Q.01

How does FDA GRAS notification work?

A GRAS notice is currently voluntary. If you conclude that your substance is generally recognized as safe (GRAS) for its intended food use, you may tell FDA about that conclusion under 21 CFR Part 170 Subpart E, but you don't have to. FDA then has 180 days from filing to reply by letter. A favourable "no questions" letter is not an approval. FDA proposed on August 10, 2026 to make notification mandatory, and the comment period runs until December 9, 2026.

Approach: I read the current eCFR text of 21 CFR Part 170 (Subparts B and E), the FD&C Act definitions in 21 U.S.C. 321, FDA's GRAS Notice Inventory and its food guidance catalogue. For the 2026 proposal I used FDA's own pages and its preliminary regulatory impact analysis, because the Federal Register page would not open.

Legal basis

  • The statute. A substance is not a "food additive" if qualified experts generally recognize it as shown to be safe under its intended conditions of use. That showing can come from scientific procedures, or, for a substance used in food before January 1, 1958, from experience based on common use in food [1].
  • The two routes in § 170.30.
    • Scientific procedures "shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive." They must rest on generally available data, which is ordinarily published. Unpublished data can only corroborate.
    • Common use before 1958. Ingredients not in common use before 1958 can only qualify through scientific procedures. Pre-1958 use outside the US must be documented and corroborated by a second, independent source.
    • No GRAS basis. A substance that is not GRAS (or prior-sanctioned) needs a food additive regulation under section 409 [2].
  • Who can notify. "Any person may notify FDA" of a GRAS conclusion (§ 170.205) [3]. The notifier is the legal entity responsible for the notice, even if an agent or expert prepares it (§ 170.203) [4].

What goes in the notice: seven mandatory parts (§ 170.220)

Each part must be on separate pages. If a part doesn't apply, you must explain why [5].

PartContent
1, signed statements (§ 170.225)This part must not contain confidential information. It covers:
  • who you are, what the substance is called and how it will be used (foods, use levels, purpose, any subpopulation)
  • which route you rely on, and your view that the substance is exempt from premarket approval
  • an agreement to give FDA access to your underlying data
  • your view on which parts are exempt from FOIA disclosure
  • a certification that the notice is "complete, representative, and balanced," including unfavourable information
[6]
2, identity and manufacture (§ 170.230)Identity (CAS or EC number, composition). For biological sources: taxon down to strain, the part used and known toxicants. Also method of manufacture, food-grade specifications and, where needed, technical effect [7]
3, dietary exposure (§ 170.235)Required on either route. Covers exposure from all dietary sources, plus reaction products and contaminants, with the consumption data and assumptions used [8]
4, self-limiting levels (§ 170.240)Only where higher levels would make the food unpalatable or technically impractical [9]
5, pre-1958 use (§ 170.245)Only on the common-use route: a substantial history of consumption by a significant number of consumers before January 1, 1958 [10]
6, narrative (§ 170.250)
  • Why the substance is safe, and why it is generally recognized as safe
  • Which data are and are not generally available
  • Discussion of inconsistent data, or a statement that you know of none
  • How GRAS status holds if experts cannot see non-public data
[11]
7, reference list (§ 170.255)All data relied on, flagged as generally available or not [12]

Submission and review

  1. Optional pre-submission meeting with FDA (FDA program page).
  2. Submit to the Office of Food Additive Safety. One electronic copy or one paper copy is enough (§ 170.210) [13]. You may incorporate by reference data already held at FDA, such as an earlier GRAS notice or food additive petition (§ 170.215) [14].
  3. Filing. FDA first screens the submission, then sends a letter giving the filing date, or saying why it was not filed.
  4. Response. FDA "will respond to you by letter" within 180 days of filing. It may extend that by 90 days, and must tell you no later than day 180. FDA considers timely amendments only where that is feasible within the timeframe (§ 170.265) [15].
  5. Options before FDA replies. You may amend the notice, or ask FDA to stop evaluating it. Withdrawing doesn't stop you from notifying again later (§ 170.260) [16]. After FDA's letter, you may file supplements (§ 170.280) [17].
  6. Meat and poultry uses. If the intended use includes products regulated by USDA's Food Safety and Inspection Service (FSIS), FDA forwards the notice to FSIS, minus trade secrets unless you authorize sharing. FDA passes FSIS's advice on in its letter (§ 170.270) [18].
  7. Public disclosure.
    • Notices count as mandatory submissions for FOIA purposes and can be disclosed from the date FDA receives them.
    • FDA publishes the list of filed notices and its response letters (§ 170.275) [19].
    • The old GRAS affirmation petition route closed on October 17, 2016 (§ 170.285) [20].

Possible outcomes

FDA's program page describes three letter types: "no questions," "insufficient basis," and "cease to evaluate" at the notifier's request. It states that a "no questions" letter is not an approval (FDA).

The GRAS Notice Inventory holds 1,360 notices:

FDA responseNotices
No questions1,071
Ceased at notifier's request226
Pending43
Does not provide a basis20

Example: GRN 42 is a "does not provide a basis" notice [21].

FDA also keeps a separate inventory of postmarket determinations that particular uses are not GRAS. Relevant FDA guidance includes:

  • Frequently Asked Questions about GRAS (final, 2016/10) [22]
  • Best Practices for Convening a GRAS Panel (final, 2022/12) [23]
  • The 2017 regulatory framework guidance covering human and animal food [24]

Pending change: mandatory notification (proposed, not final)

FDA's preliminary impact analysis for Docket FDA-2025-N-3262 (FDA PDF) says the proposal would:

  • Replace the voluntary program with a mandatory one. It would amend 21 CFR Parts 170 and 570 to "replace the voluntary GRAS notification program with a mandatory GRAS notification program." GRAS notices would be "required for certain uses" unless an exception applies.
  • Change the position for new uses. After a final rule takes effect, new uses that today would rest on an unnotified ("self-affirmed") GRAS conclusion would need a notice.
  • Offer a streamlined option for products already on the market. Substances marketed on a self-affirmed GRAS basis before the effective date could instead get a time-limited streamlined submission (proposed §§ 170.205(b)(7) and 170.305; 570.205(b)(7) and 570.305). The analysis weighs 2- and 3-year submission periods as alternatives. I did not confirm the proposed window length itself.

Comments are open until December 9, 2026 on Regulations.gov (FDA webinar page, FDA GRAS page). Until a final rule is published, Subpart E as summarized above remains the operative text.

Q.02

What belongs in the notice?

A GRAS notice under 21 CFR Part 170 Subpart E has seven parts (§§ 170.225 to 170.255). You must put each part on separate pages or sets of pages. You "must include each of the seven parts," and if one doesn't apply you must explain why (§ 170.220) [5].

Approach: I read the current eCFR text of 21 CFR §§ 170.220 to 170.255. The content rules below are the voluntary program now in force. The August 2026 mandatory-notification proposal is not final.

Part 1: Signed statements and certification (§ 170.225)

A responsible official of your organization, or your attorney or agent, must date and sign Part 1. It must not contain trade secret or confidential commercial information, apart from the FOIA statement in item 8. In Part 1 you must:

  1. Say that you are submitting a GRAS notice under Subpart E.
  2. Give your organization's name and address.
  3. Name the substance using "an appropriately descriptive term."
  4. Describe the intended conditions of use:
    • the foods it will be used in
    • the use levels
    • the purposes
    • when appropriate, any subpopulation expected to consume it
  5. State the statutory basis: scientific procedures (§ 170.30(a) and (b)) or common use in food (§ 170.30(a) and (c)).
  6. State your view that the substance is not subject to premarket approval because it is GRAS under its intended use.
  7. Agree that, if FDA asks during or after its evaluation, you will make the underlying data available. You do this in one of two ways:
    • FDA may review and copy it during business hours at an address you name.
    • You send a complete copy, electronic or paper.
  8. State your view on whether any data in Parts 2 to 7 are exempt from disclosure under FOIA.
  9. Certify that, to the best of your knowledge, the notice is "a complete, representative, and balanced submission." It must include unfavourable as well as favourable information known to you.
  10. Give the signer's name and position or title.
  11. Where USDA's Food Safety and Inspection Service (FSIS) is involved under § 170.270, say whether FDA may send trade secrets to FSIS or must leave them out.

[6]

Part 2: Identity, manufacture, specifications, technical effect (§ 170.230)

  • Identity. Examples of suitable data are:
    • chemical name
    • CAS or Enzyme Commission (EC) number
    • empirical and structural formula
    • quantitative composition
    • characteristic properties
  • Biological sources. You must identify:
    • the taxonomic source, down to variety or strain where applicable
    • the plant or animal part used
    • any known toxicants that could be present
  • Method of manufacture, in enough detail to evaluate the safety of the substance as manufactured.
  • Specifications for food-grade material.
  • Technical effect. Where needed to show safety, data on the intended physical or technical effect, including the quantity needed to produce it.

[7]

Part 3: Dietary exposure (§ 170.235)

This part is required on both the scientific-procedures route and the common-use route. You must provide:

  • The notified substance: an exposure estimate covering its intended use and all sources in the diet.
  • Substances formed in or on food because of its use (for example, hydrolytic or reaction products): an estimate, when applicable.
  • Substances present with it naturally or from manufacture (for example, contaminants or by-products): an estimate, when applicable.
  • Consumption data: the source of any food consumption data you used.
  • Assumptions: an explanation of each one.

[8]

Part 4: Self-limiting levels of use (§ 170.240)

This applies only where food would become "unpalatable or technologically impractical" above a certain level. You must then include data on those self-limiting levels [9].

Part 5: Common use in food before 1958 (§ 170.245)

This applies only on the common-use route. You must give evidence of "a substantial history of consumption" for food use "by a significant number of consumers prior to January 1, 1958" [10].

Part 6: Narrative (§ 170.250)

This is the core argument. In it you must:

  • (a)(1) Safety: explain why the data show the substance is safe under its intended use. This covers all dietary sources and any chemically or pharmacologically related substances in the diet.
  • (a)(2) Availability: identify which data you discuss are generally available and which are not, citing the Part 7 list.
  • (b) General recognition: explain how the generally available data support the conclusion that qualified experts generally recognize the substance as safe.
  • (c) Inconsistent data: do one of two things:
    • identify, discuss and put in context any data that are, or may appear to be, inconsistent with GRAS status, whether or not they are generally available; or
    • state that you have reviewed the data and know of none.
  • (d) FOIA: identify the specific data you consider exempt from FOIA.
  • (e) Non-public data: for non-public safety data you considered, explain how a GRAS conclusion could stand if qualified experts cannot see those data.

[11]

Part 7: List of supporting data and information (§ 170.255)

  • List all the data you discuss in Part 6 as the basis for safety under § 170.250(a)(1).
  • Mark each item as generally available or not generally available.

[12]

Practical points for drafting

  • Parts 4 and 5 are conditional. If you leave one out, include the explanation that § 170.220(b) requires, for example "Part 5 not applicable: conclusion based on scientific procedures."
  • Parts 6 and 7 have to match. Every safety item in Part 6 needs an entry in Part 7 with its availability flag.
  • Confidential material stays out of Part 1. Flag confidential material in your Part 1 FOIA statement and identify it specifically in Part 6(d).
Q.03

What does a no questions letter mean?

A "no questions" letter means FDA, after evaluating your notice, does not question the basis for your GRAS conclusion "at this time." It is FDA's response to your conclusion. It is not an FDA approval, and it is not an affirmation that the substance is GRAS. The conclusion stays yours, and so does responsibility for the marketed product.

Approach: I read 21 CFR §§ 170.265, 170.275 and 170.280 and FDA's GRAS Notice Inventory. Part 170 does not define what a "no questions" letter means, so for that I used FDA's GRAS program page and a published FDA response letter (GRN 769, October 2018) for the standard wording.

Where the letter comes from in the rule

  • When it arrives. Within 180 days of filing, FDA "will respond to you by letter based on our evaluation of your notice." It may extend this by 90 days. If circumstances warrant, FDA "will send you a subsequent letter about the notice" (§ 170.265(b)(1), (c)) [15].
  • What the rule doesn't say. The regulation sets no fixed outcome categories. "No questions" is one of three letter types FDA describes on its program page. That page says the letter "states that FDA does not question the basis for the notifier's GRAS determination." It may also flag issues about labeling, use in certain foods, or color additive requirements (FDA program page).
  • The letter is public. FDA "will make … readily accessible to the public" the text of its letter (§ 170.275(b)(2)) [19]. In the inventory these entries show as "FDA has no questions," for example GRN 9 [25] and GRN 99 [26].

One correction to my earlier answer: FDA's program page does not itself say the letter is "not an approval." That limit comes from the wording of the letters, below.

What the letter says, and what it does not

The Conclusions section of the GRN 769 letter (FDA letter) contains four statements:

  1. What FDA finds. "We have no questions at this time regarding [the notifier's] conclusion that [the substance] is GRAS under its intended conditions of use." This is based on what the notifier provided "as well as other information available to FDA." So the letter:
    • responds to your conclusion
    • covers only the notified intended conditions of use
    • holds "at this time"
  2. Not an affirmation. "This letter is not an affirmation that [the substance] is GRAS under 21 CFR 170.35."
  3. Limited scope. "Unless noted above, our review did not address other provisions of the FD&C Act."
  4. Responsibility stays with industry. "Food ingredient manufacturers and food producers are responsible for ensuring that marketed products are safe and compliant with all applicable legal and regulatory requirements."

Standard caveats in the body of the letter

The GRN 769 letter also sets out these limits:

  • Labeling name. FDA's use of a name for the substance "is not our recommendation of that term as an appropriate common or usual name." Ingredient naming is governed by 21 CFR 101.4 and 102.5. FDA's Office of Nutrition and Food Labeling was not consulted.
  • Standards of identity. An ingredient lawfully added to food "may be used in a standardized food only if it is permitted by the applicable standard of identity."
  • FD&C Act § 301(ll). FDA "did not consider" whether § 301(ll) applies. That section prohibits foods containing approved drugs, licensed biologics, or substances under publicly disclosed substantial clinical investigation. The letter "should not be construed to be a statement" that such foods would not violate it.

Practical consequences

  • Scope is tied to the notice. The letter covers the uses, levels and specifications in the notice as amended. Other uses are outside what FDA evaluated.
  • Changes go in a supplement. After FDA's letter you "may submit a supplement" to the filed notice if circumstances warrant (§ 170.280) [17].
  • FDA can revisit. The "at this time" wording and the § 170.265(c) power to send a later letter mean FDA can come back to the notice.
  • The other two letter types. An "insufficient basis" letter means the notice "does not provide a sufficient basis for a GRAS determination." A "cease to evaluate" letter is issued at the notifier's request (FDA program page).
Q.04