21 U.S.C. § 352 — Misbranded drugs and devices

A drug or device is "misbranded" — illegally labeled — if any of the following is true. (a) False or misleading label. Its labeling is false or misleading in any way. But there's a carve-out: "health care economic information" given to an insurer, a formulary committee, or a similar group of experts who decide whether to cover or pay for the drug or device isn't automatically false or misleading, as long as it's about a use the FDA has already approved, it's based on solid and reliable scientific evidence, and — where it applies — it clearly flags any differences between that economic information and the official approved labeling. When this exception applies, the normal labeling-approval rules don't apply to this economic information, but the company must make its supporting evidence available to the FDA on request. "Health care economic information" means any analysis — including its underlying data, assumptions, methods, and results — of the economic effects of using a drug or device, whether compared to another product, another treatment, or no treatment at all. This exception does not cover an analysis that is only about a use the FDA has not approved. (b) Package form. If sold in a package, the label must show the manufacturer's, packer's, or distributor's name and place of business, and an accurate statement of how much is inside, by weight, measure, or count. The FDA can allow reasonable variation in that statement and can exempt small packages by regulation. (c) Prominence. Any required word, statement, or piece of information on the label or labeling must be printed clearly enough — compared to everything else on it — that an ordinary person is likely to actually read and understand it under normal buying and use conditions. (d) Repealed in 1997. (e) Established names. A drug's label must show its "established name" (its official name) in place of any other non-brand name, except the exact chemical name or formula. Where the FDA requires it, the label must also give the quantity or proportion of each active ingredient, and specifically the amount of things like alcohol and certain named substances (such as bromides, morphine-family drugs, arsenic, digitalis, mercury, strychnine, and thyroid) if they're present — though this quantity rule for other, unlisted active ingredients doesn't apply to nonprescription drugs not meant for human use. The label (or, where the FDA requires it, the immediate container) must also list each inactive ingredient in alphabetical order on the outer retail package, without forcing disclosure of any trade secret; the alphabetical-order rule applies only to nonprescription drugs that aren't also cosmetics, and doesn't apply to nonprescription drugs not meant for human use. For a prescription drug, the established name must be printed at least half as large as any brand name, though the FDA can grant exemptions where following this is impractical. A device with an established name must show that name, to the exclusion of any other non-brand name, at least half as large as any brand name, again with FDA exemptions where compliance is impractical. A drug's "established name" means: the official name set under section 358; or, if there is none, the official name given in a recognized reference book (an "official compendium"); or, if neither exists, the drug's common or usual name. If the U.S. Pharmacopeia and the Homoeopathic Pharmacopoeia give the same article different official names, the U.S. Pharmacopeia's name controls — unless the product is labeled and sold as a homeopathic drug, in which case the homeopathic name controls. A device's "established name" means its official name set under section 358, or, if none, its name in a recognized compendium, or, if neither, any common or usual name. (f) Directions and warnings. The label must include adequate directions for safe use, and adequate warnings against dangerous uses — for certain medical conditions, for children, or regarding unsafe dosing, methods, or duration — as needed to protect users. The FDA can exempt a drug or device from the directions requirement by regulation if that requirement isn't needed to protect public health. Required labeling for prescription devices used in health facilities or by health professionals, and for in-vitro diagnostic devices used by health professionals or blood banks, may be provided only electronically, as long as it meets all legal requirements and the manufacturer promptly gives a free paper copy to anyone who asks. (g) Compendium labeling. A drug that claims to be recognized in an official compendium must be packaged and labeled the way that compendium requires, though the FDA can approve a modified packaging method. If a drug is listed in both the U.S. Pharmacopeia and the Homoeopathic Pharmacopoeia, the U.S. Pharmacopeia's packaging and labeling rules apply — unless the drug is labeled and sold as homeopathic, in which case the homeopathic rules apply. If this conflicts with the naming rules in (e), (e) controls. (h) Drugs that deteriorate. If the FDA has found that a drug is liable to deteriorate, it must be packaged the way the FDA requires by regulation, with a label stating the needed precautions. Before making such a rule for a drug listed in an official compendium, the FDA must first notify the group that revises that compendium of the need for the rule, and can only proceed if that group fails to act within a reasonable time. (i) Misleading containers and imitations. A drug is misbranded if its container is made or filled in a misleading way, if it imitates another drug, or if it's sold under another drug's name. (j) Dangerous as directed. If using the drug in the dosage, manner, frequency, or duration stated in its labeling is dangerous to health. (k), (l) Repealed in 1997. (m) Color additives. A color additive used purely for coloring must be packaged and labeled to match the rules issued under section 379e. (n) Prescription drug ads. Any ad or descriptive printed matter for a prescription drug must include: the established name, printed at least half as large as any brand name; the exact formula showing the quantity of each ingredient, to the same extent required on labels; and a brief FDA-required summary about side effects, contraindications, and effectiveness. Ads shown directly to consumers must also carry this exact statement: "You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1–800-FDA-1088." Two limits apply to the FDA's own power here: except in extraordinary circumstances, the FDA can't require pre-approval of an ad's content, and once the FDA has issued its regulations, such an ad isn't additionally subject to the FTC's advertising rules. This paragraph doesn't apply to material the FDA decides is "labeling" rather than advertising. The international Convention on Psychotropic Substances does not block drug-price communications to consumers. For a TV or radio ad about a prescription drug that names the drug and states its uses, the required statement on side effects and contraindications must be presented clearly, plainly, and evenhandedly. (o) Unregistered establishments and missing listings. A drug or device is misbranded if it was made in a facility that isn't properly registered with the FDA; if, for an imported drug, the commercial importer isn't registered; if the product wasn't included in a required listing; if required notice about it wasn't given under the listing rules; or if a device lacks the identification symbols the FDA requires under its uniform device-identification system. (p) Packaging violations. A drug is misbranded if its packaging or labeling violates the poison-prevention packaging regulations issued under 15 U.S.C. §§ 1472 or 1473. (q) Restricted devices — false ads or misuse. A "restricted device" is misbranded if its advertising is false or misleading in any way, or if it is sold, distributed, or used in violation of the FDA's regulations for restricted devices. (r) Restricted devices — missing ad disclosures. Ads and other descriptive printed matter for a restricted device must include the device's established name, printed at least half as large as any brand name, and a brief statement of its intended uses along with relevant warnings, precautions, side effects, and contraindications — and, for specific devices the FDA finds need it after notice and a chance to comment, a full description of its components or the formula showing the quantity of each ingredient. Except in extraordinary circumstances, the FDA can't require pre-approval of an ad's content, and once these regulations take effect, such ads aren't additionally subject to certain FTC advertising rules. This paragraph doesn't apply to material the FDA decides is "labeling." (s) Performance-standard devices. A device subject to a performance standard set under section 360d must carry whatever labeling that standard requires. (t) Failure to comply or report. A device is misbranded if there was a failure or refusal to comply with a required notification about the device, to provide required information about it, or to comply with another specified requirement concerning it. (u) Reprocessed device identification. A reprocessed single-use device, or something attached to it, must prominently show the name of the company that reprocessed it, a recognized abbreviation of that name, or a recognized symbol identifying it. If the original device didn't clearly show the original manufacturer's identity, the reprocessor can instead satisfy this rule with a detachable label meant to be placed in the patient's medical record. (v) Reprocessed device statement. All labeling for a reprocessed single-use device must prominently state: "Reprocessed device for single use. Reprocessed by __," naming the reprocessor. (w) New animal drugs. A new animal drug is misbranded if it was conditionally approved and its labeling doesn't match the approved application or the required conditional-approval statement, or if it wasn't conditionally approved and its label lacks the required statement; if it was indexed with the FDA and its labeling doesn't match the index listing, or if it wasn't indexed and its label lacks the required statement; or if it was approved and its labeling doesn't include the application number in the required format — except that this last rule doesn't apply to certain representative labeling for medicated animal feed. (x) Nonprescription drugs — contact information. A nonprescription drug marketed in the United States must have a domestic address or phone number on its label where people can report a serious adverse event. (y) Risk strategy noncompliance. A drug is misbranded if it is subject to an approved risk evaluation and mitigation strategy and the responsible party fails to follow that strategy's requirements. (z) Postmarket study or labeling violations. A drug is misbranded if the responsible party violates a requirement to run required postmarket studies or trials, or to update the drug's labeling with new safety information. (aa) Unpaid facility fees. A drug or active ingredient is misbranded if it was made in a facility that hasn't paid required fees, or hasn't submitted required identifying information — including if the drug simply contains an ingredient made in such a facility. (bb) Compounded drug ads. It is misbranded if the advertising or promotion of a compounded drug is false or misleading in any way. (cc) Missing product identifier. A drug is misbranded if it fails to bear the product identifier required for drug supply-chain tracking. (dd) Antimicrobial labeling. An antimicrobial drug is misbranded if its labeling fails to meet the specific antimicrobial-labeling requirements set by law. (ee) Certain unapproved nonprescription drugs. A nonprescription drug is misbranded if it is subject to a specific nonprescription-drug law, isn't the subject of an approved application, and doesn't comply with that law's requirements. (ff) Unpaid fees, another category. A drug is misbranded if it was made in a facility that hasn't paid a separate set of required fees. (gg) Product information before approval. Directions-for-use labeling is still required under (f). But a drug or device is not misbranded under (f) just because a company gives truthful, non-misleading "product information" about an investigational drug, device, or use to a payor, formulary committee, or similar expert group deciding on coverage or reimbursement — as long as strict conditions are met. The information must include: a clear statement that the investigational drug, device, or use has not been approved and that its safety and effectiveness haven't been established; details about where it stands in development, such as the status of relevant studies, how those studies fit the overall development plan, and whether and when an application has been or will be submitted; for any study results that are shared, a complete description — not a cherry-picked one — of the study's design, methods, results, and material limitations; where applicable, a prominent statement of what the product is actually approved for, plus a copy of the current official labeling; and updates whenever previously shared information becomes materially outdated. The information must not claim that an unapproved product has actually been approved, or has otherwise been found safe or effective for the studied purpose. It also must not claim that an unapproved use of an already-approved product is itself approved, or that the product is safe or effective for that unapproved use. For these purposes, "product information" includes: a description of the drug or device, such as its class or features; the indication being studied; the anticipated timeline to possible approval; pricing information; projected patient usage; related programs or services; and factual presentations of study results that don't draw conclusions about safety or effectiveness.