Ads for post-1962-NDA/1969-NADA/§572-index drugs may not suggest unapproved uses

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Rule

An advertisement for a prescription drug covered by an NDA (or supplement) approved after October 10, 1962, a new animal drug application (or supplement) approved after August 1, 1969, or a drug listed in the index under section 572 of the act (including any approved supplement or granted modification) may not recommend or suggest any use that is not in the accepted labeling. Prescription drugs covered by an NDA/supplement that became effective before October 10, 1962 are instead governed by 21 CFR 202.1(e)(4)(i)(b) and are outside this rule.

Check

First confirm the product is covered by a post-October-10-1962 NDA/supplement, a post-August-1-1969 NADA/supplement, or a section 572 index listing/modification (if it is instead covered by a pre-1962 NDA, apply the separate (e)(4)(i)(b) rule, not this one). Then compare every use, population, or indication claim in the ad against the labeling accepted in that application/listing; flag any claim that recommends or suggests a use not contained in it.

Escalate when

Escalate when it is unclear which approval pathway/date governs the product (pre- vs post-1962 NDA, NADA, or §572 index listing), or when whether a claim implies an unapproved use requires interpretation of wording or context.

Where this comes from

21 CFR 202.1(e)(4)(i)(a). The highlighted words are quoted exactly; a script confirms they appear in the source before the rule can be published.

…e, “blood dyscrasias” for disclosure of “leukopenia,” “agranulocytosis,” and “neutropenia”) is permitted only to the extent that the use of such a single term in place of disclosure of each specific side effect and contraindication has been previously approved or permitted in drug labeling conforming to the provisions of §§ 201.100 or 201.105. (4) Substance of information to be included in brief summary. (i)(a) An advertisement for a prescription drug covered by a new-drug application approved pursuant to section 505 of the act after October 10, 1962, or a prescription drug covered by a new animal drug application approved pursuant to section 512 of the act after August 1, 1969, or any approved supplement thereto, or for a prescription drug listed in the index pursuant to section 572 of the act, or any granted modification thereto, shall not recommend or suggest any use that is not in the labeling accepted in such approved new-drug application or supplement, new animal drug application or supplement, or new animal drug index listing or modification. The advertisement shall present information from labeling required, approved, permitted, or granted in a new-drug or new animal drug application or new animal drug index listing relating to each specific side effect and contraindication in such labeling that relates to the uses of the advertised drug dosage form(s) or shall …

Open the original at these words on ecfr.gov ↗Read our full copy →

Document: 21 CFR 202.1
Version: 2026-09-16 — the link above is pinned to this date, so it shows the text as it stood then
Retrieved: 2026-09-21 from www.ecfr.gov
Fingerprint: a542640a872b3f2702d549e8…

Applies when

Naturepromotional

Launch stagepost-approval

Productdrug

How this rule was checked

Citation proven by script and passed an independent verifier running on a different model. Not yet confirmed by a human.

Drafted
claude-sonnet-5 · 2026-09-21
Independent verification — revise
claude-opus-5 · 2026-09-21
Reviewer's reasons
- Quote is verbatim and operative: 21 CFR 202.1(e)(4)(i)(a) states an advertisement 'shall not recommend or suggest any use that is not in the labeling accepted' in the approved application. This is a binding prohibition, not a definition, example, or description of what is not required, so the rule statement and check follow from it.
- Locator is accurate: the sentence appears in paragraph (e)(4) 'Substance of information to be included in brief summary,' subparagraph (i)(a), exactly as cited.
- Authority 'binding' is correct (codified regulation). Determinism 'judgment' is correct because whether an ad 'suggests' a use outside labeling turns on wording and context, not literal presence/absence. Severity 'blocker' is defensible for off-label promotion.
- Atomic: one obligation (no uses outside accepted labeling) with one comparison operation.
- Overstated on subject matter: the source clause applies to an advertisement for a *prescription* drug; the rule statement says only 'a drug,' which would extend the prohibition to OTC advertising the paragraph does not govern.
- Overstated on scope by dropping the source's date conditions (NDA approved after October 10, 1962; NADA approved after August 1, 1969; index listing under section 572). This matters because the immediately following (e)(4)(i)(b) in the same source establishes a more permissive regime for drugs covered by a pre-October-10-1962 NDA, under which an advertisement *may* recommend certain additional uses in labeling in commercial use. As drafted, the rule would flag conduct the source expressly permits.
- applies_when values (promotional, post-approval) are justified by the source but incomplete — they omit the prescription-drug and application-date limits that the source text imposes.
Revised by the drafter
claude-sonnet-5 · 2026-09-21
Independent verification — pass
claude-opus-5 · 2026-09-21
Reviewer's reasons
- Supported: the quoted sentence is the operative text of 21 CFR 202.1(e)(4)(i)(a) and is an express mandatory prohibition ('shall not recommend or suggest any use that is not in the labeling accepted...'). It is not an example, definition, preamble, or description of what is not required.
- Not overstated: the rule statement tracks the regulatory text almost verbatim, preserves the three covered pathways (post-10/10/1962 NDA, post-8/1/1969 NADA, §572 index listing) and the 'recommend or suggest' standard rather than expanding it to a general misleadingness test. The carve-out sentence for pre-1962 NDAs is a scope clarification that is itself supported by (e)(4)(i)(b), which appears in the source text; it imposes no separate obligation.
- Atomic: a single prohibition (no use outside accepted labeling). The rule deliberately does not bundle in the second sentence of (a) concerning presentation of side effect/contraindication information from labeling, which would have been a separate checkable requirement.
- Determinism correctly 'judgment': whether a claim 'suggests' an unapproved use turns on impression and context, not on a literal match; the escalation note reflects this appropriately.
- Authority correctly 'binding': 21 CFR 202.1 is a codified FDA regulation.
- applies_when is justified and not invented: the provision by its terms reaches prescription drug advertisements (promotional) for products with an approved NDA/NADA or granted index listing (post-approval), and covers human and animal drugs under the 'drug' product-type. The applicability limit that matters most — coverage by a post-1962 NDA / post-1969 NADA / §572 listing — is carried in the rule statement and the check's first step rather than being dropped.
- Locator 21 CFR 202.1(e)(4)(i)(a) matches the quoted sentence exactly as it appears in the source under '(4) Substance of information to be included in brief summary. (i)(a)'.
- Severity 'blocker' is defensible: recommending or suggesting an unapproved use is a per se violation of the advertising regulation and a core off-label promotion issue, not a remediable presentation defect.
- Minor, non-blocking: the check's phrase 'use, population, or indication claim' slightly elaborates the statutory word 'use', but promoting a population outside the accepted labeling is fairly read as a use not in that labeling, and (e)(6)(i) ('broader range of conditions or patients') in the same section confirms the reading. Not grounds to withhold a pass.