Class III is the most stringent regulatory category for devices. Class III devices are those for which insufficient information exists to assure safety and effectiveness solely through general or special controls. They are devices that are defined as those used for “supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health” or those devices that “present a potentially unreasonable risk of illness or injury.”31 Given that such devices entail the most significant risks, in addition to meeting the aforementioned requirements, they must also be shown to be safe and effective before being marketed. Class III devices are therefore subject to a PMA process by which the FDA reviews clinical evidence as to the safety and effectiveness of the device before granting approval for the device to be marketed or manufactured.32 Examples of Class III devices which require a premarket approval include replacement heart valves,33 silicone gel-filled breast implants,34 artificial knee joints,35 and extended-wear contact lenses.36
Premarket approval is the required process of scientific review to ensure the safety and effectiveness of most Class III devices. However, not all Class III devices require an approved premarket approval application to be marketed. Some Class III devices can be marketed with a premarket notification 510(k), provided they meet the postamendment provision of being introduced to the US market after May 28, 1976, and are determined to be substantially equivalent to a preamendment (i. e., introduced to the US market before May 28, 1976) Class III device, and for which the regulation calling for the premarket approval application has not been published in the Code of Federal Regulations (21 CFR).
Class III devices which require an approved premarket approval application to be marketed are those:
1. Regulated as new drugs prior to May 28, 1976, also called transitional
devices.37
2. Devices found not substantially equivalent to devices marketed prior to May 28, 1976.
3. Class III preamendment devices which, by regulation in 21 CFR §814, require a premarket approval application.