CFR - Code of Federal Regulations Title 21

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[Code of Federal Regulations]

[Title 21, Volume 6]

[CITE: 21CFR570]

TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
					
SUBCHAPTER E - ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS
					
							PART 570FOOD ADDITIVES

Subpart A - General Provisions

Sec. 570.3 Definitions.

(a) Secretary means the Secretary of Health and Human Services.

(b) Department means the Department of Health and Human Services.

(d) As used in this part, the term act means the Federal Food, Drug, and Cosmetic Act approved June 25, 1936 (52 Stat. 1040 et seq., as amended; 21 U.S.C. 301-392).

(e) Food additives includes all substances not exempted by section 201(s) of the act, the intended use of which results or may reasonably be expected to result, directly or indirectly, either in their becoming a component of food or otherwise affecting the characteristics of food. A material used in the production of containers and packages is subject to the definition if it may reasonably be expected to become a component, or to affect the characteristics, directly or indirectly, of food packed in the container. Affecting the characteristics of food does not include such physical effects, as protecting contents of packages, preserving shape, and preventing moisture loss. If there is no migration of a packaging component from the package to the food, it does not become a component of the food and thus is not a food additive. A substance that does not become a component of food, but that is used, for example, in preparing an ingredient of the food to give a different flavor, texture, or other characteristic in the food, may be a food additive.

(f) Common use in food means a substantial history of consumption of a substance by a significant number of animals of the species to which the substance is intended to be fed (and, for food-producing animals fed with such substance, also means a substantial history of consumption by humans consuming human foods derived from those food-producing animals), prior to January 1, 1958.

(g) The word substance in the definition of the term food additive includes a food or feed or a component of a food or feed consisting of one or more ingredients.

(h) Scientific procedures include the application of scientific data (including, as appropriate, data from human, animal, analytical, or other scientific studies), information, and methods, whether published or unpublished, as well as the application of scientific principles, appropriate to establish the safety of a substance under the conditions of its intended use.

(i) Safe or safety means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the conditions of its intended use. It is impossible in the present state of scientific knowledge to establish with complete certainty the absolute harmlessness of the use of any substance. Safety may be determined by scientific procedures or by general recognition of safety. In determining safety, the following factors shall be considered:

(1) The probable consumption of the substance and of any substance formed in or on food because of its use;

(2) The cumulative effect of the substance in the diet, taking into account any chemically or pharmacologically related substance or substances in such diet;

(3) Safety factors which, in the opinion of experts qualified by scientific training and experience to evaluate the safety of food and food ingredients, are generally recognized as appropriate.

(j) The term nonperishable processed food means any processed food not subject to rapid decay or deterioration that would render it unfit for consumption. Not included are hermetically sealed foods and other processed foods requiring refrigeration.

(k) General recognition of safety shall be in accordance with § 570.30.

(l) Prior sanction means an explicit approval granted with respect to use of a substance in food prior to September 6, 1958, by the Food Drug and Administration or the United States Department of Agriculture pursuant to the Federal Food, Drug, and Cosmetic Act, the Poultry Products Inspection Act, or the Meat Inspection Act.

(m) Food includes human food, substances migrating to food from food-contact articles, pet food, and animal feed.

(n) Food-producing animal means an animal used to produce human food.

[41 FR 38644, Sept. 10, 1976, as amended at 42 FR 55206, Oct. 14, 1977; 81 FR 55051, Aug. 17, 2016]

Sec. 570.6 Opinion letters on food additive status.

(a) Over the years the Food and Drug Administration has given informal written opinions to inquirers as to the safety of articles intended for use as components of, or in contact with, food. Prior to the enactment of the Food Additives Amendment of 1958 (Pub. L. 85-929, Sept. 6, 1958), these opinions were given pursuant to section 402(a)(1) of the Federal Food, Drug, and Cosmetic Act, which reads in part: "A food shall be deemed to be adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health".

(b) Since enactment of the Food Additives Amendment, the Food and Drug Administration has advised such inquirers that an article:

(1) Is a food additive within the meaning of section 201(s) of the act; or

(2) Is generally recognized as safe (GRAS); or

(3) Has prior sanction or approval under that amendment; or

(4) Is not a food additive under the conditions of intended use.

(c) In the interest of the public health, such articles which have been considered in the past by the Food and Drug Administration to be safe under the provisions of section 402(a)(1), or to be generally recognized as safe for their intended use, or to have prior sanction or approval, or not to be food additives under the conditions of intended use, must be reexamined in the light of current scientific information and current principles for evaluating the safety of food additives if their use is to be continued.

(d) Because of the time span involved, copies of many of the letters in which the Food and Drug Administration has expressed an informal opinion concerning the status of such articles may no longer be in the file of the Food and Drug Administration. In the absence of information concerning the names and uses made of all the articles referred to in such letters, their safety of use cannot be reexamined. For this reason all food additive status opinions of the kind described in paragraph (c) of this section given by the Food and Drug Administration are hereby revoked.

(e) The prior opinions of the kind described in paragraph (c) of this section will be replaced by qualified and current opinions if the recipient of each such letter forwards a copy of each to the Department of Health and Human Services, Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance (HFV-200), 7500 Standish Pl., Rockville, MD 20855, along with a copy of his letter of inquiry, on or before July 23, 1970.

(f) This section does not apply to food additive status opinion letters pertaining to articles that were considered by the Food and Drug Administration to be food additives nor to articles included in regulations in this Subchapter E if the articles are used in accordance with the requirements of such regulations.

[41 FR 38644, Sept. 10, 1976, as amended at 54 FR 18281, Apr. 28, 1989; 57 FR 6476, Feb. 25, 1992]

Sec. 570.13 Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food.

Regulations providing for the use of food packaging materials as prior sanctioned in part 181 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food.

[42 FR 14091, Mar. 15, 1977]

Sec. 570.14 Indirect food additives resulting from packaging materials for animal feed and pet food.

Regulations providing for the use of food packaging materials in parts 174 through 179 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food.

[42 FR 14091, Mar. 15, 1977]

Sec. 570.15 Adoption of regulation on initiative of Commissioner.

(a) The Commissioner upon his own initiative may propose the issuance of a regulation prescribing, with respect to any particular use of a food additive, the conditions under which such additive may be safely used. Notice of such proposal shall be published in the Federal Register and shall state the reasons for the proposal.

(b) Action upon a proposal made by the Commissioner shall proceed as provided in part 10 of this chapter.

[41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977]

Sec. 570.17 Exemption for investigational use and procedure for obtaining authorization to market edible products from experimental animals.

A food additive or food containing a food additive intended for investigational use by qualified experts shall be exempt from the requirements of section 409 of the act under the following conditions:

(a) If intended for investigational use in vitro or in laboratory research animals, it bears a label which states prominently, in addition to the other information required by the act, the warning:

Caution. Contains a new food additive for investigational use only in laboratory research animals or for tests in vitro. Not for use in humans.

(b) If intended for use in animals other than laboratory research animals and if the edible products of the animals are to be marketed as food, permission for the marketing of the edible products as food has been requested by the sponsor, and authorization has been granted by the Food and Drug Administration in accordance with § 511.1 of this chapter or by the Department of Agriculture in accordance with 9 CFR 309.17, and it bears a label which states prominently, in addition to the other information required by the act, the warning:

Caution. Contains a new food additive for use only in investigational animals. Not for use in humans.

Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture.

(c) If intended for nonclinical laboratory studies in food-producing animals, the study is conducted in compliance with the regulations set forth in part 58 of this chapter.

[41 FR 38644, Sept. 10, 1976, as amended at 43 FR 60023, Dec. 22, 1978]

Sec. 570.18 Tolerances for related food additives.

(a) Food additives that cause similar or related pharmacological effects will be regarded as a class, and in the absence of evidence to the contrary, as having additive toxic effects and will be considered as related food additives.

(b) Tolerances established for such related food additives may limit the amount of a common component that may be present, or may limit the amount of biological activity (such as cholinesterase inhibition) that may be present or may limit the total amount of related food additives that may be present.

(c) Where food additives from two or more chemicals in the same class are present in or on a food, the tolerance for the total of such additives shall be the same as that for the additive having the lowest numerical tolerance in this class, unless there are available methods that permit quantitative determination of the amount of each food additive present or unless it is shown that a higher tolerance is reasonably required for the combined additives to accomplish the physical or technical effect for which such combined additives are intended and that the higher tolerance will be safe.

(d) Where residues from two or more additives in the same class are present in or on a food and there are available methods that permit quantitative determination of each residue, the quantity of combined residues that are within the tolerance may be determined as follows:

(1) Determine the quantity of each residue present.

(2) Divide the quantity of each residue by the tolerance that would apply if it occurred alone, and multiply by 100 to determine the percentage of the permitted amount of residue present.

(3) Add the percentages so obtained for all residues present.

(4) The sum of the percentages shall not exceed 100 percent.

Sec. 570.19 Pesticide chemicals in processed foods.

When pesticide chemical residues occur in processed foods due to the use of raw agricultural commodities that bore or contained a pesticide chemical in conformity with an exemption granted or a tolerance prescribed under section 408 of the act, the processed food will not be regarded as adulterated so long as good manufacturing practice has been followed in removing any residue from the raw agricultural commodity in the processing (such as by peeling or washing) and so long as the concentration of the residue in the processed food when ready to eat is not greater than the tolerance prescribed for the raw agricultural commodity. But when the concentration of residue in the processed food when ready to eat is higher than the tolerance prescribed for the raw agricultural commodity, the processed food is adulterated unless the higher concentration is permitted by a tolerance obtained under section 409 of the act. For example, if fruit bearing a residue of 7 parts per million of DDT permitted on the raw agricultural commodity is dried and a residue in excess of 7 parts per million of DDT results on the dried fruit, the dehydrated fruit is adulterated unless the higher tolerance for DDT is authorized by the regulations in this part. Food that is itself ready to eat, and which contains a higher residue than allowed for the raw agricultural commodity, may not be legalized by blending or mixing with other foods to reduce the residue in the mixed food below the tolerance prescribed for the raw agricultural commodity.

Subpart B - Food Additive Safety

Sec. 570.20 General principles for evaluating the safety of food additives.

(a) In reaching a decision on any petition filed under section 409 of the act, the Commissioner will give full consideration to the specific biological properties of the compound and the adequacy of the methods employed to demonstrate safety for the proposed use, and the Commissioner will be guided by the principles and procedures for establishing the safety of food additives stated in current publications of the National Academy of Sciences-National Research Council. A petition will not be denied, however, by reason of the petitioner's having followed procedures other than those outlined in the publications of the National Academy of Sciences-National Research Council if, from available evidence, the Commissioner finds that the procedures used give results as reliable as, or more reliable than, those reasonably to be expected from the use of the outlined procedures. In reaching a decision, the Commissioner will give due weight to the anticipated levels and patterns of consumption of the additive specified or reasonably inferable. For the purposes of this section, the principles for evaluating safety of additives set forth in the above-mentioned publications will apply to any substance that may properly be classified as a food additive as defined in section 201(s) of the act.

(b) Upon written request describing the proposed use of an additive and the proposed experiments to determine its safety, the Commissioner will advise a person who wishes to establish the safety of a food additive whether he believes the experiments planned will yield data adequate for an evaluation of the safety of the additive.

Sec. 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 either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. General recognition of safety requires common knowledge throughout the scientific community knowledgeable about the safety of substances directly or indirectly added to food that there is reasonable certainty that the substance is not harmful to either the target animal or to humans consuming human food derived from food-producing animals under the conditions of its intended use (see § 570.3(i)).

(b) General recognition of safety based upon scientific procedures shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive. General recognition of safety through scientific procedures shall address safety for both the target animal and for humans consuming human food derived from food-producing animals and shall be based upon the application of generally available and accepted scientific data, information, or methods, which ordinarily are published, as well as the application of scientific principles, and may be corroborated by the application of unpublished scientific data, information, or methods.

(c)(1) General recognition of safety through experience based on common use in food prior to January 1, 1958, shall address safety for both the target animal and for humans consuming human food derived from food-producing animals and may be achieved without the quantity or quality of scientific procedures required for approval of a food additive. General recognition of safety through experience based on common use in food prior to January 1, 1958, shall be based solely on food use of the substance in the same animal species prior to January 1, 1958, and shall ordinarily be based upon generally available data and information. An ingredient not in common use in food prior to January 1, 1958, may achieve general recognition of safety only through scientific procedures.

(2) A substance used in food prior to January 1, 1958, may be generally recognized as safe through experience based on its common use in food when that use occurred exclusively or primarily outside of the United States if the information about the experience establishes that the substance is safe under the conditions of its intended use within the meaning of section 201(u) of the Federal Food, Drug, and Cosmetic Act (see also § 570.3(i)) for both the target animal and for humans consuming human food derived from food-producing animals. Common use in food prior to January 1, 1958, that occurred outside of the United States shall be documented by published or other information and shall be corroborated by information from a second, independent source that confirms the history and circumstances of use of the substance. The information used to document and to corroborate the history and circumstances of use of the substance must be generally available; that is, it must be widely available in the country in which the history of use has occurred and readily available to interested qualified experts in the United States. A person who concludes that a use of a substance is GRAS through experience based on its common use in food outside of the United States should notify FDA of that view in accordance with subpart E of this part.

(d) The food ingredients listed as GRAS in part 582 of this chapter or affirmed as GRAS in part 584 of this chapter do not include all substances that are generally recognized as safe for their intended use in food. Because of the large number of substances the intended use of which results or may reasonably be expected to result, directly or indirectly, in their becoming a component or otherwise affecting the characteristics of food, it is impracticable to list all such substances that are GRAS. A food ingredient of natural biological origin that has been widely consumed for its nutrient properties in the United States prior to January 1, 1958, without known detrimental effects, which is subject only to conventional processing as practiced prior to January 1, 1958, and for which no known safety hazard exists, will ordinarily be regarded as GRAS without specific inclusion in part 582 or part 584 of this chapter.

(e) A food ingredient that is not GRAS or subject to a prior sanction requires a food additive regulation promulgated under section 409 of the act before it may be directly or indirectly added to food.

(f) A food ingredient that is listed as GRAS in part 582 of this chapter shall be regarded as GRAS only if, in addition to all the requirements in the applicable regulation, it also meets all of the following requirements:

(1) It complies with any applicable specifications, or in the absence of such specifications, shall be of a purity suitable for its intended use.

(2) It performs an appropriate function in the food or food-contact article in which it is used.

(3) It is used at a level no higher than necessary to achieve its intended purpose in that food or, if used as a component of a food-contact article, at a level no higher than necessary to achieve its intended purpose in that article.

(g) New information may at any time require reconsideration of the GRAS status of a food ingredient. Any change in status shall be accomplished pursuant to § 570.38.

(h) If a substance is affirmed as GRAS pursuant to § 570.35 and listed in a regulation with no limitation other than good manufacturing practice, it shall be regarded as GRAS if its conditions of use are not significantly different from those reported in the regulation as the basis on which the GRAS status of the substance was affirmed. If the conditions of use are significantly different, such use of the substance may not be GRAS. In such case a manufacturer may not rely on the regulation as authorizing the use but must independently establish that the use is GRAS or must use the substance in accordance with a food additive regulation.

(i) If an ingredient is affirmed as GRAS pursuant to § 570.35 and listed in a regulation with specific limitation(s), it may be used in food only within such limitation(s) (including the category of food(s), the functional use(s) of the ingredient, and the level(s) of use). Any use of such an ingredient not in full compliance with each such established limitation shall require a food additive regulation.

(j) Pursuant to § 570.35, a food ingredient may be affirmed as GRAS and listed in a regulation for a specific use(s) without a general evaluation of use of the ingredient. In addition to the use(s) specified in the regulation, other uses of such an ingredient may also be GRAS. Any affirmation of GRAS status for a specific use(s), without a general evaluation of use of the ingredient, is subject to reconsideration upon such evaluation.

[42 FR 55206, Oct. 14, 1977, as amended at 81 FR 55052, Aug. 17, 2016]

Sec. 570.35 Affirmation of generally recognized as safe (GRAS) status.

(a) The Commissioner, on his own initiative, may affirm that a substance that directly or indirectly becomes a component of food is GRAS under the conditions of its intended use.

(b)(1) If the Commissioner proposes on his own initiative that a substance is entitled to affirmation as GRAS under the conditions of its intended use, he will place all of the data and information on which he relies on public file in the office of the Dockets Management Staff and will publish in the Federal Register a notice giving the name of the substance, its proposed uses, and any limitations proposed for purposes other than safety.

(2) The Federal Register notice will allow a period of 60 days during which any interested person may review the data and information and/or file comments with the Dockets Management Staff. Copies of all comments received shall be made available for examination in the Dockets Management Staff's office.

(3) The Commissioner will evaluate all comments received. If he concludes that there is convincing evidence that the substance is GRAS under the conditions of its intended use as described in § 570.30, he will publish a notice in the Federal Register listing the GRAS conditions of use in this subchapter E.

(4) If, after evaluation of the comments, the Commissioner concludes that there is a lack of convincing evidence that the substance is GRAS under the conditions of its intended use and that it should be considered a food additive subject to section 409 of the Federal Food, Drug, and Cosmetic Act, he shall publish a notice thereof in the Federal Register in accordance with § 570.38.

[41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977; 42 FR 55207, Oct. 10, 1977; 50 FR 7517, Feb. 22, 1985; 50 FR 16668, Apr. 26, 1985; 54 FR 18281, Apr. 28, 1989; 62 FR 40600, July 29, 1997; 81 FR 55052, Aug. 17, 2016; 88 FR 45066, July 14, 2023]

Sec. 570.38 Determination of food additive status.

(a) The Commissioner may, in accordance with § 570.35(b)(4), publish a notice in the Federal Register determining that a substance is not GRAS under the conditions of its intended use and is a food additive subject to section 409 of the Federal Food, Drug, and Cosmetic Act.

(b)(1) The Commissioner, on his own initiative or on the petition of any interested person, pursuant to part 10 of this chapter, may issue a notice in the Federal Register proposing to determine that a substance is not GRAS and is a food additive subject to section 409 of the act. Any petition shall include all relevant data and information of the type described in § 571.130(b) of this chapter. The Commissioner will place all of the data and information on which he relies on public file in the Dockets Management Staff and will include in the Federal Register notice the name of the substance, its known uses, and a summary of the basis for the determination.

(2) The Federal Register notice will allow a period of 60 days during which any interested person may review the data and information and/or file comments with the Dockets Management Staff. Copies of all comments shall be made available for examination in the Dockets Management Staff.

(3) The Commissioner will evaluate all comments received. If he concludes that there is a lack of convincing evidence that the substance is GRAS or is otherwise exempt from the definition of a food additive in section 201(s) of the act, he will publish a notice thereof in the Federal Register. If he concludes that there is convincing evidence that the substance is GRAS, he will publish an order in the Federal Register listing the substance in this subchapter E as GRAS.

(c) A Federal Register notice determining that a substance is a food additive shall provide for the use of the additive in food or food-contact surfaces as follows:

(1) It may promulgate a food additive regulation governing use of the additive.

(2) It may promulgate an interim food additive regulation governing use of the additive.

(3) It may require discontinuation of the use of the additive.

(4) It may adopt any combination of the above three approaches for different uses or levels of use of the additive.

(d) If the Commissioner of Food and Drugs is aware of any prior sanction for use of the substance, he will concurrently propose a separate regulation covering such use of the ingredient under this subchapter E. If the Commissioner is unaware of any such applicable prior sanction, the proposed regulation will so state and will require any person who intends to assert or rely on such sanction to submit proof of its existence. Any regulation promulgated pursuant to this section constitutes a determination that excluded uses would result in adulteration of the food in violation of section 402 of the act, and the failure of any person to come forward with proof of such an applicable prior sanction in response to the proposal will constitute a waiver of the right to assert or rely on such sanction at any later time. The notice will also constitute a proposal to establish a regulation under this subchapter E., incorporating the same provisions, in the event that such a regulation is determined to be appropriate as a result of submission of proof of such an applicable prior sanction in response to the proposal.

[41 FR 38644, Sept. 10, 1976, as amended at 42 FR 4717, Jan. 25, 1977; 42 FR 15675, Mar. 22, 1977; 42 FR 55207, Oct. 14, 1977; 54 FR 18281, Apr. 28, 1989; 81 FR 55052, Aug. 17, 2016; 88 FR 45066, July 14, 2023]

Subparts C-D [Reserved]

Subpart E - Generally Recognized as Safe (GRAS) Notice

Sec. 570.203 Definitions.

The definitions and interpretations of terms in § 570.3 apply to such terms when used in this subpart. The following definitions also apply:

Amendment means any data and information that you submit regarding a filed GRAS notice before we respond to your notice by letter in accordance with § 570.265(b)(1) or cease to evaluate your notice in accordance with § 570.265(b)(3).

GRAS means generally recognized as safe.

GRAS notice means a submission that informs us of your view that a substance is not subject to the premarket approval requirements of the Federal Food, Drug, and Cosmetic Act based on your conclusion that the substance is GRAS under the conditions of its intended use in accordance with § 570.30.

Notified substance means the substance that is the subject of your GRAS notice.

Notifier means the person (e.g., an individual, partnership, corporation, association, or other legal entity) who is responsible for the GRAS notice, even if another person (such as an attorney, agent, or qualified expert) prepares or submits the notice or provides an opinion about the basis for a conclusion of GRAS status.

Qualified expert means an individual who is qualified by scientific training and experience to evaluate the safety of substances under the conditions of their intended use in animal food.

Supplement means any data and information that you submit regarding a filed GRAS notice after we respond to your notice by letter in accordance with § 570.265(b)(1) or cease to evaluate your notice in accordance with § 570.265(b)(3).

We, our, and us refer to the United States Food and Drug Administration (FDA).

You and your refer to a notifier.

Sec. 570.205 Opportunity to submit a GRAS notice.

Any person may notify FDA of a view that a substance is not subject to the premarket approval requirements of section 409 of the Federal Food, Drug, and Cosmetic Act based on that person's conclusion that the substance is GRAS under the conditions of its intended use.

Sec. 570.210 How to send your GRAS notice to FDA.

(a) Send your GRAS notice to the Division of Animal Feeds (HFV-220), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855.

(b) When you submit your GRAS notice, you may do so either in an electronic format that is accessible for our evaluation or on paper. If you send your GRAS notice on paper, a single paper copy is sufficient.

Sec. 570.215 Incorporation into a GRAS notice.

You may incorporate into your GRAS notice either specifically identified data and information that you previously submitted to the Center for Veterinary Medicine (CVM), or specifically identified publicly available data and information submitted by another party, when such data and information remain in CVM's records, such as data and information contained in a previous GRAS notice or a food additive petition.

Sec. 570.220 General requirements applicable to a GRAS notice.

(a) A GRAS notice has seven parts as required by §§ 570.225 through 570.255. You must submit the data and information specified in each of these parts on separate pages or sets of pages.

(b) You must include each of the seven parts in your GRAS notice. If you do not include a part, you must include with your GRAS notice an explanation of why that part does not apply to your GRAS notice.

Sec. 570.225 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.

(b) Except as required by paragraph (c)(8) of this section, you must not include any information that is trade secret or confidential commercial information in Part 1 of your GRAS notice.

(1) Inform us that you are submitting a GRAS notice in accordance with this subpart;

(2) Provide the name and address of your organization;

(3) Provide the name of the notified substance, using an appropriately descriptive term;

(4) Describe the intended conditions of use of the notified substance, including stating whether the substance will be added to food (including drinking water) for animals in which the substance will be used; identifying the foods to which it will be added, the levels of use in such foods, and the animal species for which these foods are intended (including, when appropriate, a description of a subpopulation expected to consume the notified substance); and the purposes for which the substance will be used;

(5) Inform us of the statutory basis for your conclusion of GRAS status (i.e., through scientific procedures in accordance with § 570.30(a) and (b) or through experience based on common use in animal food in accordance with § 570.30(a) and (c));

(6) State your view that the notified substance is not subject to the premarket approval requirements of the Federal Food, Drug, and Cosmetic Act based on your conclusion that the notified substance is GRAS under the conditions of its intended use;

(7) State that, if we ask to see the data and information that are the basis for your conclusion of GRAS status, either during or after our evaluation of your notice, you will:

(i) Agree to make the data and information available to us; and

(ii) Agree to both of the following procedures for making the data and information available to us:

(A) Upon our request, you will allow us to review and copy the data and information during customary business hours at the address you specify for where these data and information will be available to us; and

(B) Upon our request, you will provide us with a complete copy of the data and information either in an electronic format that is accessible for our evaluation or on paper;

(8) State your view as to whether any of the data and information in Parts 2 through 7 of your GRAS notice are exempt from disclosure under the Freedom of Information Act, 5 U.S.C. 552 (e.g., as trade secret or as commercial or financial information that is privileged or confidential);

(9) Certify that, to the best of your knowledge, the GRAS notice is a complete, representative, and balanced submission that includes unfavorable information, as well as favorable information, known to you and pertinent to the evaluation of the safety and GRAS status of the use of the substance; and

(10) State both the name and the position or title of the person who signs the GRAS notice.

Sec. 570.230 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:

(a) Scientific data and information that identifies the notified substance.

(1) Examples of appropriate data and information include the chemical name, applicable registry numbers (such as a Chemical Abstracts Service (CAS) registry number or an Enzyme Commission (EC) number), empirical formula, structural formula, quantitative composition, and characteristic properties.

(2) When the source of a notified substance is a biological material, you must include data and information sufficient to identify:

(i) The taxonomic source (e.g., genus, species), including as applicable data and information at the sub-species level (e.g., variety, strain);

(ii) The part of any plant or animal used as the source; and

(iii) Any known toxicants that could be in the source;

(b) A description of the method of manufacture of the notified substance in sufficient detail to evaluate the safety of the notified substance as manufactured;

(d) When necessary to demonstrate safety, relevant data and information bearing on the physical or other technical effect the notified substance is intended to produce, including the quantity of the notified substance required to produce such effect.

Sec. 570.235 Part 3 of a GRAS notice: Target animal and human exposures.

In part 3 of your GRAS notice, you must provide data and information about exposure to the target animal and to humans consuming human food derived from food-producing animals, regardless of whether your conclusion of GRAS status is through scientific procedures or through experience based on common use in food, as follows:

(a) For exposure to the target animal, you must provide:

(1) The amount of the notified substance that different target animal species are likely to consume in the animal food (including drinking water) as part of the animal's total diet, including the intended use and all other sources in the total diet; and

(2) When applicable, the amount of any other substance that is expected to be formed in or on food because of the use of the notified substance (e.g., hydrolytic products or reaction products);

(3) When applicable, the amount of any other substance that is present with the notified substance either naturally or due to its manufacture (e.g., contaminants or by-products);

(4) The data and information you rely on to establish the amount of the notified substance and the amounts of any other substance in accordance with paragraphs (a)(1) through (a)(3) of this section that different target animal species are likely to consume in the animal food (including drinking water) as part of the animal's total diet; and

(b) When the intended use is in food for food-producing animals, you must provide:

(1) The potential quantities of any residues that humans may be exposed to in edible animal tissues, including:

(i) Residues of the notified substance;

(ii) Residues of any other substance that is expected to be formed in or on the animal food because of the use of the notified substance; and

(iii) Residues from any other substance that is present with the notified substance whether naturally, due to its manufacture (e.g., contaminants or by-products), or produced as a metabolite in edible animal tissues when the notified substance is consumed by a food-producing animal; and

(2) The data and information you rely on to establish, in accordance with paragraph (b)(1) of this section, the potential quantities of any residues that humans may be exposed to in edible animal tissues.

Sec. 570.240 Part 4 of a GRAS notice: Self-limiting levels of use.

In circumstances where the amount of the notified substance that can be added to animal food is limited because animal food containing levels of the notified substance above a particular level would become unpalatable or technologically impractical, in Part 4 of your GRAS notice you must include data and information on such self-limiting levels of use.

Sec. 570.245 Part 5 of a GRAS notice: Experience based on common use in food before 1958.

If the statutory basis for your conclusion of GRAS status is through experience based on common use in animal food, in Part 5 of your GRAS notice you must include evidence of a substantial history of consumption of the notified substance for food use by a significant number of animals of the species to which the substance is intended to be fed prior to January 1, 1958, and evidence of a substantial history of consumption by humans consuming human foods derived from food-producing animals prior to January 1, 1958.

Sec. 570.250 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:

(a)(1) You must explain why the data and information in your notice provide a basis for your view that the notified substance is safe under the conditions of its intended use for both the target animal and for humans consuming human food derived from food-producing animals. In your explanation, you must address the safety of the notified substance, considering all animal food (including drinking water) as part of the animal's total diet, taking into account any chemically or pharmacologically related substances in such diet. In your explanation, you must also address the safety of the notified substance in regard to human exposure, considering all dietary sources and taking into account any chemically or pharmacologically related substances;

(2) In your explanation, you must identify what specific data and information that you discuss in accordance with paragraph (a)(1) of this section are generally available, and what specific data and information that you discuss in accordance with paragraph (a)(1) of this section are not generally available, by providing citations to the list of data and information that you include in Part 7 of your GRAS notice in accordance with § 570.255;

(b) You must explain how the generally available data and information that you rely on to establish safety in accordance with paragraph (a) of this section provide a basis for your conclusion that the notified substance is generally recognized, among qualified experts, to be safe under the conditions of its intended use for both the target animal and for humans consuming human food derived from food-producing animals;

(1) Identify, discuss, and place in context, data and information that are, or may appear to be, inconsistent with your conclusion of GRAS status, regardless of whether those data and information are generally available; or

(2) State that you have reviewed the available data and information and are not aware of any data and information that are, or may appear to be, inconsistent with your conclusion of GRAS status;

(d) If you view any of the data and information in your notice as exempt from disclosure under the Freedom of Information Act, you must identify the specific data and information; and

(e) For non-public, safety-related data and information considered in reaching a conclusion of GRAS status, you must explain how there could be a basis for a conclusion of GRAS status if qualified experts do not have access to such data and information.

Sec. 570.255 Part 7 of a GRAS notice: List of supporting data and information in your GRAS notice.

(a) In part 7 of your GRAS notice, you must include a list of all of the data and information that you discuss in Part 6 of your GRAS notice to provide a basis for your view that the notified substance is safe under the conditions of its intended use as described in accordance with § 570.250(a)(1).

(b) You must specify which data and information that you list in accordance with paragraph (a) of this section are generally available, and which data and information are not generally available.

Sec. 570.260 Steps you may take before FDA responds to your GRAS notice.

(a) You may submit a timely amendment to your filed GRAS notice, to update your GRAS notice or in response to a question from us, before we respond to your notice by letter in accordance with § 570.265(b)(1) or cease to evaluate your notice in accordance with § 570.265(b)(3).

(b) At any time before we respond to your notice by letter in accordance with § 570.265(b)(1), you may request in writing that we cease to evaluate your GRAS notice. Your request does not preclude you from submitting a future GRAS notice in accordance with this subpart with respect to the notified substance.

Sec. 570.265 What FDA will do with a GRAS notice.

(a)(1) We will conduct an initial evaluation of your submission to determine whether to file it as a GRAS notice for evaluation of your view that the notified substance is GRAS under the conditions of its intended use.

(2) If we file your submission as a GRAS notice, we will send you a letter that informs you of the date of filing.

(3) If we do not file your submission as a GRAS notice, we will send you a letter that informs you of that fact and provide our reasons for not filing the submission as a GRAS notice.

(4) We will consider any timely amendment that you submit to a filed GRAS notice, to update your GRAS notice or in response to a question from us, before we respond to you by letter in accordance with paragraph (b)(1) of this section, if we deem that doing so is feasible within the timeframes established in paragraph (b) of this section. If we deem that considering your amendment is not feasible within the timeframes established in paragraph (b) of this section or if we have granted your request to cease to evaluate your notice, we will inform you that we are not considering your amendment.

(b)(1) Within 180 days of filing, we will respond to you by letter based on our evaluation of your notice. We may extend the 180 day timeframe by 90 days on an as needed basis.

(2) If we extend the timeframe, we will inform you in writing of the extension as soon as practicable but no later than within 180 days of filing.

(3) If you ask us to cease to evaluate your GRAS notice in accordance with § 570.260(b), we will send you a letter informing you of our decision regarding your request.

Sec. 570.275 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:

(1) Considered a mandatory, rather than voluntary, submission for purposes of their status under the Freedom of Information Act and our public information requirements in part 20 of this chapter; and

(2) Available for public disclosure in accordance with part 20 of this chapter as of the date that we receive your GRAS notice.

(b) We will make the following readily accessible to the public:

(1) A list of filed GRAS notices, including the information described in § 570.225(c)(2) through (c)(5);

(2) The text of any letter that we issue under § 570.265(b)(1) or (c); and

(3) The text of any letter that we issue under § 570.265(b)(3) if we grant your request that we cease to evaluate your notice.

(c) We will disclose all remaining data and information that are not exempt from public disclosure in accordance with part 20 of this chapter.

Sec. 570.280 Submission of a supplement.

If circumstances warrant, you may submit a supplement to a filed GRAS notice after we respond to your notice by letter in accordance with § 570.265(b)(1) or cease to evaluate your notice in accordance with § 570.265(b)(3).

Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.
Source: 41 FR 38644, Sept. 10, 1976, unless otherwise noted.

CFR - Code of Federal Regulations Title 21

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