US FDA GRAS Notice

Updated on March 11, 2025

What is FDA GRAS Status

“GRAS” is an acronym for Generally Recognized As Safe, which is an important food regulatory category in the United States. Simply speaking, if a substance is GRAS under the conditions of its intended use among qualified experts, it is excluded from the definition of a food additive and is not subject to the premarket approval requirements of the Federal Food, Drug, and Cosmetic Act.

This means that a substance that has been concluded GRAS may be marketed for its intended use in food without FDA review or approval. It is, however, important to note that it is the use of a substance, rather than the substance itself, that is eligible for GRAS status.

Boasting widespread recognition internationally, GRAS has become a gateway for enterprises to access global markets.

The Two Pathways to Establish GRAS Status

The intended use of a substance in food may be GRAS through:

• Experience based on common use in food prior to January 1, 1958, or
• Scientific procedures.

GRAS through common use prior to January 1, 1958, requires generally available evidence of substantial history of consumption by significant numbers of consumers. It is rare for such documentation to exist.

GRAS through scientific procedures requires the same quantity and quality of scientific evidence as required to obtain approval of a food additive and that the scientific evidence is generally available to, and generally accepted by, qualified experts throughout the scientific community.

A Brief History of GRAS

• The GRAS exclusion was introduced through the enactment of the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act.
• 1952 to 1962: The FDA established a list of GRAS substances without conducting detailed scientific reviews (“the GRAS list”).
• Additionally, the FDA would issue informal opinions to manufacturers who wrote to the agency requesting opinion letters regarding their own independent conclusions of GRAS status; however, such letters were later revoked by the agency.
• Beginning in 1969, the FDA began systematic reviews of GRAS substances; if supported by the available data and information, the FDA, on its own initiative, affirmed the GRAS status of the substance through a rulemaking procedure.
• Additionally, the FDA instituted a GRAS affirmation petition process through which an individual, partnership, corporation, association, or other legal entity could voluntarily petition the FDA to review the GRAS status of a substance. Such petitions, if successful would also result in the FDA affirming the GRAS status of the substance through a rulemaking procedure.
• In 1997, due to the resource-intensive rulemaking process, the FDA proposed replacing the GRAS affirmation petition process with a voluntary GRAS notification procedure and established an interim pilot program.
• In 1998, the FDA received its first GRAS notice under the interim pilot program for the proposed GRAS notification procedure, which referred to GRAS conclusions as “self-determinations of GRAS status.”
• In 2016, after having filed more than 600 GRAS notices during the interim pilot program, the FDA finalized the rule for the voluntary GRAS notification program. At this time, the term “self-determination of GRAS status” was replaced with the term “independent conclusion of GRAS status.”

Independent Conclusion vs. FDA GRAS Notice: What’s the Difference?

When bringing a GRAS substance to market, food business operators have two primary choices:

Independent Conclusion of GRAS Status

Independent Conclusions of GRAS status may be made by a “proponent” (i.e., an individual, partnership, corporation, association, or other legal entity) based on the views of experts qualified by training and experience to evaluate the safety of the substances directly or indirectly added to food that publicly available data, information, and methods establish that there is reasonable certainty that the substance is not harmful under the conditions of its intended use. A GRAS substance may be marketed based on an independent conclusion of GRAS status that remains with the proponent. The proponent may also choose to submit their GRAS conclusion to the FDA as a GRAS notice.

FDA GRAS Notice

A proponent of a GRAS conclusion may voluntarily submit their conclusion of GRAS status to the FDA under a GRAS notification procedure as outlined in the US Code of Federal Regulations. Upon filing a GRAS notice, the FDA will evaluate the notice and provide a written response letter*. The GRAS notice and the response letter will be added to the GRAS Notices Inventory database on the official website of the FDA, where they will be publicly available for verification. While such response letters are not approvals and are no more authoritative and have no legal distinction from an independent conclusion of GRAS status, they do, generally speaking, enjoy wider recognition. Some companies have internal policies to use only GRAS substances that have received an FDA response letter with “no questions.”

* Note: FDA will issue one of three potential response letters: 1) FDA has no questions regarding the notifier’s GRAS conclusion, 2) FDA concludes the notice does not provide a sufficient basis for a GRAS conclusion, or 3) at the notifier’s request, FDA ceased evaluation of the GRAS notice.

Who can Submit a GRAS Notice?

Any person (e.g., individual, partnership, corporation, association, or other legal entity) is encouraged to make a submission to the US FDA GRAS notification program, explaining that the use of a substance is GRAS and, thus, exempting it from pre-market approval procedures required by US law.

How to Establish GRAS Conclusion: A Step-by-step Procedure

Note: Steps 1 to 5 are the general procedures for the development of the GRAS dossier in support of the GRAS conclusion, while steps 6 to 10 are additional steps required for an FDA GRAS notice (in some cases step 6 can be useful in the development of the GRAS dossier as part of step 3)

Required Materials for GRAS Application

The following materials are generally required from businesses for data analysis:

1) Detailed information related to the identity of the substance identity, such as common name (if it has one), chemical name or synonym, trade name, source, chemical structure, and relative molecular mass;

2) Production process;

3) Product specification and relevant Certificate of Analysis (COA);

4) Intended conditions of use and use level of the substance in food;

5) Self-limiting level in food;

6) Historical consumption; and

7) Safety information (e.g., toxicology studies, bioinformatic studies, and human studies).

Estimated Timeframe: Independent Conclusion vs. FDA Notice

Why Choose CIRS

With over 450 employees, CIRS Group offers one-stop global registration and filing services for new food ingredients to support companies expanding overseas, helping them efficiently and reliably gain market access to the U.S. food ingredient market.

U.S. Local Team: CIRS USA is located in Virginia. We have full-time U.S. food regulatory experts who provide compliance services such as U.S. FDA GRAS, NDI, CAP, Animal Food GRAS, FDA Animal Food Ingredient Consultation, and AAFCO SRIS.

Team of Senior Experts: CIRS Group has 24 Chinese Certified Toxicologists (DCST), 1 European Registered Toxicologist (ERT), and 2 U.S. Certified Toxicologists (DABT). DABT experts can serve as members of the GRAS expert panel, participate in panel meetings, and sign off on GRAS submissions.

Extensive Track Record: The CIRS Food Division has over 15 years of experience in food compliance services and boasts numerous successful cases, including human milk oligosaccharides (2'-FL, LNnT, LNT, etc.), steviol glycosides, inositol, brazzein, lycopene, enzymatically converted steviol glycoside Reb M2, NMN, pasteurized AKK, fungal protein, D-allulose, glucosamine hydrochloride, N-acetylglucosamine (NAG), beta-carotene, zeaxanthin, astaxanthin, PQQ, and etc.

Cross-Regional Coverage: The CIRS Food Division provides global application services for novel food ingredients, covering more than 20 countries and regions, including China, the United States, Europe, Australia, New Zealand, Canada, South Korea, Japan, Brazil, Mexico, Singapore, Malaysia, Thailand, Vietnam, Indonesia, and China Taiwan.

End-to-End Coverage: We manage the entire process—from document organization, data gap analysis, test protocol design, expert review, and dossier preparation to submission and ongoing compliance maintenance. Our proven processes and local resources ensure shorter timelines, transparent costs, and a high first-time approval rate, reducing the costs associated with repeated revisions.

Long-Term Regulatory Monitoring: We continuously track changes in FDA policies (such as NDI regulatory reforms) and provide long-term compliance guidance and market alerts

Our services

• US FDA GRAS notice consultation and training;
• Independent conclusion of GRAS status;
• FDA GRAS Notice; and
• FDA NDI Notification

US GRAS Notice: Frequently Asked Questions for Industry

Q1: What is the difference between Independent Conclusion of GRAS Status (Self GRAS) and FDA GRAS?

A1: Independent Conclusion of GRAS Status (Self-GRAS): Convened and evaluated by independent experts hired by the company, this assessment is kept on file internally rather than submitted to the FDA. While it saves time and cuts costs, it lacks official FDA backing.

FDA GRAS Notice: Requires submitting the dossier to the FDA for formal review. Substances that pass review are publicly listed on the FDA's official website, offering stronger regulatory credibility for markets requiring official endorsement.

Q2: Does a GRAS status for a substance apply to all intended uses?

A2: Not necessarily. GRAS Notice is based on the specific intended use of a substance rather than the substance itself. Even if a substance is GRAS for one intended use, it does not mean it is safe for all uses. Each intended use requires an independent safety evaluation.

Q3: Is a new food ingredient eligible for a GRAS Notice?

A3: Yes, but it subject to its intended use and chemical identity. For example, if the substance's intended use is "other than coloring," it can undergo GRAS Notice, provided any color imparted is not significant. If the intended use includes "coloring," a formal Color Additive Petition (CAP) is required.

Q4: Is an FDA "No Question" letter required before going to market?

A4: No. A company may market a GRAS substance for its intended use in the U.S. without notifying the FDA, or while the FDA is still evaluating the GRAS notice dossier.

Q5: How are trade secrets handled in GRAS dossiers?

A5: Applying for FDA GRAS notice means that the submitted materials become public, including proprietary experimental data, manufacturing process parameters, and other information that may involve trade secrets. Enterprises should prepare contingency plans and weigh trade-offs in advance to respond to potential FDA requests for supplemental materials.

Q6: Does the FDA GRAS notice process involve on-site inspections?

A6: No, it does not (unless special safety concerns are triggered that attract FDA’s attention).

Q7: Does the U.S. FDA have specific qualification requirements for manufacturing facilities notifying GRAS?

A7: There are no specific qualification requirements for the facility itself, but the production process must comply with U.S. Current Good Manufacturing Practice (cGMP) regulations.

Further Reading

Frequently Asked Questions on FDA Generally Recognized As Safe (GRAS) Notice, Vol. 2

Global Compliance Perspective on HMOs: Approvals and Applications in the US