Description
This guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the telephone number listed on the title page of this guidance.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
2Type of submission depicted in roadmap examples
Source of the new protein being evaluated.
Stakeholders
2Entity receiving written comments on the draft guidance
The party submitting a health claim petition to the FDA.
Regulatory Context
Regulatory Activities
10Formal program for the review of animal food additives.
voluntarily submit a PNC prior to submitting a FCN; Consultation prior to a formal FCN submission.
Food Contact Notification submission roadmap
Electronic Submissions Gateway for receiving regulatory information
Transmission of regulatory submissions
Process to obtain approval for unapproved color additives
An FCN should include detailed information on the chemical identity of the FCS.
A GRAS notice submission discussed in Section VI.; Regulatory submission type (GRAS notice); Voluntary procedure to inform FDA of a GRAS determination.; Submission roadmap for GRAS notices; Referenced regulatory submission type.
A regulatory submission type for biotechnology products discussed in Section VII.; submission regarding Biotechnology Final Consultation; Voluntary procedure for foods derived from new plant varieties; Referenced regulatory submission type.
A regulatory submission type for new proteins discussed in Section VIII.; submission regarding New Protein Consultation; A voluntary procedure for proteins derived from a new plant variety.
Document Types
10Documentation artifacts used to support food contact substance notifications.; Submissions containing confidential information for food additives; Documentation containing chemistry or safety information for food substances.
Creating Reference Hyperlinks in E-submission Documents
Conventions for Naming Files and Folders in an Electronic Submission
Enhanced (QbD) regulatory submissions documentation.
Downloadable foldering structure for electronic submissions.
Standardized folder structure for electronic GRAS submissions.
Labeling for substances regulated under FIFRA
Contains information on potential carcinogenicity; CTP of all unpublished and published safety studies
foldering structure for electronic FCN submissions; Standardized folder structure for electronic FCN submissions.
additional information included in a FCN submission
Attributes
10Required format for all submissions under section 505G(j)
Links to Downloadable Foldering Structures
Creating Reference Hyperlinks in E-submission Documents
Conventions for Naming Files and Folders in an Electronic Submission
Data designated as confidential by the submitter
The amount of an NDI expected to be consumed based on labeling (EDI).; The highest possible total daily intake level of an NDI determined from proposed conditions of use.
Percentage of oligomeric species below 1000 Daltons
Amount of drug product consumed per day used for calculations
Study of the potency of a sweetener
Characteristic used to distinguish dietary ingredients from food additives.
Technical Details
Substances
6substances in contact with infant formula and/or human milk
Subject of the early food safety evaluation.
Specific impurity (CAS Reg. No. 34901-14-9) mentioned in an amendment example.
Substances intended for use in food that require premarket approval
substance that meets the definition of color additive must be listed
The FCS undergoes chemical or metabolic transformation; Components of the formulation already authorized for intended uses.
Testing Methods
10Safety information in a FAP
Analytical procedure to determine the transfer of substances from food contact materials.
Determining expected levels of migration to food
Characterization using IR, NMR, and MassSpec
safety study subfolder in the FCN roadmap
Section IX of the guidance.
safety study subfolder in the FCN roadmap; Safety testing including Ames test
Method used in chemistry submissions for petitions
Safety studies conducted in rodents and non-rodents
Safety studies such as Ames tests
Processes
6Changes in method that result in substantive changes in identity
Changes in manufacturing suggesting further studies
Changes to this process may affect the identity and NDI status of an ingredient.; Changes to this process may create an NDI; you should describe the manufacturing process and provide detailed information; includes fermentation as an intrinsic part of identity
Information contained in MFs; Processes described within a Master File.
Exemption from batch certification for color additives
Type of data requiring PDF and spreadsheet formats
Clinical Concepts
4Assessing the carcinogenicity risk of immunomodulators
Safety assessment element in GRAS notices
Grade ≥ 3 neurotoxicity
Safety study type for reproduction
Standards & References
External Standards
4Referenced safety study information standard.
Extensible markup language file format
The Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM) specifications provided in this document
Standard for Exchange of Nonclinical Data; Standard for Exchange of Nonclinical Data for toxicology studies.; Standard for Exchange of Nonclinical Data provides structure for nonclinical tabulation datasets; Standard for nonclinical data tabulation; Standard for nonclinical study data; Standard for nonclinical tabulation data; dataset submitted to the FDA for nonclinical trials
Specifications
5Required in petitions if necessary to ensure safety; Proposed text for the tolerance provision to ensure safety
Quality criteria for substances in GRAS notices
Specifications for reagents, solvents, and catalysts
data not identified on Form FDA 3480
Specifications to identify dietary ingredients, other ingredients, and contaminants
Related CFR Sections (15)
- 21CFR170.39§ 170.39 Threshold of regulation for substances used in food-contact articles.
(a) A substance used in a food-contact article (e.g., food-packaging or food-processing equipment) that migrates, or that may be expected to migrate, into food will be exempted from regulation as a food additive because it becomes a component of food at levels that are below the threshold of regulatRead 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 →
- 21CFR25.32§ 25.32 Foods, food additives, and color additives.
The classes of actions listed in this section are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →
- 21CFR170.101§ 170.101 Information in a premarket notification for a food contact substance (FCN).
An FCN must contain the following:Read full regulation →
- 21CFR25.51§ 25.51 Environmental assessments and findings of no significant impact.
(a) Data and information that are protected from disclosure by 18 U.S.C. 1905 or 21 U.S.C. 331(j) or 360j(c) shall not be included in the portion of environmental documents that is made public. When such data and information are pertinent to the environmental review of a proposed action, an applicanRead full regulation →
- 21CFR25.30§ 25.30 General.
The classes of actions listed in this section and §§ 25.31 through 25.35 are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →
- 21CFR25.15§ 25.15 General procedures.
(a) All applications or petitions requesting agency action require the submission of an EA or a claim of categorical exclusion. A claim of categorical exclusion shall include a statement of compliance with the categorical exclusion criteria and shall state that to the applicant's knowledge, no extraRead full regulation →
- 21CFR25.40§ 25.40 Environmental assessments.
(a) As defined by CEQ in 40 CFR 1508.9 , an EA is a concise public document that serves to provide sufficient evidence and analysis for an agency to determine whether to prepare an EIS or a FONSI. The EA shall include brief discussions of the need for the proposal, of alternatives as required by secRead 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 →
- 21CFR71.1§ 71.1 Petitions.
(a) Any interested person may propose the listing of a color additive for use in or on any food, drug, or cosmetic or for coloring the human body. Such proposal shall be made in a petition in the form prescribed in paragraph (c) of this section. The petition shall be submitted in triplicate (quadrupRead full regulation →
- 21CFR170.3§ 170.3 Definitions.
For the purposes of this subchapter, the following definitions apply:Read full regulation →
- 21CFR11.200§ 11.200 Electronic signature components and controls.
(a) Electronic signatures that are not based upon biometrics shall:Read full regulation →
- 21CFR170.106§ 170.106 Notification for a food contact substance formulation (NFCSF).
(a) In order for the Food and Drug Administration (FDA) to accept an NFCSF, any food additive that is a component of the formulation must be authorized for its intended use in that NFCSF.Read full regulation →
- 21CFR70.19§ 70.19 Fees for listing.
(a) Each petition for the listing of a color additive shall be accompanied by a deposit of $3,000.00 if the proposal is for listing the color additive for use generally in or on foods, in or on drugs, and in or on cosmetics.Read 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 →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 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.
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.
- 2024-07-23
Adulterated Human Foods/Unapproved New Drugs
White Label Leaf, LLC/Flying Monkey US, LLC
- 2024-07-16
Interstate Commerce/Food/Adulterated/Unfair or Deceptive Marketing
Earthly Hemps
- 2024-07-16
Interstate Commerce/Food/Adulterated/Unfair or Deceptive Marketing
Life Leaf Medical CBD Center
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances (Chemistry Recommendations) (Status: Final)
- Guidance for Industry: Antimicrobial Food Additives (Status: Final)
- Guidance for Industry: Submitting Requests under 21 CFR 170.39 Threshold of Regulation for Substances Used in Food-Contact Articles (Status: Final)
- Guidance for Industry: Preparing a Claim of Categorical Exclusion or an Environmental Assessment for Submission to CFSAN (Status: Final)
- Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that Are Color Additives (Status: Final)
- Guidance for Industry: Use of Recycled Plastics in Food Packaging (Chemistry Considerations) (Status: Final)
- Guidance for Industry: Microbiological Considerations for Antimicrobial Agents Used in Food Applications (Status: Final)
- Guidance for Industry: Preparation of Food Contact Substance Notifications (Administrative) (Status: Final)