Food and Drug Administration
U.S. Department of Agriculture
March 3, 2000

A. Introduction:

In this annex, the United States shows how precaution is embedded in its food safety system. This document should be treated as an attachment to the summary of the U.S. national food safety system. At its January 24-25, 2000 meeting, the ad hoc Committee on Food Safety of the Organization for Economic Cooperation and Development (OECD) decided that each member could elect to prepare and submit an annex showing how precaution is part of its system, along with references to relevant publications, to supplement its summary of its food safety system.

U.S. regulators have been world leaders in exercising precaution in regulatory systems for food and environmental safety, since before the turn of the last century. Always seeking to improve protection of human health and the environment, the United States welcomes this opportunity to exchange experiences and information on our approach and use of precaution, which has enabled the American people to enjoy a high degree of safety and well-being.

In the more than 100 years since the country's national regulatory system for food was put in place, it has evolved into today's modern and science-based food regulatory system, with a very high level of consumer protection and consumer confidence, a high degree of transparency, and extensive involvement by stakeholders.

In this annex, the United States discusses how precaution has long been an inherent part of the U.S. food safety system. It is inherent not only in the regulatory systems of national-level Federal agencies and the complementary regulatory systems of the 50 states, but also is part of the country's bedrock system of legal responsibility system for businesses, including the food industry, from coast to coast.

This report focuses upon the role of the U.S. regulatory system in assuring food safety. However, the success of this system can be understood only if one first grasps the legal duty of sellers of products in the United States, a legal duty enforceable by injured consumers under contract and tort law under the law of the states, and reinforced by transparency and publicity.

The U.S. food safety system has both "top-down" regulatory controls and "bottom-up" producer responsibility. The meshing and interplay between the authority and responsibility of regulators--and the responsibility of producers—have resulted in a food supply that is second to none in safety and a regulatory system that, while not perfect, is likewise second to none. (And governments and producers cannot do their jobs alone: consumers also play a key role in preventing food safety problems, through their own food handling practices, and academia and other elements of civil society likewise play a role in promoting understanding of food safety.)

At the foundation of the U.S. food safety system is the responsibility of food processors to exercise caution in marketing their products. Food processors are allowed to offer consumers only food that is safe. They may be held "strictly liable" if they fail to carry out their duty. "Strict liability" means that a processor who sells a food that causes injury to a consumer may be legally responsible even in the absence of actual knowledge of the product's hazard. The legal responsibility includes both the possibility of a private lawsuit by any injured consumers and the possibility of regulatory actions. Also, processors must have a reasonable basis for believing their products to be safe; they cannot simply assume this is so. Factors in the caution exercised by producers are discussed in more detail at the end of the outline, in paragraphs 201-205.

In sum, the fundamental U.S. legal system genrally places upon processors a duty of care to the public. On top of this fundamental legal system is strong regulatory infrastructure, administered by scientific food safety regulatory agencies at the Federal and State level.

Turning to law enforced by public officials, in the United States a combination of statutory law and case law provides regulatory agency officials with very broad authority to take strong precautionary measures (see Reference Lists III-V, below).

First and foremost, the law simply forbids the marketing of unsafe food. Anyone who violates this provision may be held criminally liable, the food may be seized and destroyed, and the establishment can be required to cease doing business until it complies with the law. The law obliges anyone who chooses to go into business selling food to others to take steps to ensure that only safe food is sold (see paragraphs 201-05, below). The regulatory law thus provides an entire additional layer of consumer protection that reinforces the general liability system.

General food safety policies and specific requirements and policies under key Federal statutes such as the Federal Food, Drug and Cosmetic Act (FFDCA), the Public Health Service Act (PHSA), the Federal Meat Inspection Act (FMIA), the Poultry Products Inspection Act (PPIA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and the animal and plant health laws--and judicial decisions under these laws--show the precautionary approach in our system. Indeed, precaution is embedded in decision-making processes to ensure acceptable levels of protection.

The precautionary approaches taken are very much driven by the statutory mandates and regulations in question. This precaution is very much an inherent part of the relevant U.S. food safety statutes and regulations, as well as risk analysis policies and processes (both risk assessment and risk management).

Risk assessment procedures include several conservative assumptions about uncertainty. Under these procedures, uncertainty factors including the following are routinely identified and incorporated:

• An uncertainty factor to account for the susceptibility of sensitive subgroups; extrapolation from animal data to human application;
• A factor to account for other considerations relevant to potentially susceptible or sensitive subgroups;
• Factors to account for variations in the human population (including effects of age and gender);
• A factor to account for the implications of use of short-term data in assessing chronic effects;
• A specific factor/algorithm for use in the extrapolation from a Lowest Observed Adverse Effect level to a No Observed Adverse Effect level;
• An acknowledgment (or identification) of, and an uncertainty factor incorporated to account for, incompleteness in the data base; and
• Use of consumers in the high-percentage consumption category as a conservative assumption regarding exposure levels.

Within the context of U.S. food agencies' food safety responsibilities, precautionary approaches take different forms and are used at several points in the risk assessment and management regime in many areas, e.g., as to control of pathogens, food additives, or pesticides. Precaution is applied, not at one single point or in one single manner, but at various points depending upon the statutory regime and the underlying science.

What is striking about a review, such as this, of the precaution inherent in one country's food safety system is the variety and complexity of the scientific issues that regulators confront. What also is obvious is the improbability that any simple principle or model could serve as a useful compass to decision making, in the face of uncertainty, for a wide variety of complex issues.

National food safety policies are tied together through the Food Safety Initiative (see Reference List I, below). Furthermore, as to risk analysis, U.S. scientific institutions have prepared a number of reports that describe generally the risk analysis policies and decisions of U.S. food agencies (Reference List II). U.S. statutes incorporate precaution (Reference List III), as do U.S. regulations, guidance documents, policies, programs, and decisions implementing the statutes (Reference List IV). Court decisions interpreting and enforcing the statutes uphold their precautionary approach (Reference List V). Articles and publications are useful in understanding how the U.S. food safety system works (Reference List VI), while others explain the history leading to today's system (Reference List VII).

B. Food Safety Agencies' Caution: An Overview

FDA has exercised a precautionary approach in risk analysis-- specifically in risk assessment and risk management—since its origin, more than a century ago (see Reference List VII. below). Clearly, the history of food safety regulation in this country shows the evolution to today's highly preventive approach starting in colonial days with enactment of a Massachusetts statute in 1785 that forbade sale of "diseased, corrupted, contagious or unwholesome" food or drink, to the present.

The landmark triad of laws enacted more than 40 years ago on chemicals in food--the Pesticide Amendment of 1954, the Food Additives Amendment of 1958, and the Color Additive Amendments of 1960—authorized the national government to better ensure that producers carry out their responsibility to produce only safe food with safe ingredients. "No substance could legally be introduced into the U.S. food supply unless there has been a prior determination that it was safe. By requiring the manufacturers to do the research a problem of unmanageable size was made manageable. Preventing violations through pre-marketing clearance procedures gave consumers immeasurably better protection than merely prosecuting the few violations that could be proved after injuries were reported." Janssen, W. 1992. The U.S. Food and Drug Law: How It Came, How it Wor ks (see paragraph 215, below).

Under the FFDCA, the sponsor of an additive is required to make an affirmative showing of safety; if this showing falls short, there is no approval even if there is no affirmative showing of risk. Thus, a strict "default zero" approach is used to control substances intentionally added to food. The law deems "unsafe" a food containing an unapproved food or color additive (or pesticide, as will be discussed) unless a regulation has been issued approving this use.

Also, precaution in risk analysis decision-making, for example, may be exercised when the safety information on a hazard in a food is substantial but incomplete. This may be the case in performing a risk assessment on an additive where the knowledge of the toxicological behavior of the substance may be well-characterized in animals but not in humans and uncertainty factors are employed to compensate for this lack of knowledge. Another example is when a clear food safety concern is known to exist but where there is a substantial lack of information on the entity causing the problem. This may be the case for a newly emerging food borne microbial pathogen. Precaution in risk management may also be employed when the risk assessment indicates significant uncertainty in the probability of the risk management options to achieve an acceptable level of risk. In these latter cases, conservative risk management decisions may be taken until such time as more detailed information on the agent is known.

Two FDA program offices, the Center for Food Safety and Applied Nutrition (CFSAN) and Center for Veterinary Medicine (CVM) administer key precautionary programs in the food safety area. Also, the compliance and enforcement arm of FDA, the Office of Regulatory Affairs, includes the FDA district offices throughout the country, whose inspectors, laboratories, compliance officers and other officials play a substantial role in both preventing, and responding to, food hazards.

FSIS also has a long history of using precaution in addressing human health. The Federal Meat Inspection Act (FMIA) was originally passed in 1906 to stop the deplorable conditions in meat packing plants graphically detailed in Upton Sinclair's The Jungle. The provisions of the Act were so broadly written to address food safety concerns known at that time that no major revision was made to it until 1967, which is the same time Congress passed similar legislation for poultry inspection, the Poultry Products Inspection Act (PPIA).

The Jungle included descriptions of practices that could threaten human health, but also of diseases which animals contract that may possibly be transmitted to humans. Considering that, at that time, there was scientific knowledge about the effects of these diseases on humans, the 1906 law was an early example of precaution in a food safety statute, and as a result, for nearly a century U.S. law has barred use in food of diseased animals.

The FMIA and PPIA, as amended, retain precaution as an important consideration. They remain very broadly written and have allowed FSIS to take into account all types of emerging food safety threats without need to seek statutory changes to address them. For example, in the late 1960s into the 1970s, the biggest food safety threat from meat and poultry was in the area of chemical contaminants. Under the adulteration provisions of both Acts, FSIS was able to easily revise its policies and practices to address these potential human health risks.

To meet the human health threat from microbial contaminants, the precautionary foundation to the FMIA and PPIA has also enabled FSIS to act quickly and forcefully – without making a statutory change. In October 1994, the FSIS Administrator announced that FSIS would immediately begin testing raw ground beef for the pathogen E. coli O157:H7 and would consider raw ground beef adulterated (i.e., not eligible for use as human food) if it contained the pathogen. Federal courts have upheld this declaration.

Additionally, FSIS recently implemented its Pathogen Reduction/Hazard Analysis and Critical Control Points (HACCP) regulation. This regulation has precaution and prevention of food borne illness at its core and places the burden on industry to produce safe food and on FSIS to ensure industry meets its burden. The regulation is discussed in greater detail beginning in paragraph 36.

As for future food safety threats, FSIS believes it will continue to be able to address them and fully protect public health. Again, precaution is already present in the FMIA and PPIA, and the statutes provide more than enough latitude to allow the adoption of prevention, intervention, and control strategies throughout the food chain.

The EPA administers the FIFRA (see section A.4. , above) and section 408 of the FFDCA (21 USC 348a). Under these statutes, EPA regulates the registration and use of pesticides in the United States and issues maximum residue levels, "tolerances," for pesticide residues in food. The objective of these statutes, concisely stated, is to protect public health and the environment.

Under FIFRA, sale of pesticides is prohibited, unless registered by EPA, and EPA also has authority to limit distribution, sale and use of pesticides. The FFDCA (21 U.S.C. 348a (a)(1)) also provides that any pesticide residue in food "...shall be deemed unsafe..." unless a tolerance or a tolerance exemption has been issued. EPA's "default zero" approach to pesticides is based on the determination that pesticides, as a general class of chemicals, are inherently hazardous. The requirement for EPA action before any use is permitted, in order to assure EPA can determine its safety and prescribe conditions of use, could be considered a precautionary approach. Precaution is embedded in EPA decision-making processes to ensure acceptable levels of protection. FSIS enforces EPA's pesticide tolerances as to meat and poultry, while FDA enforces EPA's pesticide tolerances as to other foods.

As part of the pesticide registration process, EPA may make certain risk management decisions in response to a lack of scientific data or information. For example, in extrapolating risk information from laboratory studies to humans, the level of risk (e.g., how much risk a particular level of exposure will cause) may be revised by a factor of 10 or more to provide a margin of safety in light of uncertainties in the extrapolation process. A factor of 10 approach may also be used to compensate for variabilities present in the testing process.

As part of the pesticide registration process, EPA makes certain risk management decisions. For example, the agency may prescribe conditions of use to limit human exposures and protect the environment. For example: some pesticides may be applied only by those trained and certified to handle the pesticide; protective equipment may be required; methods of application may be limited; and buffer zones around areas of pesticide usage may be required. These risk management steps protect farm workers and minimize unwanted environmental effects, as well as ensure food safety.

APHIS is part of the network of federal agencies with food-safety-related responsibilities. APHIS' primary role in this network is to protect U.S. agriculture from plant and animal pests and diseases. The agency implements federal laws pertaining to animal and plant health, international sanitary and phytosanitary regulation, regulation of veterinary biologicals and vaccines, control and eradication of introduced pests and diseases, and humane treatment of animals. APHIS also conducts research and operational activities to reduce bird, rodent, and predator damage to crops and livestock. APHIS programs are implemented through cooperative activities with other federal agencies, state and foreign governments, and producers. APHIS also plays an important role in regulating biotechnology (see paragraph 125, below).

The United States has also taken progressive action in response to newly emerging food problems. The current precautionary approach to antimicrobial resistance is an example (see paragraphs 141-147, below).

Also, starting in the late 1980's, food regulatory officials worldwide became concerned about bovine spongiform encephalopathy (BSE), or "mad cow" disease, and began to take steps to prevent the spread or introduction of BSE from abroad. For example, in 1989, APHIS barred the importation of beef and beef products from BSE countries (9 CFR Part 94). Shortly thereafter, FDA warned manufacturers of biological drugs for human use to source bovine materials needed for the drugs only from nonBSE countries.

As concerns spread, FDA in 1994 advised pharmaceutical and medical device manufacturers to provide information about products containing bovine materials and to consider obtaining components from BSE-free countries (59 FR 44591, Aug. 29, 1994). In 1996, FDA strengthened its import alerts to give FDA investigators greater latitude to detain bulk shipments from five BSE countries of high-risk bovine tissue for use in dietary supplements and cosmetics. Also in 1996, as information began to link the consumption of BSE-infected beef with a previously unrecognized form of Creutzfeldt-Jakob disease, FDA developed a regulation to prohibit the use of certain animal tissues in animal feed. (See 61 FR 24253 (May 14, 1996)) (advance notice of proposed rulemaking) and 62 FR 551 (proposed regulation to prohibit the use of animal protein in ruminant feed)). FDA published the final regulation to prohibit the use of animal protein from mammalian tissue in ruminant feed in 1997 (see 62 FR 30935 (June 5, 1997)).

U.S. food agencies emphasize the importance of attracting and maintaining a cadre of top-notch scientists, in-house, to perform risk assessments. They also employ a range of techniques both to augment internal expertise and to provide a thorough vetting of scientific issues. Examples are:

• Advisory committee meetings (as with U.S. advisory committees, generally, these meetings are announced and open to the public), for example:
• The National Advisory Committee on Microbiological Criteria, a standing committee established in 1988 to advise FSIS and FDA;
• FDA's meetings before standing advisory committee meetings that permitted preapproval discussions, in public meetings, concerning approval of bovine somatotrophin (BST) and the final evaluation of the bioengineered tomato;
• EPA's Scientific Advisory Panel, created by statute to advise EPA on certain pesticide regulatory activities; and
• Several committees that help EPA to implement the statutes it administers, e.g., the Tolerance Reassessment Advisory Committee (TRAC), which advises EPA on tolerance reassessments including a pilot process for reviewing organophosphate pesticide tolerances; and
• Public meetings, e.g., the recent public meetings on U.S. policies on regulation and labeling of foods containing genetically modified organisms.
• Public meetings or expert consultations through partnerships, e.g., the meetings convened on Salmonella Enteriditis in eggs, E. coli 0157: H7 in ground beef, transmissible spongiform encephalopathies (TSEs), and modalities for effective training on good agricultural practice for fresh produce.
• Consideration of an issue by the Interagency Risk Assessment Consortium, consisting of all U.S. food agencies, which was established by the President's 1997 Food Safety Initiative to advance the science of microbial risk assessment or by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), a partnership between the University of Maryland and U.S. food agencies.
• Referral of an issue to the National Academy of Sciences/National Research Council, e.g., FDA referrals on cyclamates and saccharin, and USDA referrals regarding meat and poultry inspection and biotechnology.
• Referral of an issue to the National Institutes of Health consensus conference, e.g., BST.
• Contracts with outside scientific bodies, e.g., FDA's use of the Federated Associated Societies of Experimental Biology (FASEB) for assistance on a number of scientific reviews, particularly concerning whether food substances were "generally recognized as safe."
• Use of cooperative agreements, e.g., USDA's agreement with the School of Public Health of Harvard University for a risk analysis of BSE.
• Participation in scientific discourse in the broad scientific community, through meetings, peer-reviewed journals, and Federal Register notices, e.g., how FDA gathered and used the mounting evidence on the association between diet and cancer or cardiovascular disease, in changing U.S. nutrition labeling and health claims rules.
• Seeking peer review on particular substances, e.g., FDA's arranging for peer reviews of assessments of the color additive FD&C Blue No. 2 (21 CFR 74. 102).
• Use of a Public Board of Inquiry (21 CFR Part 13), a panel of three scientists used in lieu of a trial-type public hearing to consider the safety of aspartame.
• Participation in international expert consultations of the World Health Organization and/or Food and Agriculture Organization.

As a general rule, U.S. law requires cost-benefit analysis of regulations (Executive Order 12866, Regulatory Flexibility Act). This general rule does not apply where cost-benefit analysis is prohibited by law. Cost-benefit analysis is not applicable to most food safety decisions. Rather, these food safety decisions are based solely upon science and risk analysis. For example, FDA is not permitted to consider economic factors in determining whether a food additive, color additive, or animal drug is safe, and therefore allowed to be approved. In these determinations, economic factors are forbidden at the risk management step as well as, of course, the risk assessment step. Likewise, EPA is generally not permitted to consider economic factors in determining whether, with respect to human dietary risks, a pesticide is "safe."

There are some situations in which consideration of economic factors in food safety decisions is required or permitted. For example, a 1994 statute created the Office of Risk Assessment and Cost-Benefit Analysis in USDA (Pub. L.103-354). This office's primary role is to review drafts of USDA's "major regulations" to provide an added assurance that they are based upon sound scientific, technical, and economic analysis. A "major rule" is one that concerns human health, safety, or the environment and that has an annual economic impact of at least $100 million. For major USDA food safety regulations, this statute requires USDA to conduct a thorough analysis that makes clear the nature of the risk, alternative ways of reducing it, the reasoning that justifies the proposed rule, and a comparison of the likely costs and benefits of reducing the risk. The consideration of costs and benefits is for the purpose of identifying efficient ways of mitigating risk. This thorough analysis should describe the uncertainty and variability inherent in these analyses along with an evaluation of how these factors affect the outcome of the analyses. (Because few food safety regulations have exceeded the $100 million threshold for treatment as a major rule, the main contribution in the food safety area of the Office of Risk Assessment and Cost-Benefit Analysis, since its creation in 1995, has been its review of the Pathogen Reduction and Hazard Analysis and Critical Control Points proposed and final regulation.)

Further discussion of consideration of economic factors is found in paragraphs 209-213.

What follows are Reference Lists with discussions showing how precaution is part of the U.S. food safety system and citations to relevant documents. The Table of Contents at the beginning of this Annex can help the reader to find specific topics.

1. Useful U.S. internet addresses are provided in a separate annex for both U.S. agencies and for several non-governmental organizations. For example, the following information on the Food Safety Initiative is derived from the U.S. government's food safety internet gateway site, www.foodsafety.gov.

2. On January 25, 1997, the President announced his food safety initiative. He directed the Secretaries of Agriculture and Health and Human Services and the Administrator of the Environmental Protection Agency to identify ways to further improve the safety of the food supply. Those agencies held public meetings with consumers, producers, industry, states, universities, and the public, and reported back to the President. The Report, issued in May 1997, was entitled Food Safety from Farm to Table: A National Food-Safety Initiative. To implement the recommendations in the report, USDA and HHS submitted joint budget requests for pathogen research, surveillance, risk assessment, inspection, and education for FY 98, FY 99 and FY 2000. Through this initiative, and other activities, HHS, USDA, and EPA have laid the groundwork for a strategic planning effort. In the May 1997 report, the agencies recommended a longer-term strategic planning effort to consider how to best address important challenges and make the best use of the agencies' limited resources.

3. The President's Council on Food Safety was established in August 1998 under E.O. 13100 to strengthen and focus U.S. efforts to coordinate food safety policy and resources. The Council was directed to: 1) develop a comprehensive strategic Federal food safety plan; 2) advise agencies of priority areas for investment in food safety and ensure that Federal agencies annually develop coordinated food safety budgets for submission to the Office of Management and Budget (OMB); and 3) ensure that the Joint Institute for Food Safety Research (JIFSR) establishes mechanisms to guide Federal research efforts toward the highest priority food safety needs.

4. A coordinated food safety strategic planning effort is needed to build on common ground and to tackle some of the difficult public health, resource, and management questions facing Federal food safety agencies. The draft strategic plan—which was the subject of public meetings held in July 1999 and January 2000-- focuses on not just microbial contamination but on the full range of issues discussed in the paper on the Scope of the Council's Comprehensive Strategic Food Safety Plan. The goal is to develop a comprehensive strategic long-range plan addressing the steps necessary to achieve a seamless food safety system including key public health, resource, and management issues on food safety. The plan will be used to set priorities, improve coordination and efficiency, identify gaps in the current system and mechanisms to fill those gaps, enhance and strengthen prevention and intervention strategies, and develop performance measures to show progress. The strategic plan is due to the President in July 2000.

5. In developing the strategic plan, the Council is taking into account the 1998 recommendations of the National Academy of Sciences (NAS) in response to a Congressional request for a study of the current food safety system (NAS/NRC, August 20, 1998, Ensuring Safe Food from Production to Consumption).

6. Prevention is central to the Food Safety Initiative. For example, the 1997 recommendations in Food Safety From Farm to Table: A National Food-Safety Initiative "are based on the public-health principles that the public and private sectors should identify and take preventive measures to reduce risk of illness, should focus our efforts on hazards that present the greatest risk, and should make the best use of public and private resources".

7. The report also recommended a new early-warning system for food borne disease surveillance, an interstate outbreak containment and response coordination, strengthened risk assessments, research, improved inspections and compliance, education, and a blueprint for a better food-safety system. All of these initiatives are underway.

8. As part of the Food Safety Initiative, in 1997 FDA, USDA, and EPA established an interagency risk assessment consortium at the Joint Institute of Food Safety and Applied Nutrition at the University of Maryland. The goal of the consortium is to cooperatively advance the science of microbial risk assessment. The agencies are working to further focus critical research needs and reach consensus on the priorities of those needs based on their potential to reduce the uncertainty of risk management decisions.

9. The U. S. food agencies also make use of documents on risk analysis produced at the international level, as well as ones produced at a national level. An example is the World Health Organization's 1987 document setting forth "Principles for the Safety Assessment of Food Additives and Contaminants in Food." There are many similarities between the national and international documents, which is not surprising.

10. The United States has considered it a priority for our experts to participate actively in international activities in this area by the relevant bodies, particularly the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and their joint food standards program, Codex Alimentarius, the authoritative body for establishment of international standards for food. (Also, OECD has produced documents relevant to risk analysis for pesticides, toxic chemicals, and bioengineered foods.) In participating in the development of documents on risk analysis at the international level, U.S. experts have contributed information about U.S. national practices of interest to others in the international food safety community, and the result is a body of international work that is highly congruent with national approaches. In this annex to the U.S. national summary, international references are omitted, as OECD is certain to include them in the report on relevant international food safety activities.

11. National Research Council, National Academy of Sciences (NAS/NRC) has studied many aspects of food safety. See www.nap.edu/catalog/9453.html Examples of its studies are:

• 1982. Diet, Nutrition and Cancer: Directions for Research.
• 1999. Enhancing the Regulatory Decision-Making Process for Direct Food Ingredient Technologies.
• 1999. Ensuring Safe Food: From Production to Consumption.
• 1975. Principles for Evaluating Chemicals in the Environment.
• 1982. Risk and Decision-Making: Perspectives and Research.
• 1983. Risk Assessment in the Federal Government: Managing the Process.
• 1994. Science and Judgment in Risk Assessment.
• 1996. Understanding Risk: Informing Decisions in a Democratic Society.
• 1999. The Use of Drugs in Food Animals: Benefits and Risks.

12. The U.S. Office of Science and Technology Policy (OSTP) has also done studies:

• 1981. Technologies for Determining Cancer Risks from the Environment.1
• 1982. Report on Risk Assessment Principles.
• 1984. Chemical Carcinogens. 49 FR 21594, 21598 (1984).

13. Gaylor, D. and Kodell, R.1980. Linear interpretation algorithm for low dose assessment of toxic substances. J. Environ. Pathol. Toxicol. 4:305. This is a peer-reviewed, seminal work in the area of models for use in quantitative risk assessment of toxic chemicals at low exposure levels. Its "linear-at-low-dose" model has been used extensively by FDA and EPA as the default, appropriately protective approach in the absence of sufficient scientific data establishing the validity of alternative approaches.

Federal Food, Drug, and Cosmetic Act (FFDCA) and Related Statutes

14. The Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 et seq.) (FFDCA) prohibits distribution in the United States, or importation, of food that is adulterated or misbranded (21 U.S.C. 331).

15. A food is "adulterated" (21 U.S.C. 342) if it bears or contains any poisonous or deleterious substance that may render it injurious to health (with stricter rules for added substances than for naturally occurring substances). The word "adulterated" applies to products or materials that are unsafe, defective, filthy, or produced under insanitary conditions.

16. The FFDCA forbids distribution of any food or food ingredient required to be approved by FDA and lacking such approval. For example, it deems "adulterated," as a matter of law, any food containing an unapproved food or color additive (21 U.S.C. 342). Similar provisions govern departures from requirements as to use of veterinary drugs. The law covers food for human use and food for animals (both pets and food animals). Food irradiation and indirect additives, including food packaging containing substances that may become part of food, must be approved under the food additive regulations. Food and color additive requirements are discussed in paragraphs 99-124, below.

17. An important development, beginning in the 1970s, was FDA's use of regulations "for the efficient enforcement of the Act" (FFDCA, 21 U.S.C. 371(a)), having the force and effect of law. Regulations "for the efficient enforcement of the Act" provide a broad array of regulatory controls, discussed below (paragraphs 73-76, 206). Although FDA's statutory food safety authority has not changed significantly in 40 years, except as to infant formula, nutrition labeling and dietary supplements, the interpretation of the authority by the agency, the Congress, and the courts has evolved in response to consumer protection needs, e.g., for regulations to prevent growth of pathogens. Dozens of court decisions have interpreted the FFDCA in the consumer's interest, as is discussed in the Reference List V. below, summarizing several pivotal or representative cases.

18. Regulations are issued following a notice-and-public comment process under the procedural requirements of the Administrative Procedure Act (5 U.S.C. 553). The substantive authority for the regulations derives from the statute. For example, the statute forbids distribution of adulterated food (21 U.S.C. 331, 342). Citing to these provisions and to the general provision enabling regulations for the efficient enforcement of the FFDCA (21 U.S.C. 371 (a)), FDA can issue a regulation informing manufacturers of what they need to do to avoid running afoul of the statute. Court decisions upholding this regulatory approach thus uphold FDA's view that it possesses the flexibility under the FFDCA and other laws to develop regulations requiring the industry to take preventive steps so as to assure production of safe food. See paragraphs 73-76, Reference List V.

19. In regulating food safety, FDA relies not only on the FFDCA but also upon the Public Health Service Act (42 U.S.C. 241 et seq.) (PHSA). This law provides general and flexible authority for a range of activities to protect public health. This authority underlies the nation's hugely successful milk safety program as well as its shellfish and interstate transportation sanitation program. Specific authority in the PHSA for regulations to control communicable diseases has been delegated both to FDA to carry out its enforcement responsibilities and to the Centers for Disease Control (CDC) to carry out epidemiology and surveillance work. This authority is key to both agencies' activities to combat food borne illness, which are carried out in close cooperation with FSIS, when the outbreak implicates meat, poultry, or egg products.

20. The Federal Meat Inspection Act (21 U.S.C. 601 et seq.) (FMIA), is one of three important food safety laws administered by FSIS. It requires FSIS to administer an inspection program to ensure that meat and meat products moving in commerce, and for export, are safe, wholesome, and correctly marked, labeled, and packaged. This inspection program, which has as its goal the prevention of shipments of contaminated meat, is mandatory as to cattle, calves, swine, goats, sheep, lambs, and horses. Similar provisions apply to poultry (i.e., chickens, turkeys, ducks, geese, and guineas) under the Poultry Products Inspection Act (PPIA) and to egg products, under the Egg Products Inspection Act. While the origin of the FMIA lies in the precautionary legal concept that animal diseases can affect humans and, therefore, diseased animals should be prevented from being used for human food, the FMIA and PPIA are also flexible and precautionary enough to address today's other food safety concerns as well.

As is discussed below in the section on regulations and policies, these inspection programs are based upon application and enforcement of Hazard Analysis and Critical Control Points (HACCP) system, a fundamentally precautionary food safety system to be applied by producers and monitored and enforced by the federal and state authorities.

21. FSIS also monitors meat and poultry products in storage, distribution, and retail channels, and takes necessary compliance actions to protect the public, including detention of products, oversight of voluntary recalls, court-ordered seizures of products, administrative withdrawal of inspection, and referral for criminal prosecution.

22. Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA registers pesticides for use in the United States and prescribes labeling and other regulatory requirements to prevent unreasonable adverse effects on health or the environment. Furthermore, under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 348a), EPA establishes tolerances (maximum legally permissible levels, or MRLs) for pesticide residues in food. Tolerances are enforced by FDA for most foods and by FSIS for meat, poultry, and egg products.

23. Section 2bb of FIFRA and section 408 of the FFDCA mandate a single, health-based standard for all pesticides in all foods and provide special protections for infants and children. In addition, both statutes require periodic re-evaluation of pesticide registrations and tolerances to ensure that the scientific data supporting pesticide registrations and tolerances will remain up to date in the future. Other examples include FIFRA provisions that expedite the approval of safer pesticides.

24. Details about EPA's implementation of FIFRA and the pesticide provisions of the FFDCA may be found on the EPA homepage, http://www.epa.gov. Policy and guidance documents at various stages of development are listed at paragraphs 175 and 176, below.

25. The Environmental Protection Agency (EPA) is the principal Federal agency responsible for the safety of drinking water under the Safe Drinking Water Act (42 USC 300f). This work is carried out in close cooperation with States and municipal governments. FDA regulates bottled water, in close cooperation with EPA. FDA and FSIS carefully monitor the water used in food processing plants under their jurisdictions.

26. APHIS' Plant Protection and Quarantine (PPQ) regulates and inspects imports of plants and plant commodities to prevent the accidental introduction of plant pests and diseases such as citrus canker and exotic fruit flies and noxious weeds. PPQ regulates the planting of genetically engineered crops prevent adverse impacts upon agriculture, and facilitates the export of U.S. plants and plant products by ensuring and certifying that they comply with the requirements of the importing country. PPQ also has programs to eradicate introduced plant pests and diseases.

27. APHIS' Veterinary Services (VS) regulates the importation of animals and animal products to prevent the accidental introduction of animal diseases, thus ensuring the health, quality, and marketability of U.S. animals and animal products. VS programs are intended to prevent the introduction of foreign animal diseases such as foot-and-mouth disease, classical swine fever, rinderpest, and BSE. VS also has programs to eradicate selected animal diseases such as bovine tuberculosis, brucellosis, and pseudorabies, some of which are food-borne and potentially transmissible to humans. VS participates in and provides guidance to industry sponsored quality assurance programs such as the National Poultry Improvement Plan (NPIP), the swine industry's pork quality assurance program for trichinella certification, and the sheep industry's scrapie certification and eradication program. Veterinary Services also licenses and monitors the production of veterinary biologicals and vaccines to ensure that these products are safe and effective. Similar to PPQ, VS facilitates the export of U.S. animals and animal products by ensuring and certifying that they comply with importing countries, sanitary regulations.

28. The food safety initiative, described earlier, has greatly strengthened interagency cooperation on food safety. Coordination of food safety activities also takes place among APHIS, EPA, FDA, FSIS, and other agencies through interagency cooperative agreements and other means. For example, FSIS and FDA have an agreement to share information about potential enforcement problems in meat and poultry plants that are primarily under FSIS inspection.

29. To avoid both duplication and gaps, the meat, poultry, and egg product laws and the FFDCA contain provisions explaining their relationship to one another. Livestock being raised for food use are "food" under the FFDCA. Anyone involved in handling, transporting, or manipulating "food," as well as the "food" itself, falls under the jurisdiction of the FFDCA. Thus, meat, poultry, and egg products are foods remain "food" under the FFDCA and therefore can be reached by FDA except to the extent of the application and scope of the FSIS-administered laws. Bell v. Goddard, 366 F. 2d 177 (7^th Cir. 1966) ("The Federal Food, Drug, and Cosmetic Act and the Poultry Products Inspection Act are complementary"); United States v. Articles of Food...Buffalo Jerky, 456 F. Supp. (D. Neb. 1978) (the Federal Meat Inspection Act does not derogate from the FFDCA but creates a separate area of concern, meat and meat products, over which USDA is given additional powers in the interest of protecting public health and welfare).

30. For example, farm animals destined for food use are food under the FFDCA. Inspectors of both FSIS and FDA possess authority to detain shipments of meat, poultry, or egg products that appear to be adulterated (21 U.S.C. 672 (meat), 467(a) (poultry), 1048 (eggs)). In most situations, however, FSIS exercises this authority. FDA approves veterinary drugs (except veterinary vaccines), food and color additives for use in all food including FSIS-regulated products, and irradiation of all food including meat and poultry. Hence, the authority of the two agencies is complementary, highly consumer-protective, and characterized by very close interagency cooperation.

Federal-State Agreements and Cooperation

31. Food safety regulation is a matter of shared responsibility under the U.S. system. Under the Constitution, Federal laws have supremacy over inconsistent State laws, and States are not allowed to have laws that burden interstate or foreign commerce. In fact, however, the vast majority of State food safety laws present no issue concerning of inconsistency with Federal laws but, rather, complement the Federal laws and add resources to their enforcement. The FFDCA contains provisions for State officials to be commissioned ("deputized") to help enforce the Federal statute, i.e., the FFDCA. Furthermore, States have their own food safety statutes. For many years an association known as the Association of Food and Drug Officials has maintained and periodically updated a Model State Food and Drug Act that has been closely followed in most States' laws.

32. Many cooperative programs are carried out with the states, e.g., those under the PHSA, discussed above. Sometimes FDA-funded contracts provide for the conduct by the States of particular categories of inspections or other activities. As is discussed in paragraph 68, FDA has issued, and is promoting state and local government adoption of, a model Food Code governing restaurants, supermarkets, and food service establishments. The states' food safety role is particularly important as to the latter classes of establishments.

33. As for the FSIS food safety programs, since 1967 there has been a federal-state cooperative program under which FSIS helps fund and oversee state-conducted meat inspection programs. State inspection programs must be "at least equal to" the federal program. A similar program of federal-state cooperation has been in effect for poultry products since 1968 and for egg products since 1970. State-inspected products are not permitted to be shipped in interstate or foreign commerce.

States are authorized to enact meat laws aimed at protecting the health and well-being of its citizenry, but those laws need to be consistent with Federal laws. Mario's Butcher Shop and Food Center, Inc. v. Armour and Co., 574 F. Supp. 653 (N.D. Ill. 1983).

34. EPA and APHIS likewise carry out an array of cooperative activities with the States.

http://www.fsis.usda.gov

35. An example of a precautionary approach is the decision by FSIS to treat E. Coli O157:H7 as an adulterant under the FMIA, even if the beef contaminated with such bacteria would injurious to health only if improperly cooked, is an example of the precautionary approach. This decision was upheld in Texas Food Industry Association v. Espy, 870 F. Supp. 143 (W.D. Tex. 1994), prior to implementation of the Pathogen Reduction and HACCP regulation, discussed below. The court explained that, under the FMIA, the product is adulterated if it contains a substance which may render it injurious to health and with E. Coli O157:H7, unlike many other pathogens, thorough cooking is necessary to protect consumers.

36. FSIS has put in place a new regulatory system for meat and poultry safety within the meat and poultry plants it regulates that has at its core the more effective prevention of food borne illness due to pathogens and other contaminants. The new, science-based system is improving food safety and making better use of agency resources.

37. This regulation was published on July 25, 1996 (61 FR 38805) and is now fully operational. The system is based upon Hazard Analysis and Critical Control Points, or HACCP. HACCP is a way for industry to control and prevent problems and ensure safe food by controlling the production process from beginning to end, rather than detecting problems at the end of the line. HACCP is widely recognized by scientific authorities and international organizations and is used extensively in the food industry to produce products in compliance with health and safety requirements.

38. The system has four major components. First, FSIS has required the plants it regulates to implement HACCP. This includes intrastate plants as well as plants in foreign countries wishing to export products to the United States. Second, FSIS-established food safety performance standards that plants must meet and is conducting testing and other activities to ensure those standards are met. Third, FSIS has provided training for its inspectors to provide the oversight necessary to ensure that industry is meeting regulatory standards. Fourth, FSIS has reorganized to strengthen its enforcement methods for dealing with plants that do not meet regulatory standards.

39. The regulation addresses the serious problem of food borne illness in the United States associated with meat and poultry products by focusing more attention on the prevention and reduction of microbial pathogens on raw products that can cause illness. It also clarifies the respective roles of government and industry in food safety. Industry is accountable for producing safe food. Government is responsible for setting appropriate food safety standards, maintaining vigorous inspection oversight to ensure those standards are met, and maintaining a strong enforcement program to deal with plants that do not meet regulatory standards.

40. The Pathogen Reduction and HACCP regulation: (1) requires all meat and poultry plants to develop and implement a system of preventive controls, known as HACCP, to improve the safety of their products, (2) sets pathogen reduction performance standards for Salmonella that slaughter plants and plants producing raw ground products must meet, (3) requires all meat and poultry plants to develop and implement written standard operating procedures for sanitation, and (4) requires meat and poultry slaughter plants to conduct microbial testing for generic E. coli to verify the adequacy of their process controls for the prevention of fecal contamination.

41. FSIS prepared extensively for the implementation of the final regulation by providing technical assistance to small plants, training its workforce, undergoing a reorganization, and reforming its regulations to be consistent with HACCP. These steps help to make sure that compliance will, in fact, occur.

42. FSIS moved to the new system after nearly a century of experience with the traditional inspection program, with its emphasis on organoleptic (sight, touch, and smell) methods. The traditional program has been successful in removing diseased animals from the food supply and enforcing other consumer protection standards. At the time the first major law on meat inspection was passed, animal diseases were the major concern, and science had not advanced to the stage in which invisible hazards such as pathogenic microorganisms would attract the attention of public health authorities. Since that time, however, animals have become healthier. Changes in the meat and poultry industries have resulted in products having a wider distribution, potentially affecting large numbers of people. In addition, the growing concern with microbial pathogens, and, in particular, emerging pathogens, and the development of new technologies to control pathogens on raw products has contributed to the need for new approaches to ensuring food safety.

43. Scientific support for new approaches to ensuring food safety has existed for some time. In the 1980s, the NAS issued the reports listed in paragraph 60, which supported the need for FSIS to better address pathogenic microorganisms and to have industry implement systems that prevent food safety problems in plants. Despite overwhelming scientific support for change, progress occurred very slowly. In late 1992 and early 1993, however, an outbreak of E. coli O157:H7, attributed to undercooked hamburgers served at a fast-food restaurant, highlighted the weaknesses in the traditional system and provided a national impetus for ground breaking change.

44. Acting quickly to address the problem, USDA began by issuing a regulation requiring safe handling labels that address storage, cooking, and holding practices for raw meat and poultry products. In 1994, USDA declared E.coli O157:H7 an adulterant in ground beef and established a monitoring program for the pathogen in ground beef. USDA also began work on its Pathogen Reduction and Hazard Analysis and Critical Control Points (HACCP) rule, with the extensive public rulemaking process completed with publication of the regulation on July 25, 1996.

45. Under HACCP, a plant analyzes its processes to determine at what points hazards might exist that could affect the safety of its products. These points are called critical control points (CCPs). Examples of CCPs are chilling; the cooking process; processing procedures, such as filling and sealing cans; and certain slaughter procedures, such as removal of internal organs. The location and number of hazards will differ greatly depending on type of facility, foods prepared, processing procedures used, and many other factors. Once the CCPs are identified, the plant must establish critical limits. Critical limits are usually expressed as numbers representing such parameters as time/temperature, humidity, water activity, pH, salt concentration, and chlorine level.

46. Critical limits may be in the regulations, such as the requirement that poultry be chilled to 40 degrees F., or they may be established by the plant based on the scientific and technical literature or recommendations of experts. Next, the plant establishes monitoring requirements for each CCP and the corrective actions to be taken when monitoring indicates there is a deviation from an established critical limit. Examples of corrective actions are adjusting the process, holding and destroying all product if it cannot be brought into compliance, and developing an alternative process. The plant must also establish record keeping procedures that document the operation of the HACCP system and verify that controls are working as intended.

47. Under the new rule, all plants must develop and implement a HACCP plan for the food safety aspects of their processes. Plants are required to validate their own HACCP plans--that is, they must ensure that the plans do what they were designed to do. FSIS will not approve HACCP plans in advance but will review them for conformance with the final regulations.

Performance Standards for Salmonella

48. FSIS believes that HACCP systems must be combined with performance standards as a means of establishing the degree of protection HACCP systems must achieve. FSIS already has in place microbiological performance standards for ready-to-eat and other processed products, but, with one exception, such standards for raw products did not previously exist. (The exception is the current "zero tolerance" for the pathogen E. coli O157:H7 in raw ground beef.) Therefore, as part of the final rule, FSIS has established performance standards for Salmonella that slaughter plants, and plants that produce ground products, must achieve. The implementation dates for the standards correspond to the implementation dates for HACCP. Salmonella was selected because it is a major pathogen of concern, it is present on virtually all classes of raw food products in numbers large enough to detect, and its presence is an indicator that other pathogens may be present. FSIS expects that reducing the percentage of carcasses with Salmonella will lead to a reduction in other pathogens as well.

49. Performance standards for Salmonella are based on the current national baseline prevalence for Salmonella for each major species and product class. FSIS intends to revise its performance standards for Salmonella periodically, as new data become available, to further reduce the risk of food borne illness. FSIS will be conducting the Salmonella testing for slaughter establishments and establishments that grind products to determine whether they are meeting the pathogen reduction performance standards. The Agency will require corrective action when establishments are not meeting the standards.

50. Salmonella testing data will be available in accordance with the requirements of the Freedom of Information Act. In all cases, FSIS will provide an explanation of the purpose of the testing and the meaning of the data when data are provided.

51. A sanitary environment is a basic prerequisite for preparing safe food. As of January 27, 1997, all meat and poultry plants were required to have in place a written plan--called Sanitation Standard Operating Procedures (SSOPs)—to address sanitation. The new regulation does not impose new sanitation requirements. Instead, it institutes a process to ensure better compliance with existing Federal sanitation requirements that focus on preventing direct product adulteration. A plant's SSOPs describe all procedures it conducts daily to ensure effective sanitation, both before and during operations. Plants are also responsible for detecting, documenting, and correcting sanitation deficiencies and using that information to strengthen their sanitation control systems to prevent similar problems in the future. Inspectors will monitor plants' adherence to SSOPs while continuing to look for, and require the correction of, problems after they occur. In this way, FSIS will verify that the SSOPs are maintained and effective, and will take appropriate action if a plant fails to comply with SSOPs. Since January 1997, FSIS has temporarily withheld the mark of inspection from about 20 plants and has moved to withdraw inspection from one plant, based on violations of the SSOPs.

Testing for Generic E. coli

52. Since January 1997, slaughter plants have also been required to test carcasses for generic E. coli as an indicator of the adequacy of the plant's ability to control fecal contamination, a primary avenue of contamination for pathogenic microorganisms.

53. FSIS has adopted performance criteria for E. coli for each species of animal that reflect the frequency and levels the microorganism on carcasses according to FSIS nationwide baseline surveys. FSIS is using the term "criteria" because they are guidelines, not regulatory standards. FSIS will not use the test results by themselves to take any regulatory action, but will consider them in conjunction with other information to evaluate whether a problem exists that requires regulatory action, including plant closure. The required frequency of E. coli testing is based on production volume.

54. Implementation of the Pathogen Reduction and HACCP regulation has required a significant change in the roles and attitudes of both inspectors and industry. In the past, some plants have relied on FSIS inspectors to identify deficiencies before the company would take action to correct them. Implementation of HACCP clarifies the respective roles of industry and FSIS. Businesses that produce food are accountable for its safety. They need to look at all the things that could possibly go wrong, ensure their systems prevent those problems, and take immediate action if a problem arises.

55. FSIS' role is to set appropriate food safety standards, maintain vigorous and continuous inspection oversight to ensure those standards are met, and take enforcement action when standards are not met through system failures. By clarifying the respective roles of industry and government, the Pathogen Reduction and HACCP regulation sets the stage for enabling FSIS to better target inspection and oversight on the most significant food safety hazards. Under the new system, instead of focusing only on individual problems in plants, FSIS inspectors and compliance personnel will evaluate whether plant systems are working as intended to prevent and control contamination.

56. The conceptual shift embodied in HACCP, in which industry better assumes its proper responsibility for food safety, enhances the importance of an effective enforcement program. The agency's goal is to address plant problems at early stages, making it unnecessary for FSIS to intervene to withhold the marks of inspection for any extended period.

57. FSIS has established a new strategy for enforcement to complement the new regulation and to provide a high level of public confidence. Under the new system, FSIS has established a link between a plant's ability to control processes and the eligibility of products to bear the marks of inspection. In other words, FSIS will base its obligation under the law, to find that products are not adulterated, on the continuous demonstration that a plant's sanitation and process control systems are working to prevent adulteration. Under traditional inspection, the finding that product was not adulterated was based on inspectors examining products to catch evidence of contamination.

58. FSIS has integrated its compliance staff into the field regulatory staff and assigned new roles to compliance officers to create a team approach to enforcement. In the past, compliance officers were primarily responsible for products in distribution channels and generally contacted plants only when following up on violations involving products that had already been distributed in commerce. Under the HACCP system, compliance officers are assisting inspectors in documenting failures of plant control systems and helping to ensure appropriate due process when enforcement actions are needed, including such actions as suspending the use of the inspection marks and formally closing plants, i.e., withdrawing inspection.

59. FSIS is carrying out other activities to complete the new regulatory approach. For instance, to improve the inspection component even further, FSIS is exploring what changes should be made to the current system of carcass-by-carcass inspection that inspectors carry out to prevent diseased animals from being used for food. FSIS believes this function remains critically important but that in light of improvements in process control that are occurring under HACCP, changes to the tasks currently performed by FSIS inspectors can be made to improve inspection effectiveness and make the use of inspection resources more productive. One objective is to increase resources available for followup as to products that have left the inspected plant.

60. NAS/NRC 1983. Meat and Poultry Inspection--The Scientific Basis of the Nation's Program.

NAS/NRC. 1987. Poultry Inspection--The Basis for a Risk-Assessment Approach.

Centers for Disease Control and Prevention. March 17, 2000. MMWR (FoodNet data show decline in food borne illness).

FDA's Center for Food Safety and Applied Nutrition (CFSAN)

61. http://vm.cfsan.fda.gov/~lrd/haccp.html

As has been discussed, HACCP is a science-based, systematic approach to the identification, assessment of risk and severity, and control of the biological, chemical and physical hazards associated with a particular food production process or practice. FDA considers HACCP as a key part of the foundation of the U.S. food safety assurance program because HACCP, although simple in its basic concepts, is a sophisticated system for ensuring food safety. HACCP appropriately affirms that the food industry has the primary responsibility for producing safe food and the government has responsibility for providing a system of regulatory oversight.

62. In 1994, FDA published an Advance Notice of Proposed Rulemaking, entitled Development of Hazard Analysis and Critical Control Points for the Industry (59 FR 39888). In this document, the agency asked over one hundred questions regarding if, when, and how it should apply HACCP to industry segments. The comments received have been used by the agency in a variety of food safety activities.

63. FDA has undertaken a HACCP pilot program with volunteer food companies to aid in the understanding and evaluation of HACCP as it applies to various industries. The program has involved cheese, frozen dough, breakfast cereals, salad dressing, fresh and pasteurized juices, bread, flour and other products. The pilot program continues to provide FDA with additional experience in both evaluating companies' food control systems and gaining experience with audit-type inspections.

64. In 1995 the FDA published the seafood HACCP regulation, entitled "Procedures for the Safe and Sanitary Processing and Importing of Fish and Fishery Products" (21 CFR Part 123). It took effect in December 1997. FDA recognized that change to a HACCP-based system of controls could be a significant challenge for the seafood industry, as well for the FDA and state regulators. Therefore, the effective date of the regulation was preceded by a two year phase-in period to enable seafood processors to prepare for the new program. During this period, FDA worked with the Seafood HACCP Alliance (a consortium of Federal and state regulatory agencies, educators, and industry trade associations) to develop and deliver low-cost, nationally uniform training for processors. The training was designed to provide processors with the kind of information necessary for them to develop and operate HACCP systems that would be in compliance with the regulation.

65. FDA also assembled guidelines for processors on how to develop their HACCP systems. Processors were given the opportunity to comment and participate in the development of the guidelines, called the "Fish and Fishery Products Hazards and Controls Guide." In addition, FDA has published three editions of answers to the most frequently asked seafood HACCP questions from regulatory and industry personnel, in a document called, "HACCP Regulation for Fish and Fishery Products; Questions and Answers." These documents aid industry in taking a properly cautious approach.

66. An important factor regarding the embrace of HACCP has been that the size of the food industry and the diversity of products and processes have grown tremendously--in the amount and kinds of foods produced domestically and imported. The need for HACCP in the United States, particularly in the seafood industry, was further fueled by the growing trend at the international level to establish benchmarks for worldwide equivalence of measures to assure the safety of food products. The Codex Alimentarius Commission's 1997 adoption of HACCP set an international standard for food safety.

67. In April 1998, FDA proposed HACCP controls for fruit and vegetable juices (63 FR 20486).

68. Also, FDA has incorporated HACCP into the Food Code, a document that gives guidance to and serves as model legislation for state and territorial agencies that license and inspect food service establishments, retail food stores, and food vending operations in the United States. See Food Code, 1999 Recommendations of the United States Public Health Service, Food and Drug Administration (National Technical Information Service Publication PB99-115925).

69. http://vm.cfsan.fda.gov/~comm/lacf-toc.html

As a result of several outbreaks of botulism from consumption of improperly processed canned food products in the early 1970s, the National Food Processors Association (then the National Canners Association) petitioned FDA to adopt a comprehensive regulation which would describe good manufacturing practices for canned foods. The resulting regulations, currently found in 21 CFR Part 113, Thermally Processed Low-Acid Foods Packaged in Hermetically Sealed Containers, are frequently cited as the first regulatory use of HACCP concepts in the food industry. FDA later promulgated similarly styled regulations for the production of acidified food (AF) products (21 CFR Part 114, Acidified Foods). The LACF and AF regulations may be enforced through the emergency permit control under section 404 of the FFDCA and 21 CFR Part 108, as well as through other relevant remedies under the FFDCA (seizure, criminal prosecution, etc.).

70. The purpose of 21 CFR Parts 108, 113, and 114 is to assure safety from harmful bacteria or their toxins, especially the deadly Clostridium botulinum (C. botulinum). This assurance can be accomplished only by adequate processing, controls, and appropriate processing methods, such as cooking the food at the proper temperature for sufficient times, adequately acidifying the food, or controlling water activity. Together these regulations have been very successful in helping to assure the safety of canned food products.

71. The establishment of regulations on current good manufacturing practices (GMPs) (21 CFR Part 110) aided in the implementation of the statutory provisions that deem adulterated food that has been held under insanitary conditions (FFDCA, 21 U.S.C. 342(a)(4)). GMPs require industry to take steps to avoid the contamination of their food. For example, firms must take steps, including GMPs, to guard against cross-contamination of food by allergens (e.g., traces of peanuts in bakery products not labeled as containing peanut, due to failure through GMPs to control a processor's moving from production of peanut-containing cookies to non-peanut-containing cookies).

72. Susceptible individuals can die or suffer serious illness, due to anaphylactic reactions, if they consume products that contain unlabeled traces of the substances to which they are allergic. Accordingly, strict adherence to GMPs by processors, backed up by inspections, voluntary recalls, and enforcement by FDA and partner agencies at the State level, comprise a lifesaving form of precaution in the U.S. food safety system.

73. FDA's HACCP, LACF and AF, and GMP regulations are based upon a solid body of case law interpreting the statute as authorizing regulations to guard against food adulteration. Indeed, courts have not only upheld, but have encouraged, FDA's use of its authority for regulations to implement general statutory provisions such as those forbidding food adulteration.

74. Courts have actually encouraged FDA to issue detailed regulations and guidance specifying steps to be taken to assure that a reasonable degree of care and cleanliness be accorded the production of food. See e.g., United States v. Article of Food...Pasteurized Whole Eggs, 339 F.Supp. 131, 141 (N.D. Ga. 1972).

75. The FFDCA "imposes upon persons exercising authority and supervisory responsibility reposed in them by business organization not only a positive duty to seek out and remedy violations but also, and primarily, a duty to implement measures that will insure that violations will not occur." United States v. Park, 421 U.S. 658 (1975).

76. Many of the resulting regulations incorporate precautionary approaches, e.g., United States v. Nova Scotia Food Products, 568 F.2d 240 (2d Cir.1977) (regulation specifying requirements for processors of smoked fish); National Association of Pharmaceutical Manufacturers v. FDA, 637 F.2d 877 (2d Cir.1981) (good manufacturing practices). The regulations may require that food producers use precaution in their marketing of food products, with the objectives of preventing the marketing of unsafe food and assuring preparedness for remedial actions if mishaps occur. For example, in National Confectioners Association v. Califano, 569 F.2d 690 (D.C. Cir. 1978), the court upheld an FDA regulation requiring the manufacturers of certain food products to use product coding, and maintain records, so as to facilitate product recalls in the event of a future problem with the food.

77. FDA's Total Diet Study (TDS) has provided data on dietary intake of food contaminants for almost 40 years. Since its inception in 1961 as a program to monitor radioactive contamination of foods following atmospheric nuclear testing, TDS has grown to encompass residues of pesticides, industrial chemicals, toxic and nutritional elements, vitamins, and radionuclides. In all instances, analyses have been performed on foods prepared for consumption, so that the final results provide a realistic measure of human intake. (More information on the TDS can be found at www.fda.gov, under foods.)

78. Part of the U.S. precautionary approach to food safety is FDA's use of food additive control, tolerances, binding regulatory limits, and advisory action levels to control unavoidable contaminants in food that may be poisonous or deleterious to health (21 U.S.C. 342, 346; 21 CFR 109. 4). For example, FDA minimized food sources of lead through a series of restrictions. FDA has limited permissible levels of aflatoxin in a way that applies pressure upon producers of peanuts and corn to minimize their occurrence. 39 FR 42751 (1974). Other examples are the tolerances for polychlorinated biphenyls (PCBs) (21 CFR 109.15, 109.30) and for lead in ceramic ware (109.16) as well as many action levels, which are posted on the FDA internet homepage (www.fda.gov). In 1999, USDA and FDA restricted imports of products that might be dioxin-contaminated.

79. Early cases concerning FDA's authority to regulate chemicals showed a precautionary approach inherent in the food adulteration provisions. "The statute on its face shows that the primary purpose of Congress was to prevent injury to the public health by the sale and transportation... of adulterated foods... As against adulteration, the statute was intended to protect the public health from possible injury by adding to articles of food consumption poisonous and deleterious substances which might render such articles injurious to the health of consumers." United States v. Lexington Mill & Elevator Co., 232 U.S. 399 (1914) (interpreting language appearing in both the Food and Drugs Act of 1906 and the FFDCA). "It is not required that the article of food containing added poisonous or other added deleterious ingredients must affect the public health, and it is not incumbent upon the Government in order to make out a case to establish that fact... Congress doubtless took into consideration that flour may be used in many ways, in bread, cake, gravy, broth, etc. It may be consumed, when prepared as a food by the strong and the weak, the old and the young, the well and the sick; and it is intended that if any flour, because of any added poisonous or deleterious ingredient, may possibly injure the health of any of these, it shall come within the ban of the statute."

80. This case was one of several early U.S. government cases that "helped establish, in practice and in law, a conservative regulatory policy and a cautious commercial attitude toward artificial ingredients and other chemicals added to foods," S. Junod. 1999. Bleached Flour: The Supreme Court Mandates Regulatory Science. FDLI Update. 1: 16.

81. Beginning in 1950, a Select Committee of Congress met to consider the implications of the "chemo-gastric" revolution in food production and preparation that had occurred following World War II. Out of these hearings came three food safety laws that put the burden for insuring food safety squarely on the backs of food manufacturers and producers: a 1954 law on pesticides, a 1958 law on food additives, and a 1960 law on color additives. All three laws apply to both substances in food for human use and substances in food for animal use.

82. These amendments exemplify application of a precautionary approach in regulating food safety but were needed, in part, to create a means of securing governmental approval of chemicals for use in food. Lab testing may have shown the chemicals to be toxic when used at high levels, and yet the chemicals, with adequate uncertainty factors, can be used safely in food. An example of the U.S. law on the eve of these amendments is Flemming v. Florida Citrus Exch., 358 U.S. 153 (1958). In this case, the Supreme Court held that FDA could not allow any color that had been shown to be toxic in animals, a ruling that essentially disabled FDA from continuing the approval of virtually all color additives. Thus, a chief purpose of the Color Additive Amendments of 1960 was to restore a "safety in use" standard for the approval of color additives (with a stricter rule retained for carcinogenic additives, as will be discussed).

statutes, a vast quantity of publications have been issued to explain, or to apply, these laws. This section covers the highlights of FDA's implementation of the food and color additive laws, with a particular emphasis upon their precautionary features.

84. Later in this document, in paragraphs 139-173, are examples of precaution in related law administered by FDA as to residues of veterinary food and drugs for food animals, followed by information in paragraphs 174-181 on the recently revised pesticide laws, administered by EPA.

85. Although the 1954 Pesticide Additive Amendment did not include an anticancer clause barring the approval of a product found to induce cancer in man or other animals, FDA very quickly encountered a decision about carcinogenic pesticides. The Pesticide Additive Amendment allowed any pesticide to be registered but gave FDA the authority and option to establish a zero tolerance for residues in crops. This authority (later transferred to EPA, in 1970) put the burden squarely on farmers to use pesticide chemicals according to the label directions to ensure that no residues remained for ingestion by consumers.

86. In 1959, this provision was tested when it was discovered that carcinogenic aminotriazole residues remained on some portion of the nation's cranberry crop. In this highly publicized episode, occurring just before the traditional U.S. Thanksgiving holiday in which cranberries are an expected dish, the Secretary of Health, Education and Welfare declared that no cranberries would be marketed that year without clearance from the nation's food safety scientists at the FDA.

87. Just one year before the cranberries episode, reflecting the uncertainty of that era (when knowledge was know to be inadequate as to the causes of cancer, the relationship between diet and cancer, and the scientific testing methodology for cancer causing agents), Congress had adopted the precautionary approach first advanced by Congressman James Delaney. Junod, S. 1994. Chemistry and Controversy: Regulating the Use of Chemicals in Food, 1883-1959.

Under both the 1958 Food Additives Amendment and the 1960 Color Additives Amendment, the Commissioner of FDA is prohibited from approving the addition of any substance to the food supply that has been found to cause cancer. The wisdom of adopting such a strict prohibition was widely debated, its scientific grounding was often questioned, and the decisions made under the Delaney clause were challenged. The legislative history of the Food Additive Amendments shows that Congress recognized that perfect certainty and zero risk were not real possibilities. Nonetheless, many scientists, as well as consumer groups, supported the provisions. Scientific advances have deepened confidence in the methodology used to determine human risk from ingested carcinogens, but the Delaney clause has remained in place as a precautionary statement about the need to exercise caution in considering the addition of potential carcinogens to the food supply.

88. The standard for decision making under U.S. food additives law (21 U.S.C. 348) includes both a general food safety standard and a special rule for carcinogens. The general food safety standard provides that FDA shall not approve a food additive petition "if a fair evaluation of the data ... fails to establish that the proposed use of the food additive, under the conditions of use in the regulation will be safe..."

89. Immediately after this language is the Delaney clause (sometimes called the Delaney proviso): "Provided, that no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal, except that this proviso shall not apply with respect to the use of a substance as an ingredient of feed for animals which are raised for food production, if the Secretary finds (i) that, under the conditions of use and feeding specified in proposed labeling and reasonably certain to be followed in practice, such additive will not adversely affect the animal for which such feed is intended, and (ii) that no residue of the additive will be found (by methods of examination prescribed or approved by the Secretary by regulations, which regulations shall not be subject to subsections (f) and (g)) in any edible portion of such animal after slaughter or in any food..."

90. In 1960, the Color Additive Amendments became law and also included both a general safety clause and a Delaney clause, as well. The third Delaney clause was enacted in 1968, as part of the Animal Drug Amendments passed that year to streamline duplicative regulatory requirements. The purpose of the 1968 Act was to ensure that manufacturers of animal drugs for food animals could submit a single application, the new animal drug application, instead of both a new drug application and a food additive petition. The animal drug Delaney clause was thus a carry-over from the food additives law. Thus, there actually are three Delaney clauses--for food additives, animal drugs, and color additives (21 U.S.C. 348(c)(3)(A), 360b(d)(1)(H), and 379e(b)(5)(B). They are similar, and therefore are treated as one in this document.

91. The Color Additive Amendments "reflect a Congressional and administrative response to the need in contemporary society for a scientifically and administratively sound basis for determining the safety of artificial color additives, widely used for coloring food... The Amendments reflect a general unwillingness to allow widespread use of such products in the absence of scientific information on the effect of these products on the human body... A color additive would be permanently listed if those desirous of producing it had proven to the satisfaction of the Commissioner that it was safe for its intended use." Certified Color Mfg. Ass'n v. Mathews, 543 F. 2d 284, 286-87 (D.C.Cir. 1976).

92. Over time, however, the Delaney clause as a per se risk management law presented some challenges to FDA and to regulated industry, as is discussed in the articles cited in paragraphs 122-123.

93. The general safety standard is elaborated in 21 CFR 70. 3 and 170.3: "Safe" means that there is convincing evidence that establishes with reasonable certainty that no harm will result from the intended use of the color or food additive. A similar definition of "safe" is used for additives in animal food and feeds. Other regulations involving a precautionary approach are found in 21 CFR 70.40, 70.50, 170.20, and 170.22.

94. FDA. 1982. Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives (original FDA "Red Book"). FDA announced the availability of this influential guidebook through a notice in the Federal Register on Oct. 15, 1982 (47 FR 46141). This 253-page book shows how precaution is inherent in the U.S. risk assessment process for these additives. The testing recommended to satisfy the risk assessment process thus assures that decisions as to approval are both science-based and consistent with legal criteria. This book contains lists of references to publications showing the precaution of the U.S. system (pp. 62- 68, 128-29, 139-40, 152-53, 166-67, 180-81, 195, 204-06, 247). Considerations of space forbid more detailed description other than this cross-reference to those lists, along with a few quotations from the book itself to give a flavor of the agency's approach in this area.

95. The Red Book also includes a detailed discussion of "Criteria for Assessment of Safety: the Concept of 'Concern':"

96. The document goes on to explain related concepts such as Level of Concern (p. 20), Exposure (p. 21), Structure of a compound (p. 22), types of testing for each level of concern (pp. 22-28), and guidelines for toxicological tests (pp. 28-end).

97. In 1993, FDA announced its proposed revision of the Red Book and solicited comments via the Federal Register and scientific meetings (58 FR 16536, Mar. 29, 1993); FDA later extended the comment period for an additional 100 days (see 58 FR 40151, July 27, 1993)). FDA sought comments as part of open communication with scientists to ensure that precaution is built into the agency's decision making for food and color additives, consistent with the views of the larger scientific community, and also to avoid recommending procedures that do not add to safety. Based on the comments received, FDA is making changes in the draft revision for future publication. In the meantime, sponsors may consult both the 1982 version and the 1993 draft revision in developing data intended to show that additives are safe.

98. FDA, Guidance Document, Estimating dietary exposure to direct food additives and contaminants. www.cfsan.fda.gov. This document includes an extensive discussion of uncertainty, use of default assumptions, and ways to refine estimates to reduce uncertainty and allow for use of values/assumptions other than default, where justified.

99. FDA maintains positive lists of permitted food additives (21 CFR Parts 172-80) and color additives. The agency also maintains lists of substances of which FDA is aware that were prior-sanctioned (21 CFR Part 181); these substances, e.g., nitrates and nitrites (21 CFR 181. 33, 181.34) were allowed by FDA or USDA before the enactment of the Food Additive Amendments of 1958.

100. Also published are lists of substances found generally recognized as safe (21 CFR Parts 182-186) as well as those banned from use in food (21 CFR Part 189). These lists are not complete as to allowed or disallowed substances but are a useful starting point as to what substances are allowed in food to be distributed in the United States. See 21 CFR 170.30(d), 189. 1(b).

101. Diethylpyrocarbonate. 1972 (37 FR 15426). In this final rule, FDA rescinded a previous approval for the food additive diethylpyrocarbonate, a yeast inhibitor for use in beverages. The compound decomposes to ethanol and carbon dioxide. However, in the presence of ammonium ions (not uncommon in certain beverages), urethane, a carcinogenic chemical, may also be formed, albeit in small amounts. This document also illustrates the limited range of risk management possibilities open to FDA before the development of a policy entailing the use of formal quantitative risk assessment procedures for informing decisions regarding carcinogenic contaminants or impurities in food and color additives. (See the discussion below, in paragraph 113, of a 1988 decision on a related substance, dimethyl dicarbamate; the 1988 decision showed the enhanced sophistication of, and confidence in, quantitative risk assessment procedures in making an appropriate risk management decision in a similar situation.)

102. Sometimes the studies simply are not sufficient to determine that an additive is safe and that there is no carcinogenicity issue. Red No. 2 and Red No. 4 are examples.

103. Red No. 2. 1976 (41 FR 5823). Termination of Provisional Listing and Certification of FD&C Red No. 2. This document describes the basis for FDA's delisting (banning of the use) of FD&C Red No. 2 including referral of the data to a Toxicology Advisory Committee.

104. Red No 2. 1980 (45 FR 6252). Denial of Petition for Permanent Listing. Commissioner's Decision; Denial of Petition for Permanent Listing; Final Decision. 45 FR 6252 (Jan. 25, 1980). "The petitioner's burden to show the safety of a color additive by adequate studies has a critical effect on the outcome of this proceeding...the petitioner has not, in my judgment, shown through adequate studies that Red No. 2 is not a carcinogen. Accordingly, the petition to list the color additive for permanent use must be denied. This determination does not mean, however, that Red No. 2 has been found to be a carcinogen. The existing studies are not sufficient to show definitely either that it is a carcinogen or that it is not. The questions about its possible carcinogenicity are simply unresolvable on this record. In this type of situation, the petition must fail because it is insufficient at present to meet the statutory requirement that safety be affirmatively shown with reasonable certainty."45 FR 6253. The Commissioner's decision affirmed the initial decision of the Administrative Law Judge following an evidentiary hearing held in response to the petitioner's objections to the FDA decision to deny their petition. Corwin, E., and Pines, W. April 1976. Why FDA Banned Red No. 2. FDA Consumer.

105. Red No. 4. 1976 (41 FR 41853). Termination of provisional listing. As with Red No. 2, the petitioner's studies failed to show safety, and the petition was denied. 1983 (48 FR 48533). Commissioner's decision denying permanent listing.

106. Acrylonitrile. 1977 (42 FR 48528). Acrylonitrile was permitted for certain uses in the fabrication of beverage containers following the passage of the Food Additives Amendment of 1958. Subsequently, the development of improved methods for detection of migration of acrylonitrile into the contents of the containers raised questions regarding the safety of this use. In 1974, FDA placed limitations upon the use of acrylonitrile in food packaging, pending submission of toxicological data by manufacturers in support of the safety of the substance.

107. Thereafter, for five years (1979-84), FDA employed provisional measures and a precautionary approach to assuring the safety of a substance in food packaging that might migrate to food. "The Commissioner concludes that it is in the public interest to act prudently, albeit not definitively, at this time on the acrylonitrile copolymer beverage containers." 42 FR 13546. The sponsor challenged this decision, claiming that the minute quantities migrating from the acrylonitrile bottles did not constitute a health hazard. The U. S. Court of Appeals allowed the stay to remain in effect while a hearing was held and until the Commissioner could issue a final decision.

108. The agency did eventually, based on the science and the law, and following fair and transparent procedures, allow the material to be used, after concluding that it is safe.

109. As this case indicates, FDA regulates food packaging as a form of "indirect" food additive. For regulations on indirect food additives, including food packaging materials, see 21 CFR 170. 39, 171. 8, and 174. 6.

110. FDA. 1982 (47 FR 14464). This general policy for regulating carcinogenic chemicals in food and color additives discusses the basis for proposed regulations regarding the assessment of carcinogenic chemicals that might be present as contaminants or impurities in food and color additives. It addresses such factors as exposure estimates, dose-response relationships, and choice of algorithm(s) for use in quantitative risk assessments and shows how precaution is an inherent part of this process.

111. FDA. 1982 (47 FR 24278). D&C Green No. 5. 1982 (47 FR 24278). Again, this approval was based upon the constituents policy.

112. A consumer opposed to this policy challenged the decision, and in Scott v. FDA, 728 F. 2d 322 (6^th Cir. 1984), the court upheld FDA's decision to approve D & C Green No. 5 based upon the constituents policy. Its opinion summarized FDA's assessment of the cancer risk associated with human exposure to the trace levels of p-toluidine present in Green No. 5, and observed that the petitioner "does not contest the validity of the tests employed by FDA in determining that [the color] was safe...The FDA's conclusion that the risk levels ascertained after testing D&C Green No. 5 ... were so low as to preclude a reasonable harm from exposure to the additive within the meaning of the General Safety Clause, is also in accordance with the law." 728 F.2d 325.

113. Dimethyl dicarbamate. 1988 (56 FR 40502). In this final rule, FDA approved the use of the food additive dimethyl dicarbamate, a yeast inhibitor for use in beverages. As in the case of diethylpyrocarbonate (above), the additive decomposes, eventually, to methanol and carbon dioxide. However, in the presence of ammonium ions (not uncommon in certain beverages) methyl carbonate, a carcinogenic chemical, may also be formed, albeit in small amounts. This document describes how FDA used formal quantitative risk assessment procedures to estimate the upper-bound limit of carcinogenic risk to humans posed by urethane generated by decomposition of the additive. The agency concluded that the potential risk was sufficiently low that the additive would be safe for the requested use.

114. The statutory definition of food additives (21 U.S.C. 321(s)) includes use of sources of food irradiation in food processing. Therefore, irradiation may not be used on food for sale in the United States without FDA approval. See 21 CFR 179. 26 for existing approvals such as use of irradiation for spices, poultry, and ground meat.

115. FD&C Yellow No. 5. 1979 (44 FR 27212; 21 CFR 74. 340(d)(2)). FDA required label declaration of this color, due to mounting evidence of allergic-type reactions to FD&C Yellow No. 5. With this action, persons sensitive to the color could avoid it. There was no justification for banning the additive, as labeling dealt with the issue.

116. Similar considerations led to a requirement for the following statement on food containing aspartame, to protect susceptible individuals against harm without denying the public a generally safe, useful substance: "Phenylketonurics: Contains phenylalanine" (21 CFR 172. 804(d).

117. FSIS has the authority to promulgate regulations prohibiting or restricting the use of food additives in meat products. Chip Steak Co. v. Hardin, 332 F. Supp. 1084 (D.C. Cal. 1971). FSIS also carries out its own review of irradiation of meat and poultry.

118. As part of the Administration's National Performance Review, FSIS has published a new regulation on its approval processes for additives (Dec. 9, 1999). FDA and FSIS cooperate on approvals of additives and irradiation processes involving meat and poultry.

119. FDA. 1984. Procedures for carcinogenic risk assessment. Food Technology. This article presents an overview of scientific risk assessment techniques and their relationship to the FDA decision-making process.

120. Lipman, A. 1998. Regulation of Food Ingredients in the U.S. A. Proceedings, Global Conference on Natural Colors and Flavors. Intertech Conferences, Portland, ME. This paper describes the conservative approach mandated by law that all color additives must be listed before they can be used and describes FDA's scientific and administrative requirements for information needed to support listings. It references guidelines available from FDA on chemistry and toxicology requirements. Descriptions of the petition process and the strict interpretation of color additive regulations are included.

121. Lipman, A.1995. Safety of Xanthene Dyes According to the U.S. Food and Drug Administration. American Chemical Society Symposium Series, "Light Activated Pest Control." J. R. Heitz and K. R. Downum, eds. American Chemical Society: Washington, D. C. 616: 34-53.

122. Merrill, R. 1978. Regulating Carcinogens in Food: A Legislator's Guide to the Food Safety Provisions of the Federal Food, Drug, and Cosmetic Act. Mich L. Rev. 77: 171.

123. Merrill, R. 1988. FDA's Interpretation of the Delaney Clause. Yale J. on Reg. 1:77. "FDA's standard risk assessment procedures are calibrated to avoid underestimating human risk."

124. Scheuplein, R. 1987. Risk Assessment and Food Safety: a Scientist's and Regulator's View. Food Drug Cosm. L. J. 42: 249.

125. The U.S. government's thorough, precautionary review process for bioengineered plants and resulting foods has been well-documented in U.S. food safety agencies' documents and also at the Edinburgh conference that is part of the OECD ad hoc food safety review. Therefore, in consideration of space limitations, this discussion can (like others in this document) be abbreviated.

Three U.S. food agencies share responsibility for regulating agricultural biotechnology. APHIS is responsible for assuring that the growth of bioengineered plants does not harm the agricultural environment. EPA is responsible for assuring the human and environmental safety of pesticidal substances engineered into plants. FDA is responsible for assuring that foods derived through bioengineering are as safe as their traditionally bred counterparts. FDA maintains a consultation process through which it has been notified of, and has reviewed, safety information on all bioengineered foods marketed in the United States. FDA is not aware of any circumstance where a food safety question remains unresolved for a product of modern biotechnology that has been marketed.

126. FDA regulates the safety of food and feed products derived from modern biotechnology using the same standards and requirements as under U.S. food law generally. Substances added to food that do not meet the statutory definition of "generally recognized as safe," and that are not pesticides, are classified as food or color additives and must be pre-approved before they may be marketed.

127. Manufacturers of food and color additives are not only held responsible for the safety of their food and color additives—as they had long been held to be, under both general law in this country on legal responsibility and general provisions of the FFDCA—but, prior to marketing these additives, such manufacturers are required to submit to FDA documentation demonstrating their safety and await approval for their use.

128. FDA, Statement of Policy: Foods Derived From New Plant Varieties. May 29, 1992 (57 FR 22984). In this policy, FDA described how foods from new plant varieties, including those from bioengineered plant varieties, would be regulated under the same statutes and regulations as foods from existing plant varieties already on the market. Thus, the same adulteration, labeling, and food additive provisions apply to bioengineered foods as apply to their conventionally-derived counterparts. For example, if a plant were engineered such that food from that plant contained a food additive, the additive would be subject to the same premarket approval requirements as would a traditional food additive used in processed food.

129. In 1999, FDA held public hearings in Chicago, Washington, D.C., and Oakland California, to explain its policies on regulation and labeling of foods derived from bioengineered plants and to get receive public comment on those policies. Oct. 25, 1999 (64 FR 57470).

130. In 1986, the U. S. government issued the Coordinated Framework for the Regulation of the Products of Biotechnology (51 FR 23302). This document described how products developed through bioengineering would be regulated under the existing statutory framework by the relevant federal agencies, such as APHIS, FSIS, FDA, and EPA.

131. Starting in the 1980s and continuing through the 1990s, food safety agency scientists participated actively in OECD and Codex meetings in which nations exchanged information about their regulatory regimes for handling bioengineered products.

132. Also, FDA, APHIS and EPA have held numerous public meetings requesting input on scientific and policy questions in this area.

133. Thus, the policy development process in the United States as to foods containing genetically modified organisms has been highly transparent, with many opportunities for public comment.

134. Kessler, D. A., Taylor, M.R., Maryanski, J.H., Flamm, E.L., and Kahl, L.S. The Safety of Foods Developed by Biotechnology. 1992. Science, 256 1747.

135. Beru, N. 1994. Food Safety Aspects of Genetically Modified Products. Proceedings of the OECD Workshop on the Commercialization of Agricultural Products Derived Through Modern Biotechnology, Washington, D.C. OECD Environment Monograph 107.

136. Beru, N. 1997. Foods from Genetically Engineered Plants: Safety and Regulatory Considerations. Proceedings of the Asia Pacific Workshop on Biosafety of Transgenic Plants, Madras, India, Oxford & IBH Publishing Co.: New Delhi, India.

137. Price, W. D. 1995 FDA reviews foods devised from new plant varieties. FDA Veterinarian, March/April 1995.

138. Miller, M. A. and Matheson, J.C. 1997. Food safety evaluation of transgenic animals. In Transgenic Animals-Generation and Use, Houdebine, L.M., ed. Harwood Academic Publishers, pp. 563-568.

FDA's Center for Veterinary Medicine (CVM)

141. FDA has taken new regulatory steps to address antimicrobial resistance from the use of antimicrobials in animals. In November 1998, FDA issued draft guidance for industry on the subject. The guidance was followed by a document entitled "A Proposed Framework for Evaluating and Assuring the Human Food Safety of the Microbial Effects of Antimicrobial New Animal Drugs Intended for Use in Food-Producing Animals," which described the agency's thinking about the regulatory approach it was considering on the issue. The draft document developed the concept of antimicrobial risk management. According to the concept, monitoring and resistance thresholds would be established before a drug could be approved. Once shifts in susceptibility to a drug crossed a pre-determined monitoring threshold, FDA would call for additional information to ascertain which factors were most responsible for promoting resistance development. If resistance rose to the predefined threshold level, certain regulatory actions would take place, up to and including restrictions on the drug or removing it from the market.

142. In December 1999, FDA issued guidance to industry relating to consideration of resistance in approvals.

143. Continuous monitoring of resistance in enteric bacteria from humans and food animals is the key to effectiveness of the concepts in the draft document. For resistance monitoring, FDA is relying on the National Antimicrobial Resistance Monitoring System—Enteric Bacteria (NARMS). NARMS is a collaborative program among FDA, CDC, and USDA. The program monitors shifts in antimicrobial susceptibilities in zoonotic enteric organisms, from both human and animal sources.

144. Risk assessments are also a key part of the program. For example, to better estimate the actual risks posed from the use of antimicrobials in food animals, FDA has conducted a risk assessment that modeled the human health impact of fluoroquinolone-resistant Camphylobacter infections associated with the consumption of chicken. Significantly, this draft risk assessment has demonstrated quantitatively that resistance development in food-producing animals does have an impact upon human health.

145. The agency has contracted for a second risk assessment to examine the indirect transfer of resistance from animals to humans. For this risk assessment, FDA will be modeling the impact of virginiamycin resistance in Enterococcus faecium in animals on the ability to treat vancomycin resistant Enterococcus faecium in humans with the recently approved human antimicrobial, Synercid.

146. Research is also important. FDA has initiated its own intramural and collaborative research efforts to investigate factors associated with development, dissemination, and persistence of bacterial antibiotic resistance in both the animal production environment and food supply. Agency microbiologists are currently conducting or are participating in projects specifically targeted to gathering data. In addition to conducting intramural research, FDA also collaborates in extramural research grants and funds extramural research activities through cooperative agreements

147. Partnerships are essential. In addition to the intergovernmental cooperation already described, the agency endorses efforts by outside groups to help reduce the threat of antimicrobial resistance such as the Judicious Use program of the American Veterinary Medical Association (AVMA) and others. FDA is supporting educational initiatives about Judicious Use for veterinarians and livestock producers.

148. This program is an excellent example of effective interagency cooperation that minimizes risk to the public from residues in meat and poultry. Every year FSIS, FDA, and other federal/state agencies work together through the Surveillance Advisory Team process to develop a comprehensive, risk-based, annual sampling plan to detect drug and/or chemical residues in U.S. meat and poultry.

FSIS takes samples in meat and poultry plants across the United States, and timely information on any violative residues detected by FSIS's testing would be entered into the Residue Violation Information System, an interagency computer information system that collects information as to residue violations in domestically slaughtered livestock and poultry.

FDA's district offices throughout the country receive weekly reports of residue violations from the system and used the system to track federal/state follow-up activities. (As was explained earlier, livestock being raised for food use are "food" under the FFDCA. Anyone involved in handling, transporting, or manipulating "food," as well as the "food" itself, falls under the jurisdiction of the statute. FDA routinely exercises its authority on the farm, although more often in "for-cause" situations than in routine inspections.)

149. FDA instructs its FDA district offices to conduct on-site investigations of first-time violators when the FSIS reports a violative tissue residue of public health significance (Compliance Program 7371. 006--Illegal Drug Residues in Meat and Poultry).

150. If a violative tissue residue of public health significance is found and it is an initial residue violation, the FDA district office decides what action is warranted. For first-time violators, in general the 32 states that have cooperative agreements with FDA conduct inspections of first-time violators to determine the cause of the residue and to prevent a repeat violation through education or regulatory action, or both. State participation is thus an integral element of the United States' residue reduction effort. FDA and state officials conduct further sampling at the farm level as needed to ascertain the cause of the tissue residue violation. Feed, drug, and environmental samples are collected. Although the FDA has authority to conduct targeted live animal testing; the agency does not find it necessary to routinely include such testing in the U.S. residue control program, due to the program's regulatory strength and its emphasis on prevention. During an investigation, FDA and state investigators follow the inspection guidelines established in the compliance program described above, and they complete a standardized information that is entered into the Tissue Residue Information Management System for program evaluation and improvement purposes.

151. For repeat violators, FDA district offices are instructed to perform follow up actions in all cases and to recommend enforcement action as appropriate. A repeat violator is an individual who sells a slaughter animal whose carcass is found to contain a violative concentration of a drug, pesticide, or environmental contaminant within a 12-month period after receiving the USDA, FSIS Violation Notification Letter of a previous violation.

152. FDA works very closely with the other federal agencies involved in residue reduction efforts through monthly meetings of the Interagency Residue Control Group. National and regional meetings are also organized for federal and state residue control officials to discuss emerging issues and develop appropriate education, prevention, and/or enforcement strategies.

153. FDA's regulations and guidelines on animal drug testing and approvals demonstrate a precautionary approach to testing of animal drugs, the use of exposure estimates, and the determination of appropriate withdrawal periods. See 21 CFR Part 514 and www.fda.gov/cvm/fda/TOCs/guideline3toc.html

154. Just as bioengineered plant foods are subject to regulation as food and potentially as food additives, meat from transgenic animals is likewise regulated under these national food laws.

155. Hormones for growth promotion in food animals. FDA's approvals of hormones for use in growth promotion in food animals are based upon a thorough review of adequate and well-controlled scientific studies. See, Guest, G. and Fitzpatrick, S. (FDA, CVM). March 1987. Safety of Meat from Animals Treated With Naturally-Occurring and Synthetic Hormones.

156. Chloramphenicol. 1985 (50 FR 27059). Chloramphenicol has never been approved for use in food animals. The safety of the residues of chloramphenicol could not be determined as there was no animal model available. However, chloramphenicol had been approved for use in dogs. Several formulations as well as an oral solution were marketed. FDA withdrew the applications for the oral solution based on information that the oral formulations were being used in food-producing animals and that the label directions were not likely to followed in the future.

157. Dimetridazole. 1986 (51 FR 45244). In this notice of opportunity for a hearing, FDA proposed to withdraw approval of new animal drug applications for dimetridazole, an antiprotozoal agent approved for use in turkeys. The action was based on the determination that the drug was not shown to be safe for use (1) because new evidence provided a reasonable basis from which serious questions about the ultimate safety of dimetridazole and the residues that may result from its use may be inferred, (2) because new evidence shows that dimetridazole is no longer shown to be safe by adequate tests by all methods reasonably applicable, and (3) because new evidence shows that the labeled directions for use have not been followed in practice and not likely to be followed in the future. As no one had requested a hearing, FDA withdrew approval of the applications for dimetridazole.

158. Nitrofurans.1991 (56 FR 41902, 41903). This FDA Commissioner's Decision Withdrawing Approval also follows this approach as to allocation of burden of proof and found, among other things, that the risk standard to judge nitrofurans and their metabolites is 10^-6. Judicial review was not sought of this Commissioner's decision, and the products were withdrawn.

160. Bovine Somatotropin (rbST) 1993. On November 5, 1993, FDA's Center for Veterinary Medicine (CVM) approved a bovine somatotropin (bST) product, Posilac®, for use in lactating dairy cows to increase milk production after a thorough review characterized by precautionary approach to both human and animal health issues. bST is a proteinaceous hormone released from the anterior pituitary of cattle for normal growth and lactation. Although recombinant DNA processes are used to manufacture recombinant BST (rbST) products--similar to other new protein drug products for both humans and animals--rbST products themselves are not "genetically altered," nor are the food products derived from treated animals. In 1992, the 38th Joint Expert Committee on Food Additives (JECFA) of the WHO and FAO confirmed the human food safety of rbST products.

161. In March 1993, CVM convened its Veterinary Medicine Advisory Committee to address the question as to whether increased incidence of mastitis in dairy cows treated with Posilac® raised any concerns from the standpoint of potential risk to human health. (CVM was already satisfied as to acceptability from the standpoint of animal health.) The Committee concluded that the human health risk posed by the possible increased use of antibiotics to treat the mastitis was insignificant.

162. The sponsor agreed to conduct a post-approval monitoring program to track incidence of mastitis, animal drug use, and proportion of milk discarded due to positive drug tests. Results of the post-approval monitoring program were presented to FDA's Veterinary Medicine Advisory Committee, which met in late 1996. Each member of the Committee concluded that the labeling for Posilac® provides adequate directions for actual conditions of use. Also, the committee concluded that the post-approval monitoring program had confirmed that bST is safe and its approval had no adverse effect on the milk supply.

163. The review of rbST products and approval of Posilac® stimulated much public concern and controversy, often generated by groups opposed to rbST for socioeconomic or other reasons. For example, during the 1980s and early 1990s, rbST was the subject of a number of citizen petitions, Congressional inquiries, and state legislative initiatives. FDA conducted a thorough review, and finding that the sponsor had submitted a wealth of information demonstrating the product's safety and effectiveness, FDA applied the statutory criteria and approved this product, as it had been demonstrated safe and effective. Federal law does not provide for FDA to consider the social and economic impact of a new animal drug in its approval decision.

164. Upon approving the drug, the agency also decided that it did not have a legal basis under the FFDCA that would justify requiring labeling for milk products from cows treated with rbST. However, food companies could voluntarily label their products provided the information was truthful and not misleading. Also, Monsanto also agreed to conduct a post-approval monitoring program to track the incidence of mastitis, animal drug use, and proportion of milk discarded due to positive drug tests.

165. Control over composition of animal food and feeds: FDA's control of the safety of the animal food supply mirrors that used for human food. Additives to animal feed are approved by CVM. Standards for contaminants are established, the feed supply is monitored for unsafe contaminants and ingredients, inspections are conducted of feed mills, especially those that make medicated feed, enforcement is employed to address unsafe situations, and labeling is reviewed for compliance with agency regulations.

166. For example, FDA has approved several food additives (formaldehyde and irradiation) for controlling salmonella in animal feed and feed ingredients. Also, the agency is presently developing guidance for the industry on the levels of the mycotoxin fumonisins in human food and animal feed as a precautionary measure to prevent animal and human health problems.

167. Nearly all states have active feed safety programs too, and cooperation with them is a critical element of FDA's animal feed safety program. This cooperation occurs individually with states and through the agency's excellent working relationship with the Association of American Feed Control Officials (AAFCO). AAFCO publishes yearly its Official Publication, which contains, among other things, working definitions of all processed ingredients used in animal feeds. FDA reviews the safety of these ingredients before AAFCO accepts them. The states do not permit an ingredient in feed unless AAFCO has adopted a definition for it. FDA recognizes these definitions as the common and usual names of feed ingredients.

168. Gentian Violet. 1991 (56 FR 40502). Gentian violet had a long history of use as a mold inhibitor in poultry feed. In this final rule, FDA declared that gentian violet is not generally recognized as safe for use in animal feed and was prohibited for use as a food additive and as an animal drug, unless FDA approved a food additive petition. The decision was based on published literature demonstrating that gentian violet has mutagenic, genotoxic and other toxic properties.

169. FDA has authority to withdraw approvals of products based upon new reconsideration of data previously approved. A longstanding case on this point that also affirms the propriety of doing so for reasons of sound precautionary public policy is Bell v. Goddard, 366 F. 2d 177 (1966): "The petitioner contends that the final approval of his application was improperly suspended because the suspension was not based upon any evidence from tests or clinical experience after the effective date of his application. ...[FDA had] in fact withheld approval of his application pending further study of the same tests later used as evidence to support suspension of his application. He argues that ...the suspension of his application can only be attributed to the change in policy embarked upon by the Secretary of Health, Education and Welfare which was allegedly prompted by the latter's desire to achieve improper retrospective application of the so-called "Delaney clause' of the Food Additives Amendment of 1958. "

170. The court held that the Commissioner could properly conduct "an extensive re-evaluation, which drew together clinical experience in a manner not previously attempted and which perhaps brought its full impact to the attention of the experts for the first time, provid[ing] a basis for the Commissioner's findings. An interpretation of the statute prohibiting such a new application of existing information would do violence to the paramount interest in protecting the public from unsafe drugs. The fact that the re-evaluation may have been inspired by a change in administrative policy is irrelevant."

171. Although FDA's Center for Veterinary Medicine "must provide a basis from which serious questions about the ultimate safety of [an animal drug] and the residues that may result from its use may be inferred,"once that limited threshold burden has been satisfied, the burden passes to the sponsors to demonstrate safety. Commissioner's Decision, 44 FR 54861 (1979).

172. See Rhone-Poulenc, Inc. v. FDA, 636 F. 2d 750 (D.C.Cir.1980).

173. Also, approval of an animal drug may be withdrawn, after revocation of approval of the analytical method for detecting drug residues, if there is no other analytical method. 44 FR 54851 (1979).

174. As was discussed earlier, FIFRA and section 408 of the FFDCA establish the safety standard--reasonable certainty of no harm--that must be applied to all pesticides used on foods.

175. In an October 29, 1998 Federal Register notice, EPA published a framework to describe issues involved in the implementation of the Food Quality Protection Act (FQPA) and a preliminary schedule for the release of the policy and guidance documents associated with each issue. Among these are documents on:

1. Applying the FQPA 10-Fold Safety Factor

2. Dietary Exposure Assessment - Whether and How to Use Monte Carlo Analyses and the 99. 9th Percentile Issue

3. Exposure Assessment - Interpreting "No Residues Detected"

4. Dietary Exposure Estimates

5. Drinking Water Exposures

6. Assessing Residential Exposure

7. Aggregrating Exposures from All Non-Occupational Sources

8. How to Conduct a Cumulative Risk Assessment for Organophosphate or Other Pesticides with a Common Mechanism of Toxicity

9. Selection of Appropriate Toxicity Endpoints (or Critical Effects) for Risk Assessments of Organophosphates

176. Other papers that have also been prepared for public comment on science and risk management policies include:

• Draft Toxicology Data Requirements for Assessing Risks of Pesticide Exposure to Children's Health
• Draft Exposure Data Requirements for Assessing Risks of Pesticide Exposure to Children
• Guidance for the Submission of Probabilistic Human Health Exposure Assessments to EPA
• Choosing a Percentile of Acute Dietary Exposure as a Threshold of Regulatory Concern
• Use of the Pesticide Data Program in Acute Dietary Assessment; A Statistical Method for Incorporating Nondetected Pesticide Residues into Human Health Dietary Exposure Assessments
• Assigning Values to Nondetected/Nonquantified Pesticide Residues in Human Health Dietary Exposure Assessments
• Threshold of Regulation Policy--Deciding Whether a Pesticide With a Food Use Pattern Needs a Tolerance (Revised)
• Dietary Exposure Estimates: A User's Guide to Available EPA Information on Assessing Dietary (Food) Exposure to Pesticides
• Aggregating Exposures from All Non-Occupational Sources
• Guidance for Performing Aggregate Exposure and Risk Assessment
• Guidance for Identifying Pesticide Chemicals and Other Substances That Have a Common Mechanism of Toxicity (Revised)
• Cumulative Risk Assessment Guidance
• Science Policy on the Use of Data on Cholinesterase Inhibition for Risk Assessment
• The Role of Use-Related Information in Pesticide Risk Assessment and Risk Management
• Data for Refining Anticipated Residue Estimates Used in Dietary Risk Assessments for Organophosphate Pesticides
• Guidelines for the Conduct of Bridging Studies for Use in Probabilistic Risk Assessment
• Guidelines for the Conduct of Residue Decline Studies for Use in Probabilistic Risk Assessment
• Guidance for Performing Aggregate Exposure and Risk Assessment

177. For background, see NAS/NRC. 1987. Regulating Pesticides in Food: The Delaney Paradox; Wargo, J. 1996. Our Children's Toxic Legacy. Yale University Press: New Haven. Documents issued before the FQPA include:

• EPA. 1984 (49 FR 46294) General guidelines as to acceptable risk, including the one in a million standard.
• EPA. 1986 (51 FR 33992). Guidelines for carcinogen risk assessment.

178. APHIS exercises a so-called "precautionary approach" when it learns about a pest or disease threat, including situations where the information may be incomplete. A precautionary approach is taken when faced with an imminent hazard to animal or plant health, particularly in situations where there is a lack of sufficient time or information to complete an appropriate risk assessment. The agency, like other regulatory agencies, uses interim regulations to impose such emergency measures. These interim measures can become effective immediately where there is sufficient justification.

179. A good example of APHIS' emergency interim measures can be seen in the approach APHIS took when it banned the importation of animal products (i.e., primarily ruminants) from Europe following reports of BSE. This interim regulation, like others, can be modified eventually once the exporting countries affected by the ban provide the necessary information to APHIS and, to FDA and FSIS as well, to conduct a more complete risk assessment and to determine that less restrictive regulatory measures can be taken. This approach is consistent with Article 5. 7 of the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement), which requires members to review provisional measures within a reasonable time period and to support such measures with a more complete assessment of risk.

180. APHIS risk assessments are designed to present scientific evidence and the inferences and conclusions that can reasonably be drawn from that evidence to the agency's decision makers, stakeholders, trading partners, and the general public. APHIS believes risk assessments should neither minimize nor exaggerate the likelihood of adverse outcomes and recognizes that negative consequences may result from both excessively risk averse and excessively risk taking decisions.

181. Describing uncertainty is a key part of the risk assessment process. Indeed, the fact that the world is uncertain at times is the primary reason why risk assessment is necessary and useful. To be useful, risk assessments should describe analytical uncertainty about outcomes. Risk assessments, however, should not use that uncertainty to justify risk-averse bias in assessment findings. Decision-makers, taking account of risk assessment findings, the degree of uncertainty, and public attitudes toward risk, may reasonably use precaution while in the process of determining an acceptable level of risk.

182. The placement of this topic at the end of this annex should not be construed as indicating unimportance. Indeed, recent evidence suggests that governmental policies to encourage healthy choices may be one of the most important factors in avoiding preventable forms of cancer and other disease.

183. Therefore, mandatory nutrition labeling is precautionary in that informed consumers can, through such labeling, make choices that reduce their risk of cancer and cardiovascular diseases. Under the Nutrition Labeling and Education Act of 1990 (NLEA), food is required to bear information about serving size, number of servings per container, calories, and certain nutrients (including total fat, saturated fat, cholesterol, sodium, carbohydrates, sugars, dietary fiber, and protein.) 21 U.S.C. 343(q)(1); 21 CFR 101. 9. A uniform format promotes consumer understanding and comparisons.

184. Nutrient content claims, whether expressed or implied, are forbidden unless they are allowed specifically and follow FDA's regulations. 21 CFR 101. 13 (b). This provision protects consumers, by guarding against abuses as to claims. A substance is eligible for a health claim if its decreased or increased use is associated with a disease or health-related condition for which the general U.S. population, or a subgroup, is at risk (21 CFR 101.14).

185. Claims are allowed as to:

• calcium and osteoporosis (101. 72),
• fat and cancer (101. 73),
• sodium and hypertension (101. 74),
• saturated fat/cholesterol and heart disease (101. 75),
• fiber-containing grains/fruits/vegetables and cancer (101. 76),
• fiber-containing grains/fruits/vegetables and heart disease (101. 77),
• fruits/vegetables and cancer (101. 78),
• folic acid and neural tube defects (101. 79),
• dietary sugar alcohol and dental caries (101. 80), and
• soluble fiber from certain foods—oat bran and psyllium--and risk of coronary heart disease (101. 81).

186. Special rules govern the use of "reduced" (21 CFR 101. 62 (c)(4)), "light" or "lite" (101.56 (b)), "free" or like expressions (101.13(e)), "low" (101.60-101.62), and other expressions in order to standardize what is meant by these terms and protect consumers against misleading uses of them.

187. Government policy on fortification of food with vitamins and minerals also represents a precautionary approach, in two respects. First, food fortification policies, by setting minimum levels of nutrients in certain foods, can reduce incidence of deficiency diseases. Second, food fortification policy, by setting maximum levels of nutrients, can guard against adverse effects upon vulnerable populations, or consumers generally.

188. FDA's fortification policies are expressed in food standards, e.g., the standard for enriched flour (21 CFR 137. 165), in general guidance on fortification (21 CFR 104. 20), and in labeling. The general FDA approach has been to establish standards for enriched basic dietary staples, such as flour, through "a uniform enrichment formula that would target the major deficiency diseases of the day in a rational, well-documented fashion," S. Junod. 1999. Whose Standards Should Prevail? Quaker Oats' Battle over "Bottled Sunshine." FDLI Update. 2: 12.

189. In Federal Security Administrator v. Quaker Oats Co., 318 U.S. 218 (1943), the Supreme Court upheld FDA's use of food standards authority to regulate fortification. "The evidence of the desire of consumers to purchase vitamin-enriched foods, their general ignorance of the composition and value of the vitamin content of those foods, and their consequent inability to guard against the purchase of products of inferior or unsuitable vitamin content, sufficiently supports the Administrator's conclusions." 318 U.S. 229. In sum, the Court permitted the FDA to employ a precautionary approach to increase the likelihood that consumers, through consumption of standardized, enriched products, could avoid vitamin or mineral deficiencies.

190. Concerning a food standard on iron in bread, the Commissioner of Food and Drugs concluded, after a formal evidentiary public hearing, that there are safety concerns about raising the level of fortification of iron in bread to the level that had been proposed. "[B]ecause of a safety question, there is a greater burden on the proponents to show need and effectiveness" of the fortification level they favored...the witnesses' opinion testimony...was backed by very little good data in the form of reliable studies that answered the questions raised." FDA, Iron Fortification of Flour and Bread; Findings of Fact, Conclusions, and Final Order, 43 FR 38575, 38577 (Aug. 29, 1978).

191. The Commissioner's decision was motivated, in part, by concern that increased iron fortification could present a danger to those at risk from increased iron. In response to the suggestion of a participant in the proceeding that such persons receive a "special precautionary treatment," presumably through a warning statement on the label, rather than to withhold a regulation that would benefit many due to the possible danger to a few, the Commissioner responded that, "[t]here is no evidence in the record as to how one could identify latent hemochromatotic individuals" and therefore "this suggestion does not sufficiently protect those at risk." Id.

192. Folate and Neural Tube Defects. 1996 (44 FR 8752). FDA took several actions to assure that women of childbearing age maintain adequate folate intakes, particularly during the years before conception, to reduce the risk of a neural tube birth defect-affected pregnancy. First, FDA authorized a health claim on this subject. Second, FDA amended the food standards for enriched grain products to require inclusion of folate. Third, FDA approved new food additive uses as need for folate fortification.

193. Special regulations govern infant formulas, recognizing the extraordinary need for precaution as to foods for our vulnerable youngest group in the population (21 CFR Parts 106 and 107).

194. The FFDCA is to be liberally construed consistent with its public health purposes. United States v. Bacto-Unidisk, 394 U.S. 784 (1969).

195. The consumer protection purposes of the FMIA have been recognized in a long line of court decisions. The purpose of the FMIA is, above all, to protect the health and welfare of consumers. G. A. Portello & Co. v. Butz, 345 F. Supp. 1204 (D.C.D.C. 1972). The FMIA is intended to ensure a high level of cleanliness and safety of meat products. United States v. Mullens, 583 F. 2d 134 (5^th Cir.1978).

196. U.S. courts accord "substantial deference" to expert agencies' interpretations of their statutes. Chevron v. NRDC, 467 U.S. 837 (1984).

197. On matters of fact, agency decisions are not set aside unless they are found to be arbitrary or capricious, or not in accordance with law. See, e.g., Borden Co. v. Freeman, 256 F. Supp. 592 (D.C.N.J. 1966), affirmed 369 F. 2d 404, certiorari denied 386 U.S. 992 (upholding FSIS regulations unless their promulgation was "arbitrary, capricious, abuse of discretion, or otherwise not in accordance with law"). Even where the particular statute has prescribed a more stringent evidentiary standard, e.g., "substantial evidence," U.S. courts generally defer to agency findings as to fact.

198. Also, expert agencies possess primary jurisdiction to decide what matters are under their control. United States v. An Article of Food...Food Science Laboratories, 678 F. 2d 735 (7^th Cir. 1982). "When the quality and the magnitude of hazards potentially associated with a new food product are as uncertain as they are here, the proper judicial response is aversion to the risks and strict enforcement of the regulatory framework for risk management established by the Congress." United States v. An Article of Food...Food Science Laboratories, 678 F. 2d 735 (7^th Cir. 1982). The sponsor, Food Science must "shoulder the burden of proving" to FDA that the ingredient in question qualifies for an exemption from the food additive requirements, and if FDA is unpersuaded, "it would certainly be unwise for this Court to create a judicial exception..." In other words, the proponent of a food substance bears the burden of showing that a food substance is "generally recognized as safe," and therefore exempt from the definition of "food additive."

The lack of studies showing adverse effects of a substance cannot establish general recognition of safety. United States v. Articles of Food and Drugs, 518 F. 2d 743, 747 (5^th Cir. 1975). An affidavit by a single expert asserting that a substance is safe does not suffice. United States v. An Article of Food...Coco Rico, Inc., 652 F. 2d 11 (1^st Cir. 1985).

199. U.S. courts are particularly likely to defer to the fact finding of regulatory agencies operating on the "frontiers of science." Industrial Union Dep't v. Hodgson 499 F.2d 467 (D.C. Cir. 1974).

200. Despite the deference as to legal interpretations and facts, courts are stringent in their demands that agencies adhere to procedural requirements in the Administrative Procedure Act that ensure the public's ability to participate meaningfully in the proceeding. United States v. Nova Scotia Food Products, 568 F.2d 240 (2d Cir. 1977).

201. This discussion supplements section A.2. in the introduction. Factors in the caution exercised by many producers include the desire to avoid liability to injured consumers. Liability can result in court orders to pay damages to injured consumers or their survivors--and to pay damages to commercial partners in the food distribution chain due to breach of contract--and in adverse publicity. These factors combine with the overwhelming desire of most processors to sell only safe products and to protect their commercial reputations. The sum of all of these factors amounts to a powerful incentive for a cautious approach to food safety in the private sector. Therefore, U.S. experience suggests that a national food safety system not only rests upon strong regulatory laws and enforcement agencies, but also depends upon an effective private responsibility system, well-functioning courts, and a free press. (Both the threat of liability and knowledge that news media might publicize a processor's food safety mishaps encourage caution.)

The precaution of most processors strengthens the efficacy of the governmental regulatory controls. While the principal purpose of governmental food safety regulation is consumer protection, an ancillary purpose is assuring a level playing field, so that prudent processors who make an investment in testing, training, and control measures are not forced to compete with those who do not. In sum, strong governmental compliance programs for food safety laws protect the investment made by responsible processors who take a precautionary approach to food safety. Processors generally, not just those predisposed to be good commercial citizens, need to adhere to essential requirements for precaution in their production, processing and distribution of food.

The private legal system described is predominantly a matter of the common law and statutes of the 50 states, each of which has a private system of tort and contract law that creates a legal incentive for food producers to exercise caution. A very high degree of harmonization has occurred among the states. Many court decisions on liability for personal injury refer to decisions in similar cases in other state courts as well as to treatises such as the Restatement of Torts with its authoritative discussion of liability law. Furthermore, all states (with the possible exception of Louisiana, whose basic legal system is based upon the Napoleonic Code) have enacted the Uniform Commercial Code, with its "implied warranty of fitness" of products.

It needs to be clearly understood that a private liability system, alone, is inadequate to protect consumers. A strong regulatory system is also essential because food can contain hazards, e.g., that are invisible to consumers. Also, consumers need expert food safety regulatory agencies to perform such tasks on their behalf as scientific risk analyses, approval of new products, and enforcement actions. A strong regulatory system also compensates for weaknesses in the private liability system. Not all injured consumers bring lawsuits and collect damages, and causality is sometimes difficult to prove (e.g., was illness or death was due to a danger present in food or another factor). Also, the private liability system rests to some degree upon experts employed by the litigants, rather than the rigorous and independent scientific review of innovation provided by the U.S. food safety agencies.

It should also be mentioned that there are currently some unresolved issues in the U.S. legal system about the relationship between regulatory statutes and private personal injury cases. Most cases to date have involved products other than food; some hold that the existence of a regulatory law implies that Congress must have meant to preclude private cases, which others hold that the existence of a regulatory law implies no such preclusion. The answer depends upon Congressional intent in each individual statute. Leading illustrative cases have involved tobacco products and medical devices.

202. Turning to industry responsibility in governmental enforcement actions, officials are strictly responsible for violations of the FFDCA, whether or not they had any personal awareness of the violation. In the landmark case of United States v. Dotterweich, 320 U.S. 277 (1943), the U.S. Supreme Court held that:

"The Food and Drugs Act of 1906 was an exertion by Congress of its power to keep impure and adulterated food and drugs out of the channels of commerce. By the Act of 1938, Congress extended the range of its control over illicit and noxious articles and stiffened the penalties for disobedience. The purposes of this legislation thus touch phases of the lives and health of people which, in the circumstances of modern industrialism, are largely beyond self-protection. Regard for these purposes should infuse construction of the legislation if is to be treated as a working instrument of government and not merely as a collection of English words...[The] legislation dispenses with the conventional requirement for criminal conduct--awareness of some wrongdoing. In the interest of the larger good it puts the burden of acting at hazard upon a person otherwise innocent but standing in responsible relation to a public danger...

"Hardship there doubtless may be under a statute which thus penalizes the transaction though consciousness of wrongdoing be totally wanting. Balancing relative hardships, Congress has preferred to place it [i.e., the hardship] upon those who have at least the opportunity of informing themselves of the existence of conditions imposed for the protection of consumers before sharing in illicit commerce, rather than to throw the hazard on the innocent public who are wholly helpless." Id. 283-86.

203. "[The] public interest in the purity of its food is so great as to warrant the imposition of the highest standard of care on distributors." Smith v. California, 361 U.S. 147 (1959). "[T]he Act punishes 'neglect where the law requires care, or inaction where it imposes a duty.'" Morissette v. United States, 342 U.S. 246, 255 (1952). In United States v. Park, 421 U.S. 658 (1975), the Supreme Court affirmed the continued validity of Dotterweich's doctrine on corporate official strict liability and went on to elaborate upon the particular responsibilities of these officials:

"Thus Dotterweich and the cases which have followed reveal that in providing sanctions which reach and touch the individuals who execute the corporate mission--and this is by no means necessarily confined to a single corporate agent or agent or employee--the Act imposes upon persons exercising authority and supervisory responsibility reposed in them by business organization not only a positive duty to seek out and remedy violations but also, and primarily, a duty to implement measures that will insure that violations will not occur. The requirements of foresight and vigilance imposed on responsible corporate agents are beyond question demanding and perhaps onerous, but they are no more stringent that the public has a right to expect of those who voluntarily assume positions of authority in business enterprises whose services and products affect the health and well-being of the public that supports them. 421 U.S. 672 (emphasis added).

The court noted that, "Assuming, arguendo, that it would be objectively impossible for a senior corporate agent to control fully day-to-day conditions in retail outlets it does not follow that such a corporate agent could not prevent or remedy promptly violations of elementary sanitary conditions in 16 regional warehouses." 421 U.S. 678.

204. As an additional deterrence to violations of the laws administered by FSIS, an officer of a company who is convicted of distributing adulterated products can be prevented from engaging in any business requiring federal inspection services. If FSIS finds that the company official unfit to engage in such business, it may withdraw inspection services to that company so long as the convicted individual is associated with it. Toscony Provision Co., Inc. v. Block, 538 F. Supp. 318 (D.C.N.J. 1982); Windy City Meat Co. v. U.S. Department of Agriculture, 926 F.2d 672 (7^th Cir. 1991); Wyszynski Provision Co., Inc. v. Secretary of Agriculture, 538 F. Supp. 361 (E.D. Pa. 1982).

205. The requirements of U.S. food safety laws can be enforced through court actions, based directly upon the statute, or they can be implemented in regulations. "The total scheme of this Act contemplates judicial obligation to enjoin distribution of unsafe foods even in the absence of formally promulgated regulation and it is not mandatory for the administrator to promulgate regulations establishing tolerances." United States v. Goodman, 353 F. Supp. 250 (E.D.Wis.1972), affirmed 486 F. 2d 847, affirmed 502 F. 2d 715, certiorari denied 420 U.S. 945.

206. FDA regulations for the efficient enforcement of the FFDCA under 21 U.S.C. 371(a) have the force and effect of law. "We have come to recognize that, if the administrative process is to be practically effective, specific regulations, promulgated pursuant to a general statutory delegation of authority must be treated as authorization...especially in areas where the agency possesses expertise not shared by the courts...[W]e have learned from experience to accept a general delegation as sufficient in certain areas of expertise." National Nutritional Foods Ass'n v. Weinberger, 512 F. 2d 688, 696 (2d Cir.), certiorari denied, 423 U.S. 827 (1975). The court particularly noted the advantage of rulemaking over other decision processes, in affording the industry, and the public generally, the opportunity to participate in the process of formulating broad policies. Id. 698.

207. See, generally, National Association of Pharmaceutical Manufacturers v. FDA, 637 F.2d 877 (2d Cir. 1981).

208. Regulations promulgated under FSIS statutory authority also have the force and effect of law. United States v. Cudahy, 243 F. 443 (D.C. Conn. 1917) (case under Federal Meat Inspection Act).

209. This discussion supplements section E. of the introductory section of this annex. One issue to be covered in the submission to OECD is whether a country's food safety system requires or provides for cost-benefit analysis in decision making under the law. With respect to U.S. food safety law, this depends upon the particular statute. While, in general, U.S. government agencies are subject to the requirement that they analyze the potential costs or impacts of their regulations under the Regulatory Flexibility Act and Presidential Executive Order 12866 on Regulation, these requirements do not apply where a statute precludes use of cost-benefit analysis. Indeed, the U.S. Supreme Court has held that "[w]hen Congress has intended that an agency engage in cost-benefit analysis, it has clearly indicated such intent on the face of the statute...Congress uses specific language when intending that an agency engage in cost-benefit analysis." American Textile Manufacturers Inst., Inc. v. Donovan ("the cotton dust case"), 452 U.S. 490, 510-11 (1981).

210. Thus, in decisions such as those taken under FDA's food or color additive authority where the standard for decision making is safety, EPA's pesticide tolerance authority with a similar standard, or FDA's animal drug authority where the standard is safety (and effectiveness), the absence of explicit Congressional authorization to conduct cost-benefit analysis means that under these laws the administering agencies may not base their regulatory decisions upon the results of a cost-benefit analysis. There is no barrier to agencies' performing studies to measure and report upon the economic impact of their decisions, as a way of informing themselves and the public. However, economic impact can play no determinative role in the decision taken as to a food or color additive, animal drug, or pesticide tolerance for food: safety is the operative criterion.

211. In 1980, the Attorney General of the United States issued an authoritative decision that neither the Secretary of Health and Human Services nor the Secretary of Agriculture has the authority to balance the benefits of a carcinogenic additive against its possible carcinogenic properties. They do, however, have the discretion to adopt timetables and procedures to assure the orderly removal of food substances from use if determined to be carcinogenic. 43 Op. Atty. Gen., Mar. 30, 1980.

212. As to veterinary drugs, FDA's position has long been that, in its decision making, the agency is precluded from cost-benefit analysis. See FDA's 1979 decision banning DES (44 FR 54852) and FDA's 1991 regulation banning gentian violet as an additive in animal feed or as an animal drug (56 FR 40502) (citing the American Textile Manufacturers case).

213. One situation in which the statute permits consideration of whether a substance is unavoidable in food, or is required in food production, involves the authority granted FDA to issue formal tolerances for unavoidable food contaminants under the FFDCA (21 U.S.C. 346). See, for example, FDA's decision setting a formal tolerance of 2 parts per million of polychlorinated biphenyl's (PCBs) in fish and shellfish. 49 FR 21514 (May 22, 1984) (considering possible food loss due to a strict tolerance).

214. Other articles and publications of interest include:

• Degnan, F. The Regulation of Food Safety. 1997. Fundamentals of Law and Regulation: An in-depth look at foods, veterinary medicines, and cosmetics [hereinafter, Fundamentals]. Food and Drug Law Institute. Washington, D.C. 161-204.
• Hutt, P. 1973. The Philosophy of Regulation under the Food, Drug, and Cosmetic Act. Food Drug Cosm. L.J. 28:177.
• Lambert, E. Food and Drugs for Animals Other than Man. 1997. Id. Fundamentals. 285-314.
• Olsson, P. and Johnson, D. 1997. Meat and Poultry Inspection: Wholesomeness, Integrity, and Productivity. Id., Fundamentals. 205-236.
• Hutt, P. and Merrill, R. 1991. Safety of Food Constituents, 283-377, and Regulation of Carcinogens, 863-963. Food and Drug Law: Cases and Materials—Second Edition. Foundation Press. Westbury, N.Y.
• Taylor, M. Food and Color Additives: Recurring Issues in Safety Assessment and Regulation. 1984. Seventy-Fifth Anniversary Commemorative Volume of Food and Drug Law. Food and Drug Law Institute. Washington, D.C.

215. Other articles and publications of interest include:

• Hutt, P. 1978. The Basis and Purpose of Government Regulation of Food. Food Drug Cosm. L.J. 33.
• Janssen, W. 1992. The U.S. Food and Drug Law: How It Came, How it Works. A reprint from FDA Consumer magazine. DHHS Publication No. (FDA) 92-1054.
• Junod, S. 1994. Chemistry and Controversy: Regulating the Use of Chemicals in Food, 1883-1959.

See the Table of Contents for additional U.S. Food Safety System documents