The American Market
Among the motivations that could drive a medical device manufacturer to commercialize in the United States is certainly the size of that market. As of today (2020 data), it is a pool of approximately $176.7 billion, but in perspective (projection for 2028), it could reach $262 billion, with a 5% year-over-year compound annual growth rate (CAGR).
Imaging diagnostics dominates (31% of the market in 2020), but the growth in demand for devices in nephrology and diabetes is significant, as well as for in vitro diagnostics. The factors driving this increase? These range from the rising prevalence of chronic diseases to the growth of the elderly population, along with technological improvements in the medical sector.
USA and Europe: What are the main differences
In general, the certification process for a medical device in Europe is usually longer and more expensive than the American process, partly due to the greater emphasis on clinical documentation and long-term safety. But let’s proceed in order.
From a legislative perspective, the first substantial difference between the two markets concerns the regulatory agencies. In the United States, the commercialization of medical devices is managed by the Food and Drug Administration (Section 201, h, of the Food, Drug, and Cosmetic Act), while in Europe this task falls to the European Commission (which refers to EU Regulation 2017/45, called MDR).
Risk Classes
Medical devices are regulated and classified based on the risk associated with their use. There are four categories in Europe:
- Low (I)
- Moderate (IIa and IIb)
- High (III)
In the USA, there are three:
- Low (I)
- Moderate (II)
- High (III)
In the first case, classification considers factors such as the duration of use, invasiveness, and contact with the human body. In the second case, the reference is made to comparison with devices already legally on the market, considering their intended use and technological characteristics. In any case, the risk class also determines the conformity assessment process.
The Regulatory Process in Europe
The most significant differences between the two approaches are explicit in the regulatory process. In Europe, which follows the dictates of the MDR, independent authorized entities (called Notified Bodies) assess the device’s conformity to the regulation, ensuring its safety and performance. Class IIa, IIb, and III devices require certification from a Notified Body. Regarding documentation, stricter requirements are demanded compared to the past, particularly in terms of clinical evidence and conformity assessment. In this context, clinical data are essential to demonstrate the safety and clinical efficacy of the device. Once approved, the device can be commercialized in the EU.
The Procedures in the United States
In the United States, the regulatory pathway varies depending on the device’s risk class.
- For Class I and II devices, if a “predicate” device (i.e., already approved and on the market) exists, the manufacturer must demonstrate substantial equivalence, meaning the new device is as safe and effective as the one already on the market.
The new device must have the same intended use and technological characteristics (or different ones, provided safety and efficacy remain unchanged) as the predicate. At the end of the process, which lasts about 3–6 months, the manufacturer receives marketing clearance from the FDA, meaning the practice has been approved and the product can be commercialized. For innovative devices, clinical studies are needed, making it important to obtain feedback from the FDA by submitting a Pre-submission request.
- For Class I and II devices without an existing predicate, the De Novo submission pathway is required, used for innovative devices where safety and efficacy can be demonstrated through general or special controls.
The process takes longer (6–12 months) but is less stringent than Premarket Approval (PMA). The latter, necessary for Class III devices (high risk), requires a comprehensive evaluation of clinical, preclinical, and scientific data, as well as a rigorous demonstration of the device’s safety and efficacy. The approval process is based both on scientific data and on inspections conducted at the manufacturer to ensure the structure and production process comply with quality system regulations.
At the end of each approval pathway, the FDA sends a letter, published online (marketing clearance), effectively authorizing the commercialization of the device in the USA. Manufacturers also have the voluntary opportunity, through the Q-submission process, to request and obtain written or in-person feedback from the FDA before submitting their pre-market requests for formal review.
Post-Market Surveillance
Even in post-marketing surveillance, differences exist between the two approaches. Under MDR (Europe), the surveillance and vigilance system must be developed within a risk management process. The main steps manufacturers must implement are:
- Post-Market Surveillance (PMS): Planning activities to obtain and analyze PMS data (PMS Plan) and producing mandatory periodic reports (PMS report/PSUR).
- Post-Market Clinical Follow-Up (PMCF): Continuous monitoring of the device’s safety and clinical performance, with a dedicated plan and periodic report.
- Vigilance System: Identifying and reporting adverse events.
In the US, the FDA (via 21 CFR Part 822) focuses on immediate risk mitigation by requiring two procedures:
- Mandatory reporting of adverse events.
- In some cases, for specific device classes and characteristics, post-marketing studies may be required.
Device Registration
Once approval for marketing the device is obtained, registration in the appropriate database is required (Eudamed for Europe, Establishment Registration & Device Listing for the United States). European manufacturers must register their organization and all their devices in Eudamed. Currently, since Eudamed is not yet fully operational, each manufacturer must verify the requirements of each individual Member State where they market their devices. In Italy, for example, manufacturers must register their organization and their devices in the Ministry of Health Database.
Eudamed will also be very useful from the perspective of market surveillance and vigilance. In fact, it will allow for the homogeneous sharing of information among the various competent authorities in each European country and enable a detailed analysis of all data related to the market surveillance system.
In the United States, manufacturers are required to register their organization, devices, and the facilities where they are produced in the FDA database. Device registration must be updated annually. Regarding the surveillance and vigilance system in the USA, the Manufacturer and User Facility Device Experience Database (MAUDE) contains reports on medical devices (MDRs) submitted to the FDA by mandatory reporters (manufacturers, importers, and healthcare facilities) and users.
Quality, Traceability, and Labeling
Concerning the Quality Management System (QMS), every economic operator in Europe must implement a QMS. To comply with this requirement, it is possible to follow the voluntary standard ISO 13485. In the USA, however, such a system is mandatory (under CFR, Title 21, Part 820) for the distribution of devices on the American market. The United States, along with Brazil, Canada, Australia, and Japan, adheres to the Medical Device Single Audit Program (MDSAP).
Regarding traceability, the reference is the UDI (Unique Device Identification) system, a standardized international coding system established by the Food and Drug Administration (FDA) in the United States and adopted by many other regulatory authorities globally, including the European Union. In both Europe and the USA, one or more organizations are accredited to issue UDI codes (which must be assigned by the manufacturer). The UDI code is an alphanumeric code composed of a static part (the primary identifier of the device and uniform packaging) and a dynamic part (identifying the production unit, containing all the information necessary for product traceability and tracking).
Finally, labeling, which in both cases follows the risk management process: in the USA, the FDA (through CFR, Title 21, Part 820) covers every single aspect of this process (from UDI to translations), also highlighting monitoring controls and procedures as part of the QMS. In Europe, the MDR (Annex I, Chapter III) defines the requirements concerning the information provided with the device.
Conclusions
In conclusion, it is clear that answering the initial questions is not so simple. In Europe, we are witnessing the real impact of the MDR’s implementation on all stakeholders. The certification process appears to be longer and more complex, requiring continuous updates and reviews both by the Notified Body and the manufacturer.
This entails an increase in costs related to both the entire certification process and its maintenance. In the United States, the approval process for marketing medical devices varies significantly depending on the type of product to be brought to market. Certainly, the possibility of finding a predicate device (for Class I and II devices) to demonstrate equivalence allows manufacturers to focus documentation on proving such equivalence, obtaining marketing approval in a very short time.
On the other hand, the procedure for Class III devices shifts the manufacturer’s focus to demonstrating the safety and efficacy of their device through in-depth data, requiring a greater investment in terms of costs, resources, and time. The middle ground between these two submission options is for Class I and II devices where a predicate cannot be found, but where it is possible to demonstrate safety and efficacy through general or general and special controls.
