Description
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:
Scope & Applicability
Product Classes
6Approved substances for direct addition to food
Subject of the benefit-risk assessment guidance
Products containing dietary ingredients intended to supplement the diet; The final product category for which the NDI is intended.
Substances generally recognized as safe for intended use.
exemption from section 403(w) misbranding requirements; Food intended for animal consumption, including pet food.; scope of sanitary transportation regulation; not considered dietary supplements under section 201(ff); category for very small importer threshold; Calculation of annual sales for importer status
Evaluation of human food safety of tissue residues for new animal drugs.
Stakeholders
5Entity responsible for submitting NDINs
The manufacturer or distributor submitting the notification; The person or firm submitting the NDIN
Entity responsible for submitting NDINs
Required for GRAS status determinations
A panel of individuals convened to evaluate if scientific data establish safety.; Recommendations regarding the use of a GRAS panel, including the potential for conflict of interest.; A panel of individuals convened to evaluate scientific data for safety; A group of qualified experts who evaluate the safety of a substance.
Regulatory Context
Attributes
5The standard of safety required: reasonable certainty that the substance is not harmful.
Information in an NDIN protected from public disclosure
The regulatory standard for safety
The amount of a substance consumers are likely to eat or drink
Human food safety of tissue residues present in edible tissues.
Identified Hazards
Hazards
2Evaluating safety of antimicrobial drugs with regard to bacteria of human health concern.
substances like Salmonella or lead found in food supply
Related CFR Sections (10)
- 21CFR170.235§ 170.235 Part 3 of a GRAS notice: Dietary exposure.
In part 3 of your GRAS notice, you must provide data and information about dietary exposure ( i.e., the amount of relevant substances that consumers are likely to eat or drink as part of a total diet), regardless of whether your conclusion of GRAS status is through scientific procedures or through eRead full regulation →
- 21CFR171.1§ 171.1 Petitions.
(a) Petitions to be filed with the Commissioner under the provisions of section 409(b) of the Federal Food, Drug, and Cosmetic Act (the act) shall be submitted in triplicate (quadruplicate, if intended uses include use in meat, meat food product, or poultry product). If any part of the material submRead full regulation →
- 21CFR20.61§ 20.61 Trade secrets and commercial or financial information which is privileged or confidential.
(a) A trade secret may consist of any commercially valuable plan, formula, process, or device that is used for the making, preparing, compounding, or processing of trade commodities and that can be said to be the end product of either innovation or substantial effort. There must be a direct relationRead full regulation →
- 21CFR170.30§ 170.30 Eligibility for classification as generally recognized as safe (GRAS).
(a) 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 eitherRead full regulation →
- 21CFR170.275§ 170.275 Public disclosure of a GRAS notice.
(a) The data and information in a GRAS notice (including data and information submitted in any amendment or supplement to your GRAS notice or incorporated into your GRAS notice) are:Read full regulation →
- 21CFR170.250§ 170.250 Part 6 of a GRAS notice: Narrative.
In Part 6 of your GRAS notice, you must include a narrative that provides the basis for your conclusion of GRAS status, in which:Read full regulation →
- 21CFR170.230§ 170.230 Part 2 of a GRAS notice: Identity, method of manufacture, specifications, and physical or technical effect.
In Part 2 of your GRAS notice, you must include:Read full regulation →
- 21CFR170.3§ 170.3 Definitions.
For the purposes of this subchapter, the following definitions apply:Read full regulation →
- 21CFR570.30§ 570.30 Eligibility for classification as generally recognized as safe (GRAS).
(a) 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 eitherRead full regulation →
- 21CFR170.225§ 170.225 Part 1 of a GRAS notice: Signed statements and certification.
(a) Part 1 of your GRAS notice must be dated and signed by a responsible official of your organization, or by your attorney or agent.Read full regulation →
Related Warning Letters (10)
- 2025-09-30
Adulterated Human Foods/Misbranded
STNR Creations, LLC
- 2025-09-16
Adulterated Human Foods/Misbranded
Blue Forest Farms, LLC
- 2025-08-12
Adulterated Human Foods/Misbranded
TKO Distribution, LLC
- 2025-07-15
Unapproved New Drug/Human Food/Adulterated
Hydroxie, LLC
- 2025-07-15
Unapproved New Drug/Misbranded
Royal Diamond Imports, Inc.
- 2025-07-15
CGMP/Dietary Supplement/Adulterated/Misbranded
Thang Botanicals, Inc. d/b/a 7ΩHMZ, 7-OHMZ, or 7OHMZ
- 2025-06-03
Adulterated Human Foods/Misbranded
Latro Inc.
- 2025-04-29
Unapproved New Animal Drug Products
Holista LLC dba HolistaPet
- 2025-04-29
Unapproved New Animal Drug Products
Bailey’s Wellness, LLC dba Bailey’s CBD
- 2024-07-23
Adulterated Human Foods/Unapproved New Drugs
White Label Leaf, LLC/Flying Monkey US, LLC
See Also (8)
- Guidance For The Content Of Premarket Notifications For Esophageal And Tracheal Prostheses - Guidance For Industry (Status: Final)
- Master Files Part III - Guidance on Scientific and Technical Information (Status: Final)
- Prospective Manufacturers of Barrier Devices Used During Oral Sex for STD Protection (Status: Final)
- CVM GFI #187B Heritable Intentional Genomic Alterations in Animals: The Approval Process (Status: Final)
- 510(k) Third Party Review Program and Third Party Emergency Use Authorization (EUA) Review: Guidance for Industry, Food and Drug Administration Staff, and Third Party Review Organizations (Status: Final)
- Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection: Guidance for Industry (Status: Final)
- Guidance for Industry: New Dietary Ingredient Notification Procedures and Timeframes - Dietary Supplements (Status: Final)
- Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the FD&C Act (Status: Final)