FEMA GRAS and U.S. Regulatory Authority: U.S. Flavor and Food Labeling Implications

Flavors added to foods play an important role in our modern food supply because the flavor of food is a key determinant in food choice. In addition to the nutritional characteristics of food, consumers often base their food choices on taste. Consumers also demand assurance that the ingredients in their foods are safe. The flavor industry has played a significant role in the development of safe, convenient and nutritious foods that are popular with consumers.

The FEMA GRAS program has assured the safety of flavors added to foods for more than fifty years. In addition to safety, an important factor is information provided to consumers, primarily through food labels, that they can use to make their choices. The Food and Drug Administration (FDA) originally established regulations for flavors and foods containing added flavors during the 1970s. Although these regulations have not been significantly revised since that time, they continue to provide a useful framework for food manufacturers to inform consumers when flavors have been added to foods, and the natural or artificial nature of the added flavors.

Since 1965, the FEMA Expert Panel has published its GRAS conclusions for flavor ingredients in the readily accessible public literature, most recently publishing “GRAS 28” in 2018.

One aspect of the regulatory program for flavors in the U.S. that is important to examine and understand is the nexus between “regulatory authority to use” food ingredients such as flavors and the labeling conclusions that are consistent with the FDA’s regulations. Regulatory authority to use flavors is evidence of safety and can be established as provided for by the Federal Food, Drug, and Cosmetic Act (FFDCA) in several ways – FDA food additive status can be obtained, one can participate in the FDA voluntary GRAS notification or FEMA GRAS programs to establish that flavor ingredients are “generally recognized as safe” (GRAS), or one can make an independent, private determination that the use of a flavor ingredient is GRAS. By far, the most common route to establishing regulatory authority to use flavor ingredients in the U.S. is by participation in the FEMA GRAS program that requires a thorough evaluation of the safety of flavor ingredients by the independent FEMA Expert Panel.⁹ Since 1965, the FEMA Expert Panel has published its GRAS conclusions for flavor ingredients in the readily accessible public literature, most recently publishing “GRAS 28” in 2018. In 2015 FEMA established the Flavor Ingredient Library, available to the public on its website (www.femaflavor.org), as a comprehensive and convenient way to access the FEMA GRAS list. Once regulatory authority to use is established then the proper labeling of flavors and foods can be determined.

Flavors Added to Foods

Flavors added to foods are most often mixtures of individual substances commonly referred to as “flavor ingredients.” Flavor ingredients can be “flavoring substances” – substances that impart or modify flavor, or “flavor adjuvants” (“non-flavor ingredients”) – substances that facilitate the function of the flavoring substances in the mixture.

These flavor mixtures can be described as “compounded flavors” ⁹ and may consist of as many as 100 or more flavor ingredients. Flavoring substances in the compounded flavor that impart flavor may include chemically-defined substances such as vanillin, and natural flavoring complexes such as botanical extracts (e.g. vanilla extract) and essential oils (e.g. orange and other citrus oils). Flavoring substances also include “flavorings with modifying properties” (FMPs). FMPs may not necessarily have or impart a specific characteristic flavor of their own but can modify the flavor profile by altering the flavor attributes of the flavoring and the food to which it is added. Compounded flavors also include flavor adjuvants such as solvents, emulsifiers, carriers, and preservatives that facilitate the function of the compounded flavors to impart the overall desired flavor perception.

FDA has designated substances used to formulate compounded flavors as “flavoring agents and adjuvants,” defined by FDA as “substances added to impart or help impart a taste or aroma in food^a.” In relation to the terminology used in the FEMA GRAS program, substances designated by FDA as “flavoring agents” are considered flavoring substances by FEMA – substances that impart or modify flavor. Substances considered flavoring adjuvants by FDA (also described as “non-flavor ingredients” for labeling purposes by FDA) and FEMA do not impart or modify flavor but do “help impart a taste or aroma in food” by facilitating the function of compounded flavors in foods to which they are added.

The FDA policy on GRAS determinations is that it is only the specific, designated use of the substance that is GRAS and not the substance itself.

The classifications employed by FEMA and FDA are consistent with the classification of flavor ingredients by other groups. For example, the National Academy of Sciences (NAS) identified technical effects for food ingredients for the purposes of its Poundage and Technical Effects Update reports on substances added to foods (e.g. NAS, 1989). NAS defines its “F05” class, “flavors and flavor modifiers,” as substances that “impart, supplement, intensify or modify the taste and/or aroma of a food.”¹² Similarly, the Codex Alimentarius Commission defines “flavorings” as “products that are added to food to impart, modify or enhance the flavor of food.”¹

In addition to the designated technical effect of imparting or modifying flavor, another key aspect of appropriate characterization as a flavoring substance is to recognize that while flavoring substances impart or modify the flavor of food they do not provide significant nutrition. FDA’s regulations state that natural flavors include substances “whose significant function in food is flavoring rather than nutritional.”^b

There are approximately 2,800 flavor ingredients on the FEMA GRAS list. The vast majority of these are flavoring substances (>2,400 individual chemically-defined flavor substances and >300 natural flavor complexes) that impart flavor, and a relatively small number of these are FMPs (less than 3%). About 2% of FEMA GRAS flavor ingredients are flavor adjuvants.

Conditions of Intended Use

The FDA policy on GRAS determinations is that it is only the specific, designated use of the substance that is GRAS and not the substance itself. FDA has described its policy several times and stated that food ingredients determined to be GRAS for one use should not be used for other uses not determined to be GRAS.

It has too often been assumed that the GRAS substance may be used in any food, at any level for any purpose. As a result, the uses of some food ingredients have proliferated to the point where GRAS status was brought into serious question… Any use of the (GRAS) ingredient under conditions other than those explicitly set out in (a GRAS) regulation (e.g. a use in a different category of food, or for a different functional purpose, or at a higher level) will automatically require a food additive regulation prior to such use. Thus, these limitations have the same effect as a limitation in a food additive regulation.⁴

FDA reiterated its policy in the preamble to its 1997 proposal to implement its voluntary GRAS notification program describing the information that is required for a private GRAS determination to be recognized by FDA:

(FDA) requires that the GRAS exemption claim include the applicable conditions of use that are supported by data and information … including the foods in which the notified substance is to be used, levels of use in such foods, and the purpose for which the notified substance is used.⁶

Most recently, FDA stated the continued application of its policy in the preamble to the final rule promulgating its voluntary GRAS notification program:

We (FDA) did not receive comments disagreeing with the proposed requirement … in a GRAS notice to include the applicable conditions of use … including the foods in which the substance is to be used, levels of use in such foods, and the purposes for which the substance is used …⁷.

If a GRAS determination is the basis for regulatory authority to use that substance then it is only the specific, designated functional purpose – the specific technical effect and use – that is GRAS. Therefore, the designated technical effect of a substance – its designated use – serves as a limitation on the regulatory authority to use the substance in the U.S. The designated technical effect is one of the three elements of the conditions of intended use for FEMA GRAS conclusions with the other two being the designated food categories in which the substance may be used, and the designated use levels within those food categories.⁹ Together, these three elements of the conditions of intended use as required by FFDCA Section 201(s) comprise limitations on the use of flavor ingredients determined to be FEMA GRAS.

The FEMA Expert Panel and the FEMA GRAS Program

FEMA GRAS determinations are accomplished by the FEMA Expert Panel, the longest-tenured independent GRAS expert panel of any kind. The FEMA Expert Panel assesses the safety and GRAS status of individual flavor ingredients under the authority and requirements of FFDCA Section 201(s).⁹ The FEMA Expert Panel assesses safety and GRAS status by applying well-defined criteria^13,2 only for the individual flavor ingredient components of compounded flavors and not for compounded flavors themselves, of which there are many thousands of formulations. The Expert Panel’s principles and criteria are consistent with safety assessment requirements and procedures of the FDA and other flavor safety assessment groups that also evaluate flavor ingredients such as the Joint WHO/FAO Expert Committee on Food Additives.¹¹

U.S. Flavor and Food Labeling Regulations

The regulations governing the labeling of flavors to be added to foods and the foods containing them^c are intended by FDA to provide consumers with information on whether the packaged foods they purchase contain added flavors, and if so, whether the flavors are natural or synthetic (“artificial”) in origin which allows consumers to knowingly make a desired purchase choice. The FDA’s regulations also require the specific declaration of non-flavor ingredients (flavor adjuvants) by common or usual name on these labels unless they qualify as incidental additives, which the FDA defines as substances which are present in food at insignificant levels and do not have a technical or functional effect in that food^d. The FDA’s regulations provide for the generic declaration of flavor ingredients that impart or modify flavor (flavoring substances) on bulk flavor and packaged food labels. In order for food manufacturers to provide consumers with accurate information on the food product label they must receive such information from their flavor suppliers.

While the primary purpose of FDA’s flavor and food labeling regulations is to provide consumers with information on flavors added to foods, FDA has balanced this purpose with the business interest of protecting flavor formulas.

Flavor suppliers are required to provide their customers with information through the “bulk flavor” labeling regulations^e. These regulations require that single-ingredient flavors be identified by common or usual name. For compounded flavors, the bulk label must contain information identifying the flavoring substances by common or usual name or generically by stating that, “[a]ll flavor ingredients contained in this product are approved for use in a regulation of the Food and Drug Administration^f.” In this instance “flavor ingredients” means “flavoring agents” in FDA terminology and flavoring substances in FEMA terminology - the ingredients that impart or modify flavor. FEMA GRAS status has long been recognized as fulfilling the regulatory requirement of being “approved for use in a regulation” of FDA.⁵ In June 2018, FDA provided additional acknowledgement of FEMA GRAS by including FEMA GRAS status and designated technical effect in its new “Substances Added to Food” inventory. FDA stated, “[t]he new searchable inventory contains approximately 4,000 substances, and includes information on food additives, color additives, Generally Recognized as Safe (GRAS) and prior-sanctioned substances”.⁸

For the “non-flavor” ingredients in a compounded flavor (“flavor adjuvants” or “non-flavor ingredients” in FDA and FEMA terminology), the bulk labeling regulations require that they be specifically declared on the bulk label^g. The bulk flavor labeling regulations also require clear statements regarding the origin of the flavoring agents, whether natural, artificial or a combination of the two^h.

Food manufacturers use the information provided by flavor suppliers to determine the proper labeling for their packaged food products. Food manufacturers must label their products that contain added flavors in compliance with the FDA’s flavored food regulationsⁱ. These regulations allow for the generic declaration of added flavors as “natural flavor or artificial flavor, or any combination thereof, as the case may be^j.” As with the bulk flavor labeling regulations, the reference to “natural and artificial flavor” refers to the flavoring agents (flavoring substances) contained in the compounded flavor – substances that impart or modify flavor.

It is important to understand the proper labeling for compounded flavors containing flavorings with modifying properties (FMPs), and the foods containing these compounded flavors. FMPs that have FEMA GRAS status as their sole regulatory authority to use in the U.S. are GRAS only for their technical effect of flavoring. The technical effect of individual FMPs can be verified through appropriate sensory testing conducted under the FMP’s specified conditions of intended use as a flavoring substance.¹⁰

If an FMP were to have regulatory authority for use for a technical effect other than flavoring (and thus other than FEMA GRAS status such as FDA voluntary GRAS notification or other FDA-related regulatory authority) it could be added directly to the food as an individual ingredient, but would have to be declared specifically in the food’s ingredient statement by common or usual name. For example, a Stevia derivative which is FEMA GRAS for flavor modification that has also been notified through the FDA voluntary GRAS notification program for use for a sweetening technical effect may be added directly to food for sweetening the food, but must be declared in the food’s ingredient statement – it may not be declared as a flavor when it is present in food to provide a sweetening effect.

In some instances, more than one FMP may be included in a compounded flavor consistent with the conditions of intended use (technical effect, food categories, and use levels) for each FMP. For example, a compounded flavor may contain more than one Stevia derivative that each have only FEMA GRAS status as regulatory authority to use with flavoring as the sole designated technical effect. It is possible that the combination of two or more such materials, each functioning singly as an FMP, could provide a sweetening effect in combination in the compounded flavor, a technical effect not accounted for by FEMA GRAS status. In such instances, referred to as “stacking,” the Stevia derivatives would not have regulatory authority to be used because their technical effect in combination is sweetening in the food or beverage product and not flavoring as designated by FEMA GRAS status.

A compounded flavor may contain a FEMA GRAS FMP and, for example, a related Stevia derivative with regulatory authority to use as a sweetener that results in this mixture (the compounded flavor plus the sweetener) providing a sweetening technical effect in the food to which it is added. In this instance, the Stevia derivative creating the sweetening effect must be specifically declared on the bulk flavor label and the label of the food to which it is added

In other instances, more than one compounded flavor each containing a single FMP may be added to a food during manufacture of the food. For example, a food product may contain several independently sourced compounded flavors each containing a single FEMA GRAS Stevia derivative that has flavoring as its sole designated technical effect and this sort of “stacking” could also provide a sweetening function not accounted for by FEMA GRAS status. Foods that employ “stacking” in this manner to impart sweetness also must indicate on their labeling that stevia sweeteners have been added.

Non-flavor ingredients (flavor adjuvants) in compounded flavors must be declared by common or usual name on food ingredient statements unless they qualify as incidental additives consistent with FDA’s regulations at 21 CFR 101.22 (h)(2) and 101.100(a)(3) meaning that they are present in the packaged food in concentrations that do not provide their technical effect independent of the compounded flavor in the food. Many flavor adjuvants in compounded flavors such as solvents, emulsifiers, carriers and preservatives qualify as incidental additives because they are present in the compounded flavors at low levels that are further reduced in concentration in the food through the typical low concentrations of compounded flavors (typically <1%-5%) added to food.

While the primary purpose of FDA’s flavor and food labeling regulations is to provide consumers with information on flavors added to foods, FDA has balanced this purpose with the business interest of protecting flavor formulas. Formulas of compounded flavors have long been recognized as the valuable intellectual property of flavor manufacturers and have been protected as such through various trade secret protection methods. FDA recognized this principle when it established the existing flavor and food labeling regulations. FDA stated in 1973 that the agency “is aware that the composition of a proprietary flavor compound marketed by a flavor manufacturer to a food manufacturer is a valuable trade secret.”³

FEMA GRAS status provides consumers with assurance that the flavor ingredients used to create compounded flavors are safe.

In complying with FDA’s flavor and food labeling regulations, companies may achieve a balance between the needs of flavor manufacturers to protect their formulas, and their food manufacturer customers to have information to properly label their products. One way to achieve this balance is through the confidential sharing of limited flavor formula information pursuant to appropriate non-disclosure agreements. For example, a flavor manufacturer may disclose the presence of an FMP in a compounded flavor without disclosing the presence of other flavor substances and adjuvants. Such a limited disclosure will allow the food manufacturer to best determine the proper labeling of its products that contain one or more FMPs.

Conclusion

FEMA GRAS status provides consumers with assurance that the flavor ingredients used to create compounded flavors are safe. FDA’s flavor and food labeling regulations allow consumers to identify whether flavors have been added to a food and if so whether the flavors are natural or artificial. The FDA’s regulations provide for the generic declaration of flavor ingredients that impart or modify flavor (flavoring substances) on bulk flavor and packaged food labels. The FDA’s regulations also require the specific declaration of non-flavor ingredients (flavor adjuvants) by common or usual name on these labels unless they qualify as incidental additives^{k, l}. FDA’s flavor and food labeling regulations assure a balance between providing consumers with useful information on flavors added to foods and flavor manufacturers’ interest in protecting their valuable flavor formulas.