Injury 54 (2023) 110908

Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

Comparison of the international regulations for medical devices–USA

versus Europe✰
Matthias Fink *, Bassil Akra
Akra Team GmbH, Am Penzinger Feld 17a, 86899 Landsberg am Lech, Germany

A R T I C L E I N F O A B S T R A C T

Keywords: In May 2021, the new Medical Device Regulation in the EU came into force. While the US has a centralized
Medical Device Regulation (MDR) governmental authority, the Food and Drug Administration (FDA), the EU implemented a system of different
Medical Devices Notified Bodies responsible for the approval process of medical devices. Both regions have a similar system to
Food and Drug Administration (FDA)
classify medical devices based on their overall risks but specific devices, like joint prostheses, are classified
Equivalence Demonstration
Regulatory Approval
differently in the US and the EU. Depending on the risk class, there are differences in the quality and quantity of
clinical data required to obtain market approval. In both regions, it is possible to place a new device on the
market based on the demonstration of equivalence to an already marketed device, but the MDR significantly
increased the regulatory requirements for the equivalence pathway. While an approved medical device in the US
in most cases only requires general post-market surveillance activities, manufacturers in the EU must continu­
ously collect clinical data and submit specific reports to the Notified Bodies. In this article, we will compare the
regulatory requirements between the US and Europe and provide an overview of similarities and differences.

Introduction different regulatory pathways.

On May 26th, 2021, after a 12-month postponement due to the
global Covid-19 pandemic, the Regulation (EU) 2017/745, the European
Medical Device Regulation (MDR), came into force [1]. The MDR
combined and replaced the previous Council Directives 93/42/EEC, the
Medical Device Directive (MDD) for medical devices [2] and
90/385/EEC, the Active Implantable Medical Device Directive (AIMDD)
for active implantable medical devices [3]. The EU is in the transition
phase between the MDD and AIMDD and the new MDR. Since there is no
grandfathering, all currently available medical devices must undergo a
conformity assessment procedure pursuant to the MDR.
Contrary to pharmaceuticals and biologics, which are approved and
monitored by the European Medicines Agency (EMA), no central Euro­
pean agency for medical devices exists. The responsibility for approving
medical devices and monitoring in the post-market phase lies with
Notified Bodies.
In 1976 with the Medical Device Amendments to the Food, Drug and
Cosmetic Act (FD&C Act) [4], medical devices were regulated for the
first time in the United States. This amendment created the risk-based
classification system of medical devices in the US and established
In 1982 the Center for Devices and Radiological Health (CDRC) at the
Food and Drug Administration (FDA) was established by a merger of the
organizational units that regulated medical devices and radiation-
emitting products. The CDRH is the centralized authority responsible
for the approval of all medical devices in the US.
In the United States, medical devices, pharmaceuticals, and biologics
are all handled by one government authority, the Food and Drug
Administration (FDA).
In the EU and the US, a manufacturer who wants to place a medical
device on the market legally must comply with the respective laws and
regulations before placing a product on the market.
This overview compares the legal and regulatory requirements in the
EU and the US to place a medical device on the market, focusing on
orthopedic and orthopedic trauma devices. There are many similarities
but also significant differences in the requirements concerning clinical
evidence and post-market surveillance in the two regions.
Regulatory background in the European Union
After a series of safety issues related to medical devices in Europe, e.

✰
This paper is part of a Supplement supported by the Osteosynthesis and Trauma Care Foundation (OTCF) through a research grant from Stryker.
* Corresponding author.
E-mail address: matthias.fink@akrateam.com (M. Fink).

https://doi.org/10.1016/j.injury.2023.110908
Accepted 18 June 2023
Available online 20 June 2023
0020-1383/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
M. Fink and B. Akra
g., concerning the metal-on-metal hip prosthesis [5] and especially the
Poly Implant Prothèse (PIP) silicone breast prostheses scandal [6], the
legislators in the EU decided to accelerate the activities related to the
new regulation, which was initiated in 2008. This led to the publication
of two new legislations in 2017, the MDR and Regulation (EU)
2017/746, the In Vitro Diagnostic Regulation (IVDR) [7]. The main
intention of the new framework is to ensure a high level of safety and
health while supporting innovation. Since this article focuses on or­
thopedic medical devices, we will primarily discuss the requirements of
the MDR.
Certain parts of the MDR are similar to the previous directives, e.g.,
the implementation of a Quality Management System for manufacturers
of Class II and Class III medical devices and the Notified Body system,
but the MDR also introduced tighter requirements for clinical and post-
market data, also for low-risk Class I manufacturers.
The process of designating Notified Bodies under the MDR is com­
plex, and the Covid-19 pandemic further slowed it down.
To avoid a shortage of medical devices in Europe by the end of the
transition period, Regulation (EU) 2023/607 [8] was published in
March 2023 to extend the transition period of the MDR and the IVDR.
Based on the risk class, manufacturers of legacy medical devices have
until the end of 2027 and 2028 respectively to transition them into the
MDR if they have launched an application with a Notified Body by May
2024. That ensures that manufacturers are not delaying their MDR
preparations.
The extended timeline should provide enough time for all stake­
holders to allow for the transition of medical devices to the MDR and
ensure a continuous supply in the European market.
Legal differences between the EU and the United States
One noticeable difference between the regulation of medical devices
in the European Union and the United States is that with the FDA there is
a single government authority regulating all medical devices, pharma­
ceuticals, and biologics. While the EU also has a single competent au­
thority, the European Medicines Agency (EMA), handling the approval
and monitoring of pharmaceuticals and biologics, there is no centralized
competent authority for medical devices. In the EU, for the approval
process, the Notified Body system was established, and currently, as of
March 2023, 38 Notified Bodies are designated under the MDR. Any
Notified Body is supervised by the designated competent authority of the
member state where they are located.
While the MDR as a Regulation is fully applicable in all EU member
states, the number of competent authorities and Notified Bodies in­
troduces a potential risk of differences in interpreting specific re­
quirements. To provide more clarification and increase the alignment
between the different stakeholders, the Medical Device Coordination
Group (MDCG) published several guidance documents concerning
certain aspects of the MDR [9].
The market approval by the FDA does not limit the time the device
can be placed and remain on the US market unless it is subject to a recall.
In the EU, the CE mark has limited validity, usually five years, before the
device must undergo a conformity assessment procedure to renew the
CE mark.
Difference between the risk classes for medical devices in Europe
and the US
On a high-level basis, the risk-based classification system in the US
and the EU has three risk classes (I. II, III), with the EU splitting class II
into IIa and IIb. More details can be found in the FD&C Act in Section
513 [4] and the MDR in Article 51 and Annex VIII [1].
In both classification systems, class I is the lowest and class III the
highest risk class. The minimum requirements for preclinical and clin­
ical data for a medical device increase as the risk class increases.
Considering that most medical devices are available in both regions,
2
Injury 54 (2023) 110908
there are slight differences in the distribution of these devices in the
different risk classes. In the EU, more devices are in risk class I (40%
versus 35%) and risk class III devices (16% versus 9%) compared to the
US. The US has more devices in risk class II, 53% compared to 44%
(Class IIa and IIb combined) in the EU (Table 1). While the numbers for
the US are from the FDA database [10], there is currently no centralized
European database that would provide a similar accurate numerical
value since the European Database for Medical Devices (EUDAMED) is
not fully operational yet. The numbers for the EU are sourced from a
survey by the members of the European trade association for the medical
technology industry (MedTech Europe) and were published in July 2022
[11].
Depending on the risk class of a medical device, there are relevant
differences in the regulatory approval pathways between the EU and the
US. In general, the higher the risk class, the higher the quality and
quantity of clinical data required for the initial market approval.
While most orthopedic trauma implants like intramedullary nails,
plates, and screws are classified in the same risk class in the EU (class
IIb) and the US (class II), there are differences in the risk class for joint
prostheses and spinal implants.
While under the MDD, only hip, knee, and shoulder prostheses were
in the highest risk class III under the MDR, all partial or total joint
prostheses are now in Class III too. In the US, most joint prostheses are
class II, and only certain hip prostheses are classified in the highest risk
class. The MDR has 22 classification rules allowing manufacturers to
classify a medical device. Most orthopedic implants are classified ac­
cording to rule 8. The US Code of Federal Regulation (CFR) Title 21, Part
888, provides the classification for orthopedic medical devices. The FDA
product classification database, which is publicly available, allows a
manufacturer to classify his new device based on similar devices already
on the US market.
Regulatory pathways for class I medical devices in the EU and
the US
Class I devices, per definition, pose almost no risk to the patient’s
safety and therefore require very little regulatory oversight in the US and
the EU. Medical devices like bandages, wheelchairs, and most general
surgical instruments (e.g., scalpels or scissors) are in risk class I.
Nearly all class I medical devices in the US are exempted from a pre-
market notification and clearance by the FDA; no specific post-market
requirements are needed.
In the EU, class I devices provided in a sterile package (Class Is), are
reusable (Class Ir) or have a measuring function (Class Im), need the
involvement of a Notified Body for these specific aspects but do not
undergo the same conformity assessment procedure as class II or class III
devices. In the post-market phase, a class I medical device manufacturer
in the EU must collect general post-market data and summarize them
into a Post-market Surveillance Report to provide to the competent
authority on request.
Regulatory pathway for class II and class III medical devices in
the EU
The MDR differentiates between implantable and non-implantable
Class II devices, and the clinical and post-market data requirements
Table 1
Comparison of the risk class distribution of approved medical device in the EU
and the US.
Risk Class EU US
I 40% 35%
II 44% 53%
(21% IIa, 23% IIb)
III 16% 9%
M. Fink and B. Akra Injury 54 (2023) 110908

are less stringent for non-implantable class II devices. Since most Table 2
implantable orthopedic and orthopedic trauma devices are classified as Equivalence characteristics MDR.
class IIb or class III, the focus is on those devices. Technical • the device is of similar design
Contrary to the regulatory pathways in the US, which will be pre­ • is used under similar conditions of use
sented in the next section, the requirements for clinical data are the same • has similar specifications and properties including physicochemical
properties such as intensity of energy, tensile strength, viscosity,
for class IIb implantable and class III devices, but there are significant
surface characteristics, wavelength and software algorithms
differences between medical devices currently on the EU market and • uses similar deployment methods, where relevant
novel devices. • has similar principles of operation and critical performance
All medical devices placed on the EU market before the date of requirements
application of the MDR on the 26th of May 2021 are considered legacy Biological • the device uses the same materials or substances in contact with the
same human tissues or body fluids for a similar kind and duration of
devices, regardless of the length of their market history. They must
contact and similar release characteristics of substances, including
undergo the same conformity assessment under the MDR as a new degradation products and leachables
medical device since there is no grandfathering for legacy devices. Clinical • the device is used for the same clinical condition or purpose,
Depending on the length of market history and the existing clinical including similar severity and stage of disease, at the same site in the
body, in a similar population, including as regards age, anatomy and
data for these legacy devices, a manufacturer might need to generate
physiology
new clinical data to ensure sufficient clinical data to demonstrate con­ • has the same kind of user
formity with the MDR requirements. This could be challenging for some • has similar relevant critical performance in view of the expected
devices with a very long market history, like a Kirschner wire since only clinical effect for a specific intended purpose
limited up-to-date clinical data might be available. To ensure that these
medical devices with a long market history and are still considered to be
demonstrate to the Notified Body that both organizations have a con­
state-of-the-art will remain on the European market, an MDCG guidance
tract allowing them to share details and enabling the manufacturer to
document [12] was published to alleviate the transition of these devices
have full access to the other device’s technical and clinical
to the MDR. To be able to follow this strategy, these must fulfill the
documentation.
defined criteria in this guidance document to be considered a
A pre-market clinical investigation would be required for novel or­
well-established technology (WET):
thopedic and orthopedic trauma implantable medical devices that do
not fall under one of the exemptions. The MDR includes specific re­
• Relatively simple, common, and stable designs with little evolution
quirements for a pre-market clinical investigation in Articles 62 to 80
• Generic device group has well-known safety and no relevant safety
and Annex XV. Annex XV of the MDR is aligned with ISO 14,155 [14],
issues in the past
and the revised ISO 14,155 in 2020 is aligned with the MDR re­
• Well-known clinical performance characteristics and their generic
quirements. The EU is less stringent than the FDA, where a pre-market
group are standard of care devices with little evolution
investigation needs to be conducted, and allows for the sole use of
• Long market history
clinical data obtained outside as long as the full transferability of the
data to the European population can be justified. For example, clinical
If a manufacturer can successfully demonstrate to the Notified Body
data for the same hip prostheses used in a study on younger patients with
that a medical device can be considered a well-established technology,
sequelae of Avascular Necrosis (AVN) of the hip could not be transferred
he can use data from a lower evidence level to demonstrate conformity
to substantiate the indication of Femoral Neck Fracture in an elderly
with the MDR. This lower-level data could be pre-clinical and/or post-
population.
market data and/or data from similar devices and/or state-of-the-art
to show that the device conforms to MDR requirements.
Regulatory pathway for class II and class III medical devices in
To get the initial CE mark for a novel medical device, the MDR re­
the United States
quires a clinical investigation for all implantable and class III devices as
laid out in Article 61.4 with some exemptions:
There is a significant difference in requirements for clinical data
between class II and class III devices. The US Code of Federal Regulation
• If a device is based on modifications of a previously marketed device
has no further differentiation of class II devices, and the requirements
and equivalence to that device can be demonstrated.
are identical for implantable and non-implantable class II devices. As
• Article 61.6 (b) provides a list of implantable medical devices, e.g.,
stated above, only a small number of orthopedic devices in the US are
screws, plates, wires, and pins, which are exempted from the
class III, with the majority being in class II. That includes most joint
requirement of conducting a pre-market clinical investigation.
prostheses that were up-classified in the EU with the MDR.
• If a manufacturer claims and can demonstrate equivalence to an
For a class III device, the FDA requires clinical data with a strong
already marketed device with sufficient clinical data. To be equiva­
evidence level from a clinical study before issuing the Pre-market
lent, the technical, biological, and clinical characteristics, as defined
Approval (PMA). Since the passing of the 21st Century Act in 2015
in the MDR, must be fulfilled; any difference between the two devices
[15], it is now feasible to use clinical data from observational studies
should not be clinically relevant. For example, it would not be
and studies conducted outside the US.
feasible to consider the cemented and non-cemented versions of a
The FDA clears most of the class II devices in the US based on the Pre-
femoral stem to be equivalent despite having the same stem design
market Notification (PMN), also known as the 510(k) pathway, named
and indications.
after section 510(k) in the Code of Federal Regulation No. 21 describing
this procedure. In this case, the manufacturer must demonstrate that his
In the past, under the MDD and AIMDD, manufacturers frequently
device is substantially equivalent to an already marketed and approved
used the demonstration of equivalence pathway to obtain CE marking
predicate device. Compared to the requirements to demonstrate equiv­
for new medical devices. The three characteristics (Clinical, Biological,
alence in the MDR, the criteria for demonstrating that equivalence are
and Technical (Table 2)) defined in the MDR in Annex XIV must be
less stringent (Table 3). If the FDA accepts the predicate device, a PMA is
fulfilled to demonstrate equivalence. Some of these devices approved via
not required. The PMN process received some criticism since it a device
the equivalence pathway had safety alerts and recalls [5,6,13]; hence
can be approved on a device that was approved by a PMN. This would
demonstrating equivalence under the MDR requires more detailed and
allow for a device to be placed on the market that is based on a device
in-depth information on the proposed equivalent device. A manufac­
that was approved several device generations prior by a PMA.
turer who wants to claim equivalence to a device from a competitor must

3
M. Fink and B. Akra
Table 3
Substantial equivalence criteria 510(k).
Substantial • has the same intended use as the predicate; and
Equivalence • has the same technological characteristics as the predicate
Criteria 1
Substantial • has the same intended use as the predicate; and
Equivalence • has different technological characteristics and does not
Criteria 2 raise different questions of safety and effectiveness; and
• the information submitted to FDA demonstrates that the
device is as safe and effective as the legally marketed device
Most devices for which no predicate device exists will be automati­
cally classified as class III and would need to undergo the PMA process.
The manufacturer can petition this automatic classification for devices
with a low- or moderate risk. If the FDA follows this petition, these
devices would be reclassified and considered ‘de Novo devices. De novo
devices do not require a PMA and can follow the PMN pathway but
would still need to demonstrate that they are safe and effective with
clinical data. A device approved via the De Novo classification can be
used as a predicate for future submissions of similar devices via the 510
(k) pathway.
For rare medical conditions, defined as orphan medical devices with
fewer than 4000 individuals in the US, the manufacturer can apply for a
Humanitarian Device Exemption, which is a similar pathway to the
PMA, except that no scientific evidence for the performance would be
required due to the rationale that it might take years to generate suffi­
cient data due to the low number of patients. The legislation in the EU
does not include specific provisions for medical devices used in rare
indications [16].
Differences in the post-market requirements between the EU and
the US
Another significant difference between the EU and the US is the post-
market requirements. In the US, for most devices, only general post-
market activities, e.g., collecting feedback from physicians or access­
ing the MAUDE database, are required by the FDA. Depending on the
available clinical data and residual risks, a post-market clinical study
might be needed for certain class II and high-risk class III devices. This is
regulated by the FD&C Act Section 522, and all ongoing post-market
studies in the US are listed in the ‘522 Post-market Surveillance
Studies Database [17]. In March 2023, 21 ongoing post-market studies
were listed in the database, and only two were for an orthopedic device.
The EU, with the MDR, has tightened the requirements for post-
market surveillance. Manufacturers are required to actively and sys­
tematically collect post-market data and generate specific reports (Pe­
riodic Safety Update Report PSUR) on an annual or biennial basis,
depending on the risk class. For implantable and Class III devices, these
PSURs need to be submitted to and will be assessed by the Notified Body.
For devices that do not have sufficient clinical data, are approved based
on the equivalence pathway, or do not have long-term clinical data
addressing the expected lifetime defined in the design input phase, the
manufacturer must conduct a specific Post-market Clinical Follow-up
(PMCF) activity. For most implantable and class III medical devices,
that could mean a PMCF study unless other data sources, like an
arthroplasty registry, would provide sufficient data to answer the open
questions from the risk management file or the clinical evaluation report
of that device.
Potential impact of the MDR in Europe
The recent amendment to the MDR extending the transition period
should continuously ensure access to medical devices in Europe and the
continuity of the healthcare system.
At this early phase, after the implementation of the MDR, including
more stringent pre- and post-market requirements for clinical data, it is
4
Injury 54 (2023) 110908
impossible to conclude if the MDR will lead to reduced safety issues in
the EU. In the US, most recalls are for devices that the FDA initially
cleared via the 510(k) process without clinical data [17] for the device
itself.
With this significant tightening of the possibility to demonstrate
equivalence, it remains to be seen if there will be an increase in pre-
market clinical investigations for novel devices or if manufacturers
decide to go into other markets with less stringent regulations first and
collect clinical data there before applying for the CE mark in the EU.
There is criticism that the stringent MDR requirements might delay
novel and innovative medical devices in Europe since manufacturers
might decide to go into other markets first. Currently, most manufac­
turers are focused on transferring their medical devices from the MDD
and AIMDD, so it is too early to see if the MDR will lead to fewer in­
novations in Europe.
It is expected that physicians and patients will benefit from the
increased transparency in the EU when certain information on
implantable and high-risk medical devices becomes publicly available,
e.g., in the Summary of Safety and Performance report, in the EUDAMED
database which is expected to be fully operational by 2024 [18].
The extension of the transition period between the MDD and the
AIMDD will ensure that there will be a continuous supply of state-of-the-
art medical devices in the EU, and all stakeholders should have sufficient
time for the transfer process.
Also, other regions, like the FDA in the US, will observe closely if the
increased requirements on clinical and post-market data in the EU will
result in significantly reduced safety alerts and recalls.
We will need future studies to assess the MDR’s total impact on the
overall safety of medical devices and on the number of novel and
innovative medical devices that will be approved first in Europe.
Declaration of Competing Interest
None.
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