WHO Global Model Regulatory
Framework for Medical Devices
including in vitro diagnostic
medical devices
WHO Medical device technical series

WHO Global Model Regulatory
Framework for Medical Devices
including in vitro diagnostic
medical devices
WHO Medical device technical series

WHO global model regulatory framework for medical devices including in vitro diagnostic medical devices (WHOMedical device technical series)
ISBN 978-92-4-151235-0
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Contents
Acronyms and abbreviations

3

Acknowledgements

4

1 Introduction

5

1.1
1.2

The WHO Global Model Regulatory Framework for Medical Devices
including IVDs
Limitations of the WHO Global Model Regulatory Framework for
Medical Devices including IVDs

2. Deﬁnition, classiﬁcation, essential principles and conformity
assessment of medical devices
2.1
2.2
2.3

2.4

Deﬁnition of medical device and IVD
Medical devices classiﬁcation and classiﬁcation rules
Essential principles of safety and performance
2.3.1 Clinical evidence for non-IVDs
2.3.2 Assessing conformity to the Essential Principles
Special considerations for regulation of IVDs
2.4.1 Classiﬁcation of IVDs
2.4.2 Essential Principles of safety and performance for IVDs
2.4.3 Clinical evidence for IVDs
2.4.4 Lot veriﬁcation testing of IVDs

16
16
17
17
18
18
19
19
19

Legal requirements
Gap analysis of existing controls
Implementation plan
Monitoring implementation
Regulatory authority
Funding the regulatory system
Conﬂict of interest and impartiality
Regulatory competencies and resources

4. Establishing a stepwise approach to regulating medical devices
4.1

21
21
21
22
23
23

Stepwise approach
4.1.1 Reliance and recognition
4.1.1.1 National responsibilities
4.1.1.2 International collaboration

4.2

Basic-level controls and their enforcement
4.2.1 Publish law, including deﬁnition, and regulations withtransition period
4.2.1.1 Establish medical device classiﬁcation for regulatory purposes
4.2.1.2 Establish Essential Principles of safety and performance

4.2.2 Basic-level controls and enforcement – premarket
4.2.2.1 Establish a basis for reliance and recognition
4.2.2.2 Establish requirements for declaration of conformity
4.2.2.3 Establish requirement for manufacturers to have a QMS
4.2.2.4 Establish requirements for labels and labelling
4.2.2.5 Prohibit deceptive, misleading and false advertising
4.2.2.6 Establish provisions for exceptional premarket situations

7

8
8
9
10
11
12
13
13
14
14
15

3. Enabling conditions for effective regulation of medical devices
3.1
3.2
3.3
3.4
3.5
3.6
3.7
3.8

6

23
25
25
26
26
26
26
27
27
28

WHO Medical device technical series14.2.3 Basic-level controls and enforcement – placing on the market
4.2.3.1 Registration of establishments
4.2.3.2 Listing of medical devices
4.2.3.3 Import controls

4.2.4 Basic-level controls – postmarket
4.2.4.1 Establish a system for vigilance reporting
4.2.4.2 Require mandatory notiﬁcation by the manufacturer of FSCA
4.2.4.3 Establish a procedure to withdraw unsafe medical devices
from the market
4.2.4.4 Establish procedure to issue safety alerts to users
4.2.4.5 Undertake market surveillance

4.3

Expanded-level controls
4.3.1 Expanded-level controls – premarket
4.3.1.1 Create oversight of clinical investigations
4.3.1.2 Appoint and have oversight of CAB
4.3.1.3 Recognition of standards
4.3.1.4 Adopt a medical device nomenclature system
4.3.1.5 Control advertising and promotion

4.3.2 Expanded level controls – placing on the market
4.3.2.1 Perform in-country QMS audits
4.3.2.2 Perform review of submissions for compliance with Essential
Principles

4.3.3 Expanded-level controls – postmarket
4.3.3.1 Establish within the regulatory authority processes forpostmarket surveillance and vigilance
4.3.3.2 Require mandatory reporting of adverse events
4.3.3.3 Inspections of registered establishments
4.3.3.4 Provide for testing laboratories

4.4

Stepwise approach, harmonization, reliance, recognition

5. Additional topics
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8

Determination to establish whether a medical product is a
medical device
DisposalDonationsReprocessing of single-use medical devices
Refurbishing electromedical devices
Substandard and falsiﬁed products
WHO Prequaliﬁcation Team for IVDs
United Nations Population Fund Prequaliﬁcation Programme for
intrauterine devices and condoms

31
31
31
32
32
32
32
34
34
35
35
35
36
37
37
38
38
39
40
41
41
43
44
44
45
46
47
48

References

49

Further reading

57

Appendix 1

58
58
64

Glossary
References of the glossary

Appendix 2
Hierarchy of regulation

2

28
28
29
30
30
30
30

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

68
68

Acronyms and abbreviations
AHWP
ASEAN
ATMP
CAB
CLSI
FSCA
GDP
GHTF
GMDN
IEC
IMDRF
ISO
IVD
NRA
QMS
SF1
SUMD
UN
UNFPA
US FDAWHO
WHA

Asian Harmonization Working Party
Association of Southeast Asian Nations
advanced therapy medicinal products
conformity assessment body
Clinical and Laboratory Standards Instituteﬁeld safety corrective action
good distribution practice
Global Harmonization Task Force
Global Medical Device Nomenclature
International Electrotechnical Commission
International Medical Device Regulators Forum
International Organization for Standardizationin vitro diagnostic medical device
national regulatory authority
quality management system
substandard and falsiﬁed medical products
single-use medical device
United Nations
United Nations Population Fund
United States Food and Drug Administration
World Health Organization
World Health Assembly

1 The Member State mechanism on substandard/spurious/falsely-labelled/falsiﬁed/counterfeit (SSFFC) medical products has recommended the World Health Assembly to adopt
a simpliﬁed terminology for substandard and falsiﬁed (SF) medical products (EB140/23, Annex, Appendix 3 (dated 10 January 2017)).

WHO Medical device technical series

3

Acknowledgements
We gratefully acknowledge the members of the Working Group: Abdullah Salem Al-Dobaib,
Saudi Food and Drug Authority, Saudi Arabia; Tuncay Bayrak, Turkish Medicines and Medical
Devices Agency, Turkey; Donald Boyer, Canada; Michael Gropp, United States of America;
Alan Kent, England; Agnes Sitta Kijo, Tanzania Food and Drugs Authority, United Republic of
Tanzania; Niall MacAleenan, Health Products Regulatory Authority, Ireland; Nancy Shadeed,
Health Canada, Canada; Maura Linda Sitanggang, Ministry of Health, Indonesia; ShelleyTang, Stellar Consulting, Australia; Kim Trautman, NSF International Health Sciences, UnitedStates of America; Lupi Trilaksono, Ministry of Health, Indonesia; Recep Uslu, Ministry of
Health, Turkey; Woei Jiuang Wong, Health Sciences Authority, Singapore.
We gratefully acknowledge and recognize the contributions over many years of membersof the Global Harmonization Task Force (GHTF), the Asian Harmonization Working Party(AHWP), the International Medical Device Regulators Forum (IMDRF), and the World HealthOrganization (WHO) who developed the documents that form the basis for this Model
Framework.
We also gratefully thank: Sherry Keramidas, Regulatory Affairs Professionals Society (RAPS),
United States of America; Joanna Koh, Singapore; Bas Streef, Switzerland.
This project was supported by the following colleagues at WHO headquarters and regionalofﬁces: Claudia Alfonso, WHO headquarters, Switzerland; Laura Brown, WHO headquarters,
Switzerland; Michael Deats WHO headquarters, Switzerland; Daniela Decina, WHO
headquarters, Switzerland; Melissa Gomez Montero, WHO headquarters, Switzerland;
Adham Ismail, WHO Regional Ofﬁce for the Eastern Mediterranean, Egypt; Sinead Jones,
WHO headquarters, Switzerland; Sabine Kopp, WHO headquarters, Switzerland; Julia
Kuelzow, WHO headquarters, Switzerland; Jennette Leung, WHO headquarters, Switzerland;
Robyn Meurant, WHO headquarters, Switzerland; Micha Nuebling, WHO headquarters,
Switzerland; Razieh Ostad Delhaghi, WHO headquarters, Switzerland; Olexandr Polishchuk,
WHO Regional Ofﬁce for Europe, Denmark; Irena Prat, WHO headquarters, Switzerland;
Jakob Quirin, WHO headquarters, Switzerland; Mohamed Refaat, WHO headquarters,
Switzerland; Larissa Ratl, WHO headquarters, Switzerland; Lembit Rägo, WHO headquarters,
Switzerland; Sterre Recourt, WHO headquarters, Switzerland; Adriana Velazquez Berumen,
WHO headquarters, Switzerland; Viky Verna, WHO headquarters, Switzerland; Mike Ward,
WHO headquarters, Switzerland and David Woo, WHO headquarters, Switzerland.
This document was developed by the Department of Essential Medicines and Health
Products under the direction of Josée Hansen, WHO headquarters, Switzerland.

4

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

1 Introduction
Medical devices contribute to theattainment of the highest standards ofhealth for individuals. Without medical
devices, common medical procedures– from bandaging a sprained ankle, todiagnosing HIV/AIDS, implanting an
artiﬁcial hip or any surgical intervention– would not be possible. Medical devices
are used in many diverse settings, forexample, by laypersons at home, byparamedical staff and clinicians in remoteclinics, by opticians and dentists and byhealth-care professionals in advanced
medical facilities, for prevention andscreening and in palliative care. Such
health technologies are used to diagnose
illness, to monitor treatments, to assist
disabled people and to intervene andtreat illnesses, both acute and chronic.
Today there are an estimated 2 million
different kinds of medical devices on theworld market, categorized into more than
22 000 generic devices groups.1
In May 2007, the ﬁrst resolution on healthtechnologies was adopted by the World
Health Organization (WHO) World Health
Assembly (WHA) (WHA 60.29), which set
out the framework for an unprecedented
focus on health technologies, but more
speciﬁcally on medical devices. In 2014,
the WHA adopted a resolution regarding
regulatory system strengthening for
medical products (WHA 67.20). The
Resolution states “effective regulatory
systems are an essential componentof health system strengthening andcontribute to better health outcomes”.
In the context of Resolution 67.20, thegrowing interest in medical devices in
the global health community and the
1 The Global Medical Device Nomenclature Agency has listed more than 22 000
generic device groups for medical devices (Source: GMDN Agency).

lack of regulatory systems for medical
devices in many countries, WHO decided
to develop this document. It is intended
to provide guidance and support to WHO
Member States that have yet to develop
and implement regulatory controls
relating to medical devices, as well as
to jurisdictions that are continuing to
improve their regulatory frameworks as
they take steps to ensure the quality andsafety of medical devices available intheir countries. This WHO Global Model
Regulatory Framework for Medical
Devices including in vitro diagnostic
medical devices (IVDs) (hereafter referred
to as the Model) will provide a basis forsuch work.
Many countries have neither thefinancial resources nor the technicalexpertise to transition successfully
from an unregulated market to acomprehensive medical devices law in
a single programme. Instead, the Model
recommends a progressive, or stepwise,
approach to regulating the quality, safety
and performance of medical devices.
It provides guidance for a staged
development of the regulatory system.
This starts from basic-level controls –such as the publication of the law andresourcing the regulatory authority toundertake enforcement actions – thenprogresses to expanded-level controls– such as inspection of registeredestablishments and oversight of clinicalinvestigations.
The resources – people, funds,
technology and facilities – available in any
country for regulatory control of medical
devices are, and probably always will be,
limited. Generally, such resources will be

WHO Medical device technical series

5allocated to support overall government
policy objectives and priorities but will
also reflect the characteristics of thenational market for medical devices:public health needs and burden of
disease; demographic trends; economic
development; size of the country; sourcesof supply (e.g. primarily imported versus
domestic sources); and nature of deviceson the market.
More broadly, it should be understoodthat regulation of medical devices does
not take place in isolation, but should
be coordinated with regulation of othermedical products (e.g. medicines andvaccines) and wider government policy
objectives.

1.1 The WHO Global Model
Regulatory Framework for
Medical Devices including
IVDs
The Model recommends guiding
principles, harmonized deﬁnitions andspeciﬁes the attributes of effective andefficient regulation, to be embodied
within binding and enforceable law. Its
main elements refer to international
harmonization guidance documents
developed by the Global Harmonization
Task Force (GHTF) and its successor, theInternational Medical Device Regulators
Forum (IMDRF).
The Model is particularly relevant for WHO
Member States with little or no regulation
for medical devices currently in place butwith the ambition to improve this situation.
It foresees that such countries will
progress from basic regulatory controls
towards an expanded level to the extent

6that their resources allow. The Model iswritten for the legislative, executive andregulatory branches of government asthey develop and establish a system of
medical devices regulation. It describes
the role and responsibilities of a country’s
regulatory authority for implementing
and enforcing the regulations. Also, it
describes circumstances in which a
regulatory authority may either “relyon”, or “recognize” the work products
from trusted regulatory sources (suchas scientific assessments, audit andinspection reports) or from the WHO
Prequaliﬁcation Team.
Section 2 of this document recommends
deﬁnitions of the terms “medical devices”
and IVDs. It describes how they may begrouped according to their potential forharm to the patient or user and speciﬁes
principles of safety and performance thatthe device manufacturer must adhere to.
It explains how the manufacturer must
demonstrate to a regulatory authority thatits medical device has been designed andmanufactured to be safe and to perform
as intended during its lifetime.
Section 3 presents the principles ofgood regulatory practice and enabling
conditions for effectively regulating
medical devices. It then introduces
essential tools for regulation, explaining
the function of the regulatory entity andthe resources required.
Section 4 presents a stepwise approachto implementing and enforcing regulatory
controls for medical devices, as theregulation progresses from a basic to an
expanded level. It describes elementsfrom which a country may choose
according to national priorities and

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

challenges. Also, it provides information
on when the techniques of reliance andrecognition may be considered and on theimportance of international convergenceof regulatory practice.
Section 5 provides a list of additional
topics to be considered when developing
and implementing regulations for medical
devices. It explains the relevance of
these topics and provides guidance forregulatory authorities to ensure they are
addressed appropriately.

1.2 Limitations of the WHO
Global Model Regulatory
Framework for Medical
Devices including IVDs
The Model outlines a general approach but
cannot provide country-speciﬁc guidanceon implementation. While it does not offer
detailed guidance on regulatory topics it
contains references to relevant documents
where further information may be found.
It does not detail responsibilities of otherstakeholders such as manufacturers,
distributors, procurement agencies andhealth-care professionals, all of whom
have roles in assuring the quality, safety
and performance of medical devices.

WHO Medical device technical series72. Deﬁnition, classiﬁcation, essential principles
and conformity assessment of medical
devices
2.1 Deﬁnition of medical device
and IVDThe GHTF developed a deﬁnition of theterms medical device and IVD. Major
jurisdictions have accepted the principlesof this definition. In the interest ofinternational regulatory convergence it isrecommended to promote its widespreaduse.
Medical device1,2 means any instrument,
apparatus, implement, machine,
appliance, implant, reagent for in vitro use,
software, material or other similar or related
article, intended by the manufacturer to be
used, alone or in combination, for humanbeings, for one or more of the speciﬁc
medical purpose(s) of:• diagnosis, prevention, monitoring,treatment or alleviation of disease;• diagnosis, monitoring, treatment,
alleviation of or compensation for
an injury;• investigation, replacement,
modification or support of the
anatomy or of a physiological process;• supporting or sustaining life;• control of conception;• disinfection of medical devices;

1 Note from GHTF deﬁnition (http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/technicaldocs/ghtf-sg1-n071-2012-deﬁnition-of-terms-120516.pdf#search): Somejurisdictions include “accessories to a medical device” and “accessories to an
IVD medical device” within their deﬁnitions of “medical device” or “IVD medical
device”, respectively. Other jurisdictions do not adopt this approach but still subject
an accessory to the regulatory controls (e.g. classiﬁcation, conformity assessment,
quality management system requirements, etc.) that apply to medical devices or
IVD medical devices.
2 Spare parts, supplied for the replacement of existing components of a medical
device that has already been registered, are not usually considered to be
medical devices unless they are likely to signiﬁcantly change the characteristics
or performance of the ﬁnished device. If this is the case then such spare parts
are likely to be considered medical devices in their own right and therefore may
require regulatory control.

8• providing information by means ofin vitro examination of specimens
derived from the human body,and which does not achieve its primary
intended action by pharmacological,
immunological or metabolic means, inor on the human body, but which may beassisted in its intended function by suchmeans (1).
IVD3 means a medical device, whether
used alone or in combination, intended
by the manufacturer for the in vitro
examination of specimens derived from thehuman body solely or principally to provide
information for diagnostic, monitoring orcompatibility purposes (1).4 For a glossaryof other relevant terms, see Appendix 1.
There may also be products on themarket that are similar to medical
devices in function and risk that do notﬁt within these deﬁnitions. For reasonsof protecting public health they are
regulated as if they were medical devices.
Examples include: impregnated bed
nets to protect against malaria-bearing
mosquitoes; personal protective devices
to avoid cross-infection; lead aprons toprotect against radiation; some medical
gases; and implantable or other invasive
products for a cosmetic rather than amedical purpose (see section 5).

3 Tests that provide information on the predisposition to a medical condition or adisease (e.g. genetic tests) and tests that provide information to predict treatment
response or reactions (e.g. companion diagnostics) are IVDs.
4 Note 1 from GHTF deﬁnition (http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/technicaldocs/ghtf-sg1-n071-2012-deﬁnition-of-terms-120516.pdf#search): “IVD
medical devices include reagents, calibrators, control materials, specimen
receptacles, software and related instruments or apparatus or other articles andare used, for example, for the following test purposes: diagnosis; aid to diagnosis;
screening; monitoring; predisposition; prognosis; prediction; determination ofphysiological status.” Note 2: In some jurisdictions, certain IVDs may be coveredby other regulations.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

2.2 Medical devices
classiﬁcation andclassiﬁcation rules
The universe of medical devices is diverse
with wide variations in potential severityof harm to the patient or user. This Model
recommends that the regulatory authority
allocates its resources and imposes
controls proportional to the potential forharm associated with medical devices.
The regulation speciﬁes the manner inwhich a manufacturer should demonstrate
conformity with safety, performance andquality requirements. The regulatory
oversight by the authority should increasein line with the potential of a medical device
to cause harm to a patient or user (i.e. thehazard it presents). The risk class of a
medical device is determined by factors
such as the level of invasiveness andthe duration of use in the body and theduration in the body. In some jurisdictions,products such as viral inactivation devices
used in the manufacture of medicinalor biological products are deemed tobe higher risk medical devices and are
regulated accordingly. The risk class of an
IVD is determined primarily by the impactof an incorrect result, either on the healthof the individual or on public health. A
classiﬁcation system for medical devices
and IVDs guides the regulatory controls
to be implemented for each device class.
It is widely accepted that medical
devices are separable into groups orclasses, typically four, A, B, C and D, byapplying a set of classiﬁcation rules (2),and specifying separately the different
conformity assessment procedures thatshould apply to each group of devices(Figure A4.1).
The classification rules for medical
devices other than IVDs depend on thefeatures of the device, such as whether it:• is life supporting or sustaining;• is invasive and if so, to what extent
and for how long;• incorporates medicinal products;• incorporates human or animal tissues
or cells;• is an active medical device;• delivers medicinal products, energy
or radiation;• could modify blood or other body
ﬂuids;• is used in combination with anothermedical device.

Figure A4.1 Impact of device classiﬁcation on regulatory scrutiny

HIGHERREGULATORYREQUIREMENTS

LOWER

A

B

C

D

DEVICE CLASS

Note: As the regulatory requirements increase, so does the scrutiny by the regulatory authority.
Source: Reproduced from Principles of medical devices classiﬁcation (2).

WHO Medical device technical series

9Table A4.1 Examples of medical devices by risk classa

a

Class

Risk

ExamplesA

Low

Syringes, examination gloves, patient hoists, stethoscopes, wheelchairs, IVD instruments,
microbiological culture media

B

Low–moderate

Surgical gloves, infusion sets, pregnancy tests

C

Moderate–highCondoms (unless with spermicide (class D)), infusion pumps, neonatal incubators, therapeuticand diagnostic X-ray, lung ventilators, haemodialysers, anaesthesia equipment, self-test
glucose strips, IVDs for the diagnosis of Neisseria gonorrhoea

D

High

Implantable cardioverter deﬁbrillators, pacemakers, breast implants, angioplasty balloon
catheters, spinal needle, IVDs for the diagnosis of HIV, hepatitis C or hepatitis B

The actual classiﬁcation of each device depends on the claims made by the manufacturer for its intended use and the technology or technologies it utilizes. As an aid to interpretingthe purpose of each rule, illustrative examples of medical devices that should conform to the rule have been provided in the table above. However, it must be emphasized that amanufacturer of such a device should not rely on it appearing as an example but should instead make an independent decision on classiﬁcation taking account of its particular
design and intended use.

Classiﬁcation also takes into account thetechnical, scientiﬁc and medical expertiseof the intended user (layperson or healthcare professional).
For IVDs, the risk classiﬁcation depends
both on the risk for the individual and for
public health, taking into consideration:• the intended use (including whatis detected, the IVD function,
the specific disorder, condition
or risk factor of interest that the
IVD is intended to detect, define
or differentiate, and the testing
population);• the intended user;• the importance of the information
to the diagnosis, screening,monitoring or staging of disease (soledeterminant or one of several);• the impact of the test result on theindividual and/or on public health.
The GHTF has published documentson the classiﬁcation of medical devices
and IVDs that use the principles aboveto establish classification rules (2,3).
Additionally, the regulatory authority
may develop explanatory guidance tohelp a manufacturer apply the rules (4).
While the manufacturer has the primaryobligation to classify its medical device,its decision may be challenged by theregulatory authority.

10

2.3 Essential principles of safety
and performance
Regulations should specify that a medical
device should be safe and perform as
intended when placed on the market.
GHTF has established a list of Essential
Principles of safety and performancefor medical devices including IVDs (5).
These requirements have been widelyadopted. Manufacturers must beable to demonstrate to the regulatory
authority that their product complies
with the Essential Principles and has
been designed and manufactured to besafe and perform as intended during
its lifetime, when used according to the
manufacturer’s stated intended purpose.
The general Essential Principles apply to
all medical devices and are supplemented
by those principles speciﬁc to particular
medical device types (e.g. implants orelectrically powered devices).
The general Essential Principles of safety
and performance for medical devices
include the following.
• The processes for the design andproduction should ensure that a
medical device when used according
to the intended purpose and meetingthe conditions of technical knowledge
and training of the user is safe and

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devicesdoes not compromise the clinicalcondition of the patient or the healthof the user.
• The manufacturer should performa risk assessment to identify known
and foreseeable risks and to mitigate
these risks in the design, production
and use of the medical device.
• Medical devices should perform as
the manufacturer intended whenused under normal conditions.
• Performance and safety should not
be affected during the lifetime of a
medical device in such a way that
it affects the safety of the patient or
the user.
• Performance and safety should not
be affected by transport or packaging
and storage, provided the instructions
for packaging, transport and storage
are followed.
• Known and foreseeable risks should
be weighed against the beneﬁts of
the intended purpose.

2.3.1 Clinical evidence for non-IVDs

Ensuring that a medical device conforms
to all relevant Essential Principles (5) is
the responsibility of the manufacturer.
However, the manufacturer’s evidenceof conformity, recorded in its technicaldocumentation, may be subject to review
by the regulatory authority, either before
or after market introduction. The medical
device regulation shall specify the extent
of the regulatory authority’s involvementwith different classes of device (6). Whileretaining responsibility for the decisions
it makes, the regulatory authority
may appoint one or more conformity
assessment bodies (CABs)5 to assist it inthis task (see section 4).

Some technologies have been available
for many years and their clinical safety
and performance have been wellcharacterized. Many devices, however,utilize new technology that has had
little prior application in the diagnosis ortreatment of humans and for which safety
and clinical performance have not yet
been established.

One of the requirements of the Essential
Principles is that “the device will perform
as intended by the manufacturer andnot compromise the clinical condition or
the safety of patients”. Clinical evidence
is important to demonstrate theserequirements. It is a component of thetechnical documentation of a medical
device, which together with other design
veriﬁcation and validation documentation,
device description, labelling, risk analysis
and manufacturing information, is needed
to allow a manufacturer to demonstrate
conformity with the Essential Principles.
In deciding whether to authorize a
medical device, the regulatory authority
may consider the acceptance of datafrom clinical investigations conducted
outside its jurisdiction, provided that theapplicant has demonstrated that thedata are adequate and were obtainedin accordance with applicable global
standards.

For long-established technologies,
clinical investigation data that might berequired for novel technologies may not
be necessary. The available clinical datain the form of literature, reports of clinicalexperience, postmarket reports andadverse event data for previous versions of
the device may, in principle, be adequate

5 Certain technical elements of the regulatory framework may be delegated to“designated” or “recognized ” CABs. For example, they may be approved toperform initial certiﬁcation and surveillance audits of a device manufacturer’squality management system (QMS) and/or premarketing evaluation of device
conformity with the Essential Principles. Satisfactory compliance with requirements
is typically conﬁrmed by the CAB issuing a design examination or QMS audit
certiﬁcate. Based on the CAB’s evaluation the regulatory authority may makeﬁnal decisions on compliance. The CAB performs its evaluation under the oversightof the regulatory authority and may be subject to periodic assessments by that
authority.

WHO Medical device technical series

11to establish the safety and performance ofthe device, provided that new risks havenot been identiﬁed, and that the intendeduse(s)/purpose(s) has/have not changed.
The manufacturer should perform adocumented comprehensive evaluationof all the available clinical evidence under
the control of its quality management
system (QMS). That clinical evaluation
report becomes part of the technicaldocumentation for the device and may
serve as the basis for determining whether
a new clinical investigation is appropriate(7). A widely used international standard
for the practice of clinical investigation is
ISO 14155:2011 – Clinical investigationof medical devices for human subjects –Good clinical practice (8).

2.3.2 Assessing conformity to the
Essential Principles
To a large extent the quality, safety
and performance of a medical device
are determined by systematic controls
applied by the manufacturer to its design,development, testing, manufacture anddistribution over the device’s life cycle.
In general, the manufacturer does thisthrough implementation of a QMS. The
degree of assessment of the QMS by
the regulatory authority or CAB depends
on the medical device risk class (6) (seesection 4) (Table A4.2).
Depending on the class of the medical
device, the evidence of conformity may
be subject to regulatory assessment by
the regulatory authority or CAB.

Table A4.2 Conformity assessment processes as determined by device class

Conformity
assessment
elementa

12Class AClass BClass CClass D

Quality
management
system (QMS)

Regulatory audit
normally not required,except whereassurance of sterilityor accuracy of themeasuring function isrequired.

The regulatory
authority shouldhave conﬁdence
that a current andappropriate QMS isin place or otherwise
conduct a QMS audit
prior to marketing
authorization.

The regulatory
authority shouldhave conﬁdence
that a current andappropriate QMS isin place or otherwise
conduct a QMS audit
prior to marketing
authorization.

The regulatory
authority shouldhave conﬁdence
that a current andappropriate QMS isin place or otherwise
conduct a QMS audit
prior to marketing
authorization.

Technical
documentationa

Premarket submission
normally not
requested.

Not normally reviewed
premarket. The
regulatory authority
may request andconduct a premarket or
postmarketing review
sufﬁcient to determine
conformity with
Essential Principles.

The regulatory
authority will
undertake a review
sufﬁcient to determine
conformity with
Essential Principles
prior to the device
being placed on themarket.

The regulatory
authority will
undertake an in-depth
review to determine
conformity with
Essential Principles,prior to the device
being placed on themarket.

Declaration ofconformity

Submission normally
not requested.

Review and verify
compliance withrequirements by theregulatory authority(see footnote to Table
A4.1).

Review and verify
compliance withrequirements by theregulatory authority(see footnote to Table
A4.1).

Review and verify
compliance withrequirements by theregulatory authority(see footnote to Table
A4.1).

There are many terms used to describe a product’s technical documentation. The terms include technical ﬁle, standard technical documentation, design dossier, product design
dossier, product summary ﬁle and product master ﬁle.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Class A medical devices, except those thatare sterile or have a measuring function,
are usually notiﬁed by the manufacturer
to the regulatory authority by listing before
being placed on the market and are
generally not subject to premarket onsite QMS audits. Class A medical devices
do not require premarket submissionof technical documentation, but the
manufacturer is required to maintaintechnical documentation demonstrating
conformity with the Essential Principles.
The regulatory authority may, at its
discretion, require submission of asummary of the technical documentation
and/or other evidence of conformity withthe regulatory requirements.
For medical devices in all classes, theregulatory authority or CAB should havesufﬁcient evidence to demonstrate theconformity of the manufacturing site(s)with the QMS requirements. For Class A
devices, this would generally be on thebasis of the manufacturer’s declarationof conformity. For devices in Classes
B and C, the regulatory authority cangenerally rely upon assessments andaudits conducted by other recognizedregulatory authorities or a CAB, whensuch audits have been done. For Class
D devices, the regulatory authority or
CAB may supplement such reliance with
its own QMS audits. In all cases, theregulatory authority or CAB should retain
the enforcement power and discretion to
conduct its own QMS audits.
For medical devices in Classes C andD, the premarket assessment usually
includes a review of the summary
technical documentation. This would
typically comprise a device description,
the Essential Principles checklist, therisk management report, information
on design and manufacturing, clinicalevidence, product verification andvalidation and labelling. The regulatory
authority should specify whether
summarized or detailed information

should be submitted; typically for Class
D devices detailed information would beneeded, while Class C devices may require
only summary information. The regulatory
authority could rely upon or recognize
the work of another regulatory authority
but the ﬁnal responsibility lies with thenational regulatory authority (NRA). For
all classes of devices the manufacturer
should prepare, hold and be preparedto submit as required a declaration ofconformity that the device complies fully
with all regulatory requirements (6).

2.4 Special considerations forregulation of IVDs
According to the Model, IVDs mustcomply with regulatory requirements
similar to those for other medical devices.
However, there are some differencesthat require consideration. This section
discusses those differences and proposes
steps to address them.

2.4.1 Classiﬁcation of IVDs
As for other medical devices, riskbased classification provides a basis
for allocating and prioritizing resourcesin assessment of the IVDs supplied ina particular market. There are a large
number and variety of IVDs available,with varying impact on the diagnosis
and treatment of patients. The higher
the risk associated with an IVD, themore stringent the assessment should
be. Unlike other medical devices, therisk associated with an IVD is indirect
and is related to the risk of an incorrect
diagnosis, to both the patient being
examined and the population in general.
For instance, an undiagnosed patientwith a serious infectious disease can put
a whole community at risk.
Because of the different risk proﬁle, theclassiﬁcation rules developed for othermedical devices on the basis of interaction
with the body are not suitable for IVDs.

WHO Medical device technical series

13

The GHTF has published a documentthat provides a classification scheme
for IVDs, based on risk to the individual
and to public health (3). The highest risk
IVDs are those that may impact on publichealth, in terms of detection of infectious
disease, or in determining the safety ofblood or blood products for transfusion or
tissue for transplantation. The IVD classes
in ascending order of risk are:
• A – low individual risk;• B – low public health risk and/or
moderate individual risk;• C – moderate public health risk, buthigh individual risk;• D – high individual risk and highpublic health risk.
The importance of the result of the IVD
in making a diagnosis is also a factor; ahigher risk class is assigned where the
IVD is the sole determinant in making adiagnosis.

2.4.2 Essential Principles of safety
and performance for IVDs
The GHTF has developed additional
Essential Principles that apply to IVDs (5).
While the Essential Principles are similar innature for each product type, the different
conditions of use of IVDs require more
speciﬁc wording in some cases and moredetailed explanation in others. Values
assigned to calibrators and controls of
IVDs need to be traceable to availablereference measurement procedures
and/or available reference materials of ahigher order (ISO 17511:2003).
The main differences are that the
Essential Principles for IVDs:• do not cover incorporation ofsubstances considered to be a
medicine as even if these substances
are present, there is no effect on thehuman body;• place less emphasis on the needfor veterinary controls on animals
used as the source of biologicalmaterial, as the risk of transmissible

14

spongiform encephalopathy infection
is reduced due to the mode of useof IVDs;• include a requirement for thedesign to ensure that performance
characteristics support the intendeduse;• do not include requirements inrelation to protection against ionizing
radiation, since this is not a functionof IVDs;• have more limited requirements
in relation to electrical safety andsupply of energy, since IVDs do notconnect to, or supply energy to thepatient;• include requirements for IVDs for
self-testing;• include requirements for performance
evaluation of the IVD (whereas
clinical evaluation is appropriate for
non-IVD medical devices).
In developing and implementing a
regulatory system, jurisdictions areadvised to adopt the GHTF Essential
Principles speciﬁc to IVDs, in addition to
those for other medical devices.

2.4.3 Clinical evidence for IVDs
Clinical evidence for an IVD is all theinformation that supports the scientiﬁcvalidity and performance for its use asintended by the manufacturer. It is an
important component of the technicaldocumentation of an IVD, which
together with other design veriﬁcationand validation documentation, device
description, labelling, risk analysis andmanufacturing information, is needed
to allow a manufacturer to demonstrate
conformity with the Essential Principles.
Clinical evidence includes analytical
performance, clinical performance andclinical validity data.
In relation to collection of clinical data
for IVDs, a considerable amount of
information on performance is gained
from analytical performance studies

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

carried out using human specimens. Thischanges the risk proﬁle of a clinical study
as compared to clinical investigations
for medical devices to be used onhuman patients. The application of ISO
14155:2011 – Clinical investigation of
medical devices for human subjects –Good clinical practice (8) is therefore notsuited to IVDs. A standard speciﬁc to IVDs
is being developed by the ISO TechnicalCommittee 212 (9).

2.4.4 Lot veriﬁcation testing of IVDs
Some countries that have yet to implement
effective regulation for medical devices
but need to import high-risk (Class D)
IVDs, may implement a system of lot
verification of such IVDs before they
are put into service. The objective of
lot verification testing is to verify thateach lot supplied meets its safety, quality
and performance requirements andthat transport and/or storage conditions
have been well controlled so as not toaffect the performance of the IVD. The
need for lot veriﬁcation testing depends
upon the other controls in place in theimporting country and the extent ofpremarket evaluation conducted. Where
there are stringent controls on transportand storage, and the receiving laboratory
has in place an effective quality control
programme that will detect problems
in the performance of a new batch on
arrival, lot veriﬁcation testing may not beneeded.
The regulatory authority may designatea national reference laboratory or otherrecognized laboratory that is assigned
the overall responsibility for coordinating
and conducting lot veriﬁcation testing on
its behalf.

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15

3. Enabling conditions for effective regulationof medical devices
Public conﬁdence in medical devices
requires effective and efﬁcient regulation
built upon a sound legal and policy
foundation, as well as good regulatory
practices. WHO is developing Goodregulatory practices: guidelines fornational regulatory authorities for
medical products (10). The generalprinciples therein should be applied whenestablishing a new, or revising an existing,system of regulating medical devices and
IVDs. They include:• a foundation in law;
• consistency;• effectiveness;• efﬁciency;• impartiality;• clarity;• transparency;• ﬂexibility.

3.1 Legal requirements
Medical device regulation must have asound basis in law. There is no single
approach to the legal foundation of sucha regulatory framework since it depends
on the national constitution and existing
general national legal and administrative
systems within the country.
The law should deﬁne the products within
its scope and identify the entities subject
to regulation. It should create a general
requirement that only medical devices
that are safe, perform as intended,
and are of appropriate quality, may bemarketed or made available for use in thejurisdiction. The law should delineate theresponsibilities of the regulatory authority
and establish its enforcement powers
to include removing products from themarket as well as imposing penalties.

16

It should establish mechanisms for theaccountability of the executive, judicial
and legislative branches of government.
It should address coordination with otherbodies such as the justice ministry andthe police and customs authorities. In
countries with decentralized systems therespective powers and coordinating rolesof the central regulatory authority andauthorities in the political subunits will
have to be deﬁned.
The law should establish the
responsibilities of manufacturers,
importers, distributors and authorized
representatives. Where a regulatory
authority is delegated to an independentadministrative agency there should beclear lines of political oversight andaccountability, e.g. through the ministryof health. The legal framework should
also provide scope for administrativeand enforcement discretion that allows
the regulatory authority to apply theprinciples of “reliance” and “recognition”(see also section 4), taking into accountassessments and decisions by authorities
in other jurisdictions when taking its
own regulatory actions. The law should
accommodate a transition from basic toexpanded regulatory controls to the extent
that resources allow as experience isgained. It should also allow the regulatory
authority to respond to public healthemergencies in an appropriate and timely
manner.
The authority should adhere togood regulatory practices such as
creating opportunities to obtain andreview meaningful public commenton proposals, assessing regulatory
impacts, allowing reasonable transition
periods and adopting requirements

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

that are proportionate and offer the
least burdensome ways of achieving
policy goals. The provisions of laws,
regulations and guidelines should be astransparent, predictable and internallyconsistent as possible. Measures should
be non-discriminatory, so that all similarly
situated parties are treated in the same
way and that decisions are taken without
regard to national origin of a medical
device or to the source of ﬁnancing or
the sector of the health-care system
where it is used (e.g. whether primary,secondary, tertiary or emergency healthcare; whether delivered through a public,
private or military facility).

3.2 Gap analysis of existing
controls
It is important at an early stage toevaluate any existing regulatory controlsthat apply to medical devices. This willallow the policy-maker to understandboth the steps and resources neededto achieve national public health goals
and to develop regulatory capacity. A

gap analysis is helpful in assessing thedegree to which national regulations arealigned with international guidance andbest practices.
The authority should conduct a
gap analysis and seek the views ofinterested parties, including patient
representatives. The results of thatassessment will aid in setting priorities
for implementation. For example,
in a country with little or no domestic
production, it may be appropriate to focus
ﬁrst on import controls, rather than on
manufacturing controls; in a country witha high prevalence of sexually transmitted
diseases, it may be prudent to give priority
to regulatory controls for medical devices
used in the prevention, diagnosis andtreatment of those diseases. Box A4.1
lists elements to be considered in a gap
analysis.

3.3 Implementation plan
Once national legislation on medical
devices has been adopted, the appointed

Box A4.1 Non-exhaustive list of elements to be considered in the gap analysis for medical
device regulation• Are medical devices regulated at all?
• Are they currently regulated as medicines or some other product category?
• Is there a speciﬁc and sound legal foundation for regulation of medical devices?
• What is the public health risk in the country, associated with medical devices?
• Is there a clear deﬁnition of the term “medical device” and does it match with the deﬁnition
recommended by this Model?

• Is there a NRA with clear powers and responsibilities for medical devices?
• Do the regulators have the proper competencies required for effective implementation andenforcement?

• Where there is a published regulation, is it enforced and does the regulatory authority have sufﬁcient
resources, expertise and funding to perform its duties?

• What proportion of medical devices are imported and from where?
• Are there local manufacturers of medical devices? If so, are their activities regulated and how?
• Are all relevant stakeholders adequately represented?
• Are distributors and importers subject to appropriate controls?
• Is there evidence that SFa medical devices have been placed on the market?
• Do existing laws and regulations comply with international good practices and treaty obligations?
a The Member State mechanism on substandard/spurious/falsely-labelled/falsiﬁed/counterfeit (SSFFC) medical products has recommended the World Health Assembly
adopt a simpliﬁed terminology for substandard and falsiﬁed (SF) medical products (EB140/23, Annex, Appendix 3 (dated 10 January 2017)).

WHO Medical device technical series

17regulatory authority should adopt andpublish a plan for its implementation.
The plan will be driven by public healthpriorities and needs and by the availabilityof resources, including trained competentstaff to implement legislation.
The plan should include time forpromoting awareness, drafting proposals
for implementing regulations andseeking feedback from the public andother affected parties. Appropriate
transition periods should be deﬁned toallow industry to comply with new oramended requirements. The plan should
also address how medical devices
already in the market, in the distribution
chain, or in use will be handled, e.g.
allowing well-defined exemptions andtransition provisions. The regulatory
authority should hold meetings andpublish guidance to ensure that medical
device manufacturers, importers,
distributors and purchasers are awareof their responsibilities, thereby avoiding
disruption in the supply of medical
devices during the transition period.

3.4 Monitoring implementation
At the time of development of theregulatory implementation plan, goals
and performance indicators shouldbe established to allow progress of
implementation to be assessed against
a baseline that represents the current
status of medical devices regulation.
Progress towards those goals should bereported to the legislature, parliament
and the public. Such reports willcontribute to transparency and politicalaccountability. They may also be used toevaluate adequacy and use of resources.
Progress made may be used to help
determine the timing of future steps in
implementing the regulatory framework.
If expanded-level controls are establishedit may be appropriate to include
performance measures such as timely

18

response by the authority in monitoring
the manufacturer’s response to quality
defects and serious injury associatedwith the use of medical devices. Other,more general, performance assessments
may include periodic consultations withinterested parties such as medical device
users, patient representative groups
and industry. Ultimately, the public andparliament or legislature will want to seethat their conﬁdence in the regulatory
authority and its use of resources isjustiﬁed.

3.5 Regulatory authority
Implementation of the medical device law
will require the appointment of a NRA,
with the ability to exercise independent
decision-making within the regulatory
framework. That regulatory body may
be either within an existing government
department such as the ministry ofhealth, or an independent administrative
agency accountable to a ministry. The
governance of the authority should
be defined, together with appropriate
checks and balances and a requirement
to publish periodic public reports on
performance. In countries where the law(or decree) consists of statutes settingout broad outlines and principles only,
it must delegate power to the regulatory
authority to issue secondary legislation(also known as statutory instruments
or implementing acts), specifying
substantive requirements and procedural
regulations for implementing them. It
should also provide the necessary
enforcement powers.
While retaining in full the responsibilities
placed upon it by the law, the regulatory
authority may designate CABs to assist
it in carrying out some of its duties. In
this situation the legislation will include
requirements for appointing a CAB,
setting the scope of its responsibilities
and monitoring performance. Although

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

the CAB may perform some evaluation
functions, the final decisions andenforcement powers remain with theregulatory authority.

requirements are not harmonized withthose of other countries, manufacturers
and importers may be discouraged fromoffering their products and that may
impede achievement of national publichealth goals.

3.6 Funding the regulatory
system
Implementation of the regulatory system
will require trained staff, infrastructure,facilities and information technology (IT).
Resources allocated should be consistent
with activities mandated in the law, witha legal provision enabling them to be
increased as the regulatory system moves
from the basic level to expanded-level
controls. The pre-implementation gap
analysis should include an assessmentof the financial resources required.
Consistent with its ﬁnancial policies andlegislative intent, a country may choose
to fund all regulatory activities from publicfunds, or from a mixture of public funds
and fees collected from the regulatedindustry. If user fees are imposed, theyshould be predictable, transparent, nondiscriminatory, reasonable in relation
to the services rendered and subject
to periodic review. One way for the
regulatory authority to increase efﬁciency
and thereby reduce costs is to take into
account the outputs (e.g. reports) anddecisions of regulatory authorities inother jurisdictions in reaching its own
decisions, i.e. reliance or recognition, as
appropriate. Permission for the regulatory
authority to impose fees for selected
activities should be established throughthe medical devices law.
Costs of doing business, both direct (e.g.
through paying user fees) and indirect(e.g. the regulatory burden of compliancewith local requirements), may have aninﬂuence on whether medical devices
are introduced to a particular market.
If the costs of compliance appear
disproportionately high compared withthe potential of a market, or if regulatory

3.7 Conﬂict of interest andimpartiality
Public conﬁdence in the integrity of theregulatory authority and its actions isessential. The authority and its staff,
advisory committees and third parties
should be seen to act consistently,
impartially and transparently. Actual or
perceived lack of impartiality of regulatory
decisions can lead to unfair and unjust
competitive advantages for parties in the
medical device sector as well as a lack of
conﬁdence in medical devices supplied tothe market. This can be prevented by the
adoption and consistent adherence to acode of conduct by all members of staff.
This code should provide a framework for
decisions and actions and allow for public
and legislative scrutiny of the authority.
Staff must avoid situations where there
may be a conflict, real or perceived,
between their private interests and the
public good. Leaders in the organizationmust set the tone by good example intheir own conduct.

3.8 Regulatory competencies andresources
The practice of regulating medical
devices effectively and efficiently
requires appropriate individual expertise,reinforced by the institutional capacityof the regulatory authority, to act
according to good regulatory practices.
General competencies for regulatory
professionals include an understandingof public health principles, analyticaland communication skills, information
handling and skills in effective

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19intervention and crisis management(11). These competencies are needed
even where the regulatory authority
relies on or recognizes regulatory
decisions of other jurisdictions.
Additional specific competencies
include essential knowledge of theregulatory system for medical devices,
the responsibilities of the regulator, theconcepts of international standards andharmonization, and an understanding ofa range of different device technologies
and their application (12).
For each stage of implementing theregulatory system a sufﬁcient transition
period should be established: this allows
the regulatory authority to ensure it has
sufficient qualified and trained staff,
appropriate resources and adequate
information systems for the increased
responsibilities and functions. The
regulatory authority requires legal support
to interpret its responsibilities under thelaw, particularly in respect of monitoring,
enforcement and safeguarding activities.
In addition IT and administrative
resources are required.
The basic-level regulatory controls would
require general technical expertise on
medical devices, whereas the expandedlevel controls would require someregulatory staff to have more specifictechnical expertise. As the regulatory
system and its implementation become
more comprehensive, additional
resources will be required.
In view of the importance of the
manufacturer’s QMS, the authority
should recruit and train staff memberswith experience in that ﬁeld. Such staff
may inspect or audit manufacturers,
authorized representatives, importers anddistributors. These skills should allow theregulatory authority to provide appropriate
oversight and control throughout thelife cycle of the medical device. Whenelements of the regulatory framework are20

delegated to designated or recognizedthird-party organizations (generally known
as CABs (see section 4.3.1.2)), authorities
should have competent regulatory staff toassess compliance by the CAB with therelevant requirements (13).
Given the diverse nature of medical
devices, the regulatory authority should,
according to the priorities in regulating
specific medical devices, over time,
recruit technical staff members with avariety of appropriate expertise (14). A
career path, professional development
and recognition of the value of regulating
medical devices as a profession, may be
important in recruiting and retaining staff.
Even advanced or well-resourced
regulatory authorities ﬁnd it impractical tohave all their experts in-house. Instead theycreate advisory committee(s), consistingof independent experts in a variety ofﬁelds to advise in speciﬁc technical areas.
The process of nominating advisers andcreating an advisory board should betransparent and open to the public.
Particular attention must be paid to theimpartiality of members and the exchangeof conﬁdential information. The regulatory
authority remains responsible for thedecision based on the advice. Performinga basic-level assessment of the authority’scurrent regulatory competencies andcapacities gives insight into the identiﬁed
gaps in regulatory systems and related
functions. Guidance can be sought fromthe WHO global benchmarking tool fornational regulatory authorities (underdevelopment), the Global competency
self-assessment of the Regulatory Affairs
Professionals Society (RAPS) (15), and the
IMDRF Good regulatory review practices– competence, training, and conduct
requirements for regulatory reviewers(under development). According to
the gap analysis, initial and continuing
training of medical devices regulators
according to a training plan should be
implemented.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

4. Establishing a stepwise approach toregulating medical devices
4.1 Stepwise approachThis Model recommends establishing a
regulatory system for medical devices
taking a staged or stepwise approach –from basic to expanded controls. The
regulatory framework must be sustainable,
expandable and accommodate advancesin clinical practices, public health needs
and evolving technologies. The basic
controls will form the foundation for the
expanded controls. In order to promoteinternational regulatory convergence andharmonization, this Model encourages
countries to adopt the principles
recommended in internationallyharmonized technical guidance into theirlegislation (16).
Basic regulatory controls fall into threebroad groups:• those applied before a medical
device is placed on the market;• those applied when placing thedevice on the market;• those applied after the device has
been placed on the market.
The stepwise approach will allow
the regulatory authority to respond tonational public health priorities andto progressively develop the capacity,
knowledge and experience required. Thisapproach helps the regulatory authority
determine the resources needed forfurther implementation. Without effective
implementation of basic controls, theelements of expanded controls will beof limited value and difﬁcult to manage
effectively.

The regulatory authority has theopportunity to reduce the demands on
its own staff by either relying upon orrecognizing the work or decisions madeby another medical devices regulatory
authority. Resources may then be targeted
to postmarket controls, which are theresponsibility of the NRA. Furthermore,
the regulatory authority will indirectly gain
knowledge of the regulatory status inother jurisdictions of devices placed on its
national market. As a regulatory authority
subsequently implements expanded-level
controls, emphasis will shift to premarket
controls such as authorizing devices to beplaced on the market, while continuing torely upon or recognize the work of otherjurisdictions, where appropriate.

4.1.1 Reliance and recognition
The law should establish to what extent
the regulatory authority may reasonably
use the work of regulatory authorities inother jurisdictions in assessing evidence
that a device conforms to national
requirements. The two main examplesof these techniques are:• Reliance. This is the process wherebya regulatory authority may take into
account and give signiﬁcant weightto (i.e. rely upon) assessments 1
performed by another regulatory
authority or other trusted institution
in reaching its own decision. For
example, another regulatory authority
authorizes a medical device to beplaced on its own market and the
NRA uses this information, possibly
supplemented with information fromthe manufacturer, to reach its own
decision.
1 In this document “assessment” is used in relation to medical devices in the same
sense as “evaluation” is used for some other medical products.

WHO Medical device technical series

21• Recognition. This is the routine
acceptance by the regulatory
authority of an importing country of
the regulatory decision of anotherregulatory authority or other trusted
institution that evidence of conformity
with the regulatory requirements ofthat country is sufficient evidenceof conformity with the regulatory
requirements of the importing country.
For example, a regulatory authority
or CAB audits a manufacturer andissues it with a QMS certificate.
The NRA of the importing country
accepts certiﬁcates issued by anotherauthority as proof of compliance with
its own QMS requirements.
In order for the regulatory authority to
decide whether to use either the relianceor recognition option, it must have a clear
understanding of the regulatory systemthat applies within the country where
the medical device is manufactured. For
example, medical device regulations insome jurisdictions permit a manufacturer
to specify some devices as “export only”
and only subject these to minimal controls
rather than evaluating conformity of sucha medical device with its own regulatory
requirements. This places responsibilityon the regulatory authority of theimporting country and may make relianceand recognition inappropriate. Relianceand recognition are not appropriate forthe assessment of speciﬁc requirements,
such as language of labelling andelectrical supply that do not apply in theexporting country.
Note that sometimes devices may havedifferent configurations (regulatory
versions) for different markets; these mayvary in aspects such as the intended use,site of manufacture, power supply, labelling
language and applied quality control,

among others. It is therefore important toensure that when relying on assessment
outcomes by entities in other jurisdictions,the regulatory version is not substantiallydifferent from the product version thatis proposed for placing on the market.
Speciﬁcally for IVDs, the use of reliance orrecognition as mechanisms for marketing
authorization is complex. This is becauseof the wide variance in classiﬁcation of
IVDs in existing regulatory systems (which
determines the level of regulatory scrutiny).
For instance, the current European system
requires independent assessment for thehigh-risk IVDs (Annex II of the EU Directive
98/79/EC on in vitro diagnostic medical
devices, lists A and B) (17). This meansthat most IVDs bearing a CE mark are selfassessed by the manufacturer and havenot been subject to scrutiny by a European
CAB (known as a notiﬁed body). This is
another example where knowledge of theregulatory system upon which reliance orrecognition is based is important.2
In general, where a regulatory authority
seeks to rely upon information from acounterpart in another jurisdiction,
it must first establish confidence inthe counterpart authority and reachagreement on the exchange of conﬁdential
information (18). The same considerations
apply to the outsourcing of any activities,
for example to CABs and third-party
experts (locally or internationally based).
4.1.1.1 National responsibilities
There are certain regulatory activities that,by their nature, are inherently only within
the competence of the national authority.
Examples include import controls;
registration of domestic manufacturers,
importers, distributors and authorized
representatives; handling reports ofadverse events, including vigilance
reports; market surveillance activities; and2 All regulations are subject to occasional revision and this could affect theapplication of the reliance or recognition procedure. Importing countries must be
alert to any such plans of the exporting jurisdiction and take them into accountwhen relying upon or recognizing a regulatory decision of that jurisdiction.

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WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

communication and monitoring of ﬁeld
safety corrective actions (FSCA). Relianceand recognition are not appropriate tothese activities.
4.1.1.2 International collaboration
Where resources permit, the regulatory
authority should participate in formal andinformal information-sharing networks
with other regulatory authorities. This willoften allow earlier detection of a potential
problem than would be possible within
a single jurisdiction. It also facilitates
reliance upon and conﬁdence building
with other regulatory authorities.

4.2 Basic-level controls and theirenforcement
The Model recommends that basic-level
controls are incorporated into a medical
devices law that determines the scope of
regulation, stipulates the responsibilitiesof the regulatory authority, describes
conditions under which a medical device
can be placed on the market, requires

certain organizations to be registered,establishes import controls and requires
postmarket surveillance activities.
Typically the postmarket activities would
include a system to act proportionately
to reports of quality defects and serious
adverse events associated with medical
devices (Figure A4.2).

4.2.1 Publish law, including
deﬁnition, and regulations withtransition period
The national law for medical devices will
set out principles and broad requirements
and delegate authority to the regulatory
authority (see Appendix 2). In particular
it will:• define the products and parties
within its scope, in particular theterms medical device and IVD, using
harmonized deﬁnitions (1);• ensure the regulatory framework
is capable of adapting to newtechnologies and treatment
modalities;• designate the NRA, its enforcement
powers, market oversight

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Figure A4.2 Basic-level controls and enforcement for medical devices within the legal framework

24

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devicesresponsibilities, powers to issue
implementing regulations and to takeaction where the health of patientsor users is compromised, and the
responsibility for publishing guidance
documents to aid understanding oflegal requirements;• provide the regulatory authority withadministrative and enforcement
discretion for reliance upon andrecognition of the work or decisionsof regulatory authorities in otherjurisdictions (see 4.2.2.1);• require that only safe medical devices
that perform as the manufacturer
describes in its labelling may beplaced on the market;• specify market entry conditions for
medical devices;• establish record keeping, registration
and reporting requirements for allparties within the scope of the law,
including the regulatory authority;• specify a transition period sufﬁcient
to allow parties affected by the law
to comply with its requirements andensure minimal disruption to thecontinuing supply of medical devices
to health facilities and other users.
To allow progressive adoption andimplementation of the stepwise approach
recommended in the Model, the law
should foresee and include provisions
covering the expanded levels of control,
even though those provisions would not
be likely to be implemented in the earlystages.
Experience in many jurisdictions withestablished regulatory systems suggeststhat affected parties must be allowed time
to adapt to the law, i.e. a transition period.
Where the necessary prerequisites arein place, a reasonable transition period
is three to ﬁve years. In part, the lengthof the period will reflect the numberof potentially affected parties and thenumber of devices in the national market.
It may be helpful to ﬁrst establish new
requirements on a voluntary basis,
gain experience and then move tomandatory compliance. An importantrole of the regulatory authority during
the transition period is the development
and dissemination of voluntary guidance
documents to affected parties.
4.2.1.1 Establish medical deviceclassiﬁcation for regulatory purposes
The law should include a medical
devices classiﬁcation scheme, based oninternationally harmonized practice, toprovide an efficient way of regulatingeach medical device according to its risk
class (2). It should include provisions
for the regulatory authority to issue
implementing acts and guidance on
the classification of medical devices,
including IVDs. The manufacturer is
responsible for determining the classof its devices and its decision may bechallenged by the regulatory authority(see section 2).
4.2.1.2 Establish Essential Principles ofsafety and performance
The law should also establish thefundamental requirement that all medical
devices be shown to be safe, to perform
as intended and to be of good quality for
their intended purpose before they areplaced on the market. It would require
the manufacturer, or its authorized
representative or importer, to declare andbe prepared to provide timely evidence
that their device is in compliance with
the Essential Principles (see section 2)(5). Failure to make such a declaration ofconformity (see 4.2.2.2) (6), or making
a false declaration, would be grounds
for enforcement action by the regulatory
authority.

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The preferred, but optional, way by which
the manufacturer may demonstrate
conformity with the Essential Principles is
to apply voluntary international standards
that are appropriate and relevant. The law
should include provisions allowing theregulatory authority to formally recognize
such standards3 for that purpose (seesection 4.3.1.3).

4.2.2 Basic-level controls andenforcement – premarket
Only medical devices that are of goodquality, safe and perform as intended
may be placed on the market. The safe
use and performance of most medical
devices requires that the manufacturer,
through its labelling, provides the user
with information on how to properly
install, use and maintain them.
4.2.2.1 Establish a basis for reliance andrecognition
The medical devices law should allow
reliance and recognition techniques tobe used by the regulatory authority todetermine whether a medical device
complies with the regulatory requirementsof another jurisdiction and to use thisinformation as the basis for allowing the
medical devices to be placed on thedomestic market. However, the NRA is
ultimately responsible for determining
whether a medical device may be suppliedin its jurisdiction (see section 3.1).
4.2.2.2 Establish requirements fordeclaration of conformity
The medical devices law should require
an organization seeking to place a medical
device on the market to draw up a written
declaration of conformity to attest that its
device complies fully with the law and all
regulatory requirements.
At a minimum, this declaration should
contain the following:• the regulation under which thedeclaration is made;• the name and address of the naturalor legal person with responsibility
for design and/or manufacture of a
medical device with the intention of
making the medical device available
for use under his or her name;• description of the device and its
classification according to theregulation;• the declaration that the medical
device is of good quality, is safe andwill perform as intended during its
lifetime when used according to
the manufacturer’s instructions forthe manufacturer’s stated intended
purpose;• information sufﬁcient to identify thedevice(s) to which the declaration ofconformity applies;• the list of standards used indemonstrating compliance with
Essential Principles;• the name, position and signatureof the responsible person who hascompleted the declaration upon the
manufacturer’s behalf;• the date on which the declaration isissued.
4.2.2.3 Establish requirement for
manufacturers to have a QMS
To ensure devices are designed andmanufactured to meet safety andperformance requirements during
their lifetime, the law should require
manufacturers of all classes of medical
devices to establish and maintain a QMS
and the associated records. The QMS
should be appropriate to the specificcharacteristics of the manufacturer’s
processes and products. This Model
recommends that the QMS requirements
should be aligned with the speciﬁcationsin ISO 13485:2016 Medical devices
Quality management systems –3 Standards indicated in this document are standards current at the time of
publication. The reader should refer to the standards body to verify the current
edition.

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WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Requirements for regulatory purposes (19)and ISO 14971:2007: Medical devices– Application of risk management tomedical devices (20).
The QMS is important not only for assuring
the quality, safety and performance ofa device, but also for controlling thecollection of technical evidence used by
the manufacturer in declaring the device
conforms with the Essential Principles ofsafety and performance.
4.2.2.4 Establish requirements for labels andlabelling
The safe and effective use of most medical
devices requires that the user be given
information on how to use them properly
and, where appropriate, how to installand maintain them. Labels, instructions
for use and other labelling (e.g. displays,
service manuals and information forpatients) serve that purpose and help toreduce risks associated with the use of
medical devices. The law should include
a requirement that labels and labellingare appropriate to the intended userof a device, especially for laypersons,and set language(s) requirements.4 To
begin establishing regulatory controls,
regulatory authorities must provide
speciﬁc guidance on the labelling andlanguage requirements for medical
devices and fully describe any exceptions
to these requirements. Regulatory
4 Medical devices – Symbols to be used with medical device labels, labellingand information to be supplied – Part 1: General requirements. ISO 152231:2012 (http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.
htm?csnumber=50335, accessed 18 November 2016). Medical devices – Symbols
to be used with medical device labels and information to be supplied – Part 2:
Symbol development, selection and validation. ISO 15223-2:2010 (http://www.
iso.org/iso/catalogue_detail?csnumber=42343, accessed 18 November 2016).
In vitro diagnostics – Information supplied by the manufacturer (labelling) – Part
1: Terms, deﬁnitions and general requirements. ISO 18113-1:2009 (https://www.
iso.org/obp/ui/#iso:std:iso:18113:-1:ed-1:v1:en, accessed 18 November 2016).
In vitro diagnostic medical devices – Information supplied by the manufacturer(labelling) – Part 2: In vitro diagnostic reagents for professional use. ISO 181132:2009 (http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.
htm?csnumber=40985, accessed 18 November 2016). In vitro diagnostic medical
devices – Information supplied by the manufacturer (labelling) – Part 3: In vitro
diagnostic instruments for professional use. ISO 18113-3:2009 (http://www.iso.
org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=40986,
accessed 18 November 2016). In vitro diagnostic medical devices – Information
supplied by the manufacturer (labelling) – Part 4: In vitro diagnostic reagentsfor self-testing. ISO 18113-4:2009 (http://www.iso.org/iso/catalogue_detail.
htm?csnumber=40987, accessed 18 November 2016).

authorities should ensure that labellingis in an ofﬁcial language or in a language
acceptable for the jurisdiction. The
authority should also consider whether
instructions for use may be provided
in addition to or instead of the printed
instructions in alternative media suchas via the Internet or on CD-ROMs (21).
However, printed instructions for use shallbe provided if requested by the user.
Another function of labelling is to allow
the identiﬁcation of medical devices, forexample, lot number, or serial number.
This allows traceability to facilitate
FSCA and helps in the reporting andinvestigation of adverse events. A recent
development is the addition of aninternationally harmonized unique device
identiﬁer to the label (22).
4.2.2.5 Prohibit deceptive, misleading andfalse advertising
In addition to requirements for labellingof medical devices, consideration should
be given to inclusion in the law ofprovisions and prohibitions with respect
to advertising and promotion for medical
devices, including explicit enforcement
measures. The regulatory authority
should issue clear guidance to makethese requirements explicit.
Those basic regulatory controls should
ensure that promotion, including online
promotion:• does not target inappropriate
audiences;• makes only claims that are supported
by evidence;• covers only medical devices thathave been authorized for marketing;• is consistent with indications for use
and other information in the productlabelling;• does not make false or misleading
claims.

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As a basic-level control the regulatory
authority should investigate any suspectedviolations that are brought to its attention.
If the regulatory authority discovers thata requirement is breached, it shall takeappropriate enforcement actions, which
could include preventing the medical
device from being placed on the market
and/or recalling medical devices alreadyplaced on the market.
4.2.2.6 Establish provisions for exceptional
premarket situations
In situations such as public healthemergencies, exemptions from someregulatory requirements may be needed.
Such exemptions should, however, beapplied in such a way as to allow theregulatory authority to evaluate the risks
and beneﬁts of the speciﬁc situation andauthorize the proposed deviation. Such
exemptions should be clearly stipulated
and explained.
The law should establish defined
exemptions from, and provide
enforcement discretion for, compliancewith certain requirements, for example,
medical devices for humanitarian use,
public health emergencies, clinicalinvestigations, exhibition use and medical
devices donated to the country by
charities or the manufacturer. Regulators
should issue clear guidance on such
exemptions (see section 5).

4.2.3 Basic-level controls andenforcement – placing on the market
Many countries depend almost entirelyon imported medical devices. However,
it is impractical for a medical device
manufacturer to have a physical or legal
presence in every country. Therefore,
the law should require a manufacturer
outside the jurisdiction of the country
concerned to appoint an authorized
representative within the country (23).

28

4.2.3.1 Registration of establishments
A key element of basic-level controls is
effective oversight of medical devices
placed on the domestic market andthe parties responsible for bringing
medical devices to the market. The law
should require local manufacturers,
authorized representatives, importers
and distributors (in some cases theauthorized representative may also be
the importer and/or distributor) who place
medical devices on the market or makemedical devices available for use in thejurisdiction, to register with the regulatory
authority (24). Signiﬁcant changes in aregistered establishment (e.g. ownership,
location, name of the responsible personor scope of activities) should be notiﬁed tothe authorities to ensure that registration
information is current and correct.
Among other purposes, the registration
process allows the regulatory authority
to determine who is responsible for a
product’s conformity with the regulatory
requirements and for taking corrective
actions in the event of a problem witha device. It is also useful in facilitating
regulatory actions such as complianceinspections (e.g. of warehouses or
manufacturing plants), notifying andmonitoring of field safety corrective
action (FSCA) and for law enforcement
purposes. Making registration and listing
information publicly accessible allows
device purchasers or users of medical
devices to identify products available tothem and determine the identity andlocation of their manufacturers and/or
distributors and/or importers.
4.2.3.1.1 Authorized representatives
The minimum requirements forregistration should be that the authorized
representative provides the regulatory
authority with information on its placeof business, the name and position of a
responsible person and the manufacturer it

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devicesrepresents (23). Additionally, the regulation
may require the applicant’s authorized
representative to attest that it will act onbehalf of the manufacturer in its dealings
with the regulatory authority by:• submitting a regularly updated listingof the medical devices placed on thedomestic market;• providing the regulatory authority
with the information it requires whenthe manufacturer seeks authorization
to market its devices;• informing the manufacturer andthe regulatory authority of any
reportable adverse events involving
death or serious injury that haveoccurred either within the local
market (or outside it, if there are any
consequences for the local market)
and providing information on thecorrective action the manufacturer
has taken or intends to take;• informing the regulatory authority of
any FSCA to be taken within the local
market;• cooperating with the manufacturer’s
importers and distributors;• ensuring training is provided to theuser by the distributor, manufacturer
or third party, according to the
manufacturer’s requirements;• cooperating with the regulatory
authority and providing it with any
information it requires during market
surveillance activities.
4.2.3.1.2 Importers and distributors
The minimum requirements forregistration should be that the importerand distributor provides the regulatory
authority with information on its placeof business, the name and positionof a responsible person and the
manufacturer(s) it is acting for. Beyond
this, the regulation may require theapplicant importer or distributor to attest
that it will, for example:• ensure the medical devices it imports
or distributes comply with the medical
devices law and are accompaniedby the proper documentation andlabelling;• trace medical devices through thatpart of the supply chain with which
it is directly involved;• comply with the manufacturer’s
requirements for the storage,
handling, transport and, as
appropriate, maintenance of medical
devices.
If the device manufacturer appoints its
importer or distributor to also act as its
authorized representative, there should
be a separate registration for each activity.
4.2.3.2 Listing of medical devices
The regulatory authority should establish
a requirement and information system
for authorized representatives ofmanufacturers outside the jurisdiction,and importers and distributors, tosubmit a listing of medical devices theyplace on the national market and toensure information retained within thedevice listing system relating to those
medical devices in the market is up todate (24). Among other elements, thelisting should provide the standardized
generic descriptive names of those
medical devices, for example, those of
the Global Medical Device Nomenclature(GMDN) (see section 4.3, Expanded-level
controls). Listing of medical devices willallow the regulatory authority to determine
which products are placed on the market
and by whom. In the event of a suspected
problem with a medical device, listing also
allows the regulatory authority to contact
the parties responsible for that product.
The regulatory authority should have ameans by which to provide information toother parties, upon request, on medical
devices legally placed on the market.

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It should be understood that listing is notof itself equivalent to, or evidence of, amarketing authorization.
4.2.3.3 Import controls
Apart from the basic controls of registering
establishments and listing marketed
medical devices, additional import controls
may be appropriate. These may include
approval of importation documents before
shipment and veriﬁcation of imported
products either at the port of entry orat the importer’s premises. Knowing in
advance what medical devices are to
be imported provides an opportunity for
regulators to verify whether the medical
device has previously been listed andmarketed in the country. It also allows
a review of evidence of conformity withregulatory requirements. Collection ofsamples may be required for suspicious
products or for routine analysis (e.g.
batch testing for selected products – seesection 2.4.4, Lot veriﬁcation testing ofIVDs). Once the processes of registrationof establishments and listing of devices
become mature, the imposition of thesecontrols may be unnecessary.
There should be mechanisms forcooperation between the regulatory
authority and customs service so that
medical devices will not be released fromthe port of entry unless there is proof thatthe regulatory authority has authorized
them to be placed on the market. It may
be helpful to designate ofﬁcial ports ofentry for medical devices so that theregulatory authority may better focus its
enforcement activities.

4.2.4 Basic-level controls –postmarket
In clinical use medical devices may
not always perform as expected. This
may indicate potential problems intheir design, manufacture, labelling,storage or distribution. It could also

30

reﬂect inappropriate device selection,
installation, use or maintenance.
4.2.4.1 Establish a system for vigilance
reporting
At the basic level the regulatory authority
should establish a system whereby
users, patients and the manufacturerof medical devices, either directly or
through the authorized representative,
can report complaints involving medical
devices, including malfunction at thedevice level and adverse events at thepatient level, in particular those adverse
events resulting in death or serious injury(25). For IVDs, the risk of harm is usuallyindirect as the device is not used on the
body: for instance, for high-risk IVDs asevere adverse event may include higherthan-expected false-negative results.
Reports of adverse events received by
the regulatory authority from the patientor end-user must be passed to thedevice manufacturer for investigationand trend analysis with possible FSCA
and notiﬁcation through a ﬁeld safety
notice. Vigilance reports may trigger
investigation, trend analysis and/or
possible FSCA or enforcement actions(26). They may also prompt the regulatory
authority to exchange information withregulatory authorities in other jurisdictions
on similar occurrences elsewhere (27).
4.2.4.2 Require mandatory notiﬁcation by the
manufacturer of FSCA
The law should require a manufacturer,
either directly or through its authorized
representative, to report to the regulatory
authority in a timely manner any FSCA it
is undertaking within the country. As aregulatory authority learns, either throughits own work or from communications
with other authorities or manufacturers,of any newly identiﬁed potential hazard
associated with a device, it should havean established system for the timely
issuance of alerts or advisories on FSCAs.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Such a system should allow the targetingof speciﬁc parties, usually in consultation
with health-care professionals, so thatthey may act appropriately to protect
public health and to prevent unnecessary
concern or confusion on the part of medical
device users or patients who are notaffected. It should use communications
technologies appropriate and accessible
to the intended recipients as well as tothe urgency of the action. The regulatory
authority should establish means bywhich the effectiveness of corrective or
remedial actions may be monitored. It
should prepare the regulatory authority
to respond to questions from the public,
clinicians, media or government and to
exchange information with authorities inother jurisdictions.
4.2.4.3 Establish a procedure to withdraw
unsafe medical devices from the market
Regulatory authorities have an obligation
to enforce laws and regulations on
medical devices to ensure that the
public is protected from unsafe products.
Regulators are required to monitor
compliance with requirements byregistered entities and to take appropriate
action when the regulatory authority
believes that public health has been put
at risk.
Various approaches to enforcing
regulations may be used, for example:
suspension or withdrawal of registrationof local manufacturers, authorized
representatives, importers or distributors;
withdrawal from the list of marketed
medical devices; or recall, quarantine
and disposal of medical devices.
Manufacturers may be required toreview and to revise labelling information(including precautions and warnings),
especially for products that have beenfound to be associated with adverse
events or those whose labelling has beenshown to be inadequate. Enforcement

may also include issuance of public alerts,
warning letters, prosecution and ﬁnancial
penalties. While the regulatory authority’s
primary responsibility is for the healthof its own citizens, where it believes animported medical device is unsafe or ofpoor quality, it should consider sharing
its opinion with the regulatory authority
responsible for auditing the device
manufacturer’s QMS, for the purpose of
preventing similar devices being exported
to other markets.
Regulators are also advised to collaborate
and work closely with other bodies toensure that regulations are adhered to.
Such bodies include regulatory authorities
from other jurisdictions, customs ofﬁcials,
the judiciary, manufacturers, users andpatients.
4.2.4.4 Establish procedure to issue safety
alerts to users
Although the manufacturer, directly or
through the authorized representative,
would typically have primary responsibility
for notifying users of problems with a
medical device, this Model recommends
the regulatory authority to establish aprocedure to directly notify health-carefacilities that use the affected medical
devices, and other users, of serious
adverse incidents and FSCA by issuing
safety alerts and advisories (26). Where
possible, the text of any such alert should
be discussed with the manufacturer or
her or his authorized representative but
the ﬁnal decision lies with the regulator.
4.2.4.5 Undertake market surveillanceMarket surveillance is the activity of theregulatory authority related to oversightof medical devices on the domestic
market. The regulatory authority may
undertake targeted activities based on arisk assessment of the distribution chain,evaluation of complaints and adverse
event reporting, and information from

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31the postmarket surveillance systems of
medical device manufacturers and theirauthorized representatives (28).

4.3 Expanded-level controls
Once the basic-level controls have been
implemented effectively and efﬁciently,
the regulatory authority may consider
implementing more advanced controls.
To do so, the law should provide thelegal basis for such expanded controls,
the regulatory authority must haveeffectively enforced the basic controls,
and additional resources (e.g. ﬁnancial
and technical expertise) must be available
to it. Building on the basic-level controls,
expanded-level controls are intended tobe more comprehensive. In adopting
expanded-level controls, the regulatory
authority may choose to implement one
or more of the controls described below
according to the priorities of the country.
A stepwise approach is recommended forthe implementation of individual elementsof expanded controls depending on theavailability of technical expertise andresources (Figure A4.3).

4.3.1 Expanded-level controls –premarket
4.3.1.1 Create oversight of clinicalinvestigations
The regulatory framework should grantto the authority the power to regulate
and oversee the conduct of clinicalinvestigations. Manufacturers havevarious reasons for undertaking clinicalinvestigations in a particular country,
primarily to collect and provide clinicalevidence to a regulatory authority that adevice for which it is seeking approval issafe and performs as intended.

The regulatory framework should clearly
distinguish clinical investigations frommarket acceptability studies wherea device is tested for factors such as
ergonomics. These studies are notconsidered to be clinical investigations.
There should be a requirement that asponsor (the individual or organization
accepting responsibility and liability forthe initiation or implementation of aclinical investigation, such as the local
manufacturer, importer or local academic
institution or investigator who initiates theclinical investigation) wishing to conduct
a new clinical investigation, seek priorauthorization from the regulatory authority(29). To assure adequate consideration of
the design of studies and protection of theinterests of participating subjects, suchinvestigations should also be conductedunder the oversight of a local ethics
committee or institutional review board.5
A widely used international standard forthe practice of clinical investigation is:
ISO 14155:2011 – Clinical investigationof medical devices for human subjects –Good clinical practice (8).
The NRA should also establish amechanism for periodic progress
reports and for the reporting of serious
adverse events that occur during clinicalinvestigations (30). In-country clinicalinvestigations should generally not be
required, unless there is a compelling andsound scientiﬁc reason.
4.3.1.2 Appoint and have oversight of CAB
Certain technical elements of theregulatory framework may be delegatedto designated or recognized third-party
organizations, often private, generally
known as CABs (31, 32). Authorities
may establish criteria for designationof CABs. These bodies may perform
5 The global standard for testing in humans is the Declaration of Helsinki – ethicalprinciples for medical research involving human subjects (http://www.wma.net/
en/30publications/10policies/b3/17c.pdf, accessed 7 September 2016).

32

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Figure A4.3 Expanded-level controls and enforcement for medical devices

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33initial certification and surveillance
audits of device manufacturer QMS
and/or premarketing reviews of theconformity of a device to the Essential
Principles. The CAB may be designatedby the regulatory authority to undertake
conformity assessment of speciﬁc medical
devices where it is judged to have thenecessary skills (e.g. active implantable
and/or IVDs and/or electromedical
devices). Satisfactory compliance withrequirements is typically documented
with a CAB certiﬁcate (33). Based on the
CAB evaluation, the regulatory authority
makes ﬁnal decisions on compliance. The
CAB performs its evaluation under theoversight of the regulatory authority (34).
The regulatory authority may consider
adopting mechanisms to rely upon, or
recognize, certiﬁcates issued by a CAB,
even those outside its jurisdiction or directoversight (35).
4.3.1.3 Recognition of standards6
Conformity with voluntary standards isa means by which the manufacturer
may demonstrate that a medical device
conforms to one or more of the Essential
Principles of safety and performance,
consistently throughout its life cycle (36).
Medical device standards can largely begrouped into three categories:• basic standards (also known as
horizontal standards), which coverfundamental concepts, principles
and requirements applicable to a wide
range of products and/or processes,
e.g. QMS, risk management system,
clinical investigation;• group standards (also known assemi-horizontal standards), which
cover aspects applicable to familiesof similar products or processes
with reference to basic standards,
e.g. sterility, electrical safety,
biocompatibility;
6 Standards indicated in this document are standards current at the time of
publication. The reader should refer to the standards body to verify the current
edition.

34• product standards (also known asvertical standards), which coversafety and performance aspects ofspeciﬁc products or processes, e.g.
standards for infusion pumps, X-ray
machines, blood glucose meters for
self-testing and for IVDs (37).
At the expanded level, the regulatory
authority may wish to establish aprocedure to identify national versionsof international standards that it accepts
as providing presumption of complianceto specific Essential Principles, i.e.
“recognized standards”.
Preference for recognition should begiven to international standards, e.g.
those of the International Organizationfor Standardization (ISO) (38) andthe International ElectrotechnicalCommission (IEC), regional standards
and the national versions of international
standards. It is also important thatnational standards correspond to thecurrent version of international standards.
As international standards are periodicallyrevised, national standards will have tobe revised accordingly and the authority
should establish a transition period for
manufacturers to adopt the new versions.
To maintain the necessary ﬂexibility inutilizing standards, it is better to adopt asystem of recognizing standards throughguidance documents or guidelines thanplacing the standards into legislation (39);they can then be updated to stay current
and can be revised much faster thanlegislation can be updated.
4.3.1.4 Adopt a medical device nomenclaturesystemThe regulatory authority may require
the manufacturer to identify a medical
device using a generic nomenclaturesystem as a “descriptive language” foruse in the listing of medical devices andother requirements such as adverse event
reporting. The use of an internationallystandardized nomenclature system

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

is intended to allow for a common
understanding of, and exchange of
information regarding, a group of related
medical devices, including IVDs. It also
facilitates the exchange of information
among NRAs. For these reasons theregulatory authority should adopt aninternational nomenclature system for
medical devices.
The GMDN was endorsed by the GHTF
as the global nomenclature system to be
used by regulators for the classiﬁcation,
registration and exchange of information
regarding medical devices for regulatory
purposes (40,41). There are otherestablished nomenclature systems
such as the Universal Medical Device
Nomenclature System (UMDNS) (42) andISO 9999:2011– Assistive products for
persons with disability – Classiﬁcation andterminology (43).
To implement the selected nomenclaturesystem, the regulatory authority should
publish a regulation and guidance
specifying that that system shall be
used in any required submissions,e.g. listing, applications for marketing
authorization, postmarketing surveillance
and adverse event reports. The authority’s
administrative and information systems
will have to be adapted accordingly andupdated as new generic descriptive terms
are adopted.
4.3.1.5 Control advertising and promotion
As part of their market development efforts,
manufacturers, importers and distributors
generally seek to promote medical devices
to health-care professionals, users and/or patients. At a minimum, advertisingand promotion should not be false,
misleading or deceptive. In countries
where the presence of misleading andinaccurate advertisements is a particular
problem, the regulatory authority may
expand controls to include review ofadvertising and promotional material
before it is placed on the market. At

this time, the regulatory authority may
also contemplate a role for preclearance
agencies, which act as independent
entities to review advertising materials
to ensure compliance with the regulatory
requirements. The regulatory authority
should consider whether existing rules
for general advertising to consumers(e.g. under fair competition rules) aresufficient for application to medical
devices, including online promotion.
If not, they should consider whether
speciﬁc guidance is required.

4.3.2 Expanded level controls –placing on the market
4.3.2.1 Perform in-country QMS audits
The QMS is important not only for assuring
the quality, safety and performanceof a device, but also as the source ofmuch of the evidence in the technicaldocumentation used by the manufacturer
in demonstrating conformity of the device
with the Essential Principles and theassociated declaration of conformity.
Good record keeping practices and record
retention policies should be observed in
the QMS.
At the basic level, the Model recommends
that the law should require manufacturersof all classes of medical devices toestablish and maintain a QMS. As theregulatory authority moves to enact
expanded-level controls, the requirementin the law should be supplemented by an
implementing act or ministerial decreethat requires the regulatory authority
to verify that a QMS appropriate to the
medical devices under its control has
been implemented.
Although manufacturers of ClassA medical devices are required to
implement a QMS, they are not subject
to inspection by the regulatory authority
prior to marketing approval nor routinely
inspected by the regulatory authority
after the devices have been placed on

WHO Medical device technical series

35the market (see Table A4.2 for QMS
requirements for medical devices inClasses B, C and D).
4.3.2.1.1 QMS audit
The regulatory authority should establish
means to verify that the manufacturer
conforms to the relevant QMS
requirements. The law should include
provisions for the regulatory authority todesignate or recognize (34, 35) CABs (seesections 2.3 and 4.3.1.2) to perform
QMS audits or otherwise gather andassess evidence of the manufacturer’s
effective implementation of the QMS
requirements (6).
For countries in which most medical
devices are imported, the option ofreliance or recognition is likely to beappropriate: it will often be sufficientfor the regulatory authority to rely uponevidence, including QMS certificates,of the manufacturer’s compliancewith internationally-recognized QMS
requirements in other jurisdictions(35, 44). The receiving country thereby
relies upon the information from the QMS
audit or recognizes the decision of theother jurisdiction regarding the QMS audit(45). The regulatory authority may also
review and recognize the manufacturer’s
own declaration of conformity andcurrent certiﬁcates of conformity with
ISO 13485:2016, issued by a recognized
CAB, if any. The regulatory authority
should verify that such certiﬁcates remain
valid (typically for three to ﬁve years)
and cover the scope of medical devices
and activities appropriate for the devices
being imported.
In the event of suspected noncomplianceor problems with the product, theregulatory authority may perform aninspection, regardless of whether a CAB
has performed a QMS audit.

36

4.3.2.2 Perform review of submissions forcompliance with Essential Principles
The regulatory authority makes a decision
on marketing authorization based ontransparent criteria established in thelaw, regulation and guidance. The law
should also prescribe the form in whichapproval to market is given (such as acertiﬁcate or entry in a database) andmake provision for postmarket follow-up
where appropriate (6).
At the basic level, assessing the safety andperformance of medical devices depends
primarily on an assessment by anotherregulatory authority (see section 4.1.1)
supported by the manufacturer’s
declaration of conformity (seesection 4.2.2.2). At the expanded level,
the NRA may establish a requirement
for the premarketing review of amanufacturer’s submission. Guidance on
the process for application and approvalshould be provided. This will usually bethrough completion of a prescribed formor access to the authority’s Internet portal.
Internationally harmonized formats for
submission of technical documentation
for conformity assessment purposes
have been developed by various bodies,e.g. the GHTF Summary TechnicalDocumentation (STED (46, 47)) and the
Association of Southeast Asian Nations(ASEAN) Common Submission Dossier
Template (CSDT) (48). These formats
provide guidance for the presentation ofevidence that a medical device conforms
to the regulatory requirements for safety
and performance.
The IMDRF table of content (ToC) is more
recent. It describes a modular structureand format for such submissions inelectronic form. Separate ToCs have been
established for medical devices (49) andIVDs (50).

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

NRAs are encouraged to adopt suchharmonized formats if they require
submission of technical documentation.
Sometimes there are situations thattrigger a more extensive review of thetechnical documentation submitted by
the manufacturer. For example, when:• the device incorporates innovativetechnology;• an existing compliant device is being
used for a new intended use;
• the device type is new to the
manufacturer;• the device type tends to be associatedwith an excessive number of adverse
events, including use errors;• the device incorporates innovative or
potentially hazardous materials;• the device type raises speciﬁc publichealth concerns (particularly forIVDs).
Considerations (or “triggers”) for
notiﬁcation to the regulatory authority
after initial approval could include changeof specifications, change in mode ofaction on the human body or change in
intended population for use of the device.
In premarket assessment, nondiscriminatory country-specificrequirements should be considered,e.g. local language labelling, electricalsupply, public health policies, genetic
characteristics of the population andhealth-care delivery conditions. The
regulatory authority may also conduct
a postmarket conformity assessment
review in response to adverse eventsor uncertainty about the compliance ofthe manufacturer with the regulatory
requirements (51).
The regulatory authority may be assisted
in reaching its decision on premarket
assessment (or any other regulatory
decision) by advice from an expert
medical device committee, which
may include experts from outside theregulatory authority. Where advice fromexternal experts is sought, the regulatory
authority should ensure that thenecessary agreements for the exchangeof conﬁdential information are in place.
The ﬁnal decision rests at all times withthe regulatory authority.

4.3.3 Expanded-level controls –postmarket
4.3.3.1 Establish within the regulatory
authority processes for postmarket
surveillance and vigilance
At the basic level a system for reporting
adverse events involving medical devices
to the regulatory authority, in particular
those resulting in death or serious injury,
is established. At the expanded level,
this may be extended to postmarketingsurveillance and a capacity to monitor amanufacturer’s investigation of adverse
events. Postmarket surveillance andvigilance ensures that problems or risks
associated with the use of devices, once
marketed, are identiﬁed and reported
to the regulatory authorities so that
corrective actions may be taken to reduce
the likelihood of recurrence. Properly
structured postmarketing surveillance
can identify serious problems in thesafety, quality or performance of a medical
device that may not have been foreseenor detected during product development
or premarket evaluation, and provide
for corrective actions. This may include
exchange of alerts internationally in astandardized manner (27).
Regulators should establish a system forpostmarket surveillance and vigilanceencompassing:• adverse event reporting andcomplaint handling systems
with clear responsibilities for the
regulator, manufacturer, authorized
representative, importer anddistributors;

WHO Medical device technical series37• analysis and investigation of reported
adverse events by the manufacturer
and regulatory authority;• maintenance by parties in the
distribution chain (importers anddistributors) of appropriate records
of complaints and actions taken;• oversight of implementation ofcorrective actions and preventive
actions, including FSCA, whenappropriate.
Where the manufacturer is located outside
the jurisdiction of the regulatory authority
there should be an agreement between
the manufacturer and its authorized
representative deﬁning who fulﬁls thenational regulatory requirements andmaintains records of the distribution of
the device. The agreement should require
the authorized representative to report
serious adverse events, quality problems
and complaints to the manufacturer forinvestigation and corrective action.
4.3.3.2 Require mandatory reporting ofadverse events
To the extent that investigation andinformation management resources allow,
the regulatory authority should establish
a mandatory requirement for the timely
reporting, by the authorized representative
or manufacturer, of adverse events
associated with medical devices in thejurisdiction. It should deﬁne the thresholdfor reporting (i.e. what kinds of eventsshould be reported), reporting time limits,required information and which party (orparties) shall report. In general, thosecriteria should be consistent with GHTF
guidance on adverse event reporting (51).
4.3.3.3 Inspections of registeredestablishments
The regulatory authority may inspect
periodically, scheduled or unannounced,
all registered organizations to conﬁrm
they have the facilities, procedures
and records in place to allow them to38comply with the attestations made when
they were registered. Additionally, theregulatory authority may issue licenses
to the registered organization, renewable
on a periodic basis. The registration– or license if such has been issued– may be withdrawn or suspended if
non-conformities (52) are found during
inspection.
4.3.3.3.1 Distribution of medical devices
The manufacturer of a medical device isrequired to implement a QMS covering
activities of design and development,
production, distribution, installationand servicing. However, quality, safety
and performance of finished medical
devices may be affected after releasefrom the manufacturer by various
factors such as storage conditions,warehouse environment and practices,transportation, installation, servicing,duration of storage and user training. The
distributor shares responsibility for manyof these activities. The manufacturer has
the responsibility to:• select appropriately qualified
distributors (appropriate andadequate facilities, information
systems and qualiﬁed staff);• specify the requirements for medical
device storage, handling, transport,
installation, servicing and traceabilityof record keeping;• periodically verify the conformityof distributors with the contract
requirements.
Collection of customer feedback andimplementation of correction andcorrective actions, postmarket surveillance
activities, and implementation of FSCA for
medical devices may be conducted by
the manufacturer through cooperation
with its authorized representative anddistributors. As with a manufacturer,a distributor would benefit from
implementing a basic QMS to control its
activities.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

With the exponential increase in Internet
connectivity, those engaged in the
manufacture, distribution and supply ofSF7 medical products have gained accessto a global marketplace.8 Parties within
the distribution chain will beneﬁt fromcomplying with good practice guidelines,
such as a code of good distribution
practice (GDP), as part of the global
effort to combat SF medical products.
Fulﬁlment of the requirements of GDP
may be enabled by the implementationof a QMS in accordance with ISO 13485(19). The Asian Harmonization Working
Party (AHWP) has published guidanceon the application of ISO 13485 in an
organization that distributes or imports
medical devices (53).
4.3.3.3.2 Local production
While many countries import most of
the medical devices used in theirdomestic market, there are also likely
to be a number of local manufacturers.
In the interests of safeguarding publichealth, local manufacturers should be
subject to the same regulatory controls
as manufacturers of imported medical
devices. However, because the local
manufacturer is physically located in thejurisdiction of the authority, that regulatory
authority would generally conduct its own
QMS inspections of the manufacturer’s
plant(s) and warehouse(s), or designate
a CAB to act on its behalf. In the caseof inspections to investigate suspectednoncompliance or problems withproducts, the regulatory authority is likely
to undertake the inspection itself.
The regulatory authority should
provide guidance speciﬁcally for local
manufacturers.

4.3.3.4 Provide for testing laboratories
The work of the regulatory authority
may beneﬁt from having access to anindependent, accredited test laboratory
to supplement its own resources when
testing is deemed necessary to verify
the safety or performance of the device.
Tasks that may be undertaken by anappropriately qualified and equipped
testing laboratory include:• examination and testing of medical
devices that are suspected as SF(see section 5);• institution of a programme of
postmarket testing of specificimported devices according to
speciﬁc national public health risks;• investigation of devices allegedly
involved in a serious adverse event;• investigation of devices sent to theregulatory authority by laypersons;• post-shipment lot veriﬁcation testingof IVDs.
Given the diversity of medical devices,
it is unlikely that an NRA will have all
the necessary resources internally toestablish and maintain its own laboratory.
This Model does not recommendthat a regulatory authority sets up its
own testing laboratory as, if it is to beeffective, it requires a signiﬁcant budget
and qualiﬁed staff. In many jurisdictions
such organizations do not exist within the
country itself, but may exist regionally.
When relying upon a testing laboratory,
inside or outside the national jurisdiction,
the authority should consider whether alaboratory has:
• accreditations to recognized
standards (e.g. ISO 17025:2005, ISO
15189:2012);• technical competence;

7 The Member State mechanism on substandard/spurious/falsely-labelled/falsiﬁed/
counterfeit (SSFFC) medical products has recommended the World Health
Assembly adopt a simpliﬁed terminology for substandard and falsiﬁed (SF)medical products (EB140/23, Annex, Appendix 3 (dated 10 January 2017)).
8 http://www.who.int/entity/mediacentre/factsheets/fs275/en/ (accessed 5 July2016).

WHO Medical device technical series39• access to external experts, as
needed;• adequate resources, such as
specialized equipment;• internal QMS and instrument
calibration facilities.

4.4 Stepwise approach,harmonization, reliance,
recognition
WHA Resolution 67.20 emphasizes
the importance of collaboration andharmonization. It requests the DirectorGeneral “to prioritize support forestablishing and strengthening regionaland subregional networks of regulatory
authorities, as appropriate, including
strengthening areas of regulation of healthproducts that are the least developed,
such as regulation of medical devices
including diagnostics” and “to promote
the greater participation of Member
States in existing international andregional initiatives for collaboration andcooperation in accordance with WHO
principles and guidelines”.

40

National regulation of medical devices istaking place in an increasingly globalized
world, creating a need for closer alignmentof regulatory requirements and practices.
Accordingly, countries that align their
medical device regulations with existingharmonization guidance documents
will promote this necessary regulatory
convergence.
WHA Resolution 67.20 also urges
Member States to “engage in global,
regional and subregional networksof national regulatory authorities, as
appropriate, recognizing the importanceof collaboration to pool regulatory
capacities to promote greater access toquality, safe, efﬁcacious and affordable
medical products” and “promoteinternational cooperation, as appropriate,for collaboration and information sharing,
including through electronic platforms”.
Harmonization, recognition and reliance
contribute to more effective regulatory
systems. They are an essential componentof health system strengthening andcontribute to better public healthoutcomes (Figure A4.4).

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Figure A4.4 Controls for medical devices showing elements for which regulatory guidance has been developed
and those that may be implemented through reliance or recognition. The elements indicated in red are those forwhich international regulatory harmonization guidance documents have been developed. Elements that may be
implemented through reliance or recognition are indicated in blue.

WHO Medical device technical series

41

5. Additional topics
Beyond the general elements describedin earlier chapters, this chapter covers
speciﬁc topics to be considered whendeveloping and implementing regulations
for medical devices. It explains therelevance of these topics and provides
guidance for regulators to ensure they areappropriately addressed. The topics arelisted in alphabetical order.

5.1 Determination to establish
whether a medical product isa medical device
Many products are used in the deliveryof health care, yet not all ﬁt comfortably
within an existing definition for a
medical product, more speciﬁcally theterm “medical device” (Figure A4.5).
Examples include medical gases, somelaxatives, cosmetic articles, clinicallaboratory reagents and articles ofprotective clothing worn by medical
personnel during procedures. Productsthat may be considered to be medical
devices in some jurisdictions but not inothers include disinfection substances,
aids for persons with disabilities, devices
incorporating animal and/or humantissues, and devices for in vitro fertilization
or assisted reproduction technologies. A
lack of clarity in such cases may leadto overlapping or conﬂicting regulatory
requirements for a product, or in somejurisdictions, no separate regulation forsuch medical products. It is in the public
interest to ensure the safety, quality andperformance of all such “borderline”
products1 through appropriate regulatory
controls – either those for medical devices
or for other regulated product sectors(e.g. medicines including advanced
therapy medicinal products, biologicals
and regenerative medicine products,
cosmetics, food supplements or personal
protective equipment) (54–56).
To be predictable and transparent, theregulatory authority should develop
criteria and mechanisms for determining
the appropriate regulatory regime forsuch products through guidelines. It
should describe considerations and theprocess whereby an applicant may obtainan advisory opinion from the regulatory
authority. Where necessary, that process
should allow for consultation with subject
matter experts as well as with regulatory
authorities from other product sectors
such as medicines or foods and withthe manufacturers concerned. It may
also take into account determinations
made by regulatory authorities of otherjurisdictions. A decision by the regulatory
authority on the regulatory status of a
product should provide the option of
appeal in case the applicant does notagree with the decision.

1 Borderline products are generally medical products for which it is unclear which
legislation applies. Although they may have some of the attributes of two or
more categories of regulated products, they are not combination products. A
combination product is a product comprising two or more components which are
regulated as medical products, i.e. medicine/medical device, or vaccine/medical
device, which are physically, chemically or otherwise combined or mixed andproduced as a single entity (modiﬁed from US FDA deﬁnition – http://www.
fda.gov/CombinationProducts/AboutCombinationProducts/ucm118332.htm). As
there is no international harmonization guidance on combination products, NRAs
should consider which requirements in other benchmark jurisdictions would best
serve their country’s needs. Herbal medicines according to WHO include herbs,
herbal materials, herbal preparations and ﬁnished herbal products, which containas active ingredients parts of plants, or other plant materials, or combinations(http://www.who.int/medicines/areas/traditional/deﬁnitions/en/).

42

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

Figure A4.5 Interrelation of (medical) products inside and outside health careICT, information and communications technology; IVDs, in vitro diagnostic medical devices.

5.2 Disposal
A medical device that reaches the end of
its intended life cycle must be disposed ofsafely. In some cases it may be necessary
to dispose of a device before the end of its
life if it is conﬁrmed that the device can nolonger perform its function properly andmay cause a hazard to users or patients.
Disposal of a medical device should
follow safety procedures to ensure thatit does not cause harm to people or theenvironment. This is especially importantfor contaminated devices such as syringes
or hypodermic needles, and devices that
contain infectious, toxic or radiologicalmaterials. Medical device labelling andinstructions for use should include
information on proper disposal at the endof device’s life, as appropriate for the typeof device. Where the regulatory authority
has identiﬁed SF medical products, it
shall itself document a procedure for local
disposal (e.g. mandatory destruction at
an approved facility). This will ensure thatsuch falsiﬁed or counterfeit products are
not exported to another country where
they may cause harm.
Owing to their diversity and complexity,
there are many ways that medical
devices may be disposed of. For
durable equipment, mechanisms
may include replacement andWHO Medical device technical series

43decommissioning. For disposabledevices, decontamination and proper
waste management practices according
to the manufacturer’s instructions
should be required. The responsible
regulatory authority, in coordination withother concerned governmental bodies,should establish criteria for replacementand decommissioning based on the
manufacturer’s recommendations.
Consultation between the user andmanufacturer is critical especiallyfor high-technology and complicatedproducts in order to decide the best way
to dispose of them (57–59).

5.3 Donations
Charitable donations of medical
devices and IVDs can be very helpful,may improve the efficiency of healthfacilities, may save costs of purchasing
new equipment and may make somediagnoses or therapies accessible topatients, especially in resource-limited
settings. Donations may be beneﬁcial but
they can also cause health risks if theirsafety and performance are not veriﬁed.
Another potential issue is a lack of clear
documentation or labelling on the donatedmedical device, its state, its origin andhistory and the responsibilities of donors.
Quality problems associated with donatedmedical devices have been reported inmany countries. They include short expiry
dates, defective equipment and gifts of
unnecessary items not requested by therecipient. These factors often result inreceiving countries incurring unwanted
costs for maintenance and disposal andmay also create the impression that the
medical devices are “substandard” andhave been “dumped” on a receiving
country (60–63). For these reasons somecountries have banned donations of usedequipment.

44

To safeguard public health, medical
devices imported as donations should
comply with all regulatory requirements
on safety, quality and performance andshould not differ from those that areimported through a regular supply chain.
Regulatory authorities should therefore
establish a mechanism to verify andauthorize the importation of donatedmedical devices. Institutions that intend
to donate devices should communicate
with the recipient to determine theirneeds before the products are shipped.2
To avoid delay and additional expense,
importation documents must be
submitted to the regulatory authorityof the recipient’s country for approval
before shipment of the consignment.
Supporting documents will typically
include: a list of products to be donated,
manufacturer(s) of the products, expiry
dates (if applicable), donation certiﬁcate3
and a commitment letter that conﬁrms
the safety and performance of the devices
to be donated. All donors are required tofamiliarize themselves with the donation
requirements before they decide to
donate medical devices. Donations that
do not comply with the requirements
should be rejected and sent back to thedonor at the donor’s expense.

5.4 Reprocessing of single-use
medical devices
Single-use medical devices4 (SUMDs)
are designed and labelled for single
use. They do not come with appropriate
instructions for cleaning, disinfecting or
2 Guidelines to help donors to familiarize themselves with donations requirements
may be found at http://www.who.int/medical_devices/management_use/
manage_donations/en/.
3 The donation certiﬁcate conﬁrms that the donation complies with the “Criteria forevaluating equipment donation offers” as stated in the WHO publication: Medical
device donations: considerations for solicitation and provision (http://apps.who.
int/iris/bitstream/10665/44568/1/9789241501408_eng.pdf).
4 Single-use device: is a medical device that is intended to be used on an individual
patient during a single procedure and then disposed of. It is not intended to be
reprocessed and used again (http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/technicaldocs/ghtf-sg1-n43-2005-labelling-medical-devices-050603.pdf).

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

sterilization procedures after use andthe manufacturer has not investigatedany deterioration in performance ifthey are subject to reprocessing. This
may pose a danger to the patient when
SUMDs are reprocessed and used morethan once, because conformity to their
original standards for safety, quality andperformance cannot be assured.
The claimed advantages to healthcare practices of cost–effectivenessand waste reduction must be weighedagainst the potential risks associated withreprocessed SUMDs. These risks include
possible cross-infection as a result of theinability to assure the complete removalof viable microorganisms, inadequate
cleaning, decontamination and removalof pyrogens and material alteration.
Exposure to chemical cleaning agents
may cause corrosion or changes in thematerials of the device, and exposure torepeated sterilization processes may alsochange the properties or degrade thedevice material. The high temperatureand harsh chemicals sometimes usedduring processing may impair the qualityof reprocessed devices.
In addition to the potential health risks
associated with the use of reprocessed
SUMDs, ethical considerations arise.
These considerations include whether
it is justifiable to treat a patient witha reprocessed SUMD that may be oflower quality, performance or cleanlinessthan it had when used for the ﬁrst time,even with informed consent. Other
considerations include liability: theentity that reprocesses a medical device
becomes the new manufacturer withthe associated responsibilities, andeconomic: to reprocess a SUMD using
a validated process raises the costs; theperceived savings may therefore not berealized.

In adopting a policy on the reprocessingof SUMDs, the regulatory authority should
consider the following: reprocessing of a
SUMD as labelled by its manufacturer
is not permitted unless the reprocessed
SUMD meets the same initial standards
as those of the original manufacturer.
To allow their reuse, the entity that
reprocesses and distributes medical
devices labelled by their original
manufacturer for single-use only will
be subject to the same requirementsof safety, quality and performance as
manufacturers of new devices (64–67).
This applies equally to a health-carefacility fully reprocessing SUMDs forreuse within its own facility.
When investigating complaints andadverse events, the regulatory authority
should consider the possibility that
reprocessing of SUMDs may havecontributed to their occurrence. The
policy on the use of a reprocessed SUMD
should only be enacted after appropriate
risk–beneﬁt analyses are performed on
the potential risks described above.

5.5 Refurbishing electromedical
devices
Some medical devices, typically durable
electromedical devices, are meant to bereused many times over a long design
life. In some cases, they may be subject
to refurbishing by an organization or entity
other than the original manufacturer
to extend their service life, often foreconomic reasons.
Refurbishing can be described as a
restoration of a device to a conditionof safety and performance that iscomparable to its condition when new.
This includes reconditioning, repair,installation of certain software and/or
hardware updates that do not change the

WHO Medical device technical series

45intended use of the original device, andreplacements of worn parts. Refurbishedmedical devices should be identiﬁed assuch on the labelling.
In adopting a policy on refurbishing,
the regulatory authority should clearlystate that the entity responsible forrefurbishing or third party must meetthe same regulatory requirements asapplied to the original medical device.
A party that refurbishes medical devices
will be subject to the same requirementsof safety, quality and performance as
manufacturers of new devices (68–71).

5.6 Substandard and falsiﬁed
products
SF medical products5 are harmful to thehealth of patients, damage conﬁdence
in medical products and health-careproviders and increase the burden on
health systems.
SF medical devices can result fromgenuine manufacturing errors ordeliberate falsiﬁcation of a product. The
latter is usually a clandestine activity, isoften difﬁcult to detect and is designed
to deceive a health-care provider or
patient into believing that the device isthe genuine article and has been carefully
assessed in terms of quality, safety andeffectiveness.
Reports of SF medical devices haveemerged from all over the world.
The United States Food and Drug
Administration (US FDA) has issued aletter concerning contaminated surgicalhernia mesh.6 The United Kingdom’s
Medicines and Healthcare products
Regulatory Agency (MHRA) raided a
5 The Member State mechanism on substandard/spurious/falsely-labelled/falsiﬁed/
counterfeit (SSFFC) medical products has recommended the World Health
Assembly adopt a simpliﬁed terminology for substandard and falsiﬁed (SF)medical products (EB140/23, Annex, Appendix 3 (dated 10 January 2017)).
6 http://www.fda.gov/ICECI/CriminalInvestigations/ucm303541.htm (accessed 27
September 2016).

46

business following a complaint about
a portable dental X-ray unit available
on eBay. The unit was found to lacksufficient shielding of the X-ray tube,
which means that it could emit harmfulradiation levels to operator and patients.7
Falsified condoms, contact lenses,
catheters, syringes and needles havebeen reported from Africa, Asia andEurope (72). The trade in SF medical
devices is driven and motivated by proﬁt.
Where a demand exists, those engaged
in the manufacture and distribution of
SF devices will respond. They will utilize
online distribution channels as well as
the regulated supply chain to market
their products, often accompanied byfalse safety and quality certiﬁcation logos.
Visual identiﬁcation can be extremely
difficult and laboratory analysis (seesection 4) may be required to distinguish
the SF product from the genuine version.
The established approach is one ofprevention, detection and response(18). The existence of a legal frameworkproviding for proportionate regulatory
requirements and powers, including
dissuasive sanctions, is critical. A
regulatory system, with effective oversightof importation, distribution and saleof medical devices will assist in theprevention of SF devices reaching users
and patients. Balanced awareness-raisingamong consumers, health-care providers
and distributors can help to minimize
the threat posed by SF medical products
while retaining confidence in healthtechnologies. It is important to educate
the general public to buy from reliable
sources, particularly on the Internet.
Effective postmarket surveillance andvigilance systems are both methods ofdetecting SF medical devices early on.
Regulatory authorities should establish
mechanisms that enable and encourage
7 https://www.gov.uk/drug-device-alerts/medical-device-alert-counterfeit-or-nonce-marked-dental-medical-devices (accessed 27 September 2016).

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devicesreporting of suspicious medical devices
and regulatory authorities should be
responsive to those reports. Regulator
engagement with relevant stakeholders,
including both public and private sector
organizations, law enforcement, civilsociety, consumer groups and patients,
leads to increased reporting and earlier
detection of SF products (73– 77).
New technologies, including unique
identiﬁers and track-and-trace technology,
also provide increased assurance of the
supply chain and can lead to the early
detection of SF products.
Strengthening capacity among regulatory
authorities to respond, transparently,
consistently and proportionately, will
help to maintain conﬁdence in healthsystems. Working in partnership withother stakeholders, including, where
necessary, law enforcement and the
judiciary, will help to ensure that serious
cases of falsiﬁcation are dealt with in amanner commensurate with the risk topublic health.

good quality. The focus of this programmeis on IVDs for priority diseases such as
HIV/AIDS, malaria, hepatitis C and others,
and their suitability for use in resourcelimited settings (78).
The PQT for IVDs undertakes anassessment of individual IVDs througha standardized procedure aimed atdetermining whether the product meets
WHO prequaliﬁcation requirements. The
process includes three components:• review of the technical documentation(product dossier) (79);• independent performance evaluation;• inspection of manufacturing site(s).

5.7 WHO Prequaliﬁcation Teamfor IVDs

Prequalification requirements are
based on best international practiceand are designed around the Essential
Principles of safety and performance.
As such, prequaliﬁcation requirements
reﬂect standards, guidance and otherinternationally recognized documents
such as those of ISO, European Norm,Clinical & Laboratory Standards Institute(CLSI) and IMDRF/GHTF, to ensurecompliance with the Essential Principles.
Like other stringent regulatory reviews,
prequalification assessments coverquality, safety and performance aspects.

Lack of access to quality healthtechnologies, in particular IVDs,
reduces the opportunity for progress
towards addressing high-burden
diseases in certain countries. The WHO
Prequalification Team (PQT) provides
countries with the appropriate technicalsupport, tools and guidance on theprovision of IVDs and laboratory services.
In addition to relying upon the work ofother authorities, for some medical devices(mostly IVDs), the regulatory authority
may choose to rely upon evaluations
conducted by the PQT for IVDs. This is aquality assurance programme that aims
at promoting and facilitating access tosafe, appropriate and affordable IVDs of

Although prequaliﬁcation requirements
are aligned with the approach adopted byregulators performing stringent reviews,
they have been designed in such a way
as to best serve resource-limited settings.
Therefore, the aspects below are reﬂectedin prequaliﬁcation assessments:• the regulatory version marketed on
the global market is assessed;• the scrutiny level reﬂects individual
and public health risks in resourcelimited settings;• data submitted by the manufacturer
are assessed from the perspective of
resource-limited settings in order toreﬂect the resource-limited settings’
environment and users.

WHO Medical device technical series

47

Countries may beneﬁt from the programmeby relying on prequaliﬁcation assessment
outcomes. The list of prequaliﬁed IVDs,
together with the report summarizing theassessment ﬁndings, is made publicly
available by WHO (80).
The findings of the PQT for IVDs, inconjunction with other procurement
criteria, are typically used by UN
agencies, WHO Member States and otherinterested organizations to guide theirprocurement of IVDs.

5.8 United Nations Population
Fund Prequaliﬁcation
Programme for intrauterine
devices and condoms
A similar prequalification programme
exists for the management of malelatex condoms, female condoms andintrauterine devices (IUDs) (81). The
management of this programme wasdelegated from WHO to the United
Nations Population Fund (UNFPA) in2005 for male condoms, and in 2006 forfemale condoms. WHO still maintains
the normative role in setting guidelines
and requirements for the prequaliﬁcation
programmes.

48

As for IVDs, the prequalification
programme for male and female
condoms follows a systematic process
consisting of a detailed technical review
of required documentation, on-site
factory inspections and product testing.
This process determines whether thequality of products is in accordancewith international standards and WHO/UNFPA speciﬁcations and guidelines.
Manufacturers of female condoms are
expected to demonstrate the safety,
efﬁcacy and acceptability of new designs.
UNFPA maintains a list of prequaliﬁed
manufacturers and sites that havesuccessfully completed the WHO/UNFPA
prequaliﬁcation process and have been
approved by the WHO/Reproductive
Health and Research (RHR) Technical
Review Committee for male and female
condoms.
The findings are used to provide
independent technical information on
safety, quality and performance of the
products assessed to other UN agencies,
WHO Member States and other interested
organizations. The UNFPA/WHO
prequaliﬁcation status, in conjunction
with other procurement criteria, is used bythese entities to guide their procurementof the products covered by the PQTs.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

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Further reading•

Aide-memoire for national medical device administrations. Geneva: World HealthOrganization; 2002 (http://www.who.int/medical_devices/publications/en/AM_
Devices_EN.pdf?ua=1).

•

Aide-memoire: strengthening national regulatory authorities. Geneva: World HealthOrganization; 2003 (http://www.who.int/medical_devices/publications/en/AM_
National_Regulatory_Authorities_2003.pdf?ua=1).

•

The GHTF Regulatory Model. Global Harmonization Task Force; 2011 (GHTF/
AHWG-GRM/N1R13: 2011; http://www.imdrf.org/docs/ghtf/ﬁnal/steering-committee/
technical-docs/ghtf-sc-n1r13-2011-ad-hoc-regulatory-model-110413.pdf).

•

International Medical Device Regulators Forum (IMDRF) [website] (http://www.imdrf.
org/, accessed 20 November 2016).

•

Medical devices regulations. WHO/medical devices [website]. Geneva: World
Health Organization (http://www.who.int/medical_devices/safety/en/, accessed 20
November 2016).

•

Medical devices regulations; global overview and guiding principles.
Geneva: World Health Organization; 2003 (http://apps.who.int/iris/
bitstream/10665/42744/1/9241546182.pdf).

•

Medical devices, managing the mismatch. Geneva: World Health Organization;2010 (http://apps.who.int/iris/bitstream/10665/44407/1/9789241564045_eng.pdf,
accessed 20 November 2016).

•

A model regulatory program for medical devices: an international guide.
Washington (DC): Pan American Health Organization; 2001 (http://new.paho.
org/hq/dmdocuments/2009/AmodelRegulatoryProgramforMedicalDevices_
AnInternalGuide.pdf?ua=1, accessed 20 November 2016).

•

National drug regulatory legislation: guiding principles for small drug regulatory
authorities. In: WHO Expert Committee on Speciﬁcations for Pharmaceutical
Preparations: thirty-ﬁfth report. Geneva: World Health Organization; 1999 (WHOTechnical Report Series, No. 885: Annex 8; http://www.who.int/medicines/technical_
brieﬁng/tbs/National_drug_regulatory_legislation_Annex8TRS885_en.pdf, accessed
20 November 2016).

•

Playbook for implementation of a medical device regulatory framework. Asian
Harmonization Working Party Technical Committee; 2014 (http://www.ahwp.info/
index.php?q=node/497).

•

Regulation of medical devices. A step-by-step guide. WHO Regional Publications,
Eastern Mediterranean Series 38. Cairo: World Health Organization, Regional
Ofﬁce for the Eastern Mediterranean; 2016 (http://applications.emro.who.int/dsaf/
emropub_2016_EN_18962.pdf?ua=1, accessed 20 November 2016).

•

Wong J, Tong RKY, editors. Handbook of medical devices regulatory affairs in Asia.
Singapore: Pan Stanford; 2013.
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57

Appendix 1
Glossary
For the purposes of this document, the following deﬁnitions and descriptions apply.
They may have different meanings in other contexts.
accessory to an IVD medical device. An article intended speciﬁcally by its manufacturer
to be used together with a particular IVD medical device to enable or assist that device
to be used in accordance with its intended use (1).
accessory to a medical device. An article intended speciﬁcally by its manufacturer tobe used together with a particular medical device to enable or assist that device to be
used in accordance with its intended use (1).
accreditation. The term applied to third party attestation related to a conformity
assessment body conveying formal demonstration of its competence to carry out speciﬁc
conformity assessment tasks (2).
adverse event. Any untoward medical occurrence, unintended disease or injury, or
untoward clinical signs (including an abnormal laboratory ﬁnding) in subjects, users orother persons, whether or not related to the investigational medical device (3).
analytical performance. The ability of an IVD medical device to detect or measure aparticular analyte (4).
assessment. A systematic, independent and documented process for obtaining
assessment evidence and evaluating it objectively to determine the extent to whichassessment criteria are fulﬁlled.
audit. A systematic, independent and documented process for obtaining audit evidence
and evaluating it objectively to determine the extent to which the audit criteria are
fulﬁlled (5).
authorized representative. Any natural or legal person established within a country or
jurisdiction who has received a written mandate from the manufacturer to act on his or
her behalf for speciﬁed tasks, with regard to the latter’s obligations under that country
or jurisdiction’s legislation (6).
certiﬁcation. The term applied to third party attestation related to products, processes,
systems or persons (2).
clinical evaluation. The assessment and analysis of clinical data pertaining to a medical
device to verify the clinical safety and performance of the device when used as intended
by the manufacturer (7).

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clinical investigation. Any systematic investigation or study in or on one or more humansubjects, undertaken to assess the safety and/or performance of a medical device (7).
clinical performance. The ability of an IVD medical device to yield results that are
correlated with a particular clinical condition/physiological state in accordance withtarget population and intended user (4).
conformity assessment. The systematic examination of evidence generated, andprocedures undertaken, by the manufacturer, under requirements established by theregulatory authority, to determine that a medical device is safe and performs as intended
by the manufacturer and, therefore conforms to the Essential principles of safety andperformance for medical devices (8).
conformity assessment body (CAB). A body, other than a regulatory authority, engaged
in determining whether the relevant requirements in technical regulations or standards
are fulﬁlled (8).
convergence (regulatory). Represents a process whereby the regulatory requirements
across countries or regions become more similar or “aligned” over time as a result of thegradual adoption of internationally-recognized technical guidance documents, standards
and scientiﬁc principles, common or similar practices and procedures, or adaptationof regulatory mechanisms, that might be speciﬁc to a local legal context but that alignwith shared principles to achieve a common public health goal. It does not necessarily
represent the harmonization of laws and regulations, which is not a prerequisite forallowing the alignment of technical requirements and greater regulatory cooperation (9).
corrective action. Action to eliminate the cause of a detected nonconformity or other
undesirable situation (10).
declaration of conformity. The manufacturer’s written attestation that it has correctly applied
the conformity assessment elements relevant to the classiﬁcation of the device (8).
distribution chain. A collective term for local manufacturers, authorized representatives,
importers and distributors established within the jurisdiction.
distributor. Any natural or legal person in the supply chain who, on their own behalf,
furthers the availability of a medical device to the end-user (6).
enforcement. Action taken by an authority to protect the public from products ofsuspect quality, safety and effectiveness or to assure that products are manufactured
in compliance with appropriate laws, regulations, standards and commitments madeas part of the approval to market a product (11).
ﬁeld safety corrective action (FSCA). An action taken by a manufacturer to reduce orremove a risk of death or serious deterioration in the state of health associated with theuse of a medical device that is already placed on the market (12).

WHO Medical device technical series

59generic device group. Aset of devices having the same or similar intended purposesor commonality of technology allowing them to be classiﬁed in a generic manner not
reﬂecting speciﬁc characteristics (13).
governance. Refers to the different ways that organizations, institutions, businesses
and governments manage their affairs. Governance is the act of governing and thus
involves the application of laws and regulations, but also of customs, ethical standards
and norms. Good governance means that affairs are managed well, not that the laws,
regulations or norms are themselves necessarily “good” (14).
guidelines/guidance documents. Non-statutory advisory publications intended to assist
those parties affected by legislation to interpret requirements.
harm. A physical injury or damage to the health of people or damage to property or theenvironment (15).
harmonization (regulatory). The process by which technical guidelines are developed
to be uniform across participating authorities (9).
hazard: A potential source of harm (15).
health-care facility. Any party within the country providing health-care services.
health technologies. Refers to the application of organized knowledge and skills in theform of devices, medicines, vaccines, procedures and systems developed to solve a
health problem and improve quality of lives (16).
importer. Any natural or legal person in the supply chain who is the ﬁrst in a supply chain
to make a medical device, manufactured in another country or jurisdiction, available inthe country or jurisdiction where it is to be marketed (6).
inspection. An on-site evaluation by a regulatory authority of a manufacturing facility todetermine whether such manufacturing facility is operating in compliance with regulatory
requirements and or commitments made as part of the approval to market a product (11).
instructions for use. Information provided by the manufacturer to inform the deviceuser of the medical device’s intended purpose and proper use and of any precautions
to be taken (17).
intended use/purpose. The objective intent of the manufacturer regarding the useof a product, process or service as reﬂected in the speciﬁcations, instructions andinformation provided by the manufacturer (18).
in vitro diagnostic (IVD) medical device. A medical device, whether used alone or in
combination, intended by the manufacturer for the in vitro examination of specimens
derived from the human body solely or principally to provide information for diagnostic,
monitoring or compatibility purposes (1).
IVD for self-testing. Any IVD medical device intended by the manufacturer for use bylaypersons (19).

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WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

label. Written, printed or graphic information either appearing on the medical device
itself, or on the packaging of each unit, or on the packaging of multiple devices (17).
labelling. The label, instructions for use and any other information that is related to
identiﬁcation, technical description, intended purpose and proper use of the medical
device, but excluding shipping documents (17).
law. Binding and enforceable legislation passed by a legislative body.
layperson. Individual who does not have formal training in a speciﬁc ﬁeld or discipline (17).
life cycle. All phases in the life of a medical device, from the initial conception to ﬁnal
decommissioning and disposal.
listing. The process whereby a party submits information to the regulatory authority in ajurisdiction, regarding the identiﬁcation of a medical device(s) that is or will be supplied
to the market in that jurisdiction (20).
manufacturer. Any natural or legal person with responsibility for design and/or manufactureof a medical device with the intention of making the medical device available for use,
under its name; whether or not such a medical device is designed and/or manufacturedby that person himself or herself or on his or her behalf by another person(s) (6).
Note: This “natural or legal person” has ultimate legal responsibility for ensuring
compliance with all applicable regulatory requirements for the medical devices in the
countries or jurisdictions where it is intended to be made available or sold, unless this
responsibility is speciﬁcally imposed on another person by the regulatory authority
within that jurisdiction.
market surveillance. The activities carried out and measures taken by public authorities
to ensure that products comply with the requirements set out in legislation and do notendanger health, safety or any other aspect of public interest protection (based on EU
Council Directive EC No 765/2008 of 9 July 2008 concerning the requirements foraccreditation and market surveillance relating to the marketing of products and repealing
Regulation (EEC) No 339/93) (21).
medical device. Any instrument, apparatus, implement, machine, appliance, implant,
reagent for in vitro use, software, material or other similar or related article, intended
by the manufacturer to be used, alone or in combination, for human beings, for one ormore of the speciﬁc medical purpose(s) of:• diagnosis, prevention, monitoring, treatment or alleviation of disease;• diagnosis, monitoring, treatment, alleviation of or compensation for an injury;• investigation, replacement, modification or support of the anatomy or of aphysiological process;• supporting or sustaining life;• control of conception;• disinfection of medical devices;• providing information by means of in vitro examination of specimens derived fromthe human body,

WHO Medical device technical series

61and which does not achieve its primary intended action by pharmacological,
immunological or metabolic means, in or on the human body, but which may be assisted
in its intended function by such means (1).
medical products. A term that includes medicines, vaccines, diagnostics and medical
devices (22).
placing on the market. All controls applied by the regulatory authority to the manufacturer
and/or authorized representative at the stage of, and as a condition of, making available
an individual medical device with a view to its distribution and/or use within thejurisdiction.
Postmarket controls. All controls applied by the regulatory authority to the manufacturer
and/or authorized representative after a manufacturer’s medical device has been placedon the market or put into service.
postmarket surveillance. The activities carried out and measures taken by a regulatory
authority to ensure that medical devices placed on the market comply with regulations
and do not endanger health, safety or any other aspect of public health (based on EU
Council Directive 93/42/EEC of 14 JUNE 1993 concerning medical devices) (23).
Premarket controls. All controls applied by the regulatory authority to the manufacturer
and/or the authorized representative before the manufacturer’s medical device may beplaced on the market or put into service.
primary legislation. A form of law, created by a legislative branch of government,
consisting of statutes that set out broad outlines and principles and may delegate
authority to an executive branch of government to issue secondary legislation.
quality management system. The organizational structure, responsibilities, procedures,processes and resources for implementing quality management. For the purpose of
these guidelines “implementing quality management” is taken to include both theestablishment and maintenance of the system (24).
recall. Any measure aimed at achieving the return of a product that has already been
made available to the end-user (based on EU Council Directive EC No 7656/2008 of
9 JULY 2008 concerning the requirements for accreditation and market surveillance
relating to the marketing of products and repealing Regulation (EEC) No 339/93) (21).
recognition. The routine acceptance by the regulatory authority in one jurisdictionof the regulatory decision of another regulatory authority or other trusted institution.
Recognition indicates that evidence of conformity with the regulatory requirements ofcountry A is sufﬁcient to meet the regulatory requirements of country B. Recognition
may be unilateral or multilateral, and may be the subject of a mutual recognition
agreement (25).
refurbishing. A systematic process of rebuilding or restoring that ensures safety andeffectiveness of the medical equipment without signiﬁcantly changing the equipment’s
or system’s performance safety speciﬁcations and/or changing intended use as in its
original registration (26).

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registration. The process by which a party submits information to the regulatory
authority in a jurisdiction, regarding the identiﬁcation and establishment location(s) of
the manufacturer and other parties, responsible for supplying a medical device(s) tothe market in that jurisdiction (20).
regulation. A written instrument containing rules having the force of law.
regulatory authority. A government body or other entity that exercises a legal right tocontrol the use or sale of medical devices within its jurisdiction, and that may takeenforcement action to ensure that medical products marketed within its jurisdiction
comply with legal requirements (8).
reliance. The act whereby the regulatory authority in one jurisdiction may take into
account and give signiﬁcant weight to – i.e. totally or partially rely upon – evaluations
performed by another regulatory authority or trusted institution in reaching its own
decision. The relying authority remains responsible and accountable for decisions taken,
even when it relies on the decisions and information of others (25).
reprocessing. The process carried out on a used medical device in order to allow its
safe reuse including, where appropriate, cleaning, disinfection, sterilization and related
procedures, repackaging, relabelling, as well as testing and restoration of the technicaland functional safety of the used device based on proposal for amending Directive
2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 of 26
September 2012 concerning medical devices (27).
risk. The combination of the probability of occurrence of harm and the severity of that harm (15).
secondary legislation. A form of law, issued by an executive branch of government,
specifying substantive regulations and procedures for implementing them. The power topass delegated legislation is deﬁned and limited by the primary legislation that delegatedthose powers.
serious adverse event. Adverse event that:a) led to a death;b) led to a serious deterioration in the health of the subject that either
1) resulted in a life-threatening illness or injury;2) resulted in a permanent impairment of a body structure or a body function;3) required inpatient hospitalization or prolongation of existing hospitalization, or4) resulted in medical or surgical intervention to prevent life-threatening illness or
injury or permanent impairment to a body structure or a body function;c) led to fetal distress, fetal death or a congenital abnormality or birth defect (3).
serious injury (also known as serious deterioration in state of health) is either:› life-threatening illness or injury;› permanent impairment of a body function or permanent damage to a body;› a condition necessitating medical or surgical intervention to prevent permanent
impairment of a body function or permanent damage to a body structure (28).
single-use medical device. A medical device intended by the manufacturer to be usedon an individual patient during a single procedure and then disposed of (17).

WHO Medical device technical series

63standard. A document, established by consensus and approved by a recognized body,that provides, for common and repeated use, rules, guidelines or characteristics for
activities or their results, aimed at the achievement of the optimum degree of order ina given context (29).
substandard/spurious/falsely-labelled/falsiﬁed/counterfeit medical products. There iscurrently no universally agreed deﬁnition of what used to be widely known as “counterfeit
medicine”. Pending negotiation among Member States, WHO will continue to use theterm substandard/spurious/falsely-labelled/falsiﬁed/counterfeit medical products (30).
technical documentation. The documented evidence, normally an output of the quality
management system that demonstrates the medical device complies with the relevant
principles of safety, performance and labelling speciﬁed through legislation (8).
user. The person, either professional or lay, who uses a medical device. The patient
may be the user (17).
vigilance. A process whereby a manufacturer records and investigates any adverse event
report it receives, taking ﬁeld safety corrective action where necessary, and informing
the regulatory authority of those that meet criteria speciﬁed through legislation. The
regulatory authority may monitor the investigation.
World Health Assembly. The forum through which the World Health Organization isgoverned by its 194 Member States.

References of the glossary641.

Deﬁnition of the terms “medical device” and “in vitro diagnostic (IVD) medical
device”. Global Harmonization Task Force; 2012 (GHTF/SG1/N071:2012; http://
www.imdrf.org/docs/ghtf/ﬁnal/sg1/technical-docs/ghtf-sg1-n071-2012-deﬁnitionof-terms-120516.pdf, accessed 20 November 2016).

2.

Conformity assessment – vocabulary and general principles. Geneva: International
Organization for Standardization; 2004 (ISO/IEC 17000:2004; http://www.iso.org/
iso/catalogue_detail.htm?csnumber=29316, accessed 1 February 2017).

3.

Reportable events during pre-market clinical investigation. Global Harmonization
Task Force; 2012 (GHTF/SG5/N5:2012; http://www.imdrf.org/docs/ghtf/ﬁnal/sg5/
technical-docs/ghtf-sg5-n5-2012-reportable-events-120810.pdf, accessed 20
November 2016).

4.

Clinical evidence for IVD medical devices – key deﬁnitions and concepts. Global
Harmonization Task Force; 2012 (GHTF/SG5/N6:2012; http://www.imdrf.org/docs/
ghtf/ﬁnal/sg5/technical-docs/ghtf-sg5-n6-2012-clinical-evidence-ivd-medicaldevices-121102.pdf, accessed 1 February 2017).

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

5.

Guidelines for quality and/or environmental management systems auditing.
Geneva: International Organization for Standardization; 2002 (ISO 19011:2002;
http://www.iso.org/iso/iso_catalogue/catalogue_ics/catalogue_detail_ics.
htm?csnumber=31169, accessed 1 February 2017).

6.

Deﬁnitions of the terms manufacturer, authorised representative, distributor
and importer. Global Harmonization Task Force; 2009 (GHTF/SG1/N055:2009;http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/technical-docs/ghtf-sg1-n055-deﬁnitionterms-090326.pdf, accessed 20 November 2016).

7.

Clinical investigations. Global Harmonization Task Force; 2010 (GHTF/SG5/
N3:2010; http://www.imdrf.org/docs/ghtf/ﬁnal/sg5/technical-docs/ghtf-sg5-n3clinical-investigations-100212.pdf, accessed 20 November 2016).

8.

Principles of conformity assessment for medical devices. Global Harmonization
Task Force; 2012 (GHTF/SG1/N78:2012; http://www.imdrf.org/docs/ghtf/
ﬁnal/sg1/technical-docs/ghtf-sg1-n78-2012-conformity-assessment-medicaldevices-121102.pdf, accessed 15 March 2016).

9.

Regulatory harmonization and convergence. Silver Spring (MD): US Food andDrug Administration (US FDA) (http://www.fda.gov/BiologicsBloodVaccines/
InternationalActivities/ucm271079.htm, accessed 2 February 2016).

10.

Quality management system – Medical Devices – Guidance on corrective action
and preventive action and related QMS processes. Global Harmonization Task
Force; 2010 (GHTF/SG3/N18:2010; http://www.imdrf.org/docs/ghtf/ﬁnal/sg3/
technical-docs/ghtf-sg3-n18-2010-qms-guidance-on-corrective-preventativeaction-101104.pdf, accessed 2 February 2017).

11.

Code of Federal Regulations Title 21. Silver Spring (MD): US Food and Drug
Administration (USFDA/21CFR26.1, http://www.accessdata.fda.gov/scripts/cdrh/
cfdocs/cfcfr/CFRSearch.cfm?fr=26.1, accessed 2 February 2017).

12.

Medical devices post market surveillance: content of ﬁeld safety notices. Global
Harmonization Task Force; 2006 (GHTF/SG2/N57R8:2006; http://www.imdrf.
org/docs/ghtf/final/sg2/technical-docs/ghtf-sg2-n57r8-2006-guidance-fieldsafety-060627.pdf, accessed 4 April 2016).

13.

Global Medical Devices Nomenclature System (GMDN) [website] (https://www.
gmdnagency.org, accessed 2 February 2017).

14.

WHO global governance (http://www.who.int/healthpromotion/conferences/9gchp/
good-governance/en/)

15.

Safety aspects – Guidelines for their inclusion in standards. Geneva: International
Organization for Standardization; 2014 (ISO/IEC Guide 51:2014; http://www.iso.
org/iso/catalogue_detail.htm?csnumber=53940, accessed 2 February 2017).

16.

Resolution WHA60.29. Health technologies.

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66

17.

Label and instructions for use for medical devices. Global Harmonization Task
Force; 2011 (GHTF/SG1/N70:2011; http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/
technical-docs/ghtf-sg1-n70-2011-label-instruction-use-medical-devices-110916.
pdf, accessed 20 November 2016).

18.

Principles of medical devices classiﬁcation. Global Harmonization Task Force;2012 (GHTF/SG1/N77:2012; http://www.imdrf.org/docs/ghtf/ﬁnal/sg1/technicaldocs/ghtf-sg1-n77-2012-principles-medical-devices-classiﬁcation-121102.pdf,
accessed 15 March 2016).

19.

Principles of in vitro diagnostic (IVD) medical devices classiﬁcation. Global
Harmonization Task Force; 2012 (GHTF/SG1/N045:2008; http://www.imdrf.org/
docs/ghtf/ﬁnal/sg1/procedural-docs/ghtf-sg1-n045-2008-principles-ivd-medicaldevices-classiﬁcation-080219.pdf, accessed 15 March 2016).

20.

Registration of manufacturers and other parties and listing of medical devices.
Global Harmonization Task Force; 2010 (GHTF/SG1/N065:2010; http://www.
imdrf.org/docs/ghtf/ﬁnal/sg1/technical-docs/ghtf-sg1-n065-listing-of-medicaldevices-100827.pdf, accessed 20 November 2016).

21.

Regulation EC No 765/2008 of 9 July 2008 concerning the requirements foraccreditation and market surveillance relating to the marketing of products andrepealing Regulation (EEC) No 339/93.

22.

Resolution WHA67.20. Regulatory system strengthening for medical products.

23.

EU Council Directive 93/42/EEC of 14 June 1993 concerning medical devices(http://www.imdrf.org/docs/ghtf/archived/sg4/technical-docs/ghtf-sg4-guidelinesauditing-qms-part-1-general-requirements-080827.pdf, accessed 2 February2017).

24.

Guidelines for regulatory auditing of quality systems of medical device manufacturers– Part 1: general requirements (GHTF/SG4/N28R4:2008; http://www.imdrf.org/
docs/ghtf/archived/sg4/technical-docs/ghtf-sg4-guidelines-auditing-qms-part-1general-requirements-080827.pdf, accessed 2 February 2017).

25.

WHO good regulatory practices: guidelines for national regulatory authorities for
medical products. Geneva: World Health Organization (under development, 2017).

26.

Regulatory framework for control of refurbished medical devices. Asia Pasiﬁc
Economic Cooperation; 2012 (http://mddb.apec.org/Documents/2012/MAG/WKSP1/12_mag_wksp1_011.pdf, accessed 18 March 2016).

27.

Procedure 2012/0266/COD COM (2012) 542: Proposal for a Regulation of theEuropean Parliament and of the Council on medical devices, and amending
Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No
1223/2009.

WHO Global Model Regulatory Framework for Medical Devices including in vitro diagnostic medical devices

28.

Medical devices post market surveillance: global guidance for adverse event
reporting for medical devices. Global Harmonization Task Force; 2006 (GHTF/
SG2/N54R8:2006; http://www.imdrf.org/docs/ghtf/ﬁnal/sg2/technical-docs/ghtfsg2-n54r8-guidance-adverse-events-061130.pdf, accessed 20 November 2016).

29.

Role of standards in the assessment of medical devices. Global Harmonization
Task Force; 2008 (GHTF/SG1/N044:2008;http://www.imdrf.org/docs/ghtf/ﬁnal/
sg1/procedural-docs/ghtf-sg1-n044-2008-standards-in-assessment-of-medicaldevices-080305.pdf, accessed 20 November 2016).

30.

Substandard, spurious falsely labelled, falsiﬁed and counterfeit medical products.
Geneva: World Health Organization; 2014.

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Appendix 2
Hierarchy of regulationa68

ExamplesExamples of subject matter
regulated in the ﬁeld of
medical devices

Level

Brief description

Primary
legislation

Law, or executive law as used
Act of parliament, bill, statutory
in this WHO Global Modellaw, EU directive, ordinance,
Regulatory Framework, refers
decree, executive order.
to binding and enforceable
legislation, usually adopted at thelevel of individual countries by
their respective legislatures and/or executives.

Establishment of the regulatory
authority including enforcement
power; reliance and recognition;
deﬁnition of a medical device;placing on the market; market
withdrawal; classiﬁcation of
medical devices; Essential
Principles of safety andperformance; requirement fora quality management system;
incident reporting; clinical
trials; listing of medical devices;
registration of establishments;
process to recognize standards.

Secondarylegislation

A form of law as used in thisRegulations, schedule.
Model Regulatory Framework for
Medical Devices, refers to written
instruments that are binding andenforceable and are issued by theregulatory (executive) authority.

Requirements for reliance;
conduct of quality management
system (QMS) audits; vigilance
reporting; criteria for recalls andﬁeld safety corrective actions(FSCAs); classiﬁcation rules;
responsibilities of an authorized
representative.

Guidelinesa

Guidance documents thatrefer generally to non-binding
normative documents issued by
the regulatory authority, which
offer guidance on recommended
practices. They allow forscientiﬁcally-justiﬁed, alternative
approaches and translation of aregulatory, generally acceptableapproach. Guidelines set out
the current thinking, practices,
explanations and expectationsof the regulatory authority,
but compliance with such
documents is not mandatory.
The manufacturer (or otherparty) may choose not to apply
or comply with such guidance,
but must provide a rationale for,and justify, a deviation from that
guidance.

Technical standards,
recommendations.

Guidance on interpretation andapplication of the classiﬁcation
rules; interpretation of themeaning of “primary intended
mode of action” (related to thedeﬁnition of “medical device”);
speciﬁc labelling requirements;
good laboratory practices; goodclinical practices.

Note that the term “guideline”, as used in this WHO Global Model Regulatory Framework, does not refer to guidelines within the sense of the WHO handbook for guideline
development. Geneva: World Health Organization; 2014.

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Notes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Department of Essential Medicines and Health Products
World Health Organization
20 Avenue Appia
CH-1211 Geneva 27
Switzerland
E-mail: medicaldevices@who.int
http://www.who.int/medical_devices/en/

ISBN 978 92 4 151235 0