21 U.S.C. § 351 — Adulterated drugs and devices

A drug^* or device counts as "adulterated" under any of the following rules.

(a) Poisonous or unsanitary ingredients, inadequate manufacturing controls. It's adulterated if it contains, even partly, any filthy, putrid, or decomposed substance; or if it was prepared, packed, or stored under unsanitary conditions that could have let filth contaminate it or made it harmful; or if it's a drug whose manufacturing, processing, packing, or storage methods, facilities, or controls don't follow "current good manufacturing practice" — the standards needed to guarantee the drug is safe and truly has the identity, strength, quality, and purity it claims; or if it's a compounded positron emission tomography drug^* whose compounding methods, facilities, or controls don't follow the positron emission tomography compounding standards and the official monographs of the United States Pharmacopoeia, which exist to guarantee that same safety, identity, strength, quality, and purity. It's also adulterated if its container is partly made of a poisonous or harmful substance that could make the contents dangerous; if it contains a color additive^*, used only for coloring, that's unsafe under the color^*-additive safety rules, or if it is itself such an unsafe color additive meant for coloring drugs or devices; if it's a new animal drug^* that's unsafe under the new-animal-drug rules; or if it's animal feed containing a new animal drug that's unsafe under those same rules.

(b) Differing from an official compendium's standard. A drug supposed to be one recognized in an official compendium^*, like the United States Pharmacopoeia, is adulterated if its strength, quality, or purity doesn't match that compendium's standard, tested using the compendium's own methods. If the compendium doesn't specify a test, or its test is inadequate in the FDA's judgment, the FDA must first ask the compendium's governing body to fix it; if that body doesn't act in reasonable time, the FDA can write its own testing regulation. A drug isn't adulterated under this rule just because it differs from the compendium standard, as long as the difference is clearly stated on its label^*. A drug listed in both the United States Pharmacopoeia and the Homoeopathic Pharmacopoeia must meet the former's standards, unless it's labeled and sold as a homeopathic drug, in which case the Homoeopathic Pharmacopoeia's standards apply instead.

(c) Misrepresenting strength when not covered by a compendium. If a drug isn't covered by (b), it's adulterated if its actual strength, purity, or quality falls short of what it claims to be.

(d) Mixed with or substituted by another substance. It's adulterated if another substance has been mixed or packed into it in a way that lowers its quality or strength, or if part or all of it has been substituted with something else.

(e) Devices failing performance standards. A device is adulterated if it is, or claims to be, subject to a performance standard but doesn't fully meet it, or if it's declared or represented as meeting a recognized standard but doesn't fully meet it.

(f) Certain Class III devices without required approval. A Class III device is adulterated if an FDA order requires it to have premarket approval, it isn't exempt, and either no premarket-approval application, or product-development-protocol notice, was filed within 90 days of that order, or one was filed but denied, suspended, or withdrawn, or the protocol was declared incomplete or its approval withdrawn; or if it was classified into Class III, needs an approved premarket application, isn't exempt, and its application has been suspended or is otherwise not in effect; or if it was classified into Class III under a related provision requiring an approved application, and that application has been suspended or is otherwise not in effect. For an investigational Class III device, this rule doesn't apply until 90 days after FDA issues the regulations required for investigational-use exemptions. For a device subject to a premarket-approval order, this rule doesn't apply until the later of 30 months after the device's Class III classification took effect, or 90 days after the order issued. For a device covered by a premarket-approval regulation issued before July 9, 2012, references here to a premarket-approval order include that regulation.

(g) Banned devices. A device the FDA has banned is adulterated.

(h) Manufacturing, packing, storage, or installation not meeting requirements. A device is adulterated if its manufacturing, packing, storage, or installation methods, facilities, or controls don't meet the applicable requirements, or a condition set by an FDA order.

(i) Failing investigational-use exemption requirements. A device with an investigational-use exemption is adulterated if either the person^* who got the exemption or an investigator using the device fails to follow a requirement set under that exemption.

(j) Blocking an FDA inspection. A drug or device is adulterated if it was made, processed, packed, or stored in a facility whose owner, operator, or agent delays, denies, or limits an FDA inspection, or refuses to allow entry or inspection.

Finally, for purposes of the current-good-manufacturing-practice rule in (a), that term includes overseeing and controlling drug manufacturing to ensure quality — including managing the risks of, and confirming the safety of, raw materials, manufacturing materials, and finished drug products.