Communication is not consistent with labeling if it increases potential for harm relative to labeling

AI-verifiedblockerFDA guidance · non-bindingRaised as a question — a person decides

Rule

Even where a communication does not conflict with the labeling's stated indication, population, or dosing, it is not consistent with the FDA-required labeling if following the communication's representations or suggestions would increase the potential for harm to health relative to the labeling. This factor does not apply to 510(k)-cleared or 510(k)-exempt devices; FDA says communications about those devices are analyzed instead under 21 CFR 807.81(a)(3) and the 510(k) Modifications Guidance, or the applicable exemption limitations (Q.1/A.1).

Check

Assess whether the use represented or suggested would reasonably be expected to introduce a new risk not included in the FDA-required labeling, or to materially (clinically significantly) increase the rate of occurrence or severity of a risk already in the labeling. A violation looks like a use scenario the label does not address that would reasonably be expected to raise risk. This factor is not failed by: (a) communications that merely describe increased risks observed in clinical practice; (b) communications reflecting safety-related labeling changes described in a pending CBE supplement, which are considered consistent with the FDA-required labeling; or (c) minor differences in the rate of occurrence of common, non-serious adverse reactions (e.g., a slightly higher headache rate observed in clinical practice than in the labeled trial experience).

Escalate when

Always — this determination turns on a clinical/scientific judgment about whether risk is reasonably expected to increase.

Where this comes from

Q.2/A.2, Factor 2 · page 8. The highlighted words are quoted exactly; a script confirms they appear in the source before the rule can be published.

…e product. Under certain circumstances, FDA may also consider additional risks and potential harms in determining whether a product meets the relevant standard for marketing. For example, FDA may assess the risks of abuse or misuse of certain products, the potential for harm to the health of humans from certain animal drug uses, or the potential for harm to health from secondary exposure to certain medical products. If using a product in accordance with the representations/suggestions in a product communication increases the potential for harm to health relative to the information reflected in the FDA-required labeling, this indicates that the communication is not consistent with the FDA-required labeling. For example, if the representations or suggestions about use of the product would reasonably be expected to introduce new risks that are not included in the FDA-required labeling or to materially increase the rate of Contains Nonbinding Recommendations occurrence or severity of existing risks included in the FDA-required labeling, the communication would not be consistent with the FDA-required …

Open the original at page 8 on fda.gov ↗Read our full copy →

Document: FDA guidance: Medical Product Communications that Are Consistent With the FDA-Required Labeling – Questions and Answers (final)
Version: as retrieved — the publisher does not version this document; the fingerprint below identifies the exact file
Retrieved: 2026-09-21 from www.fda.gov
Fingerprint: 1a18b7f242bfbbf897f198df…

FDA guidance describes the agency's current thinking. It is not binding law, and this rule is a recommendation, not an obligation.

Applies when

Basisconsistent-with-labeling

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-code:sonnet · 2026-09-21
Independent verification — revise
claude-code:opus · 2026-09-21
Reviewer's reasons
- The rule statement is well supported. The quote is verbatim Factor 2, and the rule's 'even where a communication does not conflict with the labeling's stated indication, population, or dosing' is squarely backed by the source's overlap discussion: 'If a firm's communication suggests use of its product in a way that does not conflict with the FDA-required labeling but which nevertheless increases the potential for harm to health ... the communication would not be consistent with the FDA-required labeling (factor 2).'
- The Check overstates the source in two ways. First, it drops the materiality threshold: the source requires representations that 'would reasonably be expected to introduce new risks that are not included in the FDA-required labeling or to materially increase the rate of occurrence or severity of existing risks,' and footnote 18 restates this as a 'clinically significant increase.' The Check says only 'increase the rate/severity of a known risk' and 'plausibly raises risk,' which is a lower bar than 'reasonably be expected' plus materiality.
- Second, the Check ignores the carve-outs stated in footnote 18: the factor 'is not intended to restrict firms from communicating about increased risks,' communications reflecting labeling changes described in a pending CBE supplement are considered consistent (footnote 17 and 18), and 'minor differences in the rate of occurrence of common, non-serious adverse reactions' (the headache example) do not fail this factor. As drafted, the rule would flag exactly those communications.
- Atomic (one determination), 'judgment' is correct and the 'escalate always' is appropriate for a clinical risk assessment, 'guidance' is correct, 'blocker' is defensible, and the locator 'Q.2/A.2, Factor 2' is exact. applies_when (basis consistent-with-labeling, no promotional limiter) matches Q.2's 'product communication' framing — note this is inconsistent with US-IND-007 through US-IND-010 in this same packet, which add a "promotional" limiter to the same framework.
Revised by the drafter
claude-code:sonnet · 2026-09-21
Revised by the drafter
claude-code:sonnet · 2026-09-21
Independent verification — revise
claude-code:opus · 2026-09-21
Reviewer's reasons
- The quote is a complete sentence from Factor 2 of Q.2/A.2. The rule text correctly frames Factor 2 as a test of whether a communication is consistent with the FDA-required labeling. A.2 states that failing any one factor means the communication 'is not considered consistent', so the rule text's 'is not consistent' is supported.
- The title, 'Communication must not increase potential for harm relative to labeling', turns a non-binding guidance classification factor into a 'must' obligation. The source does not prohibit anything here. It says such a communication is not consistent with the FDA-required labeling, which takes it outside the CFL framework. This overstates the source and claims more than the guidance's authority.
- Q.1/A.1 sets an obvious scope limit that the rule omits. For devices cleared in 510(k)s and 510(k)-exempt devices, 'there is no need to separately analyze communications under the factors discussed in Q.2/A.2'. Those devices are analyzed under 21 CFR 807.81(a)(3) and the 510(k) Modifications Guidance, or under their exemption limitations. The vocabulary cannot express this, so it must be stated in the rule text.
- The Check's carve-outs (increased risks observed in practice, pending CBE supplements, minor differences in common non-serious AE rates) and the 'materially / clinically significant' threshold accurately reflect Factor 2 and footnotes 17-18. It is correctly marked judgment. Blocker severity is defensible for a piece whose basis is consistency with labeling, because failing this factor removes that basis.
Revised by the drafter
claude-code:sonnet · 2026-09-21
Independent verification — pass
claude-code:opus · 2026-09-21
Reviewer's reasons
- Q.2/A.2 Factor 2 states verbatim: 'If using a product in accordance with the representations/suggestions in a product communication increases the potential for harm to health relative to the information reflected in the FDA-required labeling, this indicates that the communication is not consistent with the FDA-required labeling.' A.2 adds that failing any one factor means the communication 'is not considered consistent'. The rule's conclusion is therefore not an overstatement. It is framed as FDA's consistency analysis, not as a prohibition, and the title is descriptive rather than a command.
- The quote is a complete sentence. The rule's 'even where a communication does not conflict' framing tracks A.2's discussion that a communication satisfying factor 1 can still fail factor 2.
- The 510(k)-cleared/exempt carve-out in the rule text is accurate to Q.1/A.1 ('there is no need to separately analyze communications under the factors discussed in Q.2/A.2'; analyze under 21 CFR 807.81(a)(3) and the 510(k) Modifications Guidance, or the exemption limitations).
- Every exception in the check is in the source. Footnote 18 covers communicating increased risks observed in clinical practice, the headache example of minor differences in common non-serious adverse reaction rates, and the clinically significant increase / new risk standard. Footnote 17 covers pending CBE supplements. The 'materially increase the rate of occurrence or severity' language comes from Factor 2's text.
- The rule is atomic, covering Factor 2 only (Factors 1 and 3 are separate). Judgment and always-escalate are correct, since the test turns on what would 'reasonably be expected'. Blocker severity is defensible because failing the factor takes the communication outside the consistent-with-labeling framework. applies_when (consistent-with-labeling) and the Q.2/A.2 Factor 2 locator are right.