Chapter 4
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An Industry Representative’s Views on the Regulation of GRAS Food Contact Substances and Ingredients Eric F. Greenberg* Eric F. Greenberg PC, Suite 3500, 70 West Madison Street, Chicago, Illinois 60602-4224 *E-mail:
[email protected].
The concept of general recognition of safety is central to the regulatory scheme applicable to food products, food additives, and food contact substances in the United States. This paper will examine that regulatory scheme and the place of GRAS in it, and will provide an evaluation of recent suggestions that additional regulatory intervention is necessary to assure the safety of food ingredients and food contact substances.
To understand the concept of “general recognition of safety,” or “generally recognized as safe,” or GRAS, it is necessary to understand the concept of ”food additive" as it is defined within the U.S. Federal Food, Drug, and Cosmetic Act (1). As important as the concept of GRAS is, ironically, it only appears in FFDCA as a negative conceptual framework within the definition of “food additive.” In short, the FFDCA defines “food additive” as essentially any substance that is added to or might migrate into food that is not generally recognized as safe or is not separately regulated because it has some other status as, for example, a pesticide residue or color additive, or has a prior sanction from a government agency. Specifically, the definition reads as follows: (s) The term “food additive” means 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 any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and
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including any source of radiation intended for any such use), if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, 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 experience based on common use in food) to be safe under the conditions of its intended use; except that such term does not include— (1) a pesticide chemical residue in or on a raw agricultural commodity or processed food; or (2) a pesticide chemical; or (3) a color additive; or (4) any substance used in accordance with a sanction or approval granted prior to the enactment of this paragraph 4 pursuant to this Act [enacted Sept. 6, 1958], the Poultry Products Inspection Act (21 U.S.C. 451 and the following) or the Meat Inspection Act of March 4, 1907 (34 Stat. 1260), as amended and extended (21 U.S.C. 71 and the following); (5) a new animal drug; or (6) an ingredient described in paragraph (ff) in, or intended for use in, a dietary supplement (1). There can be no doubt from reading this definition that Congress intended the legal scope of food additives to go far beyond what is probably the common understanding of the term among consumers, namely, substances such as preservatives, flavorings and other functional participants in a food formulation. The wording of the definition begins with a very broad statement of substances encompassed within the definition, then, as if to reassure the reader that the broad sweep of the definition is intentional, it provides a listing of specific functions that substances might serve that are encompassed within the definition, specifically listing substances “intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food." After introducing and reinforcing the broad scope of the definition, it then carves out an exception from coverage of the definition for substances that are GRAS. Here is how the definition explains the concept of general recognition of safety: “if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, 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 experience based on common use in food) to be safe under the conditions of its intended use.” In other words, the law says that we must examine and defer to the opinion of relevant qualified experts, (not otherwise identified), unless we are relying on the fact that a substance was commonly used in food, safely, since before January 1, 36 Komolprasert and Turowski; Food Additives and Packaging ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
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1958. And specifically what we seek to find out is whether such experts recognize the safety of the use of a substance under the intended conditions of its use. This is a crucial element of the definition of GRAS as well as the definition food additive: that what is being evaluated is not so much a substance as a specific use of the substance, taking into account the amount of it being used, the food types with which it is being used, the function it serves, and other factors. Therefore it is most useful to think of GRAS uses of substances rather than GRAS substances. Importantly, it follows that a substance that experts consider GRAS for one intended use is not necessarily GRAS for any other intended use. What one might have expected to see in this definition and is notable for its absence is any reference within the definition to approval, concurrence, license, review or even notice to the relevant regulatory agency, the US FDA. That is an aspect of the regulatory scheme that some observers consider objectionable. GRAS status is the highest level of recognition that use of a substance can achieve, reflecting both the safety of the substance and widespread knowledge and acceptance of the fact of its safety in that given use. As the name indicates, there are two elements to a GRAS conclusion: first, that a use of a substance is safe, and second, that there is general recognition of that fact among qualified experts. The safety standard employed is the same as that used for evaluating the safety of food additives, often summarized as reasonable certainty of no harm. 21 CFR Sec. 170.3(i) (2). The general recognition requirement relies on publicly available information, ideally published facts in peer reviewed scientific or medical publications or reference books. In a sense, the GRAS regulatory scheme, incorporating as it does a kind of freedom and self-determination for individual companies, reflects the American tradition preferring free markets whenever possible. In recent years, at least two entities have raised important questions about the current regulatory framework applicable uses of substances considered GRAS. The US government’s Government Accountability Office (GAO) issued a 2010 report (3) recommending steps to strengthen FDA’s oversight of GRAS determinations, and the Pew Health Group has issued a series of reports (4) about GRAS changes as well. The GAO report recommended these six measures: 1. 2. 3.
4. 5. 6.
Require any company that conducts a GRAS determination to provide FDA with notice, and make it public; Minimize the potential for conflicts of interest in companies’ GRAS determinations; Monitor the appropriateness of companies’ GRAS determinations through random audits or some other means, including issuing guidance on how to document GRAS determinations; Finalize the [1997] FDA proposed rule (5, 6) that governs the voluntary notification program, Conduct reconsiderations of the safety of GRAS substances in a more systematic manner, Ensure safety of engineered nanomaterials 37 Komolprasert and Turowski; Food Additives and Packaging ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
As evidence of FDA’s inadequate process for reconsidering safety conclusions, the GAO report pointed to 11 petitions that have been filed seeking reconsideration by FDA of GRAS conclusions that had been pending for as many as six years without FDA response. In turn, among the concerns raised in a 2012 report from the PEW Health group (4) were: 1.
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2.
3. 4.
FDA is unaware of a large number of chemical uses in food and, therefore, cannot ensure that safety decisions regarding these uses were properly made. Food manufacturers are not required to notify FDA of relevant health and safety studies, thereby placing FDA in the difficult position of tracking safety information for more than 10,000 chemicals with limited resources and information. The agency’s expedited approach to reviewing safety decisions since 1995 occurs with little public engagement. FDA lacks the resources and information needed to identify and prevent potential health problems or to set priorities for systematic reevaluation of safety decisions made during the past half-century.
The concerns raised by both of these groups appear to be more theoretical than real. Re-evaluations of the safety of a substance’s use can occur under the current scheme when warranted. Nevertheless, a relatively small number of substances have been the subject of re-evaluations and removals from use. For example, the Flavor and Extract Manufacturers Association (“FEMA”), has for decades operated a careful, thorough and well-respected GRAS evaluation program for flavorings and related substances used in food. FEMA (7) has only removed 11 out of 2,600 substances from its lists. Moreover, when, in 1997, the US FDA changed its program from accepting and reviewing GRAS determinations and issuing "affirmations" of the GRAS status of a use, replacing it instead with the GRAS notification program which resulted only in letters confirming that FDA "has no questions" about a submitter’s conclusion that a use is GRAS, the agency made remarks seeming to indicate that the evaluation of uses of substances perceived to be GRAS was a realm of general safety. (5). This is especially so when the uses of substances being evaluated are food contact materials rather than food ingredients, because exposure to food contact substances is generally quite significantly lower in quantity than exposure to food ingredients. FDA works from the common principle that the higher the level of exposure to substance, the higher the risk tends to pose. (2). It must be noted that critics of the current system are unable to point to examples of a significant number of substances that have long been widely used but later were discovered to present safety issues. If the system was inadequate or inappropriate, one would expect to see more examples of its failures. One seemingly middle-ground suggestion is the call for users to give FDA notice of their uses of substances on the basis of a conclusion that the use is GRAS. This was one of the suggestions in the GAO report, and the Pew Health Group raised the concern that FDA was unaware of many uses. However, we must be 38 Komolprasert and Turowski; Food Additives and Packaging ACS Symposium Series; American Chemical Society: Washington, DC, 2014.
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careful not to create a solution where there is no problem. Even a notification program would carry with it significant burdens on both industry and FDA that would not appear to be necessary unless there was a perception of significant safety gaps because of the current system. Remember, other protections against incorrect and faulty decision-making by companies will continue to exist with or without a role for FDA. These include civil tort liability should consumers be injured by product, FDA regulatory remedies including seizure of product, injunction against distribution, criminal prosecution should the agency conclude the food is adulterated, and adverse publicity for the company involved. Balancing the benefits that regulatory intervention might bring against the costs in light of the perceived problems, it does not appear that the suggested changes in the regulatory scheme put forth by GAO and the Pew Health Group are warranted. Going forward, this is bound to be an issue that will be the subject of healthy public debate.
References 1. 2. 3.
4.
5. 6. 7.
FFDCA definition of Food Additive Federal Food, Drug and Cosmetic Act Section 201(s) [21 U.S.C. Sec. 321(s)] FDA regulation: definition of safety, GRAS standard 21 CFR 170.3; 21 CFR 170.30. Government Accountability Office, “FDA Should Strengthen Its Oversight of Food Ingredients Determined to Be Generally Recognized as Safe (GRAS),” GAO-10-246, Feb 3, 2010. Pew Health Group report on GRAS most recent is Nov 2013 Pew Charitable Trusts, Fixing the Oversight of Chemicals Added to Our Food : Findings and Recommendations of Pew’s Assessment of the U.S. Food Additives Program, Nov 7, 2013. See www.pewhealth.org for more information. 1997 FDA proposed rule re GRAS Notices 62 Fed. Reg. 18938, April 17, 1997. 2010 FDA reopens 1997 proposed rule for comments 75 Fed. Reg. 81536, December 28, 2010. Flavor and Extract Manufacturers’ Association (FEMA) GRAS program web site http://www.femaflavor.org/gras.
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