Bringing medical devices to market in the United States can be a complex process, requiring an understanding of FDA requirements and processes. There are a number of factors to consider, including a device’s classification, premarket preparation and submission to the FDA. Being familiar with the process, as well as ever-changing guidance from the FDA, can help manufacturers get devices to market more easily and effectively.

The Process

The process of bringing a product to market in the United States can be summed up with five steps, all of which require following FDA guidance and regulation.

Classifying your device. The first step in the process is to determine the type of device you’re bringing to market. There are three different class types, based on three considerations: Risk to the patient/user, intended use and indications for use. Indications can give further specificity to a device. For example, a scalpel has an intended use to make an incision, but a scalpel indicated for ocular uses has a higher risk level and may be classified differently.

Class I devices pose the lowest risk and, as such, are subject to general controls. Class II devices illustrate moderate risk and require special controls in addition to general ones. High-risk, or Class III, devices require general controls as well as premarket approval (PMA) (Class I and some Class II devices are exempt from PMA). Given the different levels of control, and the potential for premarket approval, the classification of a device plays a key role and will also determine how to continue on the path to bringing a device to market, as it will inform the next steps in the process.

Identifying the correct premarket submission. The appropriate premarket submission will depend on the device’s classification. The most common types of submission include the 510(k) premarket notification, PMA application, De Novo Evaluation of Automatic Class III Designation and the humanitarian device exemption (HDE). In order to determine which submission will apply to a given device, consider the product’s class, indication, and existing devices and technology.

A 510(k) notification is used for a new device that is “substantially equivalent” to a predicate device as far as its intended use, technological characteristics and performance testing. This type of submission usually applies to some Class I and most Class II devices, unless they are considered exempt under the limitations of exemption stated in 21 CFR xxx 9, where xxx refers to 21 CFR 862-892.

For a new device without a valid predicate to be classified as a Class I or Class II device, the FDA developed the De Novo Evaluation designation. Previously, these devices were classified as Class III given the lack of a predicate device after their 510(k) review. However, under this designation, a device can still be classified as Class I or II, which could result in a more efficient review process, as the device will not be subject to the PMA process.

The PMA is the most stringent premarket submission, requiring information on how the device was designed, how it is manufactured and valid scientific evidence demonstrating reasonable assurance of safety and effectiveness for the device’s intended use through preclinical and clinical studies. Because of this requirement for clinical trials, a PMA is significantly more expensive than a 510(k) or De Novo Evaluation.

Most Class III devices require a premarket approval. Because of the stringent standards at play with a PMA, it is important to note that for these devices, the FDA must receive an application and provide approval before the device can be marketed.

The HDE applies specifically to devices that are intended to benefit patients in the treatment of rare diseases or conditions, meaning one that is affected or manifested in fewer than 4,000 individuals in the United States each year. To qualify for an HDE, the product must obtain a Humanitarian Use Device (HUD) designation from the FDA’s Office of Orphan Products Development (OOPD). The HDE submission is similar in form and content to a PMA, but is exempt from the effectiveness requirements. Also, it must be proven that there are not comparable devices available to treat or diagnose the disease or condition and the device could not otherwise be brought to market.

Preparing the premarket submission. To adequately prepare your premarket submission, it’s important to know what information must be included. Design controls, nonclinical testing, clinical evidence and labeling are all important items to consider, based on your device’s classification.

Keep in mind that higher risk devices require much more detailed information, including clinical and usability data, than lower risk devices, which may be cleared with non-clinical performance data and bench test information. Based on your device classification and premarket submission, it is important to plan accordingly.

Submitting to the FDA. After the information is compiled, it must be sent to the FDA for review, which can take anywhere from 90 days for a traditional 510(k) to more than 180 days for a PMA. When doing the initial submission, you will need to include an electronic copy of your application and, in the case of a 510(k) or PMA, the associated fee.

After submission, the FDA will conduct an administrative review to determine if the submission is sufficiently complete. FDA staff will communicate with applicants throughout the review process to make the process more efficient. Requests for additional information are possible, with a response time of 30–180 days accompanying said requests. Failure to respond within 180 days will result in a submission being considered withdrawn and the need to start the process over.

When conducting site inspections, priority will be given to manufacturers with pending PMAs, Class III manufacturers that have never been inspected, compliance follow up, for-cause inspections and manufacturers of high-risk devices.

Establishing registration and device listing. The final step is to register the device’s establishment and list with the FDA, after premarket approval is granted (when needed). Keep in mind that registration of a device establishment, assignment of a registration number or listing of a medical device does not denote clearance or approval by the FDA.

Current Guidance from the FDA

It is always important to stay informed of new guidance documents issued by the FDA, as they relate to medical devices. In 2016 the FDA has issued a number of new final guidance documents. Relevant to market entry are the following documents:

• Guidance for Industry and Food and Drug Administration Staff – Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications
• General Wellness: Policy for Low Risk Devices – Guidance for Industry and Food and Drug Administration Staff
• Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” – Guidance for Industry and Food and Drug Administration Staff
• Applying Human Factors and Usability Engineering to Medical Devices – Guidance for Industry and Food and Drug Administration Staff

In addition, the FDA has also issued draft guidance documents and seeks feedback from industry on their content. The recent draft guidance documents of interest to manufacturers of Internet-based devices include:

• Deciding When to Submit a 510(k) for a Software Change to an Existing Device – Draft Guidance for Industry and Food and Drug Administration Staff
• Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices – Draft Guidance for Industry and Food and Drug Administration Staff
• Postmarket Management of Cybersecurity in Medical Devices – Draft Guidance for Industry and Food and Drug Administration Staff

These are but a small subset of the guidance documents issued by the FDA. Manufacturers are recommended to review the list of current and past guidance documents on the FDA website to find any that may be relevant to the device that they intend to market. Use of and compliance with FDA guidance may provide a shorter review cycle and a higher probability of success the first time through.

Final Tips

The medical device market in the United States can offer manufacturers great opportunity, provided they can successfully navigate the many requirements and multiple-step process. Getting a device through the FDA procedure and on the U.S. market can take time. Familiarizing yourself with the process and various requirements is a good idea. You may also want to enlist the help of experts in the area who know the ins and outs of the procedure. Do the due diligence to collect information for the device application and stay in communication with the FDA throughout the process. These steps can help with the submission process and bring the product to market more efficiently.