Investigational applications and trial oversight, new drug and abbreviated routes, device classification and the clearance and approval paths, labeling and off-label communication, manufacturing quality obligations, adverse event reporting, recalls, and supply chain tracing.
Premarket notification under 21 U.S.C. 360(k) asks whether a device is substantially equivalent to a legally marketed predicate, meaning the same intended use and either the same technological characteristics or different ones raising no different questions of safety and effectiveness. Premarket approval under 21 U.S.C. 360e asks whether valid scientific evidence provides reasonable assurance of safety and effectiveness.
Under 21 CFR Part 56 a clinical investigation may not begin until an institutional review board has approved it, applying the criteria in 56.111 covering minimized risk, favorable risk-benefit balance, equitable subject selection, informed consent, data monitoring, privacy and safeguards for vulnerable subjects. Part 50 governs consent: 50.20 sets general conditions, 50.25 lists the required elements, and 50.27 requires a signed document.
Labeling under 21 U.S.C. 321(m) includes all written, printed or graphic matter on an article, its containers or wrappers, or accompanying it. A product is misbranded under 21 U.S.C. 352 where its labeling is false or misleading in any particular. Prescription labeling follows 21 CFR 201.56 and 201.57, over-the-counter labeling follows 201.66, and changes are made through the supplement categories in 21 CFR 314.70.
The drug supply chain provisions at 21 U.S.C. 360eee and following require that transaction information and a transaction statement accompany each change of ownership, that trading partners be authorized, and that product bear an identifier permitting package-level verification. A firm with reason to believe product is counterfeit, diverted, stolen or otherwise unfit must quarantine and investigate it.
A licensed practitioner may prescribe an approved product outside its labeling. A manufacturer that promotes an unapproved use faces misbranding and unapproved product theories, because under 21 CFR 201.128 intended use may be shown by labeling, advertising and representatives' statements. Narrow pathways permit responses to unsolicited requests, qualifying reprints, communications consistent with labeling, and economic information to payors.
Under 21 U.S.C. 355(j) an abbreviated application relies on the agency's prior finding for a listed drug, showing the same active ingredient, route, dosage form, strength and conditions of use, essentially the same labeling, and bioequivalence under 21 CFR Part 320. The applicant must certify to each listed patent under one of four paragraphs, and the fourth can trigger suit and a stay of approval.
Under 21 CFR Part 7 a recall is a firm's removal or correction of a marketed product that the agency considers in violation of the law. Recalls are classified by health hazard: class I for a reasonable probability of serious consequences or death, class II for temporary or reversible consequences, class III where harm is unlikely. A recall strategy sets depth, public warning and effectiveness checks.
Section 355 of Title 21 bars introducing a new drug into interstate commerce without an effective approval. The application must contain full reports of investigations showing safety and effectiveness, the composition and manufacturing methods, samples and proposed labeling. Approval requires substantial evidence from adequate and well-controlled investigations. Under 21 CFR Part 314 a review cycle ends in an approval letter or a complete response letter.
Section 360c of Title 21 divides devices into three classes by the controls needed to provide reasonable assurance of safety and effectiveness. Class I devices are adequately controlled by general controls. Class II devices require special controls such as performance standards or postmarket surveillance. Class III devices are those for which controls are insufficient and which are high risk or life-sustaining, and they require premarket approval.
A drug is adulterated under 21 U.S.C. 351 where the methods, facilities or controls used in its manufacture, processing, packing or holding do not conform to current good manufacturing practice. Devices are subject to the quality system requirements of 21 CFR Part 820, covering management responsibility, design controls, corrective action, complaint handling and records. Section 374 authorizes inspection of establishments.
Under 21 U.S.C. 355(i) and 21 CFR Part 312, a sponsor intending to administer an investigational drug to human subjects submits an application containing manufacturing, pharmacology, toxicology and prior human experience information plus protocols. Section 312.40 permits the study to begin thirty days after receipt unless a clinical hold is imposed. Section 312.42 states the grounds for a hold and how one is lifted.
Postmarket drug reporting under 21 CFR 314.80 requires expedited reports of adverse experiences that are both serious and unexpected. Device reporting under 21 U.S.C. 360i and 21 CFR Part 803 requires manufacturers to report information reasonably suggesting a device may have caused or contributed to a death or serious injury, or has malfunctioned in a way likely to cause such an outcome if it recurred.
