The GRAS Concept: An Element of Flexibility in FDA Regulation of Food Packaging

By Keller and Heckman LLP’s Packaging Practice Group

In the United States, a unique regulatory provision identifies a class of direct food ingredients and food-contact materials as "generally recognized as safe" (GRAS) and thus not requiring premarket clearance by the U.S. Food and Drug Administration (FDA).

Manufacturers are entitled to make their own determination as to whether a substance is GRAS for its intended use in food or in contact with food. Indeed, FDA expects companies to make such GRAS determinations, although there is a voluntary notification procedure for obtaining FDA review.

In this article, we provide a general overview of how the GRAS concept fits into the U.S. regulatory process and explain the criteria for reaching a GRAS determination for a food-contact material.

GRAS and the FDA Regulatory System

Under Section 409 of the Federal Food, Drug, and Cosmetic Act, any "food-contact substance" (including, but not limited to, food packaging materials) that is a "food additive," as defined in the Act, must be the subject of an applicable food additive regulation, or an effective food-contact notification (FCN)[1]. The following definition of "food additive" is provided in Section 201(s) of the Act and is the basis for the exemption of GRAS substances:

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 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. ...

As a result of this definition, GRAS substances enjoy one of several exemptions from the need for premarket food additive clearance by FDA. This provision removes from FDA the responsibility to review substances that do not require an official safety assessment and allows companies to market food-contact materials that have a scientific consensus of safety for the intended use without forcing FDA to conduct a redundant assessment.

The question that remains is how to qualify a food-contact material for GRAS status. We now turn our attention to that issue.

Determining GRAS Status

Listings by FDA

The place to start a GRAS determination is with FDA's listings of GRAS substances, which are found in FDA's food additive regulations in Title 21 of the Code of Federal Regulations (C.F.R.) §§ 182, 184, and 186.

The regulations in Section 184 cover substances that FDA has affirmed after reviewing as GRAS for direct addition to food. Section 184.1(a) provides that substances affirmed as GRAS when used as direct additives also are automatically considered GRAS for food-contact use. Furthermore, this section of FDA's regulations states that the purity specifications established for GRAS direct food ingredients do not apply to the food-contact use of these same substances. In food-contact applications, the materials only need to be of a purity suitable for the intended use, in accordance with the good manufacturing practice regulation for all food-contact materials, 21 C.F.R. § 174.5.

The regulations in Section 182 relate primarily to direct food ingredients, but some food-contact materials are included. As with the substances listed in Section 184, the substances identified as GRAS for direct addition to food in Section 182 are GRAS for food-contact use.

Section 186 contains FDA's list of materials that are GRAS for food packaging or other food-contact applications.

FDA's own GRAS regulations, however, explicitly state that the agency's lists of GRAS substances are not comprehensive and exclusive because "It is impracticable to list all substances that are generally recognized as safe for their intended use." So, how does one establish GRAS status for a material that is not on any of FDA's GRAS lists? Let's look at the criteria for this determination.

Standards for a Self-Determination of GRAS Status

If a product is not on FDA's GRAS list, the agency has identified by regulation the factors that a company must consider in making its own GRAS determination. FDA's language in 21 C.F.R. § 170.30 is the best guide on GRAS assessments.

General recognition of safety may be based only on the views of experts qualified by scientific training and experience to evaluate the safety of substances directly or indirectly added to food. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958,[2] through experience based on common use in food. General recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly or indirectly added to food.

As one might imagine, it is unusual, although not unknown, for a modern food packaging material to have been in common use prior to 1958. In most cases, GRAS status for a food-contact substance will depend on a demonstration of a scientific consensus. It is very important to recognize that a GRAS determination is not merely a private safety assessment. FDA's regulations require that GRAS status must "ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information." By "published studies," FDA means toxicological assessments in peer-reviewed scientific journals. The key safety data must be in the public domain, although proprietary data can be used as additional support.

One frequent approach to documenting and supporting GRAS status is to convene an "expert panel"—composed of toxicologists with eminent reputations and relevant experience—to review the available data and to provide their assessment.

Another possibility, with particular relevance to food-contact materials, is the "low exposure" GRAS position based on work sponsored by The Society of the Plastics Industry, Inc. (SPI) at the Canadian Centre for Toxicology (now CANTOX), FDA's Threshold of Regulation rule, and more recent studies by FDA personnel.

Conclusion

A determination of GRAS status is a legitimate way for a packaging manufacturer to avoid the need for FDA clearance of a food-contact material. Care must be taken, however, to observe the guidelines for a GRAS determination, which are more demanding than simply a private safety determination. There must be an established basis in the published scientific literature indicating the safety of the substance for its intended use. Possible mechanisms for this determination and for obtaining FDA concurrence are described above in this article and in the other articles provided elsewhere in this month's focus.

[1] FDA's "Threshold of Regulation" rule (21 C.F.R. § 170.39) remains in effect as an exception to the need for a food additive regulation for a food-contact substance but has been effectively superseded by the expedited Food Contact Notification procedure.

[2] Until recently, the common use of food was restricted to use in the United States. Now, FDA has liberalized its rules to recognize the use in other countries, but the agency requires corroboration from a published or other "independent" source and recommends that companies obtain FDA concurrence in GRAS status.