What Are 510(k) Clearance and Premarket Approval?

There are two major processes by which medical devices requiring U.S. Food and Drug Administration (FDA) review come to the American market. One process is called “Premarket Notification,” sometimes referenced by its origins in the Federal Food, Drug and Cosmetic Act as the “510(k) process.” The other major process is called Premarket Approval and is known by its submission acronym “PMA.” This article describes and explains both processes.

Premarket Notification: The 510(k) Process

Contrary to popular belief, “510(k)” is not a form. It is actually a section of the Federal Food, Drug and Cosmetic Act (FD&CA, the Act) from which this process was circuitously derived. The process is somewhat analogous to the “generic” drug concept in that Premarket Notification is used to obtain marketing clearance for a device that is “substantially equivalent” in safety and effectiveness to another lawfully marketed device or to a standard recognized by the FDA when used for the same intended purpose(s). Note that the concept allows for technological advancement; the new device does not HAVE to be manufactured from the same materials or perform its intended purpose using the same technology. In order to be eligible for 510(k) clearance, the new device must exhibit roughly the same safety and effectiveness characteristics as the “predicate” device to which the new one is being compared. An example of technological advancement under this process was marketing clearance of lasers for “cutting or ablation” of tissues when compared with a heated wire cautery device.

Premarket Notification requires that a new model of a device be compared for safety and effectiveness with another lawfully marketed model. A successful 510(k) submission results in FDA permission to market the new device. The nature of this comparison depends on the device and the degree of risk associated with its use. The comparison may comprise physical or performance characteristics as measured by standardized methods. For example, Premarket Notification submissions for medical gloves are usually based on physical characteristic testing performed under standard methods developed by the ASTM International (formerly called The American Society for Testing and Materials) and biocompatibility testing performed in accordance with the standard ISO 10993 (ISO stands for International Organization for Standardization). These tests measure the ability of a glove to resist leakage, stretching and the degree to which the materials used are compatible with human tissues.

Some Premarket Notification submissions are based upon bench testing of the new device and a comparison of the findings with the known performance characteristics of the predicate device. An example would be for Transdermal Electrical Nerve Stimulators (TENS units).

Several devices requiring Premarket Notification are subject to conformance with “Special Controls.” Special Controls can be almost anything deemed necessary by FDA’s Center for Devices and Radiologic Health (CDRH) which is responsible for the regulation of medical devices. Special Controls can be specialized labeling, conformance to specific standards or the design of connections in order to prevent accidental electrocution or accidental administration of incorrect gases or medications. Special controls are carefully detailed by CDRH and made available to all interested parties.

In some instances, a Premarket Notification submission for a new device is based on a comparison under actual conditions of clinical usage demonstrating that the device has the same safety and effectiveness characteristics as the predicate.

Because of the nature of the laws underlying this process, a successful submission is deemed to be “cleared.” Clearance of a Premarket Notification submission by CDRH confers permission to market the new device. By legal definition, it is NOT an “approval” process.

Premarket Approval

The PMA process is based on a per se demonstration of safety and effectiveness through “adequate and well-controlled” clinical trials. A successful PMA submission results in approval of the new device.

Premarket approval (PMA) is the FDA’s process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. (Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury, or are new and present unknown safety or effectiveness issues or risks.) PMA is the most stringent type of device marketing application required by the FDA. To gain approval, the manufacturer must present adequate scientific evidence to assure that the device is safe and effective for its intended use(s).

Exempted Devices

Some medical devices are sufficiently well-known—and their safety and effectiveness are sufficiently well characterized and established—that they require no premarket review by the Agency. They are still subject to a general regulations that require proper labeling, manufacture, and investigation of adverse events.  As of the end of calendar 2008, FDA’s Center for Devices and Radiological Health had exempted about 800 devices. The vast majority are designated as Class I devices, and a small number are Class II.

Misrepresentations

Unfortunately, some manufacturers have obtained FDA clearance without revealing the actual use of the device. For example:

• “Electrodermal skin testing” devices used to diagnose and/or treat the gamut of disease have been cleared because their manufacturers told the FDA they were biofeedback devices that (merely) measure the electrical resistance of the skin. The applications did not disclose that the devices are sold with software that contains diagnostic or therapeutic advice [3].
• “Spinal decompression” devices have been cleared for traction (stretching) which might relieve back pain but is not very effective for that purpose. However, many practitioners advertise that the devices can reduce herniated disks. This is unproven (and unlikely) and is not a legally permissible claim [4].
• “Heat lamps” (infrared lamps) that were cleared for the temporary relief of muscle aches have subsequently been marketed with fanciful claims covering the gamut of medical conditions including treatment of diabetes and cure of cancer.

Devices marketed for such purposes require premarket approval, which the manufacturers know they could not obtain. FDA regulatory officials are aware of the illegal marketing and have issued a few warning letters [5]. However, the agency has not made a systematic effort to drive them from the marketplace.

Addendum

The number of 510(k) clearances per year is far greater than the number of PMAs. From 2008 through 2017, an average of 2,825 devices per year received 510(k) clearance and  and 31 devices per year were approved through the PMA process [6].

In 2021, the FDA ordered 25 companies to stop issuing certificates which state that a company has registered with the FDA [7]. The agency is concerned because the certificates falsely imply that the device has been evaluated, cleared, or approvedas effective for its intended purposes. Device manufacturers are required to register with the FDA, but the agency does not issue any type of device registration certificate, and registration with FDA does not denote approval or clearance of the establishment or its devices [16]. Although the FDA action concerned registration certificates, the same principles would probably apply to “clearance certificates.”

For Additional Information

• FDA Index Page to 510(k) Information
• FDA Overview of Premarket Approval
• Search the 510(k) Database
• Search the PMA Database
• CDRH’s Device Advice
• CDRH Standards Program

References

1. 510(k) overview. FDA Web site, accessed Dec 26, 2008.
2. Overview of premarket approval (PMA). FDA Web site, Dec 26, 2008
3. Barrett S. Quack electrodiagnostic devices. Quackwatch, Sept 14, 2008.
4. Barrett S. Be wary of spinal decompression Therapy with VAX-D or similar devices. Chirobase, Dec 24, 2008.
5. Barrett S. Regulatory actions related to EAV devices. Quackwatch, Oct 1, 2008.
6. Dublin JR and others. Risk of recall among medical devices undergoing US Food and Drug Administration 510(k) clearance and premarket approval, 2008-2017. JAMA Network Open, May 6, 2021.
7. Barrett S. FDA orders 25 companies to stop issuing misleading “FDA registration certificates.” Device Watch, July 4, 2021.

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Mr. Yellin retired after 33 years with the FDA. During his career, he worked in both the Center for Drug Evaluation and Research where he regulated labeling and advertising of prescription drugs, and in the Center for Devices and Radiological Health where he regulated labeling and advertising of medical devices, served as the CDRH Health Fraud Coordinator, and later assisted the regulated industry, device user professionals, and the lay public. This article was written by Mr. Yellin in 2009. The addendum was added by Dr. Stephen Barrett in 2023.