Bringing a Medical Device to the US Market: Perspectives and Considerations

By Sarah Fitzgerald, Senior Consultant, Quality and Regulatory Affairs, Emergo by UL

The U.S. medical device market is estimated to account for approximately $199 billion (USD) in sales annually and is expected to grow by at least 5% to 8% year over year, and potentially significantly more with an aging population. Combined with a well-established regulatory framework, this makes the U.S. market one of the first that many companies choose to enter. 

It is important to consider the specifics of any market being entered, including unique expectations from consumers, requirements from regulators and payment considerations. This article describes basic expectations from the U.S. Food and Drug Administration (FDA) for devices being brought to the U.S. market. 

Why do manufacturers bring a medical device to the US? 

Within the U.S. medical device market, certain device types, such as wearables, are growing even faster than the overall sector, reflecting consumer preferences.  Many devices are covered by public or private insurance payors through reimbursement. A device brought to the U.S. market with appropriate reimbursement plans can be profitable. However, there may be many competitors, especially for commodity-type medical devices, so a careful business case should be considered.

The FDA is considered one of the most influential regulators for medical devices. It regulates medical devices and publishes an extensive number of guidance documents to assist companies in understanding its expectations, both in general and for specific device types, including new technologies and challenging topics such as artificial intelligence/machine learning (AI/ML). It also recognizes a wide range of industry standards, either in total or in part. There are formal mechanisms, such as Q-Submissions, to obtain feedback and align on expectations before filing a marketing submission with the FDA, and there are regulatory statutes that prescribe review timelines. These elements transparent and consistent requirements. 

FDA authorization is now recognized by some regulators (global harmonization/regulatory reliance). While there will always be country-specific requirements (such as labeling, in-country representation, registration and possibly more), leveraging FDA authorization can significantly streamline other regulators’ reviews, as described in a recent regulatory update. 

Combined, these factors explain why many companies choose the U.S. as one of their first markets. 

Overview of US FDA requirements: QMS, classification, regulatory pathway, regulatory submission, UDI, FDA authorization, FURLS registration and total product life cycle approach

The FDA has several requirements for most companies involved in the production and distribution of medical devices in the U.S., as summarized below. Note that in some cases, there are exceptions or additional requirements that are not covered in this brief overview, but these apply to most medical devices. 

1. Establish a quality management system (QMS) in compliance with Part 820 of Title 21 of the Code of Federal Regulations (CFR). The FDA expects that the portions of a QMS that are relevant for a specific activity, including detailed requirements for design and development of a medical device, should be implemented before that activity is finished. The records from relevant activities need to be maintained. This includes all necessary verification and validation testing. 
2. Determine the appropriate classification and regulatory pathway for a medical device. The regulatory pathway is often a premarket submission, such as a 510(k), De Novo request or Premarket Approval (PMA) application to the FDA, or another less common submission.
3. Compile the regulatory submission and develop appropriate labeling that provides adequate instructions for use.
4. Obtain a unique device identifier (UDI) for the device from an FDA-accredited issuing agency.
5. If applicable, submit the appropriate premarket submission to the FDA and obtain FDA authorization. 
   • Note that the FDA charges a user fee for most premarket submissions.
6. For facilities outside of the U.S., establish a U.S. agent and an initial importer. 
7. Register the appropriate facilities in the FDA Unified Registration and Listing System (FURLS) based on their activities (see below). Most facilities must also list the relevant devices. 
   • Note that the FDA charges an annual fee for establishment registration. 
8. Enter the UDI into the FDA’s Global Unique Device Identification Database (GUDID). 
9. Begin selling the device.
10. Continue to apply a total product life cycle approach, including monitoring feedback, reporting certain adverse events and malfunctions, evaluating changes before implementation (including whether additional submissions to the FDA are needed), and maintaining the QMS. Depending on the device, there may be special requirements, such as periodic reports and notifications of interruption or discontinuance of manufacturing. A company should maintain inspection readiness, as the FDA has the authority to inspect any medical device facility that is registered with the agency.

Who are these requirements applicable to? 

The requirements above are relevant for facilities conducting one or more of the following activities:

• Design and development of a device (specification developer)
• Physical manufacturing or assembly of the device for sale in the U.S. (manufacturer or contract manufacturer) or for export from the U.S. (export facility)
• Sterilization of the device (manufacturer or contract sterilizer) 
• Maintenance of complaint files per 21 CFR 820.198 (complaint file establishment)
• Repackaging or relabeling (repackagers or relabelers)
• Reprocessing of single-use devices or remanufacturing (reprocessors or remanufacturers)
• Exporting devices to the U.S. (foreign exporter)
• Initial importing into the U.S. (initial importer; exempt from device listing requirements)

It is important to note that distributors that do not conduct any of the above activities are not required to register with the FDA. 

Note that a company that conducts only some of these activities does not need a QMS that covers the activities it does not conduct. 

Other US agencies to consider in addition to the FDA: FCC, HHS, EPA and NIOSH

A company also needs to consider whether there are requirements from other agencies. The focus of this article is solely on FDA requirements. Other U.S. agencies that may have requirements for a specific medical device include:

• The Federal Communications Commission (FCC) – Has jurisdiction over radio frequency use 
• Department of Health and Human Services (HHS) – Has requirements related to protected health information
• Environmental Protection Agency (EPA) – Has jurisdiction over some products intended to kill microorganisms, including certain disinfectant (pesticidal) products 
• National Institute for Occupational Safety and Health (NIOSH) – Has jurisdiction over N95 and greater respirators 

Additionally, many states have requirements for facilities in their state, such as business licenses. Some also have requirements for specific medical device types. 

It is also important to note that reimbursement authorization is separate from FDA authorization.

Main potential challenges related to the US FDA requirements

Ultimately, the FDA is responsible for establishing that the device is safe and effective for its intended use. This includes confirming that applicable general and special controls are met, that the device performs as expected, and that the benefits outweigh the risks related to the device. For most moderate- or low-risk devices, this means ensuring the device meets certain performance expectations in bench testing, animal testing or both. For high-risk devices, this generally includes a requirement for clinical evidence.

Many FDA expectations align with those of other medical device regulators, but several important differences  should be carefully considered. The three main areas are:

• Biocompatibility
• Cybersecurity
• Reprocessing (cleaning, disinfection or sterilization)

Additionally, like many other regulators, the FDA is concerned with certain aspects that can vary by patient or user demographics, experience and standard of care. Specific evaluation for relevance to the U.S. for these topics, as applicable for the device, must be conducted, and justification must be provided if a company intends to use data for these from outside of the U.S. In many cases, the FDA will not accept justification because of concerns about generalizability to the U.S. Additional usability/human factors testing and clinical evidence are often necessary.

Because these tests are generally expensive, they can create a barrier to entry to the U.S. market and should be carefully analyzed. 

In addition, because the FDA evaluates medical devices based in part on whether their benefits outweigh the risks, certain devices can face challenges. For example, the FDA considers aesthetic improvement to have a relatively limited benefit. Because the FDA expects the risks to be even lower, bringing a device with aesthetic indications to the U.S. can be very challenging and potentially prohibitive, even when the market opportunity is significant. The FDA’s expectations for these devices are often more extensive than those of many other regulators.

Understanding and addressing common FDA challenges

The challenges are best addressed proactively. If a company is uncertain about a requirement or expectation, it may need to dedicate staff time and effort to understanding it, or it may wish to work with a third party with the relevant expertise. For example, Emergo by UL can help with most FDA regulatory and quality expectations, including establishing a QMS, determining the regulatory pathway for a device and compiling premarket submissions. Emergo by UL has worked with a wide range of devices, from AI/ML software as a medical device (SaMD) to implants to powered exoskeletons.

There are cases, such as expectations for a specific device, that may be best resolved by contacting the FDA. In many cases, the FDA’s Q-Submission process may be the best way to obtain FDA feedback and align on expectations. In general, a Q-Submission is strongly recommended before conducting animal performance testing or clinical testing. Obtaining feedback is also important for novel devices. Depending on the questions, there are other possible mechanisms of contact, such as a 513(g) request for information or a Request for Designation (RFD), that may be appropriate.

Concluding remarks 

The U.S. medical device market provides significant opportunities for manufacturers. The FDA has extensive requirements for bringing a medical device to the U.S. Most — but, critically, not all — of the expectations are similar to those from regulators of other regions. In addition to the general requirements for all medical device manufacturers, the regulatory pathway and requirements for each device should be carefully evaluated, and, if necessary, alignment with the FDA should be sought before extensive testing to minimize the risk of FDA rejection.