several years of field tests, an applicant can petition the agency to be released from requirements under the APHIS regulatory process. If the applicant can provide evidence that there is no plant pest potential (including the lack of change in disease and pest resistance, as well as the absence of the potential of new genetic material to create a new pathogen or pest), along with answers to a variety of other environmental questions, APHIS will grant the petition. At that time, the applicant is free to commercialize the plant line or use it in other breeding programs without coming to APHIS for permission, subject to obtaining any necessary approvals from EPA or FDA. To date, 51 petitions have been granted and more than 5,000 permits and notifications have been issued for field testing at more than 22,000 sites. Although no petitions have been denied, 13 have been withdrawn due to insufficient information or other inadequacies in the application.
APHIS maintains comprehensive field testing and petition databases. These databases are used not only by domestic customers and stakeholders, but increasingly by foreign governments to verify that the U.S. government has reviewed the risk for products being considered for field testing or importation. These databases, as well as access to federal home pages on biotechnology regulation, are available at www.aphis.usda.gov.
EPA's responsibility is to ensure the safety of pesticides, both chemical and biological, under the authority of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) through regulation of the distribution, sale, use, and testing of plants and microbes producing pesticidal substances. Under the Federal Food, Drug and Cosmetic Act (FFDCA), EPA sets tolerance limits for substances used as pesticides on and in food and feed, or establishes an exemption from the requirement of a tolerance if such a tolerance is not necessary to protect the public health (determined after evaluation by the agency).
EPA issues experimental use permits for field testing of "pesticidal" plants and registrations for commercialization of these plants. The Bacillus thuringiensis (Bt) toxin, which occurs naturally in soil bacterium, is considered a biological pesticide. For plants containing Bt toxin, the manufacturer must prepare a resistance management plan as a condition for registration with EPA. The plan describes how the manufacturer registering the plant product will assure that resistance does not build up in affected insect populations and reduce the effectiveness of Bt applied topically or used through the plant's genetics. EPA also evaluates the new use of herbicides on herbicide-tolerant transgenic plants.
FDA assesses food (including animal feed) safety and nutritional aspects from new plant varieties as part of a consultation procedure published in the 1992 Statement of Policy: Foods Derived From New Plant Varieties. Consistent with its 1992 policy, FDA expects developers of new plant varieties to consult with the agency on safety and regulatory questions under the authority of the FFDCA. FDA policy is based on existing food law and requires that genetically engineered foods meet the same rigorous safety standards as is required of all other foods. The FDA biotechnology policy treats substances intentionally added to food through genetic engineering as food additives if they are significantly different in structure, function, or amount from substances currently found in food. Many of the food crops currently being developed using biotechnology do not contain substances that are significantly different from those already in the diet and thus do not require pre-market approval.
Science informs the decision-making process of the regulators at a variety of levels. The available published scientific literature, particularly from peer-reviewed journals, is used by regulators in evaluating specific products. Applicants cite this literature in their applications for regulatory approval. As in the case of the NAS, the scientific enterprise can be asked to identify the scientific issues and recommend approaches to particular types of products. Meetings of scientists can be called to address specific issues, as have past meetings on Bt, viral recombination, and relevant biological factors for evaluating crop plants. Information can even be requested on specific products. The EPA meets with its scientific advisory panels. The FDA refers questions to its Food Advisory Committee. Recently, U.S. Agriculture Secretary Dan Glickman requested that the NAS review the scientific underpinnings of the regulatory decisions made by USDA. The USDA also has a Risk Assessment Grants Program that specifically funds research on emerging issues with genetically engineered organisms. All of this information is used by regulators to assure that the most current information and thinking is available to inform regulatory decisions.
BEYOND THE UNITED STATES
Internationally, the appropriate scientifically based standards, guidelines, and recommendations for transgenic products and other products as they move into the international marketplace are being developed by the representatives of national governments at working groups and task forces devoted to these issues under the standard-setting bodies -- Codex Alimentarius, the International Plant Protection Convention, and Office des International Epizooties. The use of the existing standard-setting bodies to address concerns about products of biotechnology focuses attention on harmonization of risk-assessment methodologies and evaluation of specific products or classes of products.