Drug Safety

https://doi.org/10.1007/s40264-019-00878-3

CURRENT OPINION

Medical Devices: Definition, Classification, and Regulatory

Implications
Jeffrey K. Aronson1,2   · Carl Heneghan1 · Robin E. Ferner2,3,4

© Springer Nature Switzerland AG 2019

Abstract
We propose the following definition of a medical device: “A contrivance designed and manufactured for use in healthcare,
and not solely medicinal or nutritional.” Current regulatory classifications of medical devices are complex and designed
primarily for regulators. We propose a simpler classification, based on (1) the site of application of the device, (2) the time
scale of its use, and (3) whether it has an external power source. The regulation of medical devices is less well developed
than the regulation of medicinal products, which it could follow more closely. In particular, devices that incorporate medi-
cines should be required to meet the same regulatory standards as medicinal products. This would remove the anomaly
that some delivery systems that incorporate medicines are classified as devices while other similar systems that deliver the
same medicines are classified as medicinal products. Some improvements might also result from more widespread use of
registries, such as those used for prosthetic joint replacements. Registries would allow both a prospective examination of
the performance of high-risk devices and a retrospective analysis when signals from other sources of information suggest
problems. Those who apply for a marketing authorization for a new device should have to assure regulators of its quality of
manufacture, safety, and efficacy before licensing. Even the most straightforward device should be shown to be useable in
practice. Trials on patients, or at least simulations of use in the real world, should be practicable for most devices.

1 Introduction
Key Points 
A medical device is formally defined by the World Health
Organization as “any instrument, apparatus, implement, The many medical devices on the market are not regu-
machine, appliance, implant, reagent for in vitro use, soft- lated as rigorously as medicinal products.
ware, material, or other similar or related article, intended Current definitions and regulatory classifications of
by the manufacturer to be used, alone or in combination, for medical devices are complex and designed primarily for
human beings, for one or more specific medical purpose … regulators. We define a medical device as a contrivance
and does not achieve its primary intended action by phar- designed and manufactured for use in healthcare, and
macological, immunological, or metabolic means, but which not solely medicinal or nutritional. We classify medical
may be assisted in its intended function by such means” [1]. devices based on the sites of use, the time scale of use,
and whether they are externally powered.
* Jeffrey K. Aronson
jeffrey.aronson@phc.ox.ac.uk More widespread use of registries could improve the
scrutiny of medical devices, particularly high-risk
1
Centre for Evidence Based Medicine, Nuffield Department devices.
of Primary Care Health Sciences, University of Oxford,
Radcliffe Observatory Quarter, Woodstock Road, Applicants for marketing authorization for a new device
Oxford OX2 6GG, UK should have to assure regulators, from studies in patients,
2
West Midlands Centre for Adverse Drug Reactions, City of its quality of manufacture, safety, efficacy and practi-
Hospital, Birmingham, UK cal usability before licensing.
3
Institute of Clinical Sciences, University of Birmingham,
Birmingham, UK
4
Institute of Cardiovascular Medicine, University College
London, London, UK

Vol.:(0123456789)

Almost any contrivance used in medicine that is not either
a medicinal product [2] or a nutritional product (such as a
parenteral feed) [3] can be designated as a medical device.
This gives rise to problems for regulators and users. For
example, in some cases a medicinal product is included in a
medical device, as in drug-eluting stents [4]. This can lead
to confusion, as in the case of products containing lidocaine
gel for local anaesthesia when inserting a urinary catheter,
some of which are classified as medicinal products and some
as devices. Clarification is needed.
In this article, we propose a clearer definition of a medical
device, supported by a classification, and critically review
current regulatory processes. We note discrepancies between
different regulatory definitions and regulations, which would
benefit from harmonization. We concentrate on regulations
promulgated by the US Food and Drug Administration
(FDA) and the European Medicines Agency (EMA), but
we note discrepancies not only between these jurisdictions
but also with jurisdictions elsewhere (e.g. in Japan [5]). In
this context, we note that the International Medical Device
Regulators Forum, a voluntary group of medical device
regulators, is working towards regulatory harmonization
for devices [6], although differences in legal restrictions in
different countries may make this difficult to achieve.
2 Definitions
Given the multiplicity of types of medical devices, regula-
tory definitions have been framed to be inclusive, and go far
beyond what are commonly thought of as devices.
2.1 European Union
The EMA defines a “medical device” by its use, alone or in
combination, in human beings, for one or more of the fol-
lowing specific medical purposes [7]:
• diagnosis, prevention, monitoring, prediction, prognosis,
treatment, or alleviation of disease;
• diagnosis, monitoring, treatment, or alleviation of or
compensation for an injury or disability;
• investigation, replacement, or modification of the anat-
omy, or of a physiological or pathological process or state;
• providing information by means of in vitro examination
of specimens derived from the human body, including
organ, blood, and tissue donations.
The following types of product are also deemed to be
medical devices:
• devices for the control or support of conception;
J. K. Aronson et al.
• products specifically intended for the cleaning, disinfec-
tion, or sterilization of devices.
This description closely follows the definition framed
by the European Union (EU) in 1993 [8], and incorporates
amendments made to the UK legislation in 2008 [9]. The EU
defines combination products as follows [10]:
• If the principle [sic] intended action of the combination
product is achieved by the medicine, the entire prod-
uct is regulated as a medicinal product under Directive
2001/83/EC or Regulation (EC) No 726/2004.
• There are two types of combination:
• integral: the medicinal product and device form a
single integrated product, e.g. pre-filled syringes and
pens, patches for transdermal drug delivery, and pre-
filled inhalers;
• co-packaged: the medicinal product and the device
are separate items contained in the same pack, e.g. a
reusable pen for insulin cartridges and a tablet deliv-
ery system with controller for pain management.
2.2 USA
In the USA, the FDA defines a medical device similarly to
the EMA, as:
• “an instrument, apparatus, implement, machine, contriv-
ance, implant, in vitro reagent, or other similar or related
article, including a component part or accessory which
is: recognized in the official National Formulary, or the
United States Pharmacopeia, or any supplement to them,
• intended for use in the diagnosis of disease or other con-
ditions, or in the cure, mitigation, treatment, or preven-
tion of disease, in man or other animals, or
• intended to affect the structure or any function of the
body of man or other animals, and which does not achieve
its primary intended purposes through chemical action
within or on the body of man or other animals and which
is not dependent upon being metabolized for the achieve-
ment of any of its primary intended purposes” [11].
However, strictly speaking, these are not definitions, but
descriptions of the attributes that are currently regarded as
being typical of devices for the purposes of regulation. They
may be helpful to regulators, but they are long and com-
plex, they provide no insights on use, site of application,
or potential risks, and they may have to be amended when
newer forms of devices are invented. A simpler definition
that would not need to be so adapted would be useful. We
therefore propose such a definition below.
Medical Devices: Definition, Classification and Regulatory Implications
The FDA’s definition of a combination product [12] is
more detailed than the EMA’s definition.
• A product comprising two or more regulated compo-
nents, i.e. drug/device, biologic/device, drug/biologic,
or drug/device/biologic, that are physically, chemically,
or otherwise combined or mixed and produced as a single
entity.
• Two or more separate products packaged together in
a single package or as a unit and comprising drug and
device products, device and biological products, or bio-
logical and drug products.
• A drug, device, or biological product packaged separately
that according to its investigational plan or proposed label-
ling is intended for use only with an approved individually
specified drug, device, or biological product where both are
required to achieve the intended use, indication, or effect
and where upon approval of the proposed product the label-
ling of the approved product would need to be changed, e.g.
to reflect a change in intended use, dosage form, strength,
or route of administration, or significant change in dose.
• Any investigational drug, device, or biological product
packaged separately that according to its proposed label-
ling is for use only with another individually specified
investigational drug, device or biological product where
both are required to achieve the intended use, indication
or effect.
3 Proposed Definitions of a Medical Device
and a Combination Product
A device is defined in the Oxford English Dictionary as
“something devised or framed by art or inventive power; an
invention, contrivance; esp. a mechanical contrivance (usu-
ally of a simple character) for some particular purpose” [13].
This definition contains three important elements: a device
is (1) a contrivance that is (2) designed and manufactured
(“devised or framed”) (3) for a particular purpose. To define
a medical device, we can add to these three characteristics
the stipulation that the product is for use in healthcare and is
neither medicinal nor nutritional. We therefore propose the
following definition:
This definition implies that any device that incorporates
medicinal agents should be regarded as a combination prod-
uct, which can be defined separately:
We also propose that devices that incorporate a medicine
or medicines should be regulated to the same standards as
pure medicinal products, rather than those currently applied
to devices, which are less stringent.
4 Classifications of Medical Devices
Difficulties in classifying devices arise from their multiplic-
ity and their many uses [14]. For example, the FDA’s Global
Unique Device Identification Database (GUDID) lists over
2.2 million items and is growing daily by an estimated
2500 [15]. The FDA has grouped devices into those used
in each of 19 specified medical specialties or panels [16].
Table 1 shows an analysis of 6450 devices, out of a total
of about 110,000 registered by the FDA, that are included
in MAUDE (the FDA’s database of Manufacturer and User
Facility Device Experiences, which lists spontaneous reports
of problems with devices).
The MAUDE database (6450 devices at the time of writing)
runs, in alphabetical order of the codes, from a device for pro-
tecting the teeth during anaesthesia (AN|AN|BRW|Protector,
Dental|1||N|N||868.5820|4|||||N|N) to a system to measure
minoxidil sulfotransferase activity “as an aid in assess-
ing the likelihood that a patient will respond to minoxidil”
(TX||PSS|Minoxidil Sulfotransferase Or Isoenzymes Test
System|N|3|N|N|||7|), followed by 208 items not assigned
to any panel [17]. Of these 6450 items, 307 are assays, 286
are kits, 207 are catheters, 69 are tests, 69 are trays, 29 are
stents, and 24 are cannulae (or cannulaes as one entry has it).
Many of the entries on kits carry a statement that includes the
information that “This product code has been established in
accordance with the May 20, 1997, Guidance entitled, Con-
venience Kits Interim Regulatory Guidance.”
The quality of the text accompanying these product codes
is variable. Some have no descriptions at all. Indications are
not uniformly described; in 540 cases, the word “intended”
is used and in 129 “indicated”; in 44 cases, we are told what
the device is not intended for; 53 devices are referred to as
being partly or wholly reusable or, in 33 cases, potentially
so (“if the device is reusable”), even though one would have
expected it to be known in advance whether it was, was not,
or might be. In 76 cases, a code is assigned to a product that
has been processed for reuse (“reprocessed”), for example:
HO|HO|FMI|Needle, Hypodermic, Single Lumen|2||N|Y|M
|880.5570|1|||||N|N|Eligible
 J. K. Aronson et al.

Table 1  The US Food and Drug Administration’s grouping of medical devices by panels and an analysis of 6450 listed devices (on 21 October
2018)
Panel Abbreviation Number (%) of entries in Number (%) affected in the Number (%) of devices
­MAUDEa specialty assessed c­ oncordantlyb

Anesthesiology AN 230 (3.6) 215 (3.3) 205 (89)

Cardiovascular CV 358 (5.6) 291 (4.5) 267 (75)
Chemistry CH 482 (7.5) 501 (7.8) 445 (92)
Dental DE 335 (5.2) 312 (4.8) 301 (90)
Ear, nose, and throat EN 243 (3.8) 216 (3.4) 212 (87)
Gastroenterology and urology GU 565 (8.8) 517 (8.0) 487 (86)
General and plastic surgery SU 515 (8.0) 503 (7.8) 426 (83)
General hospital HO 351 (5.4) 281 (4.4) 262 (75)
Hematology HE 277 (4.3) 371 (5.8) 213 (77)
Immunology IM 277 (4.3) 275 (4.3) 239 (86)
[Unspecified] MG 2 – –
Microbiology MI 476 (7.4) 445 (6.9) 439 (92)
Neurology NE 235 (3.6) 182 (2.8) 170 (72)
Obstetrical and gynecological OB 261 (4.1) 245 (3.8) 230 (88)
Ophthalmic OP 319 (5.0) 284 (4.4) 283 (89)
Orthopedic OR 302 (4.7) 241 (3.7) 234 (77)
Pathology PA 290 (4.5) 118 (1.8) 101 (35)
Physical medicine PM 198 (3.1) 210 (3.3) 189 (95)
Radiology RA 192 (3.0) 171 (2.7) 160 (83)
Toxicology TX 434 (5.2) 262 (4.1) 259 (78)
Not assigned – 208 (3.2) 808 (12.6) –
Total 6450 6448 5122 (79)
Top four GU, SU, CH, MI PM, CH, MI, DE

MAUDE Food and Drug Administration’s database of Manufacturer and User Facility Device Experiences
a
 See text
b
 The number of devices coded to a specialty and assessed by the same specialty panel

HO|HO|NKK|Needle, Hypodermic, Single Lumen, Reproc 4.2 European Union

essed|2||N|N||880.5570|1|||||N|N|Eligible
The FDA also specifies devices used to sustain life as a
separate category, regarded as being of high risk.
4.1 US Food and Drug Administration’s Product
Codes
The FDA also gives devices product codes according to 18
characteristics (Fig. 1). Many devices can be used in more
than one of the 19 specialties, and thus the classification is
at least in part pragmatic: presumably the FDA assigns the
application for a device licence to the panel it considers best
qualified to assess the application, and about 80% of the time
that is the panel that one would expect to be chosen (Table 1,
right-hand column). It is not clear how this classification
helps the user, as opposed to the regulator.
The EU separates devices by the intended duration of use,
the extent of their contact with the body when in use, and
whether they are “active” (that is, use an external power
source), and differentiates devices used in the central car-
diovascular and central nervous systems from other devices,
presumably because they are regarded as involving greater
risks. This classification has the merit of ordering devices
according to the risks that they may cause harms, and we
propose a classification based on this approach, as shown in
Table 2 and Fig. 2.
In this classification, there is a relationship between the
ordering of the categories and the risks of harms that devices
can cause. For example, in the section “site of application”,
the probability of harm is expected to be least in category S1
(“does not touch the surface”) and greatest in category S3
(“enters the body”); in category S3, the probability of harm
is expected to increase across the subcategories.
Medical Devices: Definition, Classification and Regulatory Implications

11. Submission Type ID

9. Third Party Review Code 13. Physical State

7. GMP Exempt Flag 15. Target Area

1. Review Panel
(Anesthesia) 3. Product Code 5. Device Class 17. Life Sustain Support Flag

AN|AN|BRW|Protector, Dental|1| |N|N| |868.5820|4| | | | |N|N|Eligible

2. Medical Specialty (Anesthesia) 4. Device Name 18. Summary Malfunction Reporting

6. Unclassifed Reason Code 16. Implant Flag

8. Third Party Review Eligible 12. Definition 14. Technical Method

10. Regulation number

Fig. 1  US Food and Drug Administration’s devices product codes, according to 18 characteristics, as listed in the Product Code Classification
Files (https​://www.fda.gov/medic​al-devic​es/class​ify-your-medic​al-devic​e/downl​oad-produ​ct-code-class​ifica​tion-files​)

Table 2  The STP classification of medical devices by site of application (S), time scale of use (T), and power source (P)
Category Example

Site of application (S)

 S1. Does not touch the surface
  S1.1. Accessory Prescribing software; gestation calculators; devices for preparing pharma-
ceutical products
  S1.2. Associated with biological samples (e.g. blood or tissues) Point-of-care test equipment (e.g. blood glucose meters); laboratory equip-
ment (e.g. biochemistry, bacteriology, histology, genetic sequencers)
  S1.3. Acting on the patient Dermatoscopes; ophthalmoscopes; radiological equipment (e.g. CT, MRI)
 S2. Is applied to the surface
  S2.1. Applied to the surface Bandages and splints; some thermometers
  S2.2. Applied to the surface and attached to another device or O2 saturation monitors; electrocardiographic electrodes; external defibril-
attached to a device that is applied to the surface lators; radiological equipment (e.g. ultrasound, transthoracic echocardi-
ography)
 S3. Enters the body
  S3.1. Though an orifice Endoscopes; some thermometers; RFID-tagged gelatin capsules; radiologi-
cal equipment (e.g. ultrasound, transoesophageal echocardiography);
endotracheal tube; laryngeal spray
  S3.2. Through the surface Scalpels; biopsy needles; intra-arterial blood pressure transducers; haemo-
dialysis equipment; percutaneous endoscopic gastrostomy (PEG) tubes;
infusion pumps
  S3.3. Implanted Pacemakers; artificial lenses; artificial heart valves; implantable defibrilla-
tors; implantable ventricular assist devices; vaginal mesh
Time scale of use (T)
 T1. Transient (single use or repeated use) Scalpels; biopsy needles
 T2. Short-term Bandages; plaster casts; steinmann pins; IV cannulae; ventilators
 T3. Long-term Pacemakers; artificial lenses; artificial heart valves; artificial joints; ven-
triculoperitoneal shunts; vaginal mesh; Hickman lines
Power source (P)
 P1. Inactive (no power source) Scalpels; biopsy needles; foil blankets
 P2. Active source (e.g. electrical) Lasers as surgical instruments; ventilators; forced air body warmers; blood
glucose meters; ­O2 saturation monitors; ophthalmoscopes; telemetry

CT computed tomography, IV intravenous, MRI magnetic resonance imaging, RFID radio-frequency identification

Regulation (EU) 2017/745 of 5 April 2017 establishes an
electronic system for Unique Device Identification (the “UDI
database”), which enables unique identification in the EU
market and facilitates their traceability [18]. According to
Annex VI, Part C, the UDI is a series of numeric or alphanu-
meric characters of a globally accepted device identification
and coding standard.
The exact nomenclature has not yet been specified by the
EU [19]. However, the data elements of the UDI will prob-
ably include:
• risk class and additional characteristics necessary to
identify specific conformity assessment features (e.g.
implantable, measuring function);
• medical device nomenclature code;
• name or model identifying the Basic UDI-DI group in the
technical documentation and/or certificate and declara-
tion of conformity.
[The UDI-DI is the key identifier of a device in Eudamed,
the EU’s equivalent of the FDA’s GUDID.]
5 Regulation of Medical Devices
through Risk Classification
Regulation of medical devices is evolving. For example,
in the EU, devices currently have a CE [“Conformité
Européenne”] mark, but the requirements for obtaining
one vary from device to device, depending largely on a
system based on risk assessment. The Medical Devices
Regulation and the In Vitro Diagnostic Regulations will
be implemented in the EU in May 2020 and 2022 respec-
tively [20].
5.1 European Union
European Union legislation distinguishes four classes of
devices (I, IIa, IIb, III; see Appendix 1) [7]. The class of a
device is decided according to rules that consider its duration
of use, whether it is invasive or surgically invasive, whether
it is implantable or non-implantable, whether it is active, and
whether it contains a substance that in its own right is con-
sidered to be a medicinal substance and has action ancillary
to that of the device. It is not practical to subject all medi-
cal devices to the most rigorous CE assessment procedures.
The classification of devices therefore reflects the level of
potential hazard of a device, and the purpose of the classi-
fication is to channel the device into the correct assessment
procedure for approval.
The rules also examine whether the device comes into
one or more of the following categories: reusable surgical
instruments, active medical devices, active therapeutical
J. K. Aronson et al.
[sic] devices and active devices for diagnosis. Furthermore,
there are specific regulations for advanced therapy products
that combine a medicine and a device [21]. European stand-
ards organizations regulate, for example, the symbols to be
used on labels, the forms of connectors for liquids and gases,
and the risk management of devices [22].
5.2 USA
The US legislation divides medical devices into three classes
(1, 2, and 3; see Table 3, Appendix 2), intended to reflect the
risks that the device poses [23]. The classes specify which
of a range of controls (General Controls, Special Controls,
and Premarket Clearance) are relevant to their regulation,
but have also occasionally been used in studies of adverse
events attributed to devices [24].
Assignment to one of the three classes is determined by
a series of decisions based on the perceived risks of the
device when used for its intended purpose [25]. In princi-
ple, the least stringent requirements are that the device is
perceived to be of low risk, and that the manufacturer has
complied with the standards of good manufacturing prac-
tices. A device can be approved through a 510(k) application
if it is thought to be “substantially equivalent” to a previ-
ously approved device. Any device that is perceived to pose
a significant risk and is not similar to a previously approved
device may be required to undergo investigation. However,
these regulations have not always succeeded in preventing
serious harm to patients, as demonstrated by the case of
vaginal mesh [26]. In Fig. 2, we show a proposed system of
regulation of medical devices based on our proposed clas-
sification of the types of medical devices.
6 Discussion
Regulation of medicinal products has been developed over
many years [27, 28]. The regulation of medical devices is
less well developed than the regulation of medicinal prod-
ucts, which it could follow more closely. For example, infor-
mation about individual devices is of variable quality and
sometimes difficult to find.
Because medicines are currently more stringently regu-
lated than devices, it makes sense that devices that incorpo-
rate medicines should be required to meet the same regula-
tory standards as medicinal products. This would apply, for
example, to drug-eluting stents and to lidocaine provided in
syringes. It would remove the anomaly that some delivery
systems that incorporate medicines are classified as devices
while other similar systems that deliver the same medicines
are classified as medicinal products.
Some improvements might also result from more wide-
spread use of registries, such as those used for prosthetic
Medical Devices: Definition, Classification and Regulatory Implications

Regulatory implication
Classification
• ISO 13485 Medical devices―quality management systems
• Accessory
• Associated with biological • The ISO 10993 set entails a series of standards for
Not touching
the body samples evaluating the biocompatibility of medical devices
• Acting on the patient • ISO 14971 is an ISO standard for applying risk
management to medical devices

• Not attached to another • Regulation (EU) 2017/745―5 April 2017 on medical

Site of Applied to the device devices*
application surface • Attached to another device • Regulation (EU) 2017/746―5 April 2017 on in vitro
(electrical) diagnostic medical devices†

• Regulation (EU) 2017/745―Interpretation of clinical

• Through an orifice investigations with mandatory clinical registries, using a
Enters the body • Through the surface unique ID and premarket approval clinical trials with
• Implanted expedited licences (follow up at 2 and 5 years)

• ISO 14971:2007 provides manufacturers globally with a

• Single use framework for application of risk management to medical
Transient
• Repeated use devices
Time scale • EN ISO 14971:2012 applies only to manufacturers with
Temporary
of use devices intended for the European market
Permanent
• CENELEC is the European Committee for Electrotechnical
Standardization
Active • Electrical standard IEC/TC 62 is the international
Power committee where many standards for medical electrical
Inactive equipment are developed.
• Key standards are contained in the IEC 60601

Fig. 2  Classification of medical devices based on the site of application, the time scale of use, and whether it is electrically powered, with the
regulatory implications of the classification

joint replacements [29]. These would allow both prospective
examination of the performance of high-risk devices and
retrospective analysis when signals from other sources of
information [30] suggest problems. The EU also envisages
a European Database on Medical Devices, whose “vigilance
module will inform Member States on incidents or near-
incidents in relation to certain devices on the market” [31].
The key attributes of registries in contributing effectively
to the work of regulators in medical device regulation have
been reviewed [32].
Those who apply for a market authorization for a new
medicine need to assure regulators of its quality of manufac-
ture, safety and efficacy before licensing. Copies of existing
medicines need to be demonstrably similar to the origina-
tor. The same is not true of devices. It may be that even the
most straightforward device should be shown to be useable
in practice. While trials on patients may be unreasonable,
simulations of use in the real world should be practicable,
even for devices such as implants. Scrutiny by experts, as
will be required in the EU from May 2020 [18], should
improve matters.
We recognise the problems facing designers of medical
devices, and barriers that need to be overcome, detailed con-
sideration of which is outside our scope here. For example,
human factors that act as barriers to the adequate design of
medical devices have been recognised, and four main chal-
lenges in implementing international standards of design of
devices have been identified [33]: (1) a lack of direct access
to users for the purposes of device development; (2) a lack
of understanding by users regarding the effects of feedback
on the development process; (3) contract formalities limiting
user exchanges; and (4) how the attitudes of clinical users
directly affect the development processes. Good design prac-
tice has been reviewed [34] and specific design problems
have also been discussed, in relation, for example, to drug-
eluting devices [35], three-dimensional printed devices [36],
and the use of biopolymers [37].
7 Conclusions
We propose defining a medical device as “A contrivance
designed and manufactured for use in healthcare, and not
solely medicinal or nutritional.” Current regulatory classifi-
cations of medical devices are complex and designed primar-
ily for regulators. We propose a simpler classification, based
on (1) the site of application of the device, (2) the time scale
of its use, and (3) whether it has an external power source.

Devices that incorporate medicines should be required to
meet the same regulatory standards as medicinal products.
This would remove the anomaly that some delivery systems
that incorporate medicines are classified as devices while
other similar systems that deliver the same medicines are
classified as medicinal products.
Some improvements might also result from more wide-
spread use of registries, such as those used for prosthetic
joint replacements. Registries would allow both a prospec-
tive examination of the performance of high-risk devices and
a retrospective analysis when signals from other sources of
information suggest problems.
Those who apply for a marketing authorization for a new
device should have to assure regulators of its quality of
manufacture, safety, and efficacy before licensing. Even the
most straightforward device should be shown to be useable
in practice. Trials on patients, or at least simulations of use
in the real world, should be practicable for most devices.
Acknowledgements  We are grateful to the International Society of
Pharmacovigilance for allowing us to organize a symposium on medi-
cal devices, held at the International Society of Pharmacovigilance
2018 meeting in Geneva, on which this and a companion paper are
based.
Compliance with Ethical Standards 
Funding  No sources of funding were used to assist in the preparation
of this article.
Conflict of interest  Jeffrey K. Aronson has received royalties for ma-
terial published in Meyler’s Side Effects of Drugs: the International
Encyclopedia of Adverse Drug Reactions and Interactions and the Side
Effects of Drugs Annuals, which include material on medical devices.
Carl Heneghan receives funding from the National Institute for Health
Research (NIHR) Oxford Biomedical Research Centre and the NIHR
School of Primary Care Research Evidence Synthesis Working Group
[Project 390]. He receives expenses for teaching evidence-based medi-
cine and is paid for his general practitioner work in the National Health
Service out of hours. He is the Editor-in-Chief of BMJ Evidence-Based
Medicine and an NIHR Senior Investigator. Robin E. Ferner has no
conflicts of interest that are directly relevant to the content of this ar-
ticle.
Ethical approval  Patients were not involved in this study and ethics
approval was not required.
Data sharing  The data on which this work is based are freely available
on request.
Appendix 1: European Union regulation
of medical devices
The European Union legislation distinguishes four classes (I,
IIa, IIb, III) [6]. The class of a device is decided according
to rules that consider:
J. K. Aronson et al.
1. Duration of use of the device
Transient
Short-term
Long-term
2. Invasiveness of the device
Non-invasive
Invasive
Body Orifice
Surgically invasive
Implantable
The rules also examine whether the device comes into
one or more of the following categories:
3. Reusable surgical instrument
“Instrument intended for surgical use by cutting,
drilling, sawing, scratching, scraping, clamping,
retracting, clipping or similar procedures, with-
out connection to any active medical device and
which can be reused after appropriate procedures
have been carried out.”
4. Active medical device
“Any medical device operation of which depends
on a source of electrical energy or any source of
power other than that directly generated by the
human body or gravity and which acts by convert-
ing this energy.”
5. Active therapeutical [sic] device
“Any active medical device, whether used alone
or in combination with other medical devices,
to support, modify, replace or restore biological
functions or structures with a view to treatment
or alleviation of an illness, injury or handicap.”
6. Active device for diagnosis
7. Central circulatory system
Including the pulmonary circulation
8. Central nervous system
All medical devices in the European Union must fulfil the
essential requirements, which are that “The devices must be
designed and manufactured in such a way that, when used
under the conditions and for the purposes intended, they
will not compromise the clinical condition or the safety of
patients, or the safety and health of users or, where appli-
cable, other persons, provided that any risks which may be
associated with their use constitute acceptable risks when
weighed against the benefits to the patient and are compat-
ible with a high level of protection of health and safety.”
Medical Devices: Definition, Classification and Regulatory Implications

Those devices deemed to be in Classes IIa, IIb, and III must
fulfil additional requirements. The classification rules are
detailed. For example, “Rule 17: All devices manufactured
utilizing animal tissues or derivatives rendered non-viable
are Class III except where such devices are intended to come
into contact with intact skin only.”
There are specific regulations for advanced therapy prod-
ucts that combine a medicine and a device [16].
European standards organizations set out the criteria for a
large range of devices, including, for example, the symbols
to be used on labels; the form of connectors for liquids and
gases; and risk management [17].
Appendix 2: US regulation of medical
devices
The US legislation divides medical devices into three
classes, intended to reflect the risks that the device poses
(Table 3) [18].
Assignment to one of the three classes is determined by a
series of decisions based on the perceived risks of the device
when used for its intended purpose [19]. In principle, the
least stringent requirements are that the device is perceived
to be of low risk, and that the manufacturer has complied
with the standards of good manufacturing practices (GMP).
A device can be approved through a so-called 510(k) appli-
cation if it is thought to be “substantially equivalent” to a
previously approved device. Any device that is perceived
to pose a significant risk and is not similar to a previously
approved device may be required to undergo investigation.
The following are the full definitions of the three classes
shown in Table 3 [38].
1. Class I means the class of devices that are subject to
only the general controls authorized by or under sec-
tions 501 (adulteration), 502 (misbranding), 510 (reg-
istration), 516 (banned devices), 518 (notification and
other remedies), 519 (records and reports), and 520
(general provisions) of the act. A device is in class I if
(1) general controls are sufficient to provide reasonable
assurance of the safety and effectiveness of the device,
or (2) there is insufficient information from which to
determine that general controls are sufficient to provide
reasonable assurance of the safety and effectiveness of
the device or to establish special controls to provide such
assurance, but the device is not life-supporting or life-
sustaining or for a use which is of substantial importance
in preventing impairment of human health, and which
does not present a potential unreasonable risk of illness
of injury.
2. Class II means the class of devices that is or eventually
will be subject to special controls. A device is in class
II if general controls alone are insufficient to provide
reasonable assurance of its safety and effectiveness
and there is sufficient information to establish special
controls, including the promulgation of performance
standards, postmarket surveillance, patient registries,
development and dissemination of guidance documents
(including guidance on the submission of clinical data
in premarket notification submissions in accordance
with section 510(k) of the act), recommendations, and
other appropriate actions as the Commissioner deems
necessary to provide such assurance. For a device that
is purported or represented to be for use in supporting
or sustaining human life, the Commissioner shall exam-
ine and identify the special controls, if any, that are
necessary to provide adequate assurance of safety and
effectiveness and describe how such controls provide
such assurance.
3. Class III means the class of devices for which premarket
approval is or will be required in accordance with sec-
tion 515 of the act. A device is in class III if insufficient
information exists to determine that general controls are
sufficient to provide reasonable assurance of its safety
and effectiveness or that application of special controls
described in paragraph (c)(2) of this section would pro-
vide such assurance and if, in addition, the device is

Table 3  The US Food and Drug Administration’s classification of medical devices; the full definitions are given in the text
Class Description Number of items
in MAUDE (%)

I Devices subject to general controls: general controls are sufficient to provide reasonable assurance of the safety and 2351 (36)
effectiveness of the device
II Devices subject to general controls and special controls: performance standards can be set out that will provide rea- 3145 (49)
sonable assurance of the safety and effectiveness of the device
III Devices subject to general controls, special controls, and premarket clearance: premarket approval is required if a 471 (7.3)
device is for a use in supporting or sustaining human life or of substantial importance in preventing impairment of
human health, or presents a potential unreasonable risk of illness or injury, and if there is insufficient information on
which to base a performance standard
Unclassified 483 (7.5)

MAUDE Food and Drug Administration’s database of Manufacturer and User Facility Device Experiences

life-supporting or life-sustaining, or for a use which is
of substantial importance in preventing impairment of
human health, or if the device presents a potential unrea-
sonable risk of illness or injury.
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