Guidance for Industry: Regulatory Framework for Substances Intended for Use in Human Food or Animal Food on the Basis of the Generally Recognized as Safe (GRAS) Provision of the Federal Food, Drug, and Cosmetic Act

November 2017

This guidance is intended for any person (you) who intends to market a food substance on the basis of a conclusion that the substance is GRAS under the conditions of its intended use (a GRAS conclusion), including a manufacturer of the food substance, a manufacturer of a food product containing the food substance, and a distributor of a food product containing the food substance. We are issuing this guidance to:

• Direct you to the statutory and regulatory criteria that govern eligibility for classification of a substance as GRAS under the conditions of its intended use, and remind you of your responsibilities to comply with those criteria;
• Advise you to carefully consider whether the intended use of the food substance fully satisfies the criteria for eligibility for classification as GRAS and is lawful under sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and our regulations in Title 21 of the Code of Federal Regulations (21 CFR);
• Remind you that a GRAS conclusion based upon scientific procedures requires the same quantity and quality of scientific evidence as is required to obtain approval of a food additive and direct you to a series of our guidance documents that address scientific issues associated with demonstrating the safety of a food substance;
• Remind you that a GRAS conclusion based on common use in food requires evidence of a substantial history of consumption prior to January 1, 1958;
• Remind you that all GRAS conclusions must be considered in context based on the knowledge and information available at a point in time, because scientific knowledge and information about a particular substance can evolve and sometimes change over time;
• Strongly encourage you to contact us and follow the available procedures for our oversight of GRAS conclusions by submitting a GRAS Notice to us in accordance with the procedures in 21 CFR part 170, subpart E (for a substance that would be used in human food) or 21 CFR part 570, subpart E (for a substance that would be used in animal food); and
• Recommend that you use the framework for a GRAS notice in documenting a GRAS conclusion if you decide to market a food substance on the basis of an independent GRAS conclusion (i.e., a GRAS conclusion that you do not submit to FDA as a GRAS notice).

We also are issuing this guidance to advise you that when a substance is not GRAS under the conditions of its intended use (or is not otherwise excepted from the definition of “food additive” in section 201(s) of the FD&C Act), that use of the substance is a food additive use subject to FDA’s premarket review as mandated by the FD&C Act. Any food that is, or bears or contains, an unapproved food additive is deemed unsafe and is therefore adulterated under the FD&C Act. When a substance added to food is not GRAS (and is not otherwise excepted from the definition of a “food additive”) and is not approved as a food additive under the conditions of its intended use, we can take various actions, including issuing a warning letter (which we make public on our Web site) to companies that manufacture or distribute the food additive and/or food containing the food additive; issuing a public alert; and taking enforcement action to stop distribution of the food substance and foods containing it on the grounds that such foods are or contain an unlawful food additive. As appropriate, we can issue a declaratory order determining that the substance is not GRAS under the conditions of its intended use and is a food additive subject to section 409 of the FD&C Act. As we implement the GRAS notification procedure that is established in 21 CFR part 170, subpart E and 21 CFR part 570, subpart E, we intend to continue to closely monitor and assess the ramifications of the use of substances without food additive approval or evaluation by FDA through the GRAS notification procedure. We intend to take action as appropriate, particularly when the available data and information raise a safety concern about the use of a substance.

FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe our current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidances means that something is suggested or recommended, but not required.

This guidance represents the current thinking of the Food and Drug Administration (FDA or we) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.

   Guidance for Industry.pdf