In enacting the 1958 Food Additives Amendment, Congress recognized that many substances intentionally used in a manner whereby they are added to food would not require a formal premarket review by FDA to assure their safety, either because their safety had been established by a long history of use in food or by virtue of the nature of the substances, their customary or projected conditions of use, and the information generally available to scientists about the substances. Congress thus adopted, in section 201(s) of the act, a two-step definition of "food additive." The first step broadly includes any substance, the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of food. The second step, however, excludes from the definition of "food additive" substances that are generally recognized, among experts qualified by scientific training and experience to evaluate their safety ("qualified experts"), as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or through experience based on common use in food) to be safe under the conditions of their intended use.
The FDA first published a list of these generally recognized as safe (GRAS) substances in the Federal Register of December 9, 1958 . This list came to be called the GRAS list . The current GRAS list appears as Parts 182, 184, and 186 of the Code of Federal Regulations (CFR). It totals hundreds of substances including those that are added to cotton fabrics or paper and paperboard used as food packaging materials.
Congress also recognized that FDA or the U.S. Department of Agriculture had granted explicit approval of specific uses of substances in food prior to September 6, 1958 through regulations specifying their use, through directives or formal opinions, or by letters offering no objection to such uses. Some of these so-called "prior sanctioned" food substances are listed in Part 181 of the CFR, but some prior-sanctioned substances remain unlisted.
Following the publication of the GRAS list, FDA made no systematic attempt to evaluate available scientific information on the GRAS substances. On October 30, 1969, largely as a result of a recommendation in the report of the White House conference on Food, Nutrition, and Health, President Richard M. Nixon, in his consumer message to Congress, directed the FDA to make such a critical evaluation of the safety of GRAS food substances. The GRAS review became a major project at FDA's former Bureau of Foods (now the Center for Food Safety and Applied Nutrition).
The FDA considered the alternatives of staffing to accomplish the evaluation in-house or of arranging to have the work done under contract. It elected a combination of approaches, one of which included contracting with the Life Sciences Research Office (LSRO), established by the Federation of American Societies for Experimental Biology (FASEB) in 1962. FDA contracted with LSRO to make scientific assessments concerning the health aspects of GRAS food substances or prior sanctioned food substances to summarize the available scientific literature, and to provide a recommendation as to what restrictions, if any, on the use of the substances would be needed to ensure their safe use in food.
The LSRO selected qualified scientists as consultants to review and evaluate the available information on each of the GRAS substances. These scientists, designated as the Select Committee on GRAS Substances (SCOGS), were chosen for their experience and judgment with due consideration for balance and breadth in the appropriate professional disciplines. From time to time as needed, the Select Committee retained the services of ad hoc consultants in specialized areas. These consultants did not participate, however, in the formulation of the opinions and conclusions of the Select Committee. The Select Committee's evaluations were made independently of FDA or any other group, governmental or nongovernmental. FDA requested LSRO to perform full safety reviews of the more than 235 substances, including some substances listed in the CFR, as well as some substances not listed in the CFR. By 1982, after 10 years of work, SCOGS had produced 151 detailed reports covering over 400 substances.
The FDA made tentative reports from SCOGS available to the public for review in the Office of the Hearing Clerk, via announcements in the Federal Register, and provided opportunity for any interested person to appear before the Select Committee at a public hearing to make oral presentation of data, information, and views on the substances covered by the report. The Select Committee considered the data, information, and views presented at the hearing in reaching its final conclusions. Reports were approved by the Select Committee and the Director of LSRO, and subsequently reviewed and approved by the LSRO Advisory Committee (which consists of representatives of each constituent society of FASEB) under authority delegated by the Executive Committee of the Federation Board. The Executive Director of FASEB approved and transmitted the reports to FDA.
Subsequent to receipt of a report, FDA reviewed the Select Committee report on scientific evidence for or against adverse health effects, reviewed related information as it affected possible use of the substance, and then, formulated a tentative regulatory decision. If FDA tentatively concluded that the available data and information supported a conclusion that a substance was GRAS for certain uses in food, FDA issued a notice of proposed rulemaking in the Federal Register to affirm GRAS status. If, after reviewing comments received from the public about its proposal to affirm GRAS status, FDA reached a final conclusion that the available data and information supported GRAS status, FDA issued a final rule affirming GRAS status by amending 21 CFR 184 or 186. FDA conducted rulemaking to establish the procedures that the agency would use, on its own initiative, to affirm the GRAS status of substances that were the subject of the GRAS review (21CFR 170.35 (a) and (b); proposed rule, 37 FR 6207, March 25, 1972; final rule, 37 FR 25705, December 2, 1972). Because the GRAS review did not cover all GRAS substances (e.g., it did not cover many substances that were marketed based on a manufacturer's independent conclusion that a use of a substance was GRAS), that rulemaking included a mechanism (the GRAS affirmation petition process; 21 CFR 170.35(c)) whereby an individual could petition FDA to review the GRAS status of substances not being considered as part of the agency's GRAS review. Many of the substances currently listed in 21 CFR Part 184 (e.g., menhaden oil, 21 FR 184.1472) were affirmed as GRAS as a result of FDA's review of a GRAS affirmation petition rather than as a result of FDA's agency-initiated GRAS review.
In 1997, FDA issued a proposed rule that, if finalized, would eliminate the GRAS affirmation petition process and replace it with a notification procedure (62 FR 18938; April 17, 1997). FDA issued this proposed rule to enable the agency to use its resources more efficiently and effectively. In that proposed rule, FDA invited interested persons who conclude that a use of a substance is GRAS to notify us of those conclusions during the interim between the proposed and final rules (the interim period). FDA stated that the agency would determine whether its experience in administering GRAS notices suggests modifications to the proposed notification procedure. During this interim period, FDA's Office of Food Additive Safety received approximately 25 GRAS notices per year. FDA has listed these GRAS notices on its Internet site together with FDA's response to each GRAS notice. In general, FDA's response has fallen into one of three categories:
- FDA has no questions about the notifier's conclusion of GRAS status.
- The notice does not provide a basis for a conclusion of GRAS status.
- At the notifier's request, FDA ceased to evaluate the notice.
FDA has not yet issued a final rule establishing the GRAS notification procedure.