Description
Under section 413(a)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 350b(a)(2)), the manufacturer or distributor of a new dietary ingredient (NDI) that has not been present in the food supply as an article used for food, or a dietary supplement containing such an NDI, must submit a premarket safety notification to FDA at least 75 days before introducing the product into interstate commerce.
Scope & Applicability
Product Classes
5Products containing dietary ingredients intended to supplement the diet; The final product category for which the NDI is intended.
A dietary ingredient that was marketed in the U.S. before October 15, 1994
Approved substances for direct addition to food
A dietary ingredient that was not marketed in the United States before October 15, 1994.; A dietary ingredient not marketed in the U.S. before October 15, 1994; A dietary ingredient that was not marketed in the U.S. before October 15, 1994.; Abbreviated as NDI in the text; Ingredients that may require notification if chemically altered.; Ingredient requiring safety notification before marketing.; defined as an ingredient not marketed in the U.S. before October 15, 1994; Identity Information Abou
Food marketed for general consumption, distinct from dietary supplements.; Comparison point for intake levels
Stakeholders
5Entity responsible for submitting NDINs
Governs top dose in clinical studies
Supervising individual for medicinal products
internationally recognized third-party repository
Entity responsible for submitting NDINs
Regulatory Context
Attributes
10The highest dose at which no adverse effects are observed (NOAEL).; identified by the subchronic oral study to assess safety
A formula that lists the identity and quantity of each dietary ingredient and other ingredients
Repeated exposure for 1 to 3 months.
Exposure for more than 3 months or toxicology studies of at least 1 year.
NOAEL is divided by a safety factor to derive the ADI; Uncertainty factors used to account for differences between animals and humans and sensitivity among humans.; A multiplier used to account for uncertainty in safety data extrapolation
state the basis for the margin of safety for the NDI; Calculated by dividing the NOAEL by the estimated daily intake (EDI).; A measure of how close the estimated daily intake is to the NOAEL
acceptable daily intake (ADI) for the NDI
document resistance to any clinically relevant antibiotics
No-observed adverse effect level for histological changes
Highest dose in animal studies to detect toxicity; identified by subchronic oral toxicity studies
Identified Hazards
Hazards
9A substance that can cause genetic mutations or cancer.
Identified by positive findings in standard tests
species known to contain human pathogens; identify pathogens phylogenetically related to the fermentation microorganism; identify any human pathogens phylogenetically related to the microbial NDI
identify toxins or classes of toxins in related plants; identify toxins known to be present in the same species; identify any toxins known to be present in the same species
establish a specification to limit mold contamination of a component
identity and level of any impurities and contaminants
identity and level of any impurities and contaminants
substances like Salmonella or lead found in food supply
Safety concern associated with certain botanical extracts.
Related CFR Sections (7)
- 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 →
- 21CFR190.6§ 190.6 Requirement for premarket notification.
(a) At least 75 days before introducing or delivering for introduction into interstate commerce a dietary supplement that contains a new dietary ingredient that has not been present in the food supply as an article used for food in a form in which the food has not been chemically altered, the manufaRead full regulation →
- 21CFR101.4§ 101.4 Food; designation of ingredients.
- 21CFR111.70§ 111.70 What specifications must you establish?
(a) You must establish a specification for any point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record.Read full regulation →
- 21CFR316.3§ 316.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the act apply to those terms when used in this part.Read full regulation →
- 21CFR10.30§ 10.30 Citizen petition.
(a) This section applies to any petition submitted by a person (including a person who is not a citizen of the United States) except to the extent that other sections of this chapter apply different requirements to a particular matter.Read full regulation →
- 21CFR10.115§ 10.115 Good guidance practices.
(a) What are good guidance practices? Good guidance practices (GGP's) are FDA's policies and procedures for developing, issuing, and using guidance documents.Read full regulation →
Related Warning Letters (10)
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-05-20
Bioresearch Monitoring Program/Institutional Review Board (IRB)
United Health Products, Inc.
- 2025-03-25
Clinical Investigator
Americo F. Padilla, M.D.
- 2025-01-21
CGMP/Dietary Supplement/Adulterated
Western Innovations, Inc.
- 2024-11-05
Institutional Review Board (IRB)
Armstrong County Memorial Hospital
- 2024-10-22
Clinical Investigator
Namita A. Goyal, M.D.
- 2024-10-08
Institutional Review Board (IRB)
Louisiana State University Health Science Center IRB
- 2024-07-23
New Drugs/Dietary Supplements/Food Labeling/Misbranded
Formulation Technology, Inc.
- 2024-07-16
Bioresearch Monitoring Program/IRB
Massachusetts Institute of Technology MIT
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)
- Draft Guidance for Industry: Providing Regulatory Submissions in Electronic or Paper Format to the Office of Food Additive Safety (Status: Draft)
- 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)