FDA Classification of Medical Devices
In accordance with the Federal Food, Drug, and Cosmetic Act, FDA places all medical devices into one of three regulatory classes based on the level of control necessary to ensure safety and effectiveness of the device. Classification is risk based, that is, the risk the device poses to the patient and/or the user is a major factor in determining the class to which it is assigned.
Devices in all three classes are subject to general controls which require, in part, that companies: (1) register their establishments and list the medical devices they market with FDA; (2) manufacture their devices in accordance with Good Manufacturing Practices; and (3) label their devices in accordance with labeling regulations.
Class I devices are subject only to general controls. They typically present the lowest potential for harm and are simpler in design than Class II or Class III devices. Examples of Class I devices include elastic bandages, examination gloves, and hand-held surgical instruments.
Class II devices are those for which general controls alone are insufficient to provide a reasonable assurance of safety and effectiveness. In addition to complying with general controls, Class II devices are also subject to special controls identified by the agency, which may include special labeling requirements, performance standards and postmarket surveillance. Examples of Class II devices include powered wheelchairs, infusion pumps, and surgical drapes.
Class III devices generally are those for which insufficient information exists to determine that general or special controls are sufficient to provide a reasonable assurance of safety and effectiveness. Examples of Class III devices include replacement heart valves, silicone gel-filled breast implants, and implanted cerebellar stimulators. The premarket approval process (PMA)is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of class III medical devices.
Medical Device is defined in 21 U.S.C. 321 (h) as "... an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is -
- recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
- intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
- intended to affect the structure or any function of the body of man or other animals,
and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes."
The following selected definitions applicable to devices come from 21 CFR 812.3.
(g) Investigational device means a device, including a transitional device, that is the object of an investigation.
(h) Investigation means a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.
(i) Investigator means an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
(p) Subject means a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a med- ical condition or disease.
By applying the definitions above, it becomes clear that simply using a device as part of a study does not make the device investigational. For example, if an non-invasive, unapproved device is used to make measurements as part of a study, but the study is not about the device, then the device is not an investigational device for the purposes of that study. For example, if an investigator wishes to use an unapproved device to measure cerebral blood flow but the study is not about the device (not assessing the safety or effectiveness of the device), then for that study, the unapproved device would not be investigational. Whereas the device would be an investigational device when used in a study designed to assess the feasibility and safety of making cerebral blood flow measurements during cardiac surgery.
FDA Regulatory Approval Pathways
The regulatory pathway for approval by the FDA depends on whether or not there is an existing device that is substantially equivalent – a predicate device – and the number of potential patients who might use the device. Whether or not clinical trials are required to support the approval of a new device will depend on these factors.
Premarket Approval is the regulatory pathway for devices for devices that do not have a predicate device or where the new device is not substantially equivalent. These devices require reasonable evidence of safety and effectiveness to obtain FDA approval. Once a device has received FDA PMA, supplements are often submitted to modify the device. Supplements are reviewed via 5 different pathways, the majority of which do not to require any clinical trials. Manufacturers tend to release multiple minor changes rather than releasing a single substantive change allowing them to avoid the need to conduct additional clinical trials. For a more in depth discussion see Rome et al. FDA Approval of Cardiac Implantable Electronic Devices via Original and Supplement Premarket Approval Pathways, 1979-2012.
Premarket Notification - 510(k) is the regulatory pathway for devices that are substantially equivalent to a predicate device. Clinical trials and data in humans are not required for devices approved via this pathway. Requiring clinical trials for every minor change to medical devices would be expensive. Minor changes to devices as complex as heart valves, joint replacements, surgical instruments, implanted pacemakers, or insulin pumps might not require any clinical trials if there is a predicate device that can be referenced. Sometimes the ancestry of a predicate device can be quite labyrinthine and involve dozens of devices. The 510(k) Ancestry of a Metal-on-Metal Hip Implant outlines the long a twisted history of the various predicate devices that allowed metal-to-metal hip implants approval under the 510(k) pathway. For a history of the successes and failures of the 510(k) approval process see the Institute of Medicine Report Medical Devices and the Public Health. The FDA 510(k) Clearance Process at 35 Years.
Humanitarian Device Exemption is the regulatory pathway for devices for devices that are intended for certain rare conditions where it would not be possible to develop sufficient evidence of safety and effectiveness to support a PMA. More information on HDEs is available on the Humanitarian Use Devices page.