Premarket Approval and the Quality System Regulation
Premarket approval is the process used by FDA to review and evaluate the safety and effectiveness of Class III medical devices. Class III medical devices are those that are life-supporting or life-sustaining, are for a use that is of substantial importance in preventing impairment of human health, or that present a potential unreasonable risk of illness or injury.1 All Class III devices (with the exception of certain preamendment Class III devices) must obtain premarket approval from FDA before they can be introduced into interstate commerce. Manufacturers are required to submit a PMA application with substantial evidence that demonstrates the device is safe and effective for the intended use.
Assuring that only safe and effective devices are distributed is a two-phase process.
- The inherent safety and effectiveness of a device is established during the design phase. A quality system will include proper consideration of such factors as performance requirements, the needs of the user, operational environments, proper selection of components, etc. Assurance that the design will embody the proper degree of safety and effectiveness is obtained through application of an appropriate design and development process requiring design verification and design validation, which includes clinical evaluation and/or laboratory testing.
- Once the design has been determined to be safe and effective, the adequacy of the manufacturing process will determine whether the design can be consistently reproduced without degrading this inherent quality. The adequacy of the manufacturing process is established through proper process design and proven through appropriate process validation where applicable. Where deviations from device specifications could occur as a result of the manufacturing process, process control procedures must be established to include procedures for the monitoring and control of the process parameters and component and device characteristics during production.
In a PMA application, manufacturers are required to include descriptions of the methods used in, and the facilities and controls used for, the design, manufacture, processing, packing, storage, and, where appropriate, installation of the device. These requirements for FDA-regulated products are known as current good manufacturing practice (CGMP) requirements, which are promulgated in the Quality System (QS) regulation. The final QS regulation (21 CFR 820) was published in the Federal Register in October 1996 and became effective June 1, 1997. This regulation requires each manufacturer to prepare and implement QS procedures to assure that a formally-established and documented quality system is accomplished. The requirements in this part govern the methods used in, and the facilities and controls used for, the design, manufacture, processing, packing, storage, and, where appropriate, installation of all finished devices intended for human use. The requirements in this part are intended to ensure that finished devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (FD&C Act). Under the authority of section 515(d)(2)(C) of the FD&C Act, approval of a PMA application for a device can be denied if a manufacturer does not conform to the QS regulation requirements.
The Medical Device Reporting Regulation
The first Medical Device Reporting (MDR) regulation became final on December 13, 1984. As a result of changes mandated by the Safe Medical Devices Act of 1990 and the Medical Device Amendments of 1992, the 1984 MDR regulations (21 CFR 803 & 807) were revised and published on December 11, 1995. The FDA Modernization Act of 1997 made additional changes and a revised MDR regulation was proposed in May 1998. The final revised MDR regulation was published in the Federal Register on January 26, 2000. The latest version of the MDR regulation includes reporting requirements for manufacturers, user facilities, and importers. MDR reporting for medical device distributors (except importers) was revoked by the FDA Modernization Act of 1997. Distributors are, however, still required to maintain complaint records, per 21 CFR 803.18(d)(1-3). 21 CFR Part 803 requires manufacturers of medical devices, including in vitro diagnostic devices, to report to FDA whenever the manufacturer or importer receives or otherwise becomes aware of information that reasonably suggests that one of its marketed devices:
- may have caused or contributed to a death or serious injury or,
- has malfunctioned and the device, or any other device marketed by the manufacturer or importer, would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.
Note: importers (initial distributors) of medical devices are subject to 21 CFR Part 803. In addition, foreign manufacturers whose devices are distributed in the US are also subject to the MDR regulation requirements, per 21 CFR 803.58.
The Medical Device Tracking Regulation
Under the authority of section 519(e) of the FD&C Act, the agency may issue a written tracking order that tells a manufacturer to implement a tracking program that meets the requirements of 21 CFR Part 821. Devices subject to tracking may include those that are permanently implanted or life sustaining/life supporting devices that are used outside a device user facility. These devices are considered reasonably likely to cause serious adverse health consequences if they fail. The regulation is intended to ensure that, in the event of a recall or safety alert, a tracked device can be traced by the manufacturer from the device manufacturing facility to the end user or patient.
The Corrections and Removal Regulation
The Corrections and Removal regulation, 21 CFR 806, requires manufacturers and importers to report promptly to FDA any corrections or removals of devices being undertaken to reduce risk to health.
The Registration and Listing Regulation
The Registration and Listing regulation, 21 CFR 807, requires manufacturers and foreign exporters to register and list their devices; and importers to register.
Note: A complete list of the types of domestic and foreign establishments that must register and list can be found at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/
1 21 CFR 860.3