Medical device manufacturers (sponsors) should understand how their product is viewed by regulatory bodies to proceed with the appropriate regulatory pathway to market. This means knowing the regulatory definition of a medical device, the division(s) in the US Food and Drug Administration (FDA) that will have oversight over the medical device, and the applicable product-specific regulations.
To better understand the product-specific regulations, sponsors should be aware of the classifications (Class I, II or III) under which their device will be categorised. Therefore, sponsors should be informed about the FDA oversight of medical devices, the definition of a medical device, and the FDA Medical Device Classification system.
History and Background
The FDA comprises three major divisions for the review and regulation of medical products. The three FDA divisions include:
- Center for Drug Evaluation and Research (CDER),
- Center for Biologic Evaluation and Research (CBER), and the
- Center for Devices and Radiological Health (CDRH). The CDRH is the FDA division that oversees medical device regulations.
The definition of a medical device was first described in the 1976 Medical Device Amendments of the Food, Drug, and Cosmetic Act, wherein it was established that a medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent or other similar or related article, including any component, part, or accessory, which is:
- Recognised in the official National Formulary, or the US Pharmacopeia (USP), 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
- 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 metabolised for the achievement of any of its principal intended purposes
A medical product does not always comprise only one single entity, such as just a drug, a biologic, or a device. In the event that a medical product is designed with a combination of more than one of these components, the product is designated as a combination product.
Before 2021, the Office of Combination Products (OCP) had the power to determine regulatory pathways for products deemed to be medical devices. It changed after the FDA sought complete control of the regulation process after the implementation of the Medical Device User Fee Act of 2002. This decision had major implications on testing, design, and manufacturing requirements of certain combination products.
Due to the potential complexities of a combination product, and considering the recent court decision mentioned above, the FDA published a guidance for industry and for FDA staff in January 2022 to clarify the current regulatory pathways for premarket applications, stating combination products can be of several different types, including:
- Device-led combination products
- Drug-led combination products
- Biologic-led combination products
Basic Device Classifications and Associated Regulatory Requirements
Class I Medical Devices
Class I medical devices are simply designed medical devices which present a low risk on application. Approximately 50% of all medical devices are Class I. They are subject to general controls and exempt from the 510(k) clearance in the Code of Federal Regulations (CFR) Part 807, Subpart E which requires the sponsor to provide information that higher Class devices must provide. A 510(k) is a premarket submission made to the FDA that demonstrates the device is as safe and effective (ie, substantially equivalent) as a legally-marketed device (section 513 (i) (1) (A) FD&C Act) and not subject to premarket approval (PMA).
Class II Medical Devices
A Class II medical device is considered to have moderate risk, making it more complicated than Class I. These devices comprise approximately 40% of all marketed medical devices. They must obtain market clearance via the 510(k) premarket notification process, unlike Class 1 devices. To obtain clearance, sponsors must demonstrate substantial equivalence of the medical device to another device, known as the ‘predicate device’. A predicate device is one that has already obtained FDA 510(k) clearance, or one that was on the market prior to the passage of the Medical Device Amendments Act (28 May 1976). To obtain 510(k) clearance from the FDA, sponsors are required to apply one of the four pathways:
- Traditional 510 (k), requiring sponsors to demonstrate equivalence to a device cleared through 510 (k) process
- Abbreviated 510 (k) when sponsors claim conformance to one or more recognised standards of device manufacturing
- Special 510 (k), where they already have a clearance and are only modifying the device
- De Novo 510 (k), when there is no ‘predicate device’ in market and sponsors must prove that the device demonstrates lower risk than Class III devices and does not require PMA
Class II medical devices are subject to general controls like Class I. They are also subject to special controls, which are regulatory requirements for Classes II and III medical devices. Special controls include several regulatory requirements such as following guidance documents from the FDA, ISO standards applicable to different types of devices, and clinical trials to demonstrate efficacy of the devices.
Class III Medical Devices
Class III medical devices are considered the most complex and high risk. As such, they must follow general and special controls regulations, similar to Class II medical devices. In addition, Class III medical devices follow the PMA regulatory pathway. This pathway is more complex than the 510(k) process and the FDA review times may be greater than 12 months for full market approval and require clinical trial sites to be inspected by the FDA’s Bioresearch Monitoring team (BIMO). Class III medical devices must follow stringent post-marketing requirements such as annual FDA reporting and prior approval by the FDA before implementing any changes to the device labeling, manufacturing, materials, quality methods, and specifications.
A good starting point for sponsors to determine device classification is to review the market for similar devices to the one being developed. The device should have a similar indication for use and technological characteristics. If sponsors find a device that is consistent with the product described in the CFR, it is very likely that the device will fall into the same classification category. Sponsors can refer to the FDA website for more information on device classification.
Other searchable databases on devices include 510 (k), De Novo and PMA databases. If sponsors do not feel comfortable with determining the initial classification of the device, they can request an informal discussion with the FDA branch chief within the Office of Device Evaluation (ODE) via telephone or email. Informal discussions do not generate binding commitments on either party. A definitive classification decision can also be obtained by submitting a formal Request for Classification (513g), which contains information such as the description of the device, similar devices on the market, proposed indication for use, etc. Sponsors can also submit a Request for Designation (RFD) to the OCP for a formal medical device designation.
- U.S. Food and Drug Administration. A History of Device Regulation and Oversight in the U.S.
- U.S. Food and Drug Administration. Medical Device Overview.
- U.S. Food and Drug Administration. Background on MDUFA.
- Walsh, Ann K. and Koblitz, Sara W., May 5, 2021. Genus Medical Technologies, LLC v. U.S. Food and Drug Administration, Food and Drug Law Institute.
- DuBiner, Royce, Gruner, Katherine, Hardey, Kate, Rieckhoff, Rebecca, February 3, 2022. FDA Guidance clarifies classification of combination Drug-device Products.
- Amor, David, Medical Device Online, January 22, 2016. How to Determine A Combination Product’s Primary Mode of Action (PMOA).
- U.S. Food and Drug Administration. CFR Title 21 Part 807.
- U.S. Food and Drug Administration. Premarket Notification – 510(K).
- ISO Popular Standards. ISO 13485 – Medical devices.
- U.S. Food and Drug Administration. Premarket Approvals.
- U.S. Food and Drug Administration. BioResearch Monitoring Program (BIMO).
- U.S. Food and Drug Administration. PMA Application Methods.
- U.S. Food and Drug Administration. Device Classification Panels.
- U.S. Food and Drug Administration. Device Advice: Comprehensive Regulatory Assistance.
- Packard, Rob Nov. 25, 2019. Medical device Academy. 513g Request for Information.
- Principles of Premarket pathways for combination products. Guidance for Industry and FDA Staff. January, 2022.