1. Device Classification
To start, a manufacturer must determine how a device will be classified. A device’s class is based on three fundamental criteria: the risk it poses to the patient and/or user, its intended use, and its indications for use. These factors determine a device’s and it is brought to market moving forward. There are three classes of medical devices in the U.S.:
- Class I: These devices pose the lowest risk and thus have the least amount of regulation attached to them. They are subject only to general controls. Manual toothbrushes, elastic bandages, and enema kits are all examples of Class I devices. According to the FDA, 47 percent of medical devices are Class I; of those, 95 percent are exempt from the regulatory process.1
- Class II: Devices in this class pose moderate risk and are subject to both general and special controls to prove their safety and efficacy. Examples of Class II devices include non-invasive blood pressure monitors, powered wheelchairs, and most pregnancy test kits. About 43 percent of medical devices fall into this class.1 Some Class II devices are exempt from premarket approval and the regulatory process, depending on limitations on the exemptions.
- Class III: As more complex devices, these products pose the highest risk and are subject to the highest level of scrutiny—general controls, special controls, and the requirement to obtain premarket approval. They have more stringent requirements to illustrate safety and efficacy. Examples of Class III devices include heart valves, implants, and external defibrillators. About 10 percent of medical devices fall into this class.1
In addition to the inherent risks of a device, classification also depends on the device’s intended use and indications for use. As mentioned above, all device classes are subject to general controls established by the Food, Drug, and Cosmetic Act. However, there are additional considerations for specific classifications. Premarket approvals are required for Class III devices, as well as Class I and Class II devices that are not exempt. For these, a premarket notification submission is required for marketing of the product.
2. Premarket Submission
After properly classifying a device, the next step is to select the correct premarket submission. There are four common types of premarket submissions, each with different conditions and obligations.
- 510(k) Premarket Notification: The purpose of the 510(k) is to demonstrate the device is “substantially equivalent” to a predicate device in terms of intended use, technological characteristics, and performance testing, as needed. Most Class II devices require a 510(k), as do some Class 1 products. Others are exempt if they do not exceed the limitations of exemptions in .9 of the device classification regulation chapters. When submitting a 510(k), it is necessary to compare the device to one or more similar legally marketed devices, and to both make and support the substantial equivalence claims. Once the FDA determines the device to be substantially equivalent, the product can be marketed in the U.S.
- Premarket Approval (PMA): A PMA is the most stringent premarket submission, requiring the sponsor to provide valid scientific evidence demonstrating reasonable assurance of safety and effectiveness for the device’s intended use. Most Class III medical devices require a PMA, given their higher level of risk and intended use. Approval is based on illustrating that the device is safe and effective for its intended use(s) via sufficient valid scientific evidence. An approved PMA is, essentially, a private license granting the applicant/owner permission to market the device. The owner can then authorize use of its data by another.
- De Novo Evaluation of Automatic Class III Designation: The De Novo process provides a means to classify novel medical devices as Class I or Class II when there is no legally marketed predicate device. The FDA developed this designation to provide an alternative for Class I and Class II devices that were automatically classified as Class III after receiving an “not substantially equivalent” (NSE) determination response to a 510(k) submission.
- Humanitarian Device Exemption (HDE): An HDE applies specifically to devices intended to benefit patients in treatment of rare diseases or conditions (affects fewer than 200,000 people in the U.S.). For a device to qualify for an HDE, a sponsor must obtain a designation for the product as a Humanitarian Use Device (HUD), which is approved through application to FDA’s Office of Orphan Products Development (OOPD). An HDE submission is similar to a PMA in form and content, but is exempt from the PMA’s effectiveness requirements. The sponsor is also required to demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.
When preparing a premarket submission, it’s important to know the appropriate information to include given the device’s classification. Manufacturers should also objectively consider the level of risk associated with their devices. Submissions for high-risk devices require more information, including clinical and usability data. In contrast, submissions for low-risk devices may be cleared with nonclinical performance and bench tests.
Most PMAs and some HDEs, 510(k)s, and De Novos require clinical evidence. If a clinical study is to take place, the study sponsor may need to obtain approval from the FDA for an Investigational Device Exemption (IDE). In addition, any studies must be approved by the appropriate Institutional Review Board (IRB). Along with these approvals, any clinical studies must comply with all applicable IDE regulations and good clinical practices (GCPs).
All Class II and Class III devices must be designed in accordance with design controls under the Quality System Regulation (21 CFR 820.30). While the FDA establishes these requirements for Class II and Class III products, some Class I devices are exempt entirely from design controls. Additionally, the labeling for the device must be written according to labeling regulations and included with the submission.
After compiling the appropriate information, the next step is to send the premarket submission to the FDA for review. Submissions must include an electronic copy in the form of a CD, DVD, or flash drive and, in the case of a 510(k) or PMA, an associated user fee. The FDA then conducts an administrative review to determine if the submission is sufficiently complete. During this review, FDA staff communicates with applicants to increase the efficiency of the process.
The review time varies depending on the type of submission. An initial traditional or modular PMA typically has a review time of 140 days for manufacturing section review and site inspection. Traditional 510(k) submissions require 90 days for review. Major or minor changes, deficiencies or issues, and requests for additional information can all lead to delays and additional review time.
3. Establishment Registration and Device Listing
The last step is to register the establishment and list the device with the FDA. If a device requires premarket clearance or approval prior to marketing (i.e., the device is not exempt), the facility must wait until it receives FDA clearance or approval before registering and listing. Registration of a device establishment, assignment of a registration number, or listing of a medical device does not in any way denote clearance or approval of the establishment or its products by the FDA.
When conducting inspections, the FDA reserves priority for manufacturers with pending PMA approval, Class III manufacturers that have never been inspected, compliance follow up/for cause inspections, and manufacturers of high-risk devices. Class III high-risk device manufacturers should expect an FDA inspection every two years. No additional fees are required for FDA inspections.
Bringing medical devices to market in the U.S. can be a lengthy, complicated process, but one that can be done. Keeping in mind the various steps and options for a device can help in preparations. Take some time to learn the different classes, premarket submission options, and requirements and make sure to plan accordingly. Taking these into considerations can make a big difference in the successful launch of a device.
1 U.S. Food and Drug Administration. Learn if a Medical Device Has Been Cleared by FDA for Marketing. https://www.fda.gov/MedicalDevices/ResourcesforYou/Consumers/ucm142523.htm Accessed January 30, 2018.