# EUR-Lex - 52012PC0541 - EN

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# 52012PC0541

**Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on in vitro diagnostic medical devices /* COM/2012/0541 final - 2012/0267 (COD) */**

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EXPLANATORY MEMORANDUM

1.
CONTEXT OF THE PROPOSAL

The current EU regulatory framework for in
vitro diagnostic medical devices ('IVDs') consists of Directive 98/79/EC of
the European Parliament and of the Council ('the IVD Directive')[1] IVDs cover a wide range of
products that can be used for population screening and disease prevention,
diagnosis, monitoring of prescribed treatments and assessment of medical
interventions.

Like Council Directive 90/385/EEC on active
implantable medical devices (AIMDD)[2]
and Council Directive 93/42/EEC on medical devices (MDD)[3] the IVD Directive is based on
the 'New Approach' and aims to ensure the smooth functioning of the internal
market and a high level of protection of human health and safety. IVDs are not
subject to any pre-market authorisation by a regulatory authority but to a
conformity assessment which, for the majority of devices, is carried out under
the sole responsibility of the manufacturer. For the high-risk devices listed
in Annex II and devices for self-testing, the conformity assessment involves an
independent third party, known as 'notified body'. Notified bodies are
designated and monitored by the Member States and act under the control of the
national authorities. Once certified, devices bear the CE marking which allows
them to circulate freely in the EU/EFTA countries and Turkey.

The existing regulatory framework for in
vitro diagnostic medical devices has demonstrated its merits but has also
come under criticism in recent years.

In an internal market with 32 participating
countries[4]
and subject to constant scientific and technological progress, substantial
divergences in the interpretation and application of the rules have emerged,
thus undermining the main objectives of the Directive, i.e. the safety and performance
of IVDs and their free movement.

This revision aims to overcome these flaws
and divergences and to further strengthen patient safety. A robust, transparent
and sustainable regulatory framework for in vitro diagnostic medical
devices that is 'fit for purpose' should be put in place. This framework should
be supportive of innovation and the competitiveness of the in vitro
diagnostic medical device industry and should allow rapid and cost-efficient
market access for innovative IVDs to the benefit of patients and healthcare
professionals.

This proposal is adopted alongside a
proposal for a Regulation on medical devices that are currently covered by the
AIMDD and the MDD. While the specific features of IVDs and of the IVD sector require the adoption of a specific
legislation distinct from the legislation on other medical devices, the
horizontal aspects common to both sectors have been aligned.

2.
RESULTS OF CONSULTATIONS WITH THE INTERESTED PARTIES
AND IMPACT ASSESSMENTS

In preparation for the impact assessment on
this proposal and the proposal for a Regulation on medical devices, the
Commission held two public consultations, the first from 8 May to 2 July 2008,
and the second from 29 June to 15 September 2010. In both public consultations,
the general principles and minimum standards for consultation of interested
parties by the Commission were applied; responses received within a reasonable
period after the deadlines were taken into account. After analysing all the
responses, the Commission published a summary outcome and the individual
responses on its website[5].

The majority of respondents to the 2008
public consultation (in particular Member States and industry) considered the
proposed revision to be premature. They pointed to Directive 2007/47/EC of the
European Parliament and of the Council[6],
which amended the AIMDD and the MDD and was to be implemented by 21 March 2010,
and also to the New Legislative Framework for the Marketing of Products which
was due to enter into force with effect from 1 January 2010, and argued that it
would be advisable to wait for these changes to be implemented, in order to
assess the need for further adjustments better.

The 2010 public consultation focussed on
aspects related to the revision of the IVD Directive and showed wide support
for this initiative.

During 2009, 2010 and 2011, the issues to
be tackled in the revision of the regulatory framework for medical devices and in
vitro diagnostic medical devices were regularly discussed at meetings of
the Medical Devices Expert Group (MDEG), the Competent Authorities for Medical
Devices (CAMD) and specific working groups in the fields of in vitro
diagnostic medical devices (IVDs), notified bodies, borderline and
classification, clinical investigation and evaluation, vigilance and market
surveillance, and in an ad hoc working group on Unique Device
Identification (UDI). A special meeting of the MDEG was held on 31 March and 1
April 2011 to discuss issues related to the impact assessment. Moreover, the
Heads of Medicines Agencies (HMA) and the CAMD organised joint workshops on the
development of the legal framework for medical devices on 27 April and 28
September 2011.

A further special meeting of the MDEG was
held on 6 and 13 February 2012 to discuss issues related to the two legislative
proposals, based on working documents containing initial drafting proposals.
Written comments made on these working documents were taken into account, where
appropriate, for the further development of the proposals.

In addition, Commission's representatives
regularly participated in conferences to present ongoing work on the
legislative initiative and hold discussions with stakeholders. Targeted
meetings took place at senior level with representatives from associations
representing industry, notified bodies, healthcare professionals and patients.

Aspects linked to the appropriate
regulatory framework were also discussed in the course of the 'Exploratory
Process on the Future of the Medical Device Sector' organised by the Commission
from November 2009 to January 2010. On 22 March 2011, the Commission and the
Hungarian Presidency organised a high-level conference on innovation in medical
technology, the role of the medical device sector in addressing the healthcare
challenges facing Europe and the appropriate regulatory framework for this
sector to meet the needs of tomorrow. This conference was followed by
Conclusions of the Council of the European Union on innovation in the medical
device sector adopted on 6 June 2011[7].
In its Conclusions, the Council requested the Commission to adapt the EU
medical device legislation to the needs of tomorrow so as to achieve a
suitable, robust, transparent and sustainable regulatory framework, which is
central to fostering the development of safe, effective and innovative medical
devices for the benefit of European patients and healthcare professionals.

Triggered by the PIP breast implants
scandal, the European Parliament adopted on 14 June 2012 a Resolution on
defective silicone gel breast implants made by the French company PIP[8] also calling on the Commission
to develop an adequate legal framework to guarantee the safety of medical
technology.

3.
LEGAL ELEMENTS OF THE PROPOSAL
3.1.
Scope and definitions (Chapter I)

To a large extent, the scope of the
proposed Regulation matches the scope of Directive 98/79/EC, i.e. it covers in
vitro diagnostic medical devices. The proposed changes clarify and extend
the scope of the IVD Directive. They concern:

·
high-risk devices manufactured and used within a
single health institution, which are subject to most of the requirements set
out in the proposal;

·
tests providing information about the
predisposition to a medical condition or a disease (e.g. genetic tests) and
tests providing information to predict treatment response or reactions (e.g.
companion diagnostics), which are considered as in vitro diagnostic
medical devices ;

·
medical software, which is explicitly mentioned
in the definition of IVDs.

To support Member States and the Commission
in determining the regulatory status of products, the Commission may set up, in
accordance with its internal rules[9],
a group of experts from various sectors (such as IVDs, medical devices,
medicinal products, human tissues and cells, cosmetics and biocides).

The definitions section has been
significantly extended, aligning the definitions in the field of in vitro diagnostic
medical devices with well-established European and international practice, such
as the New Legislative Framework for the Marketing of Products[10] and guidance documents
produced for in vitro diagnostic medical devices by the Global
Harmonization Task-Force (GHTF)[11] .

3.2.
Making available of devices, obligations of
economic operators, CE marking, free movement (Chapter II)

This chapter covers
mainly horizontal issues similar for both medical devices and IVDs. It contains
provisions that are typical for product-related internal market legislation and
sets out the obligations of the relevant economic operators (manufacturers,
authorised representatives of non-EU manufacturers, importers and distributors).
It also provides clarification with regard to the adoption and the scope of
common technical specifications (CTS) for in vitro diagnostic medical
devices.

The legal obligations on manufacturers are
proportionate to the risk class of the devices they produce. For example, this
means that even though all manufacturers should have a quality management
system (QMS) in place to ensure that their products consistently meet the
regulatory requirements, the QMS-related responsibilities are stricter for manufacturers
of high-risk devices than for manufacturers of low-risk devices.

Key documents for the manufacturer to
demonstrate compliance with the legal requirements are the technical
documentation and the EU declaration of conformity to be drawn up in respect of
the devices placed on the market. Their minimum contents are laid down in
Annexes II and III.

The following concepts are new in the field
of IVDs:

·
A requirement has been introduced that within
the manufacturer's organisation a 'qualified person' should be responsible for
regulatory compliance. Similar requirements exist in EU legislation on
medicinal products and in the national laws transposing the Directive on
medical devices in some Member States.

·
Since in the case of 'parallel trade' with in
vitro diagnostic medical devices application of the principle of free
movement of goods varies considerably from one Member State to another and, in
many cases, de facto prohibits this practice, clear conditions are set
for enterprises involved in relabelling and/or repackaging IVDs.

3.3.
Identification and traceability of devices,
registration of devices and of economic operators, summary of safety and
performance, Eudamed (Chapter III)

This chapter addresses one of the main
shortcomings of the current system: its lack of transparency. It consists of:

·
a requirement that economic operators shall be
able to identify who supplied them and to whom they have supplied IVDs;

·
a requirement that manufacturers fit their
devices with a Unique Device Identification (UDI) which allows traceability.
The UDI system will be implemented gradually and proportionate to the risk
class of the devices;

·
a requirement that manufacturers/authorised
representatives and importers shall register themselves and the devices they
place on the EU market in a central European database;

·
an obligation for manufacturers of high-risk
devices to make publicly available a summary of safety and performance with key
elements of the supporting clinical data;

·
and the further development of the European databank
on medical devices (Eudamed), set up by Commission Decision 2010/227/EU[12], which will contain integrated
electronic systems on a European UDI, on registration of devices, relevant
economic operators and certificates issued by notified bodies, on clinical
performance studies, on vigilance and on market surveillance. A large part of
the information in Eudamed will become publicly available in accordance with
the provisions regarding each electronic system.

The establishment of a central registration
database will not only provide a high level of transparency but also do away
with diverging national registration requirements which have emerged over
recent years and which have significantly increased compliance costs for
economic operators. It will therefore also contribute to reducing the
administrative burden on manufacturers.

3.4.
Notified bodies (Chapter IV)

Proper functioning of notified bodies is
crucial for ensuring a high level of health and safety and citizens' confidence
in the system, which has come under severe criticism in recent years due to
significant differences as regards, on the one hand, the designation and
monitoring of notified bodies and, on the other, the quality and depth of the
conformity assessment performed by them.

In line with the New Legislative Framework
for the Marketing of Products, the proposal sets out requirements for national
authorities responsible for notified bodies. It leaves the ultimate
responsibility for designating and monitoring notified bodies, based on stricter
and detailed criteria laid down in Annex VI, with the individual Member State. The proposal thus builds on
existing structures already available in most Member States instead of lifting
the responsibility to the Union level which might have caused concerns in terms
of subsidiarity. But any new designation and, in regular intervals, the
monitoring of notified bodies are made subject to 'joint assessments' with
experts from other Member States and the Commission, thus ensuring an effective
control at Union level.

At the same time, the position of notified
bodies vis-à-vis manufacturers will be significantly strengthened, including
their right and duty to carry out unannounced factory inspections and to
conduct physical or laboratory tests on devices. The proposal also requires
rotation of the notified body's personnel involved in the assessment of IVDs at
appropriate intervals to strike a reasonable balance between the knowledge and
experience required to carry out thorough assessments and the need to ensure continuous
objectivity and neutrality in relation to the manufacturer subject to those
assessments.

3.5.
Classification and conformity assessment
(Chapter V)

Annex II to the IVD Directive addresses the
level of risk posed by IVD medical devices by means of a positive list system.
While this system was adapted to scientific and technological development at
the time the IVD Directive was written, today it can no longer keep up with the
fast pace of scientific and technological progress. The proposal introduces a new
risk-rule based classification system, built on GHTF principles, which replaces
the current list of IVD medical devices in Annex II to Directive 98/79/EC.

In the new classification system, IVDs will
be divided into four classes of risk: A (lowest risk), B, C and D (highest
risk). The conformity assessment procedures have been adapted to match each of
these four device classes, using the existing modules established under the
'New Approach'. The conformity assessment procedure for class A devices will be
carried out, as a general rule, under the sole responsibility of the
manufacturer in view of the low level of vulnerability associated with these
products. However, when class A devices are intended for near-patient testing,
have a measuring function or are sold sterile, a notified body shall verify
respectively the aspects related to design, the measuring function or to the
sterilisation process. For devices of classes B, C and D an appropriate level
of involvement of a notified body is compulsory proportionate to the risk
class, with devices of class D requiring explicit prior approval of the design
or of the type of the device and of the quality management system before they
may be placed on the market. In the case of class B and C devices, the notified
body checks the quality management system and, for class C, the technical
documentation of representative samples. After initial certification, notified
bodies shall regularly conduct surveillance assessments in the post-market
phase.

The different conformity assessment
procedures during which the notified body audits the manufacturer's quality
management system, checks the technical documentation, examines the design
dossier or approves the type of a device are laid down in Annexes VIII to X.
They have been tightened and streamlined. One conformity assessment procedure
provided for under the IVD Directive (EC verification) has been deleted as the
responses to the public consultation highlighted that it was under-used. The
concept of batch testing has been clarified. The proposal reinforces the powers
and responsibilities of notified bodies and specifies the rules according to
which notified bodies perform their assessments, both in the pre-market and the
post-market phase, (e.g. documentation to be submitted, scope of the audit,
unannounced factory inspections, sample checks) to ensure a level playing field
and avoid notified bodies being overly lenient. Manufacturers of devices for
performance evaluation continue to be subject to specific provisions.

In addition, the proposal introduces the
obligation for notified bodies to notify an expert committee of new
applications for conformity assessment of high-risk devices. On scientifically
valid health grounds, the expert committee will have the power to request the
notified body to submit a preliminary assessment on which the committee can
issue comments within a deadline of 60 days[13],
before the notified body can issue a certificate. This scrutiny mechanism
empowers the authorities to have a 'second look' at individual assessments and
make their views heard before a device is placed on the market. A similar
procedure is currently already applied for medical devices manufactured
utilising animal tissues (Commission Directive 2003/32/EC[14]). Its use should be the exception
rather than the rule and should follow clear and transparent criteria.

3.6.
Clinical evidence (Chapter VI)

The proposal spells out the requirements
for clinical evidence for in vitro diagnostic medical devices which are
proportionate to the risk class. The key obligations are set out in Chapter VI
while more detailed provisions are laid down in Annex XII.

While most clinical performance studies
follow an observational design and therefore the results obtained are not used
for patient management and do not impact treatment decisions, specific
requirements have been introduced in Annex XIII for the conduct of
interventional clinical performance studies and other clinical performance
studies where the conduct of the study, including specimen collection, involves
invasive procedures or other risks for the subjects of the studies.

The concept of 'sponsor' is introduced and
aligned with the definition used in the recent Commission's proposal for a
Regulation of the European Parliament and of the Council on clinical trials on
medicinal products for human use which aims at repealing Directive 2001/20/EC[15].

The sponsor can be the manufacturer, his
authorised representative or another organisation, in practice often a
‘contract research organisation’ conducting clinical performance studies for
the manufacturers. The scope of the proposal, however, remains restricted to
clinical performance studies carried out for regulatory purposes, i.e. for
obtaining or confirming regulatory approval for market access. Non-commercial
clinical performance studies that do not pursue a regulatory purpose are not
covered by this Regulation.

In accordance with recognised international
ethical principles, every interventional clinical performance study and other
clinical performance study involving risks for the subjects of the study shall
be registered in a publicly accessible electronic system which the Commission
will set up. To ensure synergies with the area of clinical trials on medicinal
products, the electronic system on interventional clinical performance studies
and other clinical performance studies involving risks for the subjects of the
studies should be interoperable with the future EU database to be set up in
accordance with the future Regulation on clinical trials on medicinal products
for human use.

Before commencing an interventional
clinical performance study or any other clinical performance study involving
risks for the subjects of the study, the sponsor shall submit an application to
confirm that there are no health and safety aspects or ethical aspects which
would oppose it. A new possibility will be opened up for sponsors of an
interventional clinical performance study or any other clinical performance
study involving risks for the subjects of the study to be conducted in more
than one Member State: in future they may, if they wish, submit a single
application through the electronic system to be set up by the Commission. As a
consequence, the health and safety-related aspects regarding the device for
performance evaluation will be assessed by the Member States concerned under
the direction of a coordinating Member State. The assessment of intrinsically
national, local and ethical aspects (e.g. liability, suitability of the
investigators and clinical performance studies sites, informed consent), will
however, need to be carried out at the level of each Member State concerned
which will retain the ultimate responsibility for deciding whether the clinical
performance study may be conducted on its territory. In line with the above-mentioned
Commission's Proposal for a Regulation on clinical trials on medicinal
products, also this proposal leaves it to the Member States to define the
organisational set-up at national level for the approval of interventional
clinical performance studies or any other clinical performance study involving
risks for the subjects of the study. In other words, it moves away from a
legally required dualism of two distinct bodies, i.e. a national competent
authority and an ethics committee.

3.7.
Vigilance and market surveillance (Chapter VII)

A well-functioning vigilance system is the
'backbone' of a robust regulatory framework because complications with devices
may come to light only after a certain period of time. The main progress which
the proposal will bring in this field is the introduction of an EU portal where
manufacturers shall report serious incidents and corrective actions they have
taken to reduce the risk of recurrence. The information will be automatically
made available to the national authorities concerned. Where the same or similar
incidents have occurred, or where a corrective action has to be taken, in more
than one Member State, a coordinating authority will take the direction in
coordinating the analysis of the case. The emphasis is placed on work- and
expertise- sharing to avoid inefficient duplication of procedures.

As regards market surveillance, the main
objectives of the proposal are to reinforce the rights and obligations of the
national competent authorities, to ensure effective coordination of their
market surveillance activities and to clarify the applicable procedures.

3.8.
Governance (Chapters VIII and IX)

The Member States will be responsible for
implementation of the future Regulation. A central role in achieving harmonised
interpretation and practice will be assigned to an expert committee (the
Medical Device Coordination Group or MDCG) made up of members appointed by the
Member States due to their role and experience in the fields of medical devices
and in vitro diagnostic medical devices and set up by Regulation (EU) [Ref.
of future Regulation on medical devices] on medical devices[16]. The
MDCG and its subgroups will allow to build a forum for discussions with
stakeholders. The proposal creates the legal basis that for specific hazards or technologies or for verifying compliance
with common technical specifications by devices posing the highest risk, EU
reference laboratories, a concept that has proven successful in the food
sector, may in the future be designated by the Commission.

As regards the management at EU level, the impact assessment identified
as preferred option either the extension of the responsibility of the European
Medicines Agency (EMA) to in vitro diagnostic medical devices or the
management of the in vitro diagnostic medical devices regulatory system
by the Commission. Taking into account the clear preference expressed by
stakeholders, including many Member States, the proposal mandates the Commission to provide technical, scientific and logistic support to
the MDCG.

3.9.
Final provisions (Chapter X)

The proposal empowers the Commission to
adopt, where appropriate, either implementing acts to ensure uniform
application of this Regulation, or delegated acts to complement the regulatory
framework for in vitro diagnostic medical devices over time.

The new Regulation will become applicable
five years after its entry into force in order to take into account the
significant changes to the classification system for IVDs and to the conformity
assessment procedures. This will, on the one hand, allow time to set up a
sufficient number of notified bodies, and, on the other hand, mitigate the
economic impact on manufacturers. The Commission needs also time to put in
place the IT infrastructure and the organisational arrangements necessary for
the functioning of the new regulatory system. The designation of notified
bodies pursuant to the new requirements and process needs to start shortly after
the entry into force of this Regulation in order to ensure that by the date of
its application, sufficient notified bodies are designated in accordance with
the new rules to avoid any shortage of in vitro diagnostic medical
devices on the market. Special transitional provisions are foreseen for the
registration of in vitro diagnostic medical devices, relevant economic
operators and certificates issued by notified bodies to allow for a smooth
transition from registration requirements at national level to a central
registration at EU level.

The future Regulation will replace and
repeal Directive 98/79/EC of the European Parliament and of the Council.

3.10.
Union competence, subsidiarity and legal form

The proposal has a 'double legal basis',
i.e. Article 114 and Article 168(4)(c) of the Treaty on the Functioning of the
European Union. With the entry into force of the Lisbon Treaty, the legal basis
for the establishment and functioning of the internal market, on which the
current Medical Devices Directives were adopted, has been complemented by a
specific legal basis to set high standards for the quality and safety of
devices for medical use. In regulating IVDs, the Union is exercising its shared
power under Article 4(2) of the Treaty on the Functioning of the European
Union.

Under the current IVD Directive, IVDs that
bear the CE marking can, in principle, move freely within the EU. The proposed
revision of the existing directive, which will integrate the changes introduced
by the Lisbon Treaty regarding public health, can be achieved only at Union
level. This is necessary in order to improve the level of protection of public
health for all European patients and users, and also to prevent Member States
from adopting diverging product regulations which would result in further
fragmentation of the internal market. Harmonised rules and procedures allow
manufacturers, especially SMEs which make up more than 90% of the IVD sector,
to reduce costs related to national regulatory differences, while ensuring a
high and equal level of safety throughout the Union. In accordance with the
principles of proportionality and subsidiarity, as set out in Article 5 of the
Treaty on European Union, this proposal does not go beyond what is necessary in
order to achieve those objectives.

The proposal takes the form of a
Regulation. This is the appropriate legal instrument as it imposes clear and
detailed rules which will become applicable in a uniform manner and at the same
time throughout the Union. Diverging transposition of the IVD Directive by
Member States has led to different levels of health and safety protection and
created obstacles to the internal market which only a Regulation can avoid.
Replacing the national transposition measures also has a strong simplification
effect since it allows economic operators to conduct their business on the
basis of a single regulatory framework, rather than a 'patchwork' of 27
national laws.

The choice of a Regulation, however, does
not mean that decision-making is centralised. Member States retain their
competence for implementing the harmonised rules, e.g. as regards
approval of clinical performance studies, the designation of notified bodies,
the assessment of vigilance cases, the conduct of market surveillance and
enforcement action (e.g. penalties).

3.11.
Fundamental Rights

In line with the Charter of Fundamental
Rights of the EU, this proposal seeks to ensure a high level of human health
protection (Article 35 of the Charter) and consumer protection (Article 38) by
assuring a high level of safety of in vitro diagnostic medical devices
made available on the Union market. The proposal affects the freedom of
economic operators to conduct business (Article 16) but the obligations imposed
on manufacturers, authorised representatives, importers and distributors of in
vitro diagnostic medical devices are necessary to guarantee a high level of
safety of those products.

The proposal sets guarantees for the
protection of personal data. In respect to medical research, the proposal
requires that any clinical performance study with participation of human
subjects is conducted respecting the human dignity, the right to physical and
mental integrity of the persons concerned and the principle of free and
informed consent, as required by Articles 1, 3(1) and 3(2)(a) of the Charter.

4.
BUDGETARY IMPLICATION

This proposal does not have any additional
direct budgetary implication because the cost-relevant arrangements are already
covered by the proposal for a Regulation on medical devices. The financial
statement of that proposal lists the details of the costs related to the
implementation of both Regulations. A thorough discussion on the costs is
contained in the impact assessment report.

2012/0267 (COD)

Proposal for a

REGULATION OF THE EUROPEAN PARLIAMENT
AND OF THE COUNCIL

on in vitro diagnostic medical devices

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE
COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the
Functioning of the European Union, and in particular Article 114 and Article
168(4)(c) thereof,

Having regard to the proposal from the
European Commission,

After transmission of the draft legislative
act to the national Parliaments,

Having regard to the opinion of the
European Economic and Social Committee[17],

Having regard to the opinion of the
Committee of the Regions[18],

After consulting the European Data
Protection Supervisor[19],

Acting in accordance with the ordinary
legislative procedure,

Whereas:

(1)
Directive 98/79/EC of
the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic
medical devices[20]
constitutes the Union regulatory framework for in
vitro diagnostic medical devices. However, a fundamental revision of that
Directive is needed to establish a robust, transparent, predictable and sustainable regulatory framework for
devices which ensures a high level of safety and health whilst supporting
innovation.

(2)
This Regulation aims to ensure the functioning
of the internal market as regards in vitro diagnostic medical devices,
taking as a base a high level of protection of health. At the same time, this
Regulation sets high standards of quality and safety for devices to meet common
safety concerns as regards those products. Both objectives are being pursued
simultaneously and are inseparably linked whilst one not being secondary to the
other. As regards Article 114 of the Treaty on the Functioning of the European
Union, this Regulation harmonises the rules for the placing on the market and
putting into service of in vitro diagnostic medical devices and their
accessories on the Union market which may then benefit from the principle of
free movement of goods. As regards Article 168(4)(c) of the Treaty on the
Functioning of the European Union, this Regulation sets high standards of
quality and safety for those devices by ensuring, among other things, that data
generated in clinical performance studies is reliable and robust and that the
safety of subjects participating in clinical performance studies is protected.

(3)
Key elements of the existing regulatory
approach, such as the supervision of notified bodies, risk classification,
conformity assessment procedures, clinical evidence, vigilance and market
surveillance should be significantly reinforced, whilst provisions ensuring
transparency and traceability regarding in vitro diagnostic medical
devices should be introduced to improve health and safety.

(4)
To the extent possible, guidance developed for in
vitro diagnostic medical devices at international level, in particular in
the context of the Global Harmonization Task Force (GHTF) and its follow-up
initiative the International Medical Devices Regulators Forum, should be taken
into account to promote the global convergence of regulations which contributes
to a high level of safety worldwide and to facilitate trade, in particular in
the provisions on Unique Device Identification, general safety and performance
requirements, technical documentation, classification criteria, conformity
assessment procedures and clinical evidence.

(5)
There are specific features of in vitro diagnostic medical devices, in
particular in terms of risk classification, conformity assessment procedures
and clinical evidence, and of the in vitro diagnostic medical device
sector which require the adoption of a specific legislation, distinct from the
legislation on other medical devices, whereas the horizontal aspects common to
both sectors should be aligned.

(6)
A Regulation is the appropriate legal instrument
as it imposes clear and detailed rules which do not give room for divergent
transposition by Member States. Moreover, a Regulation ensures that legal
requirements are implemented at the same time throughout the Union.

(7)
The scope of application of this Regulation
should be clearly delimited from other legislation concerning products such as
medical devices, general
laboratory products and products for research use only.

(8)
It should be the responsibility of the Member
States to decide on a case-by-case basis whether or not a product falls within
the scope of this Regulation. If necessary, the Commission may decide, on a
case-by-case basis, whether or not a product falls within the definition of an in
vitro diagnostic medical device or of an accessory to an in vitro
diagnostic medical device.

(9)
To ensure the highest level of health
protection, the rules governing in vitro diagnostic medical devices manufactured and used, including measurement and delivery of
results, only within a single health institution should be clarified and
strengthened.

(10)
It should be clarified that software specifically intended by the manufacturer to be used for
one or more of the medical purposes set out in the definition of an in vitro
diagnostic medical device is qualified as an in vitro diagnostic medical
device, while software for general purposes,
even when used in a healthcare setting, or software intended for well-being
applications is not qualified as an in vitro diagnostic medical device.

(11)
It should be made clear that all tests that
provide information on the predisposition to a medical condition or a disease (e.g.
genetic tests) and tests that provide information to predict treatment response
or reactions, such as companion diagnostics, are in
vitro diagnostic medical
devices.

(12)
Aspects addressed by Directive 2004/108/EC of
the European Parliament and of the Council of 15 December 2004 on the
approximation of the laws of the Member States relating to electromagnetic
compatibility and repealing Directive 89/336/EEC[21] and aspects addressed by
Directive 2006/42/EC of the European Parliament and of the Council of 17 May
2006 on machinery and amending Directive 95/16/EC[22] are an integral part of the
general safety and performance requirements for in
vitro diagnostic medical
devices. Consequently, this Regulation should be considered a lex specialis
in relation to those Directives.

(13)
This Regulation should include requirements
regarding the design and manufacture of in vitro diagnostic medical
devices emitting ionising radiation without affecting the application of
Council Directive 96/29/Euratom of 13 May 1996 laying down basic safety
standards for the protection of the health of workers and the general public
against the dangers arising from ionising radiation[23], nor of Council Directive
97/43/Euratom of 30 June 1997 on health protection of individuals against the
dangers of ionising radiation in relation to medical exposure and repealing
Directive 84/466/Euratom[24]
which pursue other objectives.

(14)
It should be made clear that the requirements of
this Regulation also apply to the countries that have entered into
international agreements with the Union which confer on that country the same
status as a Member State for the purpose of application of this Regulation, as
it is currently the case with the Agreement on the European Economic Area[25], the Agreement between the
European Community and the Swiss Confederation on mutual recognition in
relation to conformity assessment[26]
and the Agreement of 12 September 1963 establishing an association between the
European Economic Community and Turkey[27].

(15)
It should be made clear that in vitro
diagnostic medical devices offered to persons in the Union by means of
information society services within the meaning of Directive 98/34/EC of the
European Parliament and of the Council of 22 June 1998 laying down a procedure
for the provision of information in the field of technical standards and
regulations[28]
as well as devices used in the context of a commercial activity to provide a
diagnostic or therapeutic service to persons within the Union must comply with
the requirements of this Regulation at the latest when the product is placed on
the market or the service is provided in the Union.

(16)
To recognise the important role of
standardisation in the field of in vitro diagnostic medical devices,
compliance with harmonised standards as defined in Regulation (EU) No [Ref. of
future Regulation on European standardisation] on European standardisation[29] should be a means for
manufacturers to demonstrate conformity with the general safety and performance
requirements and other legal requirements, such as quality and risk management.

(17)
The definitions in the field of in vitro
diagnostic medical devices, for example, regarding economic operators, clinical
evidence and vigilance, should be aligned with well-established practice at
Union and international level in order to enhance legal certainty.

(18)
The rules applicable to in vitro
diagnostic medical devices should be aligned, where appropriate, with the New
Legislative Framework for the Marketing of Products, which consists of
Regulation (EC) No 765/2008 of the European Parliament
and of the Council of 9 July 2008 setting out the
requirements for accreditation and market surveillance relating to the
marketing of products and repealing Regulation (EEC) No 339/93[30] and Decision
No 768/2008/EC of the European Parliament and of the Council of 9 July 2008 on
a common framework for the marketing of products, and repealing Council
Decision 93/465/EEC[31].

(19)
The rules on Union market surveillance and
control of products entering the Union market provided for in Regulation (EC) No 765/2008 apply to in vitro diagnostic medical devices and their
accessories covered by this Regulation which does not prevent Member States
from choosing the competent authorities to carry out those tasks.

(20)
It is appropriate to set out clearly the general
obligations of the different economic operators, including importers and
distributors, as laid down in the New Legislative Framework for the Marketing
of Products, without prejudice to the specific obligations laid down in the
different parts of this Regulation, to enhance understanding of the legal
requirements and thus to improve regulatory compliance by the relevant
operators.

(21)
To ensure that in vitro diagnostic
medical devices manufactured in series production continue to be in conformity
with the requirements of this Regulation and that experience from the use of
their in vitro diagnostic medical devices is taken into account for the
production process, all manufacturers should have a quality management system
and a post-market surveillance plan in place which should be proportionate to
the risk class and the type of the in vitro diagnostic medical device.

(22)
It should be ensured that supervision and
control of the manufacture of in vitro diagnostic medical devices is
carried out within the manufacturer's organisation by a person who fulfils minimum conditions
of qualification.

(23)
For manufacturers who are not established in the
Union, the authorised representative plays a pivotal role in ensuring the
compliance of the in vitro diagnostic medical devices produced by those
manufacturers and in serving as their contact person established in the Union. The tasks of an authorised representative should be defined
in a written mandate with the manufacturer which for
example may allow the authorised representative to lodge an application for a
conformity assessment procedure, to report events under the vigilance system or
to register devices placed on the Union market. The
mandate should empower the authorised representative to duly fulfil certain defined tasks. Considering the role
of authorised representatives, the minimum requirements to be met by them
should be clearly defined, including the requirement of having available a
person who fulfils minimum conditions of qualification which should be similar
to those for a manufacturer's qualified person but, with a view to the
authorised representative's tasks, could also be satisfied by a person with
qualification in law.

(24)
To ensure legal certainty in respect of the
obligations incumbent on economic operators, it is necessary to clarify when a
distributor, importer or other person is to be considered the manufacturer of
an in vitro diagnostic medical device.

(25)
Parallel trade in products already placed on the
market is a lawful form of trade within the internal market on the basis of
Article 34 of the Treaty on the Functioning of the
European Union subject to the limitations set by the
protection of health and safety and by the protection of intellectual property
rights provided by Article 36 of the Treaty on the
Functioning of the European Union. Application of this
principle is, however, subject to different interpretations in the Member
States. The conditions, in particular the requirements for relabelling and
repackaging, should therefore be specified in this Regulation, taking into
account the case-law of the European Court of Justice[32] in other relevant sectors and
existing good practices in the field of in vitro diagnostic medical
devices.

(26)
In vitro
diagnostic medical devices should, as a general rule,
bear the CE marking to indicate their conformity with this Regulation so that
they can move freely within the Union and be put into service in accordance
with their intended purpose. Member States should not create obstacles to their
placing on the market or putting into service for reasons related to the
requirements laid down in this Regulation.

(27)
The traceability of in vitro diagnostic
medical devices by means of a Unique Device Identification (UDI) system based
on international guidance should significantly enhance the effectiveness of the
post-market safety of in vitro diagnostic medical devices due to
improved incident reporting, targeted field safety corrective actions and better
monitoring by competent authorities. It should also help to reduce medical
errors and to fight against counterfeit devices. Use of the UDI system should
also improve purchase-policy and stock-management by hospitals.

(28)
Transparency and better information are
essential to empower patients and healthcare professionals and to enable them
to make informed decisions, to provide a sound basis for regulatory
decision-making and to build confidence in the regulatory system.

(29)
One key aspect is the creation of a central
database that should integrate different electronic systems, with the UDI as an
integral part of it, to collate and process information regarding in vitro
diagnostic medical devices on the market and the relevant economic operators,
certificates, interventional clinical performance studies and other clinical
performance studies involving risks for the subjects of
the studies, vigilance and market surveillance. The
objectives of the database are to enhance overall transparency, to streamline and facilitate the flow of information between economic
operators, notified bodies or sponsors and Member States as well as between
Member States among themselves and with the Commission, to avoid multiple
reporting requirements and to enhance the coordination between Member States. Within an internal market, this can be ensured effectively only at
Union level and the Commission should therefore further develop and manage the
European databank on medical devices (Eudamed) by further developing the
databank set up by Commission Decision 2010/227/EU of 19 April 2010 on the
European Databank for Medical Devices[33].

(30)
Eudamed's electronic systems regarding devices
on the market, the relevant economic operators and certificates should enable
the public to be adequately informed about devices on the Union market. The
electronic system on clinical performance studies should serve as tool for the
cooperation between Member States and for enabling sponsors to submit, on a
voluntary basis, a single application for several Member States and, in this
case, to report serious adverse events. The electronic system on vigilance
should enable manufacturers to report serious incidents and other reportable
events and to support the coordination of their assessment by national
competent authorities. The electronic system regarding market surveillance
should be a tool for the exchange of information between competent authorities.

(31)
In respect of data collated and processed
through the electronic systems of Eudamed, Directive 95/46/EC of the European
Parliament and of the Council of 24 October 1995 on the protection of
individuals with regard to the processing of personal data and on the free
movement of such data[34]
applies to the processing of personal data carried out in the Member States,
under the supervision of the Member States competent authorities, in particular
the public independent authorities designated by the Member States. Regulation
(EC) No 45/2001 of the European Parliament and of the Council of 18 December
2000 on the protection of individuals with regard to the processing of personal
data by the Community institutions and bodies and on the free movement of such
data[35],
applies to the processing of personal data carried out by the Commission within
the framework of this Regulation, under the supervision of the European Data
Protection Supervisor. In
accordance with Article 2(d) of Regulation (EC) No 45/2001, the Commission
should be designated as the controller of Eudamed and its electronic systems.

(32)
For high-risk in vitro diagnostic medical
devices, manufacturers should summarise the main safety and performance aspects of the device and the
outcome of the clinical evaluation in a document that should be publicly
available.

(33)
The proper functioning of notified bodies is
crucial for ensuring a high level of health and safety and citizens' confidence
in the system. Designation and monitoring of notified bodies by the Member
States, in accordance with detailed and strict criteria, should therefore be
subject to controls at Union level.

(34)
The position of notified bodies vis-à-vis
manufacturers should be strengthened, including their right and duty to carry
out unannounced factory inspections and to conduct physical or laboratory tests
on in vitro diagnostic medical devices to ensure continuous compliance
by manufacturers after receipt of the original certification.

(35)
For high risk in vitro diagnostic medical
devices, authorities should be informed at an early stage about devices which
are subject to conformity assessment and be given the right, on scientifically
valid grounds, to scrutinise the preliminary assessment conducted by notified
bodies, in particular regarding devices for which no common technical
specifications exist, devices which are novel or for which a novel technology
is being used, devices belonging to a category of devices with increased
serious incident rates, or devices for which significant discrepancies in the
conformity assessments by different notified bodies have been identified in
respect of substantially similar devices. The process foreseen in this
Regulation does not prevent a manufacturer from informing voluntarily a
competent authority of his intention to file an application for conformity
assessment for a high risk in vitro diagnostic medical device before
submitting the application to the notified body.

(36)
To enhance patient safety and to take due
account of technological progress, the risk classification system for in
vitro diagnostic medical devices set out in Directive 98/79/EC should be
fundamentally changed, in line with international practice, and the
corresponding conformity assessment procedures should be accordingly adapted.

(37)
It is necessary, in particular for the purpose
of the conformity assessment procedures, to classify in vitro diagnostic medical devices into four risk classes and to establish a set of robust
risk-based classification rules, in line with international practice.

(38)
The conformity assessment procedure for class A in vitro diagnostic medical devices should be carried out, as a general rule, under the sole
responsibility of the manufacturers, since such devices pose a low risk to
patients. For in vitro diagnostic
medical devices in classes B, C and D, the involvement
of a notified body should be compulsory to the appropriate degree.

(39)
The conformity assessment procedures should be
further developed whilst the requirements for notified bodies as regards the
performance of their assessments should be clearly specified to ensure a level
playing field.

(40)
It is necessary to clarify the requirements
regarding batch release verification for the highest risk in vitro
diagnostic medical devices.

(41)
European Union reference laboratories should be
enabled to verify compliance of such devices with the applicable common
technical specifications, when such common technical specifications are
available, or with other solutions chosen by the manufacturer to ensure a level
of safety and performance that is at least equivalent.

(42)
To ensure a high level of safety and
performance, demonstration of compliance with the general safety and performance
requirements should be based on clinical evidence. It
is necessary to clarify the requirements for such
clinical evidence. As a general rule, clinical evidence should be sourced from
clinical performance studies to be carried out under the responsibility of a
sponsor who can be the manufacturer or another legal or natural person taking
responsibility for the clinical performance study.

(43)
The rules on clinical performance studies should
be in line with major international guidance, such as the international
standard ISO 14155:2011 on good clinical practice for clinical investigations
of medical devices for human subjects and the most recent (2008) version of the
World Medical Association Declaration of Helsinki on Ethical Principles for
Medical Research Involving Human Subjects to ensure that clinical performance
studies conducted in the Union are accepted elsewhere and that clinical
performance studies conducted outside the Union in accordance with
international guidelines can be accepted under this Regulation.

(44)
An electronic system should be set up at Union
level to ensure that every interventional clinical performance studies and
other clinical performance studies involving risks for the subjects of the
studies are registered in a publicly accessible database. To protect the right
to protection of personal data, recognised by Article 8 of the Charter of
Fundamental Rights of the European Union, no personal data of subjects
participating in a clinical performance studies should be recorded in the electronic
system. To ensure synergies with the area of clinical trials on medicinal
products, the electronic system on clinical performance studies on in vitro
diagnostic medical devices should be interoperable with the EU database to be
set up for clinical trials on medicinal products for human use.

(45)
Sponsors of interventional clinical performance
studies and other clinical performance studies involving risks for the subjects
to be conducted in more than one Member State should be given the possibility
to submit a single application in order to reduce administrative burden. In
order to allow for resource-sharing and to ensure consistency regarding the
assessment of the health and safety related aspects of the device for
performance evaluation and of the scientific design of the clinical performance
study to be conducted in several Member Stats, such single application should
facilitate the coordination between the Member States under the direction of a
coordinating Member State. The coordinated assessment should not include the
assessment of intrinsically national, local and ethical aspects of a clinical
performance study, including informed consent. Each Member State should retain the ultimate responsibility for deciding whether the clinical performance
study may be conducted on its territory.

(46)
Sponsors should report certain adverse events
occurring during interventional clinical performance studies and other clinical
performance studies involving risks for the subjects to the Member States
concerned which should have the possibility to terminate or suspend these
studies if considered necessary to ensure a high level of protection of the
subjects enrolled in such studies. Such information should be communicated to
the other Member States.

(47)
This Regulation should only cover clinical
performance studies which pursue regulatory purposes
laid down in this Regulation.

(48)
In order to better protect health and safety
regarding devices on the market, the vigilance system for in vitro
diagnostic medical devices should be made more effective by creating a central
portal at Union level for reporting serious incidents and field safety
corrective actions.

(49)
Healthcare professionals and patients should be
empowered to report suspected serious incidents at national level using
harmonised formats. The national competent authorities should inform
manufacturers and share the information with their peers when they confirm that
a serious incident has occurred in order to minimise recurrence of those
incidents.

(50)
The assessment of reported serious incidents and field safety corrective actions should be conducted
at national level but coordination should be ensured where similar incidents
have occurred or field safety corrective actions have to be carried out in more
than one Member State, with the objective of sharing resources and ensuring
consistency regarding the corrective action.

(51)
The reporting of serious adverse events during interventional clinical performance studies and other clinical
performance studies involving risks for the subjects, and
the reporting of serious incidents occurring after an in vitro
diagnostic medical device has been placed on the market should be clearly
distinguished to avoid double reporting.

(52)
Rules on market surveillance should be included
in this Regulation to reinforce the rights and obligations of the national
competent authorities, to ensure effective coordination of their market
surveillance activities and to clarify the applicable procedures.

(53)
The Member States shall levy fees for the
designation and monitoring of notified bodies to ensure sustainability of the
monitoring of those bodies by Member States and to establish a level playing
field for notified bodies.

(54)
Whilst this Regulation should not affect the
right of the Member States to levy fees for activities at national level,
Member States should inform the Commission and the other Member States before they adopt the level and structure of the fees to ensure transparency.

(55)
An expert committee, the Medical Device
Coordination Group (MDCG), composed of persons designated by the Member States,
based on their role and expertise in the field of medical devices and in
vitro diagnostic medical devices, should be established in accordance with
the conditions and modalities defined in Article 78 of Regulation (EU) [Ref. of
future Regulation on medical devices] on medical devices[36] to fulfil the tasks conferred
on it by this Regulation and by Regulation (EU) [Ref. of future Regulation on medical devices]
on medical devices, to provide advice to the Commission
and to assist the Commission and the Member States in ensuring a harmonised
implementation of this Regulation.

(56)
Closer coordination between national competent
authorities through information exchange and coordinated assessments under the
direction of a coordinating authority is fundamental for ensuring a uniform
high level of health and safety within the internal market, in particular in
the areas of clinical performance studies and vigilance. This should also lead
to more efficient use of scarce resources at national level.

(57)
The Commission should provide scientific,
technical and corresponding logistic support to the coordinating national
authority and ensure that the regulatory system for in vitro diagnostic
medical devices is effectively implemented at Union level based on sound
scientific evidence.

(58)
The Union should actively participate in
international regulatory cooperation in the field of in vitro diagnostic
medical devices to facilitate the exchange of safety-related information
regarding in vitro diagnostic medical devices and foster the further
development of international regulatory guidelines promoting the adoption of
regulations in other jurisdictions with a level of health and safety protection
equivalent to that set by this Regulation.

(59)
This Regulation respects the fundamental rights
and observes the principles recognised in particular by the Charter of
Fundamental Rights of the European Union and notably human dignity, the
integrity of the person, the protection of personal data, the freedom of art
and science, the freedom to conduct business and the right to property. This
Regulation should be applied by the Member States in accordance with those
rights and principles.

(60)
In order to maintain a high level of health and
safety, the power to adopt acts in accordance with
Article 290 of the Treaty on the Functioning of the European Union should be delegated to the Commission in respect of the
adaptation to technical progress of the general safety and performance
requirements, of the elements to be addressed in the technical documentation,
of the minimum content of the EU declaration of conformity and of the
certificates issued by notified bodies, of the minimum requirements to be met
by notified bodies, of the classification rules, of the conformity assessment
procedures, and of the documentation to be submitted for the approval of
clinical performance studies; the establishment of the UDI system; the
information to be submitted for the registration of in vitro diagnostic
medical devices and certain economic operators; the level and structure of fees
for the designation and monitoring of notified bodies; the publicly available
information in respect of clinical performance studies; the adoption of
preventive health protection measures at EU level; and the tasks of and criteria
for European Union reference laboratories and the level and structure of fees
for scientific opinions delivered by them.

It is of particular importance that the
Commission carry out appropriate consultations during its preparatory work,
including at expert level. The Commission, when
preparing and drawing up delegated acts, should ensure a simultaneous, timely
and appropriate transmission of relevant documents to the European Parliament
and to the Council.

(61)
In order to ensure uniform conditions for the implementation
of this Regulation, implementing powers should be conferred on the Commission.
Those powers should be exercised in accordance with Regulation (EU) No 182/2011
of the European Parliament and of the Council of 16 February 2011 laying down
the rules and general principles concerning mechanisms for control by Member
States of the Commission's exercise of implementing powers[37].

(62)
The advisory procedure should be used for the
adoption of the form and presentation of the data elements of the manufacturers'
summary of safety and performance, of the codes defining the notified bodies'
scopes of designation and of the model for certificates
of free sale, given that those acts have a procedural
character and do not directly impact the health and safety at Union level.

(63)
The Commission should adopt immediately
applicable implementing acts where, in duly justified cases relating to the extension to the territory of the Union of a national derogation
from the applicable conformity assessment procedures in exceptional cases; relating to the Commission's position whether
a provisional national measure against an in vitro diagnostic medical
device presenting a risk or a provisional national preventive health protection
measure is justified or not; and relating to the adoption of a Union measure
against an in vitro diagnostic medical device presenting a risk, imperative grounds of urgency so require.

(64)
To allow economic operators, notified bodies, Member States and the Commission to adapt to the changes introduced by this Regulation, it
is appropriate to provide for a sufficient transitional period for that
adaptation and for the organisational arrangements to
be taken for its proper application. It is particularly important that by the date of application, a
sufficient number of notified bodies are designated in accordance with the new
requirements to avoid any shortage of in vitro diagnostic medical devices on the market.

(65)
In order to ensure a smooth transition to the
registration of in vitro diagnostic medical devices, of relevant
economic operators and of certificates, the obligation to submit the relevant
information to the electronic systems put in place by this Regulation at Union
level should become fully effective only 18 months after the date of
application of this Regulation. During this transitional period, Article 10 and points (a) and (b) of Article 12(1) of Directive 98/79/EC should remain in force. However,
economic operators and notified bodies who register in the relevant electronic
systems provided for at Union level should be considered in compliance with the
registration requirements adopted by the Member States pursuant to those
provisions of the Directive to avoid multiple registrations.

(66)
Directive 98/79/EC should be repealed to ensure
that only one set of rules applies to the placing of in vitro diagnostic
medical devices on the market and the related aspects covered by this
Regulation.

(67)
Since the objective of this Regulation, namely
to ensure high standards of quality and safety for in vitro diagnostic medical devices, thus ensuring a high level of protection of health and safety of
patients, users and other persons, cannot sufficiently
be achieved by the Member States and can, by reason of the scale of the
measure, be better achieved at Union level, the Union may adopt measures, in
accordance with the principle of subsidiarity as set out in Article 5 of the
Treaty on European Union. In accordance with the principle of proportionality,
as set out in that Article, this Regulation does not go beyond what is
necessary in order to achieve that objective.

HAVE ADOPTED THIS REGULATION:

Chapter I

Scope and definitions

Article 1

Scope

1.
This Regulation establishes rules to be complied
with by in vitro diagnostic medical devices and accessories to in vitro
diagnostic medical devices that are placed on the market or put into service in
the Union for human use.

For the purposes of this Regulation, in
vitro diagnostic medical devices and accessories to in vitro
diagnostic medical devices shall hereinafter be referred to as 'devices'.

2.
This Regulation shall not apply to:

(a)
products for general laboratory use, unless such
products, in view of their characteristics, are specifically intended by their
manufacturer to be used for in vitro diagnostic examination;

(b)
invasive sampling devices or those which are
directly applied to the human body for the purpose of obtaining a specimen;

(c)
higher metrological order reference materials.

3.
Any device which, when placed on the market or
used in accordance with the manufacturer's instructions, incorporates as an
integral part a medical device as defined in Article 2 of Regulation (EU) [Ref.
of future Regulation on medical devices] on medical devices without being an in
vitro diagnostic medical device, shall be governed by this Regulation, provided
that the principal intended purpose of the combination is that of an in
vitro diagnostic medical device referred to in Article 2(2) of this
Regulation. The relevant general safety and performance requirements set out in
Annex I to Regulation (EU) [Ref. of future Regulation on medical devices] shall
apply as far as the safety and performance of the medical device part that is
not an in vitro diagnostic medical device are concerned.

4.
This Regulation is a specific Union legislation
within the meaning of Article 1(4) of Directive 2004/108/EC and within the
meaning of Article 3 of Directive 2006/42/EC.

5.
This Regulation shall not affect the application
of Council Directive 96/29/Euratom, nor of Council Directive 97/43/Euratom.

6.
This Regulation shall not affect national laws
which require that certain devices may only be supplied on a medical
prescription.

7.
References to a Member State in this Regulation
shall be understood as including any other country with which the Union has
concluded an agreement which confers on that country the same status as a Member State for the purpose of application of this Regulation.

Article 2

Definitions

For the purposes of this Regulation, the
following definitions shall apply:

Definitions related to devices:

(1)
‘medical device’ means any instrument,
apparatus, appliance, software, implant, reagent, material or other article,
intended by the manufacturer to be used, alone or in combination, for human
beings for one or more of the specific medical purposes of:

–
diagnosis, prevention, monitoring, treatment or
alleviation of disease,

–
diagnosis, monitoring, treatment, alleviation of
or compensation for an injury or disability,

–
investigation, replacement or modification of
the anatomy or of a physiological process or state,

–
control or support of conception,

–
disinfection or sterilisation of any of the
above-mentioned products,

and which does not achieve its principal
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.

(2)
'in vitro diagnostic medical device’
means any medical device which is a reagent, reagent product, calibrator,
control material, kit, instrument, apparatus, equipment, software or system,
whether used alone or in combination, intended by the manufacturer to be used in
vitro for the examination of specimens, including blood and tissue
donations, derived from the human body, solely or principally for the purpose
of providing information:

–
concerning a physiological or pathological
state;

–
concerning a congenital abnormality;

–
concerning the predisposition to a medical
condition or a disease;

–
to determine the safety and compatibility with
potential recipients;

–
to predict treatment response or reactions;

–
to define or monitor therapeutic measures.

Specimen receptacles are considered to be in
vitro diagnostic medical devices. For the purposes of this Regulation,
‘specimen receptacle’ means devices, whether vacuum-type or not, specifically
intended by their manufacturers for the primary containment and preservation of
specimens derived from the human body for the purpose
of in vitro diagnostic examination.

(3)
'accessory to an in vitro diagnostic
medical device' means an article which, whilst not being an in vitro
diagnostic medical device, is intended by its manufacturer to be used together
with one or several particular in vitro diagnostic medical device(s) to
specifically enable or assist the in vitro diagnostic medical device(s)
to be used in accordance with its/their intended purpose(s);

(4)
'device for self-testing' means any device
intended by the manufacturer to be used by lay persons;

(5)
'device for near-patient testing' means any
device that is not intended for self-testing but is intended to perform testing
outside a laboratory environment, generally near to, or at the side of, the
patient;

(6)
'companion diagnostic' means a device
specifically intended to select patients with a previously diagnosed condition
or predisposition as eligible for a targeted therapy;

(7)
'generic device group' means a set of devices
having the same or similar intended purposes or commonality of technology
allowing them to be classified in a generic manner not reflecting specific
characteristics;

(8)
'single-use device' means a device that is
intended to be used on an individual patient during a single procedure;

The single procedure may involve several uses
or prolonged use on the same patient.

(9)
'intended purpose' means the use for which the
device is intended according to the data supplied by the manufacturer on the
label, in the instructions for use or in promotional or sales materials or
statements;

(10)
'label' means the written, printed, or graphic
information appearing either on the device itself, or on the packaging of each
unit, or on the packaging of multiple devices;

(11)
'instructions for use' means the information
provided by the manufacturer to inform the user of the device’s intended
purpose and proper use and of any precautions to be taken;

(12)
'Unique Device Identification' ('UDI') means a
series of numeric or alphanumeric characters that is created through
internationally accepted device identification and coding standards and that
allows unambiguous identification of specific devices on the market;

Definitions related to the making available
of devices:

(13)
'making available on the market' means any
supply of a device, other than a device for performance evaluation, for
distribution, consumption or use on the Union market in the course of a
commercial activity, whether in return for payment or free of charge;

(14)
'placing on the market' means the first making
available of a device, other than a device for performance evaluation, on the
Union market;

(15)
'putting into service' means the stage at which
a device, other than a device for performance evaluation, has been made
available to the final user as being ready for use on the Union market for the
first time for its intended purpose;

Definitions related to economic operators,
users and specific processes:

(16)
'manufacturer' means the natural or legal person
who manufactures or fully refurbishes a device or has a device designed,
manufactured or fully refurbished, and markets that device under his name or
trademark.

For the purposes of the definition of
manufacturer, fully refurbishing is defined as the complete rebuilding of a
device already placed on the market or put into service, or the making of a new
device from used devices, to bring it in conformity with this Regulation,
combined with the assignment of a new lifetime to the refurbished device;

(17)
'authorised representative' means any natural or
legal person established within the Union who has received and accepted a
written mandate from a manufacturer to act on his behalf in relation to
specified tasks with regard to the latter's obligations under this Regulation;

(18)
'importer' means any natural or legal person
established within the Union who places a device from a third country on the
Union market;

(19)
'distributor' means any natural or legal person
in the supply chain, other than the manufacturer or the importer, who makes a
device available on the market;

(20)
'economic operators' means the manufacturer, the
authorised representative, the importer and the distributor;

(21)
'health institution' means an organisation whose
primary purpose is the care or treatment of patients or the promotion of public
health;

(22)
'user' means any healthcare professional or lay
person who uses a device;

(23)
'lay person' means an individual who does not
have formal education in a relevant field of healthcare or medical discipline;

Definitions related to conformity
assessment:

(24)
'conformity assessment' means the process
demonstrating whether the requirements of this Regulation relating to a device
have been fulfilled;

(25)
'conformity assessment body' means a body that
performs third-party conformity assessment activities including calibration,
testing, certification and inspection;

(26)
'notified body' means a conformity assessment
body designated in accordance with this Regulation;

(27)
'CE marking of conformity' or 'CE marking' means
a marking by which the manufacturer indicates that the device is in conformity
with the applicable requirements set out in this Regulation and other
applicable Union harmonisation legislation providing for its affixing;

Definitions related to clinical evidence:

(28)
'clinical evidence' means the information that
supports the scientific validity and performance for the use of a device as
intended by the manufacturer;

(29)
'scientific validity of an analyte' means the
association of an analyte to a clinical condition or a physiological state;

(30)
'performance of a device' means the ability of a
device to achieve its intended purpose as claimed by the manufacturer. It
consists of the analytical and, where applicable, the clinical performance
supporting the intended purpose of the device;

(31)
'analytical performance' means the ability of a
device to correctly detect or measure a particular analyte;

(32)
'clinical performance' means the ability of a
device to yield results that are correlated with a particular clinical
condition or a physiological state in accordance with the target population and
intended user;

(33)
'clinical performance study’ means a study
undertaken to establish or confirm the clinical performance of a device;

(34)
'clinical performance study protocol' means the
document(s) setting out the rationale, objectives, design and proposed analysis,
methodology, monitoring, conduct and record-keeping of the clinical performance
study;

(35)
'performance evaluation' means the assessment
and analysis of data to establish or verify the analytical and, where
applicable, the clinical performance of a device;

(36)
'device for performance evaluation' means a
device intended by the manufacturer to be subject to one or more performance
evaluation studies in laboratories for medical analyses or in other appropriate
environments outside the manufacturer's own premises. Devices intended to be
used for research purposes, without any medical objective, are not regarded as
devices for performance evaluation;

(37)
'interventional clinical performance study'
means a clinical performance study where the test results may influence patient
management decisions and/or may be used to guide treatment;

(38)
'diagnostic specificity' means the ability of a
device to recognize the absence of a target marker associated with a particular
disease or condition;

(39)
'diagnostic sensitivity' means the ability of a
device to identify the presence of a target marker associated with a particular
disease or condition;

(40)
'predictive value' means the probability that a
person with a positive device test result has a given condition under
investigation, or that a person with a negative device test result does not
have a given condition;

(41)
'positive predictive value' means the ability of
a device to separate true positive results from false positive results for a
given attribute in a given population;

(42)
'negative predictive value' means the ability of
a device to separate true negative results from false negative results for a
given attribute in a given population;

(43)
'likelihood ratio' means the likelihood that a
given result would be expected in an individual with the target clinical
condition or physiological state compared to the likelihood that the same
result would be expected in an individual without that clinical condition or
physiological state;

(44)
'calibrators and control materials' means any
substance, material or article intended by the manufacturer either to establish
measurement relationships or to verify the performance characteristics of a
device in conjunction with the intended purpose of that device;

(45)
'sponsor' means any individual, company,
institution or organisation which takes responsibility for the initiation and
management of a clinical performance study;

(46)
'adverse event' means any untoward medical
occurrence, unintended disease or injury or any untoward clinical signs,
including an abnormal laboratory finding, in subjects, users or other persons
in the context of a clinical performance study, whether or not related to the
device for performance evaluation;

(47)
'serious adverse event' means any adverse event
that led to any of the following:

–
death,

–
serious deterioration in the health of the
subject, that resulted in any of the following:

(i)      life-threatening illness or injury,

(ii)      permanent impairment of a body
structure or a body function,

(iii)     hospitalisation or extending the
duration of hospitalisation,

(iv)     medical or surgical intervention to
prevent life-threatening illness or injury or permanent
impairment to a body structure or a body function,

–
foetal distress, foetal death or a congenital
abnormality or birth defect.

(48)
'device deficiency' means any inadequacy in the
identity, quality, durability, reliability, safety or performance of a device
for performance evaluation, including malfunction, use errors or inadequacy in
the information supplied by the manufacturer;

Definitions related to vigilance and market
surveillance:

(49)
'recall' means any measure aimed at achieving
the return of a device that has already been made available to the end user;

(50)
'withdrawal' means any measure aimed at
preventing a device in the supply chain from further being made available on the
market;

(51)
'incident' means any malfunction or
deterioration in the characteristics or performance of a device made available
on the market, any inadequacy in the information supplied by the manufacturer
and any unexpected undesirable effect;

(52)
'serious incident' means any incident that
directly or indirectly led, might have led or might lead to any of the
following:

–
death of a patient, user or other person,

–
temporary or permanent serious deterioration of
the patient's, user's or other person's state of health,

–
serious public health threat;

(53)
'corrective action' means action taken to
eliminate the cause of a potential or real non-conformity or other undesirable
situation;

(54)
'field safety corrective action' means
corrective action taken by the manufacturer for technical or medical reasons to
prevent or reduce the risk of a serious incident in relation to a device made
available on the market;

(55)
'field safety notice' means the communication
sent by the manufacturer to users or customers in relation to a field safety corrective
action;

(56)
'market surveillance' means the activities
carried out and measures taken by public authorities to ensure that products
comply with the requirements set out in the relevant Union harmonisation
legislation and do not endanger health, safety or any other aspect of public
interest protection;

Definitions related to standards and other
technical specifications:

(57)
‘harmonised standard’ means a European standard
as defined in Article 2(1)(c) of Regulation (EU) No [Ref. of future Regulation
on European standardisation];

(58)
'common technical specifications’ means a
document other than a standard that prescribes technical requirements that
provide a means to comply with the legal obligations applicable to a device,
process or system.

Article 3

Regulatory
status of products

1.
The Commission may, at the request of a Member
State or on its own initiative, by means of implementing acts, determine
whether or not a specific product, or category or group of products, falls
within the definitions of an in vitro diagnostic medical devices or of
an accessory to an in vitro diagnostic medical device. Those
implementing acts shall be adopted in accordance with the examination procedure
referred to in Article 84(3).

2.
The Commission shall ensure the sharing of
expertise between Member States in the fields of in vitro diagnostic
medical devices, medical devices, medicinal products, human tissues and cells,
cosmetics, biocides, food and, if necessary, other products in order to
determine the appropriate regulatory status of a product, or category or group
of products.

Chapter II

Making available of devices, obligations of economic operators, CE
marking, free movement

Article 4

Placing on the
market and putting into service

1.
A device may be placed on the market or put into
service only if it complies with this Regulation when duly supplied and
properly installed, maintained and used in accordance with its intended
purpose.

2.
A device shall meet the general safety and
performance requirements which apply to it, taking into account its intended
purpose. General safety and performance requirements are set out in Annex I.

3.
Demonstration of conformity with the general
safety and performance requirements shall be based on clinical evidence in
accordance with Article 47.

4.
Devices that are manufactured and used within a
single health institution shall be considered as being put into service.

5.
With the exception of Article 59(4), the
requirements of this Regulation shall not apply to devices classified as class
A, B and C, in accordance with the rules set out in Annex VII, and manufactured
and used only within a single health institution, provided manufacture and use
occur solely under the health institution's single quality management system,
and the health institution is compliant with standard EN ISO 15189 or any other
equivalent recognised standard. Member States may require that the health
institutions submit to the competent authority a list of such devices which
have been manufactured and used on their territory and may make the manufacture
and use of the devices concerned subject to further safety requirements.

Devices classified as class D in accordance
with the rules set out in Annex VII, even if manufactured and used within a
single health institution, shall comply with the requirements of this
Regulation. However, the provisions regarding CE marking set out in Article 16
and the obligations referred to in Articles 21 to 25 shall not apply to those
devices.

6.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85, amending or supplementing, in the
light of technical progress and considering the intended users or patients, the
general safety and performance requirements set out in Annex I, including the
information supplied by the manufacturer.

Article 5

Distance sales

1.
A device offered by means of information society
services as defined in Article 1(2) of Directive 98/34/EC to a natural or legal
person established in the Union shall comply with this Regulation at the latest
when the device is placed on the market.

2.
Without prejudice to national legislation
regarding the exercise of the medical profession, a device that is not placed
on the market but is used in the context of a commercial activity for the
provision of a diagnostic or therapeutic service offered by means of
information society services as defined in Article 1(2) of Directive 98/34/EC
or by other means of communication to a natural or legal person established in
the Union shall comply with this Regulation.

Article 6

Harmonised
standards

1.
Devices which are in conformity with the
relevant harmonised standards, or parts thereof, the references of which have
been published in the Official Journal of the European Union shall be
presumed to be in conformity with the requirements of this Regulation covered
by those standards or parts thereof.

The first subparagraph shall also apply to
system or process requirements to be fulfilled by economic operators or
sponsors in accordance with this Regulation, including those related to the
quality management system, risk management, the post-market surveillance plan,
clinical performance studies, clinical evidence or post-market follow-up.

2.
Reference to harmonised standards also includes
the monographs of the European Pharmacopoeia adopted in accordance with the
Convention on the Elaboration of a European Pharmacopoeia.

Article 7

Common
technical specifications

1.
Where no harmonised standards exist or where
relevant harmonised standards are not sufficient, the Commission shall be
empowered to adopt common technical specifications (CTS) in respect of the
general safety and performance requirements set out in Annex I, the technical
documentation set out in Annex II or the clinical evidence and post-market
follow-up set out in Annex XII. The CTS shall be adopted by means of implementing
acts in accordance with the examination procedure referred to in Article 84(3).

2.
Devices which are in conformity with the CTS
referred to in paragraph 1 shall be presumed to be in conformity with the
requirements of this Regulation covered by those CTS or parts thereof.

3.
Manufacturers shall comply with the CTS unless
they can duly justify that they have adopted solutions ensuring a level of
safety and performance that is at least equivalent thereto.

Article 8

General
obligations of the manufacturer

1.
When placing their devices on the market or
putting them into service, manufacturers shall ensure that they have been
designed and manufactured in accordance with the requirements of this
Regulation.

2.
Manufacturers shall draw up the technical
documentation which shall allow assessment of the conformity of the device with
the requirements of this Regulation. The technical documentation shall include
the elements set out in Annex II.

The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 amending or supplementing, in the
light of technical progress, the elements in the technical documentation set
out in Annex II.

3.
Where compliance of a device with the applicable
requirements has been demonstrated following the applicable conformity
assessment procedure, manufacturers of devices, other than devices for
performance evaluation, shall draw up an EU declaration of conformity in
accordance with Article 15 and affix the CE marking of conformity in accordance
with Article 16.

4.
Manufacturers shall keep the technical
documentation, the EU declaration of conformity and, if applicable, a copy of
the relevant certificate including any supplement, issued in accordance with
Article 43, available to the competent authorities for a period of at least
five years after the last device covered by the declaration of conformity has
been placed on the market.

Where the technical documentation is voluminous
or held in different locations, the manufacturer shall provide, upon request by
a competent authority, a summary technical documentation (STED) and grant
access to the full technical documentation upon request.

5.
Manufacturers shall ensure that procedures are
in place to keep series production in conformity with the requirements of this
Regulation. Changes in product design or characteristics and changes in the
harmonised standards or CTS by reference to which conformity of a product is
declared shall be adequately taken into account. Proportionate to the risk
class and the type of device, manufacturers of devices, other than devices for
performance evaluation, shall institute and keep up to date a quality
management system that shall address at least the following aspects:

(a)
the responsibility of the management;

(b)
resource management, including selection and
control of suppliers and sub-contractors;

(c)
product realisation;

(d)
processes for monitoring and measurement of
output, data analysis and product improvement.

6.
Proportionate to the risk class and the type of
device, manufacturers of devices shall institute and keep up to date a
systematic procedure to collect and review experience gained from their devices
placed on the market or put into service, and to apply any necessary corrective
action, hereinafter referred to as 'post-market surveillance plan'. The post-market
surveillance plan shall set out the process for collecting, recording and
investigating complaints and reports from healthcare professionals, patients or
users on suspected incidents related to a device, keeping a register of
non-conforming products and product recalls or withdrawals, and if deemed
appropriate due to the nature of the device, sample testing of marketed
devices. Part of the post-market surveillance plan shall be a plan for
post-market follow-up in accordance with Part B of Annex XII. Where post-market
follow-up is not deemed necessary, this shall be duly justified and documented
in the post-market surveillance plan.

If in the course of the post-market
surveillance a need for corrective action is identified, the manufacturer shall
implement the appropriate measures.

7.
Manufacturers shall ensure that the device is
accompanied by the information to be supplied in accordance with Section 17 of
Annex I in an official Union language which can be easily understood by the
intended user. The language(s) of the information to be supplied by the
manufacturer may be determined by the law of the Member State where the device
is made available to the user.

For devices for self-testing or
near-patient-testing, the information supplied in accordance with Section 17 of
Annex I shall be provided in the language(s) of the Member State where the device reaches its intended user.

8.
Manufacturers who consider or have reason to
believe that a device which they have placed on the market is not in conformity
with this Regulation shall immediately take the necessary corrective action to
bring that product into conformity, withdraw it or recall it, as appropriate.
They shall inform the distributors and, where applicable, the authorised
representative accordingly.

9.
Manufacturers shall, in response to a reasoned
request from a competent authority, provide it with all the information and
documentation necessary to demonstrate the conformity of the device, in an
official Union language which can be easily understood by that authority. They
shall cooperate with that authority, at its request, on any corrective action
taken to eliminate the risks posed by devices which they have placed on the
market or put into service.

10.
Where manufacturers have their devices designed
and manufactured by another legal or natural person, the information on the
identity of that person shall be part of the information to be submitted in
accordance with Article 23.

Article 9

Authorised
representative

1.
A manufacturer of a device that is placed on the
Union market, or bears the CE marking without being placed on the Union market,
who does not have a registered place of business in a Member State or does not
carry out relevant activities at a registered place of business in a Member
State, shall designate a single authorised representative.

2.
The designation shall be valid only when
accepted in writing by the authorised representative and shall be effective at
least for all devices of the same generic device group.

3.
The authorised representative shall perform the
tasks specified in the mandate agreed between the manufacturer and the
authorised representative.

The mandate shall allow and require the
authorised representative to perform at least the following tasks in relation
to the devices that it covers:

(a)
keep the technical documentation, the EU
declaration of conformity and, if applicable, a copy of the relevant
certificate, including any supplement, issued in accordance with Article 43 at
the disposal of competent authorities for the period referred to in Article
8(4);

(b)
in response to a reasoned request from a
competent authority, provide that competent authority with all the information
and documentation necessary to demonstrate the conformity of a device;

(c)
cooperate with the competent authorities on any
corrective action taken to eliminate the risks posed by devices;

(d)
immediately inform the manufacturer about
complaints and reports from healthcare professionals, patients and users about
suspected incidents related to a device for which they have been designated;

(e)
terminate the mandate if the manufacturer acts
contrary to his obligations under this Regulation.

To allow the authorised representative to
fulfil the tasks mentioned in this paragraph, the manufacturer shall at least
ensure that the authorised representative has permanent immediate access to the
necessary documentation in one of the official Union languages.

4.
The mandate referred to in paragraph 3 shall not
include the delegation of the manufacturer's obligations laid down in Article 8(1), (2), (5), (6),
(7) and (8).

5.
An authorised representative who terminates the
mandate on the grounds referred to in point (e) of paragraph 3 shall
immediately inform the competent authority of the Member State in which he is
established and, where applicable, the notified body that was involved in the
conformity assessment for the device of the termination of the mandate and the
reasons therefor.

6.
Any reference in this Regulation to the
competent authority of the Member State where the manufacturer has his
registered place of business shall be understood as a reference to the
competent authority of the Member State where the authorised representative,
designated by a manufacturer referred to in paragraph 1, has his registered
place of business.

Article 10

Change of
authorised representative

The modalities of a change of authorised
representative shall be clearly defined in an agreement between the
manufacturer, the outgoing authorised representative and the incoming
authorised representative. This agreement shall address at least the following
aspects:

(a)
the date of termination of the mandate with the
outgoing authorised representative and date of beginning of the mandate with
the incoming authorised representative;

(b)
the date until which the outgoing authorised
representative may be indicated in the information supplied by the
manufacturer, including any promotional material;

(c)
the transfer of documents, including
confidentiality aspects and property rights;

(d)
the obligation of the outgoing authorised
representative after the end of the mandate to forward to the manufacturer or
to the incoming authorised representative any complaints or reports from
healthcare professionals, patients or users about suspected incidents related
to a device for which he had been designated as authorised representative.

Article 11

General
obligations of importers

1.
Importers shall place on the Union market only
devices that are in conformity with this Regulation.

2.
Before placing a device on the market importers
shall ensure the following:

(a)
that the appropriate conformity assessment
procedure has been carried out by the manufacturer;

(b)
that an authorised representative in accordance
with Article 9 has been designated by the manufacturer;

(c)
that the EU declaration of conformity and the
technical documentation has been drawn up by the manufacturer;

(d)
that the device bears the required CE marking of
conformity;

(e)
that the device is labelled in accordance with
this Regulation and accompanied by the required instructions for use and EU
declaration of conformity;

(f)
that, where applicable, a Unique Device
Identification has been assigned by the manufacturer in accordance with Article
22.

Where an importer considers or has reason to
believe that a device is not in conformity with the requirements of this
Regulation, he shall not place the device on the market until it has been
brought into conformity. Where the device presents a risk, the importer shall
inform the manufacturer and his authorised representative to that effect, as
well as the competent authority of the Member State in which he is established.

3.
Importers shall indicate their name, registered
trade name or registered trade mark and the address of their registered place
of business at which they can be contacted and their location can be
established on the device or on its packaging or in a document accompanying the
device. They shall ensure that any additional label does not obscure any
information on the label provided by the manufacturer.

4.
Importers shall ensure that the device is
registered in the electronic system in accordance with Article 23(2).

5.
Importers shall ensure that, while a device is
under their responsibility, storage or transport conditions do not jeopardise
its compliance with the general safety and performance requirements set out in
Annex I.

6.
When deemed appropriate with regard to the risks
presented by a device, importers shall, in order to protect the health and
safety of patients and users, carry out sample testing of marketed products,
investigate complaints and keep a register of complaints, of non-conforming
products and of product recalls and withdrawals, and shall keep the
manufacturer, authorised representative and distributors informed of such
monitoring.

7.
Importers who consider or have reason to believe
that a device which they have placed on the market is not in conformity with
this Regulation shall immediately inform the manufacturer and his authorised
representative and, if appropriate, take the necessary corrective action to
bring that device into conformity, withdraw or recall it. Where the device
presents a risk, they shall also immediately inform the competent authorities
of the Member States in which they made the device available and, if
applicable, the notified body that issued a certificate in accordance with
Article 43 for the device in question, giving details, in particular, of the
non-compliance and of any corrective action taken.

8.
Importers who have received complaints or
reports from healthcare professionals, patients or users about suspected
incidents related to a device which they have placed on the market shall
immediately forward this information to the manufacturer and his authorised
representative.

9.
Importers shall, for the period referred to in
Article 8(4), keep a copy of the EU declaration of conformity at the disposal
of the market surveillance authorities and ensure that the technical
documentation and, if applicable, a copy of the relevant certificate including
any supplement, issued in accordance with Article 43, can be made available to
those authorities, upon request. By written mandate, the importer and the
authorised representative for the device in question may agree that this
obligation is delegated to the authorised representative.

10.
Importers shall, in response to a request from a
competent national authority, provide it with all the information and
documentation necessary to demonstrate the conformity of a product. This
obligation shall be considered fulfilled when the authorised representative for
the device in question provides the required information. Importers shall
cooperate with a competent national authority, at its request, on any action
taken to eliminate the risks posed by products which they have placed on the
market.

Article 12

General
obligations of distributors

1.
When making a device available on the market,
distributors shall act with due care in relation to the requirements
applicable.

2.
Before making a device available on the market
distributors shall verify that the following requirements are met:

(a)
the product bears the required CE marking of
conformity;

(b)
the product is accompanied by the information to
be supplied by the manufacturer in accordance with Article 8(7);

(c)
the manufacturer and, where applicable, the
importer have complied with the requirements set out in Article 22 and Article
11(3) respectively.

Where a distributor considers or has reason to
believe that a device is not in conformity with the requirements of this
Regulation, he shall not make the device available on the market until it has
been brought into conformity. Where the device presents a risk, the distributor
shall inform the manufacturer and, where applicable, his authorised
representative and the importer to that effect, as well as the competent
authority of the Member State in which he is established.

3.
Distributors shall ensure that, while a device
is under their responsibility, storage or transport conditions do not
jeopardise its compliance with the general safety and performance requirements
set out in Annex I.

4.
Distributors who consider or have reason to
believe that a device which they have made available on the market is not in
conformity with this Regulation shall immediately inform the manufacturer and,
where applicable, his authorised representative and the importer and make sure
that the necessary corrective action to bring that device into conformity,
withdraw or recall it, if appropriate, is taken. Where the device presents a
risk, they shall also immediately inform the competent authorities of the
Member States in which they made the device available, giving details, in particular,
of the non-compliance and of any corrective action taken.

5.
Distributors who have received complaints or
reports from healthcare professionals, patients or users about suspected
incidents related to a device they have made available, shall immediately
forward this information to the manufacturer and, where applicable, his
authorised representative.

6.
Distributors shall, in response to a request
from a competent authority, provide it with all the information and
documentation necessary to demonstrate the conformity of a device. This
obligation shall be considered fulfilled when the authorised representative for
the device in question, where applicable, provides the required information.
Distributors shall cooperate with competent national authorities, at their
request, on any action taken to eliminate the risks posed by devices which they
have made available on the market.

Article 13

Person responsible for regulatory compliance

1.
Manufacturers shall have available within their
organisation at least one qualified person who possesses expert knowledge in
the field of in vitro diagnostic medical devices. The expert knowledge
shall be demonstrated by either of the following qualifications:

(a)
a diploma, certificate or other evidence of
formal qualification awarded on completion of a university degree or of an
equivalent course of study, in natural sciences, medicine, pharmacy,
engineering or another relevant discipline, and at least two years of
professional experience in regulatory affairs or in quality management systems
relating to in vitro diagnostic medical devices;

(b)
five years of professional experience in
regulatory affairs or in quality management systems relating to in vitro
diagnostic medical devices.

2.
The qualified person shall at least be
responsible for ensuring the following matters:

(a)
that the conformity of the devices is
appropriately assessed before a batch is released;

(b)
that the technical documentation and the
declaration of conformity are drawn up and kept up-to-date;

(c)
that the reporting obligations in accordance
with Articles 59 to 64 are fulfilled.

(d)
in the case of devices for performance
evaluation intended to be used in the context of interventional clinical
performance studies or other clinical performance studies involving risks for
the subjects, that the statement referred to in Section 4.1 of Annex XIII is
issued;

3.
The qualified person shall suffer no
disadvantage within the manufacturer's organisation in relation to the proper
fulfilment of his duties.

4.
Authorised representatives shall have available
within their organisation at least one qualified person who possesses expert
knowledge regarding the regulatory requirements for in vitro diagnostic
medical devices in the Union. The expert knowledge shall be demonstrated by
either of the following qualifications:

(a)
a diploma, certificate or other evidence of
formal qualification awarded on completion of a university degree or of an
equivalent course of study, in law, natural sciences, medicine, pharmacy,
engineering or another relevant discipline, and at least two years of
professional experience in regulatory affairs or in quality management systems
relating to in vitro diagnostic medical devices;

(b)
five years of professional experience in
regulatory affairs or in quality management systems relating to in vitro
diagnostic medical devices.

Article 14

Cases in which
obligations of manufacturers apply to importers, distributors or other persons

1.
A distributor, importer or other natural or
legal person shall assume the obligations incumbent on manufacturers if he does
any of the following:

(a)
makes available on the market a device under his
name, registered trade name or registered trade mark;

(b)
changes the intended purpose of a device already
placed on the market or put into service;

(c)
modifies a device already placed on the market
or put into service in such a way that compliance with the applicable
requirements may be affected.

The first subparagraph shall not apply to any
person who, while not considered a manufacturer as defined in number (16) of
Article 2, assembles or adapts a device already on the market to its intended
purpose for an individual patient.

2.
For the purposes of point (c) of paragraph 1,
the following shall not be considered to be a modification of a device that
could affect its compliance with the applicable requirements:

(a)
provision, including translation, of the
information supplied by the manufacturer in accordance with Section 17 of Annex
I relating to a device already placed on the market and of further information
which is necessary in order to market the product in the relevant Member State;

(b)
changes to the outer packaging of a device
already placed on the market, including a change of pack size, if the
repackaging is necessary in order to market the product in the relevant Member
State and if it is carried out in such conditions that the original condition
of the device cannot be affected by it. In the case of devices placed on the
market in sterile condition, it shall be presumed that the original condition
of the device is adversely affected if the package that shall ensure the
sterile condition is opened, damaged or otherwise negatively affected by the
repackaging.

3.
A distributor or importer who carries out any of
the activities mentioned in points (a) and (b) of paragraph 2 shall indicate
the activity carried out together with his name, registered trade name or
registered trade mark and the address at which he can be contacted and his
location can be established on the device or, where that is not possible, on
its packaging or in a document accompanying the device.

He shall ensure that he has in place a quality
management system that includes procedures which ensure that the translation of
information is accurate and up-to-date, and that the activities mentioned in
points (a) and (b) of paragraph 2 are performed by means and under conditions
that preserve the original condition of the device and that the packaging of
the repackaged device is not defective, of poor quality or untidy. Part of the
quality management system shall be procedures ensuring that the distributor or
importer is informed of any corrective action taken by the manufacturer in
relation to the device in question in order to respond to safety issues or to
bring it in conformity with this Regulation.

4.
Prior to making the relabelled or repackaged
device available, the distributor or importer referred to in paragraph 3 shall
inform the manufacturer and the competent authority of the Member State where
he plans to make the device available and, upon request, shall provide them
with a sample or a mock-up of the relabelled or repackaged device, including
any translated label and instructions for use. He shall submit to the competent
authority a certificate, issued by a notified body referred to in Article 27,
designated for the type of devices that are subject to activities mentioned in
points (a) and (b) of paragraph 2, attesting that the quality management system
complies with the requirements laid down in paragraph 3.

Article 15

EU declaration
of conformity

1.
The EU declaration of conformity shall state
that fulfilment of the requirements specified in this Regulation has been
demonstrated. It shall be continuously updated. The minimum content of the EU
declaration of conformity is set out in Annex III. It shall be translated into
the official Union language or languages required by the Member State(s) in
which the device is made available.

2.
Where, concerning aspects not covered by this
Regulation, devices are subject to other Union legislation which also requires
a declaration of conformity by the manufacturer that fulfilment of the
requirements of that legislation has been demonstrated, a single EU declaration
of conformity shall be drawn up in respect of all Union acts applicable to the
device containing all information required for identification of the Union
legislation to which the declaration relates.

3.
By drawing up the EU declaration of conformity,
the manufacturer shall assume responsibility for compliance with the
requirements of this Regulation and all other Union legislation applicable to
the device.

4.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 amending or supplementing the
minimum content of the EU declaration of conformity set out in Annex III in the
light of technical progress.

Article 16

CE marking of
conformity

1.
Devices, other than devices for performance
evaluation, considered to be in conformity with the requirements of this
Regulation shall bear the CE marking of conformity, as presented in Annex IV.

2.
The CE marking shall be subject to the general
principles set out in Article 30 of Regulation (EC) No 765/2008.

3.
The CE marking shall be affixed visibly, legibly
and indelibly to the device or its sterile pack. Where that is not possible or
not warranted on account of the nature of the device, it shall be affixed to
the packaging. The CE marking shall also appear in the instructions for use and
on the sales packaging where those are provided.

4.
The CE marking shall be affixed before the
device is placed on the market. It may be followed by a pictogram or any other
mark indicating a special risk or use.

5.
Where applicable, the CE marking shall be
followed by the identification number of the notified body responsible for the
conformity assessment procedures set out in Article 40. The identification
number shall also be indicated in any promotional material which mentions that
a device fulfils the legal requirements for CE marking.

6.
Where devices are subject to other Union
legislation concerning other aspects which also provide for the affixing of the
CE marking, the CE marking shall indicate that the devices also fulfil the
provisions of the other legislation.

Article 17

Devices for
special purposes

1.
Member States shall not create any obstacle to
devices for performance evaluation which are supplied for that purpose to
laboratories or other institutions, if they meet the conditions laid down in
Articles 48 to 58.

2.
Those devices shall not bear the CE marking,
with the exception of the devices referred to in Article 52.

3.
At trade fairs, exhibitions, demonstrations or
similar events, Member States shall not create any obstacle to the showing of
devices which do not comply with this Regulation, provided such devices are not
used on specimens taken from the participants and a visible sign clearly
indicates that such devices are intended for presentation or demonstration
purposes only and cannot be made available until they have been made to comply
with this Regulation.

Article 18

Systems and
procedure packs

1.
Any natural or legal person shall draw up a
statement referred to in paragraph 2 if he puts devices bearing the CE marking
together with the following other devices or products, in accordance with the
intended purpose of the devices or other products and within the limits of use
specified by their manufacturers, in order to place them on the market as a
system or procedure pack:

–
other devices bearing the CE marking;

–
medical devices bearing the CE marking in
conformity with Regulation (EU) [Ref. of future Regulation on medical devices];

–
other products which are in conformity with the
legislation applicable to those products.

2.
In the statement, the person referred to in
paragraph 1 shall declare the following:

(a)
that he verified the mutual compatibility of the
devices and, if applicable other products, in accordance with the
manufacturers' instructions and has carried out his operations in accordance
with those instructions;

(b)
that he packaged the system or procedure pack
and supplied relevant information to users incorporating the information to be
supplied by the manufacturers of the devices or other products which have been
put together;

(c)
that the activity of putting devices and, if
applicable, other products together as a system or procedure pack was subject
to appropriate methods of internal monitoring, verification and validation.

3.
Any natural or legal person who sterilises
systems or procedure packs referred to in paragraph 1 for the purpose of
placing them on the market shall, at his choice, follow one of the procedures
referred to in Annex VIII or in Annex X. The application of those Annexes and
the involvement of the notified body shall be limited to the aspects of the
procedure relating to ensuring sterility until the sterile package is opened or
damaged. The person shall draw up a statement declaring that the sterilisation
has been carried out in accordance with the manufacturer's instructions.

4.
Where the system or procedure pack incorporate
devices which do not bear the CE marking or where the chosen combination of
devices is not compatible in view of their original intended purpose, the
system or procedure pack shall be treated as a device in its own right and
shall be subjected to the relevant conformity assessment procedure pursuant to
Article 40.

5.
The systems or procedure packs referred to in
paragraph 1 shall not themselves bear an additional CE marking but they shall
bear the name, registered trade name or registered trade mark of the person
referred to in paragraph 1 as well as the address at which he can be contacted
and his location can be established. Systems or procedure packs shall be
accompanied by the information referred to in Section 17 of Annex I. The
statement referred to in paragraph 2 of this Article shall be kept at the
disposal of the competent authorities, after the system or procedure pack has
been put together, for the period that is applicable to the devices put
together in accordance with Article 8(4). Where these periods differ, the
longest period shall apply.

Article 19

Parts and
components

1.
Any natural or legal person who makes available
on the market an article intended specifically to
replace an identical or similar integral part or component of a device that is
defective or worn in order to maintain or re-establish the function of the
device, without significantly changing its performance or safety
characteristics, shall ensure that the article does not adversely affect the
safety and performance of the device. Substantiating evidence shall be kept
available to the competent authorities of the Member States.

2.
An article that is intended specifically to
replace a part or component of a device and that significantly changes the
performance or safety characteristics of the device shall be considered a
device.

Article 20

Free movement

Member States shall not refuse, prohibit or
restrict the making available or putting into service within their territory of
devices which comply with the requirements of this Regulation.

Chapter III

Identification and traceability of devices, registration of devices
and of economic operators, summary of safety and performance, European databank
on medical devices

Article 21

Identification
within the supply chain

For devices, other than devices for
performance evaluation, economic operators shall be able to identify the
following, for the period referred to in Article 8(4):

(a)
any economic operator to whom they have supplied
a device;

(b)
any economic operator who has supplied them with
a device;

(c)
any health institution or healthcare
professional to whom they have supplied a device.

Upon request, they shall inform the
competent authorities thereof.

Article 22

Unique device
identification system

1.
For devices, other than devices for performance
evaluation, a system for Unique Device Identification shall be put in place in
the Union. The UDI system shall allow the identification and traceability of
devices and shall consist of the following:

(a)
production of a UDI that comprises the
following:

(i)      a device identifier specific to a
manufacturer and a device model, providing access to the information laid down
in Part B of Annex V;

(ii)      a production identifier that
identifies data related to the unit of device production.

(b)
placement of the UDI on the label of the device;

(c)
storage of the UDI by the economic operators and
the health institutions through electronic means;

(d)
establishment of an electronic system on UDI.

2.
The Commission shall designate one or several
entities that operate a system for assignment of UDIs pursuant to this
Regulation and that satisfy all of the following criteria:

(a)
the entity is an organisation with legal
personality;

(b)
its system for the assignment of UDIs is
adequate to identify a device through its distribution and use in accordance
with the requirements of this Regulation;

(c)
its system for the assignment of UDIs conforms
to the relevant international standards;

(d)
the entity gives access to its system for the
assignment of UDIs to all interested users according to a set of predetermined
and transparent terms and conditions;

(e)
the entity undertakes the following:

(i)      to operate its system for the
assignment of UDIs for the period to be determined in the designation which
shall at least be three years after its designation;

(ii)      to make available to the Commission
and to the Member States, upon request, information concerning its system for
the assignment of UDIs and concerning manufacturers that place an UDI on the
label of their device in accordance with the entity's system;

(iii)     to remain in compliance with the
criteria for designation and the terms of designation during the period for
which it is designated.

3.
Before placing a device on the market, the
manufacturer shall assign to the device a UDI provided by an entity designated
by the Commission in accordance with paragraph 2, if that device belongs to the
devices, categories or groups of devices determined by a measure referred to in
point (a) of paragraph 7.

4.
The UDI shall be placed on the label of the
device, in accordance with the conditions laid down by a measure referred to in
point (c) of paragraph 7. It shall be used for reporting serious incidents and
field safety corrective actions in accordance with Article 59. The device
identifier shall appear on the EU declaration of conformity referred to in
Article 15 and in the technical documentation referred to in Annex II.

5.
Economic operators and health institutions shall
store and keep, by electronic means, the device identifier and the production
identifier of the devices which they have supplied or they have been supplied
with, if they belong to the devices, categories or groups of devices determined
by a measure referred to in point (a) of paragraph 7.

6.
The Commission, in cooperation with the Member
States, shall set up and manage an electronic system on UDI to collate and
process the information mentioned in Part B of Annex V. This information shall
be accessible to the public.

7.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85:

(a)
determining the devices, categories or groups of
devices, whose identification shall be based on the UDI system, as set out in
paragraphs 1 to 6, and the timelines for implementing this. Following a
risk-based approach, implementation of the UDI system shall be gradual,
starting with devices falling in the highest risk class;

(b)
specifying the data to be included in the
production identifier which, following a risk-based approach, may vary
depending on the risk class of the device;

(c)
defining the obligations of economic operators,
of health institutions and of professional users, in particular regarding
allocation of the numeric or alphanumeric characters, placement of the UDI on
the label, storage of information in the electronic system on UDI, and use of
the UDI in documentation and reporting related to the device provided for in
this Regulation;

(d)
amending or supplementing the list of
information set out in Part B of Annex V in the light of technical progress.

8.
When adopting the measures referred to in
paragraph 7, the Commission shall take into account the following:

(a)
the protection of personal data;

(b)
the legitimate interest in protecting
commercially sensitive information;

(c)
the risk-based approach;

(d)
the cost-effectiveness of the measures;

(e)
the convergence of UDI systems developed at
international level.

Article 23

Electronic
system on registration of devices and economic operators

1.
The Commission, in collaboration with the Member
States, shall set up and manage an electronic system to collate and process
information that is necessary and proportionate to describe and identify the
device and to identify the manufacturer and, where applicable, the authorised
representative and the importer. The details regarding the information to be
submitted by the economic operators are laid down in Part A of Annex V.

2.
Before a device, other than a device for
performance evaluation, is placed on the market the manufacturer or his
authorised representative shall submit to the electronic system the information
referred to in paragraph 1.

3.
Within one week after placing a device, other
than a device for performance evaluation, on the market, importers shall submit
to the electronic system the information referred to in paragraph 1.

4.
Within one week of any change occurring in
relation to the information referred to in paragraph 1, the relevant economic
operator shall update the data in the electronic system.

5.
Not later than two years after submission of the
information in accordance with paragraphs 2 and 3, and then every second year,
the relevant economic operator shall confirm the accuracy of the data. In the
event of failure to confirm within six months of the due date, any Member State may take measures to suspend or otherwise restrict the making available of the
device in question within its territory until the obligation referred to in
this paragraph is complied with.

6.
The data contained in the electronic system
shall be accessible to the public.

7.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 amending the list of information
to be submitted as set out in Part A of Annex V in the light of technical
progress.

Article 24

Summary of
safety and performance

1.
In the case of devices classified as class C and
D, other than devices for performance evaluation, the manufacturer shall draw
up a summary of safety and performance. It shall be written in a way that is
clear to the intended user. The draft of this summary shall be part of the
documentation to be submitted to the notified body involved in the conformity
assessment in accordance with Article 40 and shall be validated by that body.

2.
The Commission may, by means of implementing
acts, set out the form and the presentation of the data elements to be included
in the summary of safety and performance. Those implementing acts shall be
adopted in accordance with the advisory procedure referred to in Article 84(2).

Article 25

European
databank

The Commission shall develop and manage the
European databank on medical devices (Eudamed) in accordance with the
conditions and modalities established by Article 27 of Regulation (EU) [Ref. of
future Regulation on medical devices].

Eudamed shall include the following as
integral parts:

(a)
the electronic system on UDI referred to in
Article 22;

(b)
the electronic system on registration of devices
and economic operators referred to in Article 23;

(c)
the electronic system on information on
certificates referred to in Article 43(4);

(d)
the electronic system on interventional clinical
performance studies and clinical performance studies involving risks for the
subjects set up in Article 51;

(e)
the electronic system on vigilance referred to
in Article 60;

(f)
the electronic system on market surveillance
referred to in Article 66.

Chapter IV

Notified Bodies

Article 26

National
authorities responsible for notified bodies

1.
A Member State that intends to designate a
conformity assessment body as a notified body, or has designated a notified
body, to carry out third-party conformity assessment tasks under this
Regulation shall designate an authority that shall be responsible for setting
up and carrying out the necessary procedures for the assessment, designation
and notification of conformity assessment bodies and for the monitoring of
notified bodies, including subcontractors or subsidiaries of those bodies,
hereinafter referred to as the 'national authority responsible for notified
bodies'.

2.
The national authority responsible for notified
bodies shall be established, organised and operated so as to safeguard the
objectivity and impartiality of its activities and to avoid any conflicts of
interest with conformity assessment bodies.

3.
It shall be organised so that each decision
relating to notification of a conformity assessment body is taken by personnel
different from those who carried out the assessment of the conformity
assessment body.

4.
It shall not perform any activities that
conformity assessment bodies perform nor provide consultancy services on a
commercial or competitive basis.

5.
The national authority responsible for notified
bodies shall safeguard the confidentiality of the information it obtains.
However, it shall exchange information on a notified body with other Member States and the Commission.

6.
The national authority responsible for notified
bodies shall have a sufficient number of competent personnel at its disposal
for the proper performance of its tasks.

Without prejudice to Article 31(3), where a
national authority is responsible for the designation of notified bodies in the
field of products other than in vitro diagnostic medical devices, the
competent authority for in vitro diagnostic medical devices shall be
consulted on all aspects specifically related to such devices.

7.
Member States shall provide the Commission and
the other Member States with information on their
procedures for the assessment, designation and
notification of conformity assessment bodies and for the monitoring of notified bodies, and
of any changes thereto.

8.
The national authority responsible for notified
bodies shall be peer-reviewed every second year. The peer-review shall include
an on-site visit to a conformity assessment body or a notified body under the
responsibility of the reviewed authority. In the case referred to in the second
subparagraph of paragraph 6, the competent authority for medical devices shall
participate in the peer-review.

The Member States shall draw up the annual plan
for the peer-review, ensuring an appropriate rotation in respect of reviewing
and reviewed authorities, and submit it to the Commission. The Commission may
participate in the review. The outcome of the peer-review shall be communicated
to all Member States and to the Commission and a summary of the outcome shall
be made publicly available.

Article 27

Requirements
relating to notified bodies

1.
Notified bodies shall satisfy the organisational
and general requirements and the quality management, resource and process
requirements that are necessary to fulfil their tasks for which they are
designated in accordance with this Regulation. Minimum requirements to be met
by notified bodies are set out in Annex VI.

2.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 amending or supplementing the
minimum requirements in Annex VI, in the light of technical progress and
considering the minimum requirements needed for the assessment of specific
devices, or categories or groups of devices

Article 28

Subsidiaries
and subcontracting

1.
Where a notified body subcontracts specific
tasks connected with conformity assessment or has recourse to a subsidiary for
specific tasks connected with conformity assessment, it shall verify that the
subcontractor or the subsidiary meets the relevant requirements set out in
Annex VI and shall inform the national authority responsible for notified
bodies accordingly.

2.
Notified bodies shall take full responsibility
for the tasks performed on their behalf by subcontractors or subsidiaries.

3.
Conformity assessment activities may be
subcontracted or carried out by a subsidiary only with the agreement of the
legal or natural person that applied for conformity assessment.

4.
Notified bodies shall keep at the disposal of
the national authority responsible for notified bodies the relevant documents
concerning the verification of the qualifications of the subcontractor or the
subsidiary and the work carried out by them under this Regulation.

Article 29

Application by
a conformity assessment body for notification

1.
A conformity assessment body shall submit an
application for notification to the national authority responsible for notified
bodies of the Member State in which it is established.

2.
The application shall specify the conformity
assessment activities, the conformity assessment procedures and the devices for
which the body claims to be competent, supported by documentation proving
compliance with all the requirements set out in Annex VI.

In respect of the organisational and general
requirements and the quality management requirements set out in Sections 1 and
2 of Annex VI, the relevant documentation may be submitted in form of a valid certificate and the corresponding evaluation report delivered
by a national accreditation body in accordance with Regulation
(EC) No 765/2008. The conformity assessment body shall be presumed to be in
conformity with the requirements covered by the certificate delivered by such
accreditation body.

3.
After being designated, the notified body shall
update the documentation referred to in paragraph 2 whenever relevant changes
occur in order to enable the national authority responsible for notified bodies
to monitor and verify continuous compliance with all the requirements set out
in Annex VI.

Article 30

Assessment of
the application

1.
The national authority responsible for notified
bodies shall check that the application referred to in Article 29 is complete
and draw up a preliminary assessment report.

2.
It shall submit the preliminary assessment
report to the Commission which shall immediately transmit it to the Medical
Device Coordination Group ('MDCG') referred to in Article 76. Upon request by
the Commission, the report shall be submitted by the authority in up to three
official Union languages.

3.
Within 14 days of the submission referred to in
paragraph 2, the Commission shall designate a joint assessment team, made up of
at least two experts chosen from a list of experts who are qualified in the
assessment of conformity assessment bodies. The list shall be drawn up by the
Commission in cooperation with the MDCG. At least one of these experts shall be
a representative of the Commission who shall lead the joint assessment team.

4.
Within 90 days after designation of the joint
assessment team, the national authority responsible for notified bodies and the
joint assessment team shall review the documentation submitted with the
application in accordance with Article 29 and conduct an on-site assessment of
the applicant conformity assessment body and, where relevant, of any subsidiary
or sub-contractor, located inside or outside the Union, to be involved in the
conformity assessment process. Such on-site assessment shall not cover
requirements for which the applicant conformity assessment body has received a
certificate delivered by the national accreditation body as referred to in
Article 29(2), unless the Commission representative mentioned in Article 30(3)
requests the on-site assessment.

Findings regarding non-compliance of a body
with the requirements set out in Annex VI shall be raised during the assessment
process and discussed between the national authority responsible for notified
bodies and the joint assessment team with a view to finding common agreement
with respect to the assessment of the application. Divergent opinions shall be
identified in the assessment report of the national authority responsible.

5.
The national authority responsible for notified
bodies shall submit its assessment report and its draft notification to the
Commission which shall immediately transmit those documents to the MDCG and to
the members of the joint assessment team. Upon request by the Commission, those
documents shall be submitted by the authority in up to three official Union
languages.

6.
The joint assessment team shall provide its
opinion regarding the assessment report and the draft notification within 21
days of receipt of those documents and the Commission shall immediately submit
this opinion to the MDCG. Within 21 days after receipt of the opinion of the
joint assessment team, the MDCG shall issue a recommendation with regard to the
draft notification which the relevant national authority shall duly take into
consideration for its decision on the designation of the notified body.

7.
The Commission may, by means of implementing
acts, adopt measures setting out the modalities for the application for
notification referred to in Article 29 and the assessment of the application
set out in this Article. Those implementing acts shall be adopted in accordance
with the examination procedure referred to in Article 84(3).

Article 31

Notification
procedure

1.
Member States shall notify the Commission and
the other Member States of the conformity assessment bodies they have
designated, using the electronic notification tool developed and managed by the
Commission.

2.
Member States may notify only conformity
assessment bodies which satisfy the requirements set out in Annex VI.

3.
Where a national authority responsible for
notified bodies is responsible for designation of notified bodies in the field
of products other than in vitro diagnostic medical devices, the
competent authority for in vitro diagnostic medical devices shall
provide, prior to the notification, a positive opinion on the notification and
its scope.

4.
The notification shall clearly specify the scope
of the designation indicating the conformity assessment activities, the
conformity assessment procedures and the type of devices which the notified
body is authorised to assess.

The Commission may, by means of implementing
acts, set up a list of codes and the corresponding types of devices to define
the scope of the designation of notified bodies which the Member States shall
indicate in their notification. Those implementing acts shall be adopted in
accordance with the advisory procedure referred to in Article 84(2).

5.
The notification shall be accompanied by the
final assessment report of the national authority responsible for notified
bodies, the opinion of the joint assessment team and the recommendation of the
MDCG. Where the notifying Member State does not follow the recommendation of
the MDCG, it shall provide a duly substantiated justification.

6.
The notifying Member State shall provide the
Commission and the other Member States with documentary evidence regarding the
arrangements in place to ensure that the notified body will be monitored
regularly and will continue to satisfy the requirements set out in Annex VI. It
shall furthermore submit evidence of the availability of competent personnel
for monitoring the notified body in accordance with Article 26(6).

7.
Within 28 days of a notification, a Member State or the Commission may raise written objections, setting out its arguments,
with regard either to the notified body or to its monitoring by the national
authority responsible for notified bodies.

8.
When a Member State or the Commission raises
objections in accordance with paragraph 7, the effect of the notification shall
be suspended. In this case, the Commission shall bring the matter before the
MDCG within 15 days after expiry of the period referred to in paragraph 7.
After consulting the parties involved, the MDCG shall give its opinion at the
latest within 28 days after the matter has been brought before it. If the
notifying Member State does not agree with the opinion of the MDCG, it may
request the Commission to give its opinion.

9.
Where no objection is raised in accordance with
paragraph 7 or where the MDCG or the Commission, after having been consulted in
accordance with paragraph 8, is of the opinion that the notification may be
accepted fully or partially, the Commission shall publish the notification
accordingly.

10.
The notification shall become valid the day
after its publication in the database of notified bodies developed and managed
by the Commission. The published notification shall determine the scope of
lawful activity of the notified body.

Article 32

Identification
number and list of notified bodies

1.
The Commission shall assign an identification
number to each notified body for which the notification is accepted in
accordance with Article 31. It shall assign a single identification number even
when the body is notified under several Union acts.

2.
The Commission shall make accessible to the
public the list of the bodies notified under this Regulation, including the
identification numbers that have been assigned to them and the activities for
which they have been notified. The Commission shall ensure that the list is
kept up to date.

Article 33

Monitoring of
notified bodies

1.
The national authority
responsible for notified bodies shall continuously
monitor the notified bodies to ensure ongoing compliance with the requirements set out in Annex VI. The notified bodies shall, on request, supply all relevant
information and documents required to enable the authority to verify compliance
with those criteria.

Notified bodies shall, without delay, inform
the national authority responsible for notified bodies of any changes, in
particular regarding their personnel, facilities, subsidiaries or
subcontractors, which may affect compliance with the requirements set out in
Annex VI or their ability to conduct the conformity assessment procedures
relating to the devices for which they have been designated.

2.
Notified bodies shall respond without delay to
requests relating to conformity assessments they have carried out, submitted by
their or another Member State's authority or by the Commission. The national
authority responsible for notified bodies of the Member State in which the body
is established shall enforce requests submitted by authorities of any other Member State or by the Commission unless there is a legitimate reason for not doing so in
which case both sides may consult the MDCG. The notified body or their national
authority responsible for notified bodies may request that any information
transmitted to the authorities of another Member State or to the Commission
shall be treated as confidential.

3.
At least once a year, the national authority
responsible for notified bodies shall assess whether each notified body under its responsibility still satisfies
the requirements set out in Annex VI. This assessment shall include an on-site
visit to each notified body.

4.
Three years after notification of a notified
body, and again every third year thereafter, the assessment to determine
whether the notified body still satisfies the requirements set out in Annex VI
shall be conducted by the national authority responsible for notified bodies of
the Member State in which the body is established and a joint assessment team designated in accordance
with the procedure described in Article 30(3) and (4). At the request of the
Commission or of a Member State, the MDCG may initiate the assessment process
described in this paragraph at any time when there is reasonable concern about
the ongoing compliance of a notified body with the
requirements set out in Annex VI.

5.
The Member States shall report to the Commission
and to the other Member States,
at least once a year, on their monitoring activities. This report shall contain
a summary which shall be made publicly available.

Article 34

Changes to
notifications

1.
The Commission and the other Member States shall
be notified of any subsequent relevant changes to the notification. The
procedures described in Article 30(2) to (6) and in Article 31 shall apply to
changes where they entail extension of the scope of the notification. In all
other cases, the Commission shall immediately publish the amended notification
in the electronic notification tool referred to in Article 31(10).

2.
Where a national authority responsible for
notified bodies has ascertained that a notified body no longer meets the
requirements set out in Annex VI, or that it is failing to fulfil its
obligations, the authority shall suspend, restrict, or fully or partially
withdraw the notification, depending on the seriousness of the failure to meet
those requirements or fulfil those obligations. A suspension shall not exceed a
period of one year, renewable once for the same period. Where the notified body
has ceased its activity, the national authority responsible for notified bodies
shall withdraw the notification.

The national authority responsible for notified
bodies shall immediately inform the Commission and the other Member States of any suspension, restriction or withdrawal of a notification.

3.
In the event of restriction, suspension or
withdrawal of a notification, the Member State shall take appropriate steps to
ensure that the files of the notified body concerned are either processed by
another notified body or kept available for the national authorities
responsible for notified bodies and for market surveillance at their request.

4.
The national authority responsible for notified
bodies shall assess whether the reasons which gave rise to the change to the
notification have an impact on the certificates issued by the notified body
and, within three months after having notified the changes to the notification,
shall submit a report on its findings to the Commission and the other Member
States. Where necessary to ensure the safety of devices on the market, that
authority shall instruct the notified body to suspend or withdraw, within a
reasonable period of time determined by the authority, any certificates which
were unduly issued. If the notified body fails to do so within the determined
period of time, or has ceased its activity, the national authority responsible
for notified bodies itself shall suspend or withdraw the certificates unduly issued.

5.
The certificates, other than those unduly
issued, which were issued by the notified body for which the notification has
been suspended, restricted or withdrawn shall remain valid in the following
circumstances:

(a)
in the case of suspension of a notification: on
condition that, within three months of the suspension, either the competent
authority for in vitro diagnostic medical devices of the Member State in
which the manufacturer of the device covered by the certificate is established,
or another notified body responsible for in vitro diagnostic medical
devices confirms in writing that it is assuming the functions of the notified
body during the period of suspension;

(b)
in the case of restriction or withdrawal of a
notification: for a period of three months after the restriction or withdrawal.
The competent authority for in vitro diagnostic medical devices of the Member State in which the manufacturer of the device covered by the certificate is
established may extend the validity of the certificates for further periods of
three months, which altogether may not exceed twelve months, provided it is
assuming the functions of the notified body during this period.

The authority or the notified body assuming the
functions of the notified body affected by the change of notification shall
immediately inform the Commission, the other Member States and the other
notified bodies thereof.

Article 35

Challenge to
the competence of notified bodies

1.
The Commission shall investigate all cases where
concerns have been brought to its attention regarding the continued fulfilment
by a notified body of the requirements set out in Annex VI or the obligations
to which it is subject. It may also commence such investigations on its own
initiative.

2.
The notifying Member State shall provide the
Commission, on request, with all information regarding the notification of the
notified body concerned.

3.
Where the Commission ascertains that a notified
body no longer meets the requirements for its notification, it shall inform the
notifying Member State accordingly and request it to take the necessary
corrective measures, including the suspension, restriction or withdrawal of the
notification if necessary.

Where the Member State fails to take the
necessary corrective measures, the Commission may, by means of implementing
acts, suspend, restrict or withdraw the notification. Those implementing acts
shall be adopted in accordance with the examination procedure referred to in
Article 84(3). It shall notify the Member State concerned of its decision and
update the database and list of notified bodies.

Article 36

Exchange of
experience between national authorities responsible for notified bodies

The Commission shall provide for the
organisation of exchange of experience and coordination of administrative
practice between the national authorities responsible for notified bodies under
this Regulation.

Article 37

Coordination of
notified bodies

The Commission shall ensure that
appropriate coordination and cooperation between notified bodies is put in
place and operated in the form of the coordination group of notified bodies referred
to in Article 39 of Regulation [Ref. of future Regulation on medical devices].

The bodies notified under this Regulation
shall participate in the work of that group.

Article 38

Fees

1.
The Member State where the
bodies are established shall levy fees on applicant conformity assessment
bodies and on notified bodies. These fees shall, wholly or partly, cover the
costs relating to the activities exercised by the national authorities responsible
for notified bodies in accordance with this Regulation.

2.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 setting out the structure and the
level of the fees referred to in paragraph 1, taking into account the
objectives of protection of human health and safety, support of innovation and
cost-effectiveness. Particular attention shall be paid to the interests of
notified bodies that received a certificate delivered by the national
accreditation body as referred to in Article 29(2) and notified bodies that are
small and medium-sized enterprises as defined by the Commission Recommendation
2003/361/EC[38].

Chapter V

Classification and conformity assessment

Section 1 – Classification

Article 39

Classification
of in vitro diagnostic medical devices

1.
Devices shall be divided into class A, B, C and
D, taking into account their intended purpose and inherent risks.
Classification shall be carried out in accordance with the classification
criteria set out in Annex VII.

2.
Any dispute between the manufacturer and the
notified body concerned, arising from the application of the classification
criteria, shall be referred for a decision to the competent authority of the Member State where the manufacturer has his registered place of business. In cases where
the manufacturer has no registered place of business in the Union and has not
yet designated an authorised representative, the matter shall be referred to
the competent authority of the Member State where the authorised representative
referred to in the last indent of point (b) of Section 3.2. of Annex VIII has
his registered place of business.

At least 14 days prior to any decision, the
competent authority shall notify the MDCG and the Commission of its envisaged
decision.

3.
The Commission may, at the request of a Member
State or on its own initiative, by means of implementing acts, decide on the
application of the classification criteria set out in Annex VII to a given
device, or category or group of devices with a view to determining their
classification.

Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

4.
In the light of technical progress and any
information which becomes available in the course of the vigilance and market
surveillance activities described in Articles 59 to 73, the Commission shall be
empowered to adopt delegated acts in accordance with Article 85 as regards the
following:

(a)
deciding that a device, or category or group of
devices, should, by way of derogation from the classification criteria set out
in Annex VII, be classified in another class,

(b)
amending or supplementing the classification
criteria set out in Annex VII.

Section 2 – Conformity assessment

Article 40

Conformity
assessment procedures

1.
Prior to placing a device on the market,
manufacturers shall undertake an assessment of the conformity of that device.
The conformity assessment procedures are set out in Annexes VIII to X.

2.
Manufacturers of devices classified as class D,
other than devices for performance evaluation, shall be subject to a conformity
assessment based on full quality assurance, design dossier examination and
batch verification, as specified in Annex VIII. Alternatively, the manufacturer
may choose to apply a conformity assessment based on type examination as
specified in Annex IX, coupled with a conformity assessment based on production
quality assurance including batch verification, as specified in Annex X.

In addition, where a reference laboratory is
designated in accordance with Article 78, the notified body performing the
conformity assessment shall request that reference laboratory to verify
compliance of the device with the applicable CTS, when available, or with other
solutions chosen by the manufacturer to ensure a level of safety and
performance that is at least equivalent, as specified in Section 5.4 of Annex
VIII and in Section 3.5 of Annex IX.

For companion diagnostics intended to be used
to assess the patient eligibility for treatment with a specific medicinal
product, the notified body shall consult one of the competent authorities
designated by the Member States in accordance with Directive 2001/83/EC of the
European Parliament and of the Council of 6 November 2001 on the Community code
relating to medicinal products for human use [39]
or the European Medicines Agency (EMA) in accordance with the procedures set
out in Section 6.2 of Annex VIII and in Section 3.6 of Annex IX.

3.
Manufacturers of devices classified as class C,
other than devices for performance evaluation, shall be subject to a conformity
assessment based on full quality assurance, as specified in Annex VIII, with
assessment of the design documentation within the technical documentation on a
representative basis. Alternatively, the manufacturer may choose to apply a conformity
assessment based on type examination, as specified in Annex IX coupled with
conformity assessment based on production quality assurance, as specified in
Annex X.

In addition, for devices for self-testing and
near-patient testing, the manufacturer shall fulfil the supplementary
requirements set out in Section 6.1 of Annex VIII or in Section 2 of Annex IX.

For companion diagnostic intended to be used to
assess the patient eligibility to a treatment with a specific medicinal
product, the notified body shall consult one of the competent authorities
designated by the Member States in accordance with Directive 2001/83/EC or the
European Medicines Agency (EMA) in accordance with the procedures set out in
Section 6.2 of Annex VIII and in Section 3.6 of Annex IX.

4.
Manufacturers of devices classified as class B,
other than devices for performance evaluation, shall be subject to a conformity
assessment based on full quality assurance, as specified in Annex VIII.

In addition, for devices for self-testing and
near-patient testing, the manufacturer shall fulfil the supplementary
requirements set out in Section 6.1 of Annex VIII.

5.
Manufacturers of devices classified as class A,
other than devices for performance evaluation, shall declare the conformity of
their products by issuing the EU declaration of conformity referred to in
Article 15, after drawing up the technical documentation set out in Annex II.

However, if the devices are intended for
near-patient testing, or if they are placed on the market in sterile condition
or have a measuring function, the manufacturer shall apply the procedures set
out in Annex VIII or in Annex X. Involvement of the notified body shall be
limited:

(a)
in the case of devices for near-patient testing,
to the requirements set out in Section 6.1 of Annex VIII,

(b)
in the case of devices placed on the market in
sterile condition, to the aspects of manufacture concerned with securing and
maintaining sterile conditions,

(c)
in the case of devices with a measuring
function, to the aspects of manufacture concerned with the conformity of the
devices with the metrological requirements.

6.
Manufacturers may choose to apply a conformity
assessment procedure applicable to devices of a higher class than the device in
question.

7.
Devices for performance evaluation shall be
subject to the requirements set out in Articles 48 to 58.

8.
The Member State in which the notified body is
established may determine that all or certain documents, including the
technical documentation, audit, assessment and inspection reports, relating to
the procedures referred to in paragraphs 1 to 6 shall be available in an
official Union language. Otherwise they shall be available in an official Union
language acceptable to the notified body.

9.
The Commission may, by means of implementing
acts, specify the modalities and the procedural aspects with a view to ensuring
harmonised application of the conformity assessment procedures by the notified
bodies, for any of the following aspects:

–
the frequency and the sampling basis of the
assessment of the design documentation within the technical documentation on a
representative basis as set out in Sections 3.3.(c) and 4.5 of Annex VIII, in
the case of devices classified as class C;

–
the minimum frequency of unannounced factory
inspections and sample checks to be conducted by notified bodies in accordance
with Section 4.4 of Annex VIII, taking into account the risk-class and the type
of device;

–
the frequency of samples of the manufactured
devices or batches of devices classified as class D to be sent to a reference
laboratory designated under Article 78 in accordance with Section 5.7 of Annex
VIII and Section 5.1 of Annex X, or

–
the physical, laboratory or other tests to be
carried out by notified bodies in the context of sample checks, design dossier
examination and type examination in accordance with Sections 4.4 and 5.3 of
Annex VIII and Sections 3.2 and 3.3 of Annex IX.

Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

10.
In the light of technical progress and any
information which becomes available in the course of the designation or
monitoring of notified bodies set out in Articles 26 to 38, or of the vigilance
and market surveillance activities described in Articles 59 to 73, the
Commission shall be empowered to adopt delegated acts in
accordance with Article 85 amending or supplementing the conformity assessment
procedures set out in Annexes VIII to X.

Article 41

Involvement of
notified bodies

1.
Where the conformity assessment procedure
requires the involvement of a notified body, the manufacturer may apply to a
notified body of his choice, provided that the body is notified for the
conformity assessment activities, the conformity assessment procedures and the
devices concerned. An application may not be lodged in parallel with more than
one notified body for the same conformity assessment activity.

2.
The notified body concerned shall inform the
other notified bodies of any manufacturer who withdraws his application prior
to the notified body's decision regarding the conformity assessment.

3.
The notified body may require any information or
data from the manufacturer which is necessary in order to properly conduct the
chosen conformity assessment procedure.

4.
Notified bodies and the personnel of notified
bodies shall carry out their conformity assessment activities with the highest
degree of professional integrity and the requisite technical competence in the
specific field and shall be free from all pressures and inducements,
particularly financial, which might influence their judgment or the results of
their conformity assessment activities, especially as regards persons or groups
with an interest in the results of those activities.

Article 42

Mechanism for
scrutiny of certain conformity assessments

1.
Notified bodies shall notify the Commission of
applications for conformity assessments for devices classified as class D, with
the exception of applications to supplement or renew existing certificates. The
notification shall be accompanied by the draft instructions for use referred to
in Section 17.3 of Annex I and the draft summary of safety and performance
referred to in Article 24. In its notification the notified body shall indicate
the estimated date by which the conformity assessment is to be completed. The Commission
shall immediately transmit the notification and the accompanying documents to
the MDCG.

2.
Within 28 days of receipt of the information
referred to in paragraph 1, the MDCG may request the notified body to submit a
summary of the preliminary conformity assessment prior to issuing a
certificate. Upon suggestion by any of its members or by the Commission, the
MDCG shall decide on making such request in accordance with the procedure set
out in Article 78(4) of Regulation [Ref. of future Regulation on medical
devices]. In its request the MDCG shall indicate the scientifically valid
health reason for having selected the specific file for submission of a summary
of the preliminary conformity assessment. When selecting a specific file for
submission, the principle of equal treatment shall be duly taken into account.

Within 5 days after receipt of the request by
the MDCG, the notified body shall inform the manufacturer thereof.

3.
The MDCG may submit comments on the summary of
the preliminary conformity assessment at the latest 60 days after submission of
this summary. Within that period and at the latest 30 days after submission,
the MDCG may request the submission of additional information that for
scientifically valid grounds are necessary for the analysis of the notified
body's preliminary conformity assessment. This may include a request for
samples or an on-site visit to the manufacturer's premises. Until submission of
the additional information requested, the period for comments referred to in
the first sentence of this subparagraph shall be suspended. Subsequent requests
for additional information from the MDCG shall not suspend the period for the
submission of comments.

4.
The notified body shall give due consideration
to any comments received in accordance with paragraph 3. It shall convey to the
Commission an explanation of how they have been taken into consideration,
including any due justification for not following the comments received, and
its final decision regarding the conformity assessment in question. The
Commission shall immediately transmit this information to the MDCG.

5.
Where deemed necessary for the protection of
patient safety and public health, the Commission may determine, by means of
implementing acts, specific categories or groups of devices, other than devices
classified as class D, to which paragraphs 1 to 4 shall apply during a
predefined period of time. Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

Measures pursuant to this paragraph may be
justified only by one or more of the following criteria:

(a)
the novelty of the device or of the technology
on which it is based and the significant clinical or public health impact
thereof;

(b)
an adverse change in the risk-benefit profile of
a specific category or group of devices due to scientifically valid health
concerns in respect of components or source material or in respect of the
impact on health in case of failure;

(c)
an increased rate of serious incidents reported
in accordance with Article 59 in respect of a specific category or group of
devices;

(d)
significant discrepancies in the conformity
assessments carried out by different notified bodies on substantially similar
devices;

(e)
public health concerns regarding a specific
category or group of devices or the technology on which they are based.

6.
The Commission shall make a summary of the
comments submitted in accordance with paragraph 3 and the outcome of the
conformity assessment procedure accessible to the public. It shall not disclose
any personal data or information of commercially confidential nature.

7.
The Commission shall set up the technical
infrastructure for the data-exchange by an electronic means between notified
bodies and MDCG for the purposes of this Article.

8.
The Commission, by means of implementing acts,
may adopt the modalities and the procedural aspects concerning the submission
and analysis of the summary of the preliminary conformity assessment in
accordance with paragraphs 2 and 3. Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

Article 43

Certificates

1.
The certificates issued by the notified bodies
in accordance with Annexes VIII, IX and X shall be in an official Union
language determined by the Member State in which the notified body is
established or otherwise in an official Union language acceptable to the
notified body. The minimum content of the certificates is set out in Annex XI.

2.
The certificates shall be valid for the period
they indicate, which shall not exceed five years. On application by the
manufacturer, the validity of the certificate may be extended for further
periods, each not exceeding five years, based on a re-assessment in accordance
with the applicable conformity assessment procedures. Any supplement to a
certificate shall remain valid as long as the certificate which it supplements
is valid.

3.
Where a notified body finds that requirements of
this Regulation are no longer met by the manufacturer, it shall, taking account
of the principle of proportionality, suspend or withdraw the certificate issued
or impose any restrictions on it unless compliance with such requirements is
ensured by appropriate corrective measures taken by the manufacturer within an
appropriate deadline set by the notified body. The notified body shall give the
reasons for its decision.

4.
The Commission, in collaboration with the Member
States, shall set up and manage an electronic system to collate and process
information on certificates issued by notified bodies. The notified body shall
enter into the electronic system information regarding certificates issued,
including amendments and supplements, and information regarding suspended,
reinstated, withdrawn or refused certificates and restrictions imposed on
certificates. This information shall be accessible to the public.

5.
In the light of technical progress, the
Commission shall be empowered to adopt delegated acts in accordance with
Article 85 amending or supplementing the minimum content of the certificates
set out in Annex XI.

Article 44

Voluntary
change of notified body

1.
In cases where a manufacturer terminates his
contract with a notified body and enters into a contract with another notified
body in respect of the conformity assessment of the same device, the modalities
of the change of notified body shall be clearly defined in an agreement between
the manufacturer, the outgoing notified body and the incoming notified body.
This agreement shall address at least the following aspects:

(a)
the date of invalidity of certificates issued by
the outgoing notified body;

(b)
the date until which the identification number
of the outgoing notified body may be indicated in the information supplied by
the manufacturer, including any promotional material;

(c)
the transfer of documents, including confidentiality
aspects and property rights;

(d)
the date as of which the incoming notified body
assumes full responsibility for the conformity assessment tasks.

2.
On their date of invalidity, the outgoing
notified body shall withdraw the certificates it has issued for the device
concerned.

Article 45

Derogation from
the conformity assessment procedures

1.
By way of derogation from Article 40, any
competent authority may authorise, on duly justified request, the placing on
the market or putting into service, within the territory of the Member State
concerned, of a specific device for which the procedures referred to in Article
40 have not been carried out and use of which is in the interest of public
health or patient safety.

2.
The Member State shall inform the Commission and
the other Member States of any decision to authorise the placing on the market
or putting into service of a device in accordance with paragraph 1 where such
authorisation is granted for use other than for a single patient.

3.
Upon request by a Member State and where this is
in the interest of public health or patient safety in more than one Member
State, the Commission may, by means of implementing acts, extend for a
determined period of time the validity of an authorisation granted by a Member
State in accordance with paragraph 1 to the territory of the Union and set the
conditions under which the device may be placed on the market or put into
service. Those implementing acts shall be adopted in accordance with the
examination procedure referred to in Article 84(3).

On duly justified imperative grounds of urgency
relating to the health and safety of humans, the Commission shall adopt
immediately applicable implementing acts in accordance with the procedure
referred to in Article 84(4).

Article 46

Certificate of
free sale

1.
For the purpose of export and upon request by a
manufacturer, the Member State in which the manufacturer has its registered
place of business shall issue a certificate of free sale declaring that the
manufacturer is properly established and that the device in question bearing
the CE marking in accordance with this Regulation may be legally marketed in
the Union. The certificate of free sale shall be valid for the period indicated
on it which shall not exceed five years and shall not exceed the validity of
the certificate referred to in Article 43 issued for the device in question.

2.
The Commission may, by means of implementing
acts, establish a model for certificates of free sale taking into account
international practice as regards the use of certificates of free sale. Those
implementing acts shall be adopted in accordance with the advisory procedure
referred to in Article 84(2).

Chapter VI

Clinical evidence

Article 47

General
requirements regarding clinical evidence

1.
The demonstration of conformity with the general
safety and performance requirements set out in Annex I, under normal conditions
of use, shall be based on clinical evidence.

2.
The clinical evidence shall support the intended
purpose of the device as stated by the manufacturer.

3.
The clinical evidence shall include all the
information supporting the scientific validity of the analyte, the analytical
performance and, where applicable, the clinical performance of the device, as
described in Section 1 of Part A of Annex XII.

4.
Where demonstration of conformity with the
general safety and performance requirements based on clinical performance data
or parts thereof is not deemed appropriate, adequate justification for any such
exception shall be given based on the results of the manufacturer's risk management
and on consideration of the characteristics of the device and, in particular,
its intended purpose(s), the intended performance and the claims of the
manufacturer. The adequacy of demonstration of conformity with the general
safety and performance requirements based on the results of analytical
performance evaluation alone shall be duly substantiated in the technical
documentation referred to in Annex II.

5.
The scientific validity data, the analytical
performance data and, where applicable, the clinical performance data shall be
summarised as part of a clinical evidence report referred to in Section 3 of
Part A of Annex XII. The clinical evidence report shall be included or fully
referenced in the technical documentation referred to in Annex II relating to
the device concerned.

6.
The clinical evidence and its documentation
shall be updated throughout the
life cycle of the device concerned with data obtained
from implementation of the manufacturer's post-market surveillance plan
referred to in Article 8(6).

7.
The manufacturer shall ensure that the device
for performance evaluation complies with the general requirements of this
Regulation apart from the aspects covered by the performance evaluation and
that, with regard to those aspects, every precaution has been taken to protect
the health and safety of the patient, user and other persons.

The manufacturer shall undertake to keep
available to the competent authorities and the EU reference laboratories the
documentation allowing an understanding of the design, manufacture and
performances of the device, including its expected performance, so as to allow
assessment of conformity with the requirements of this Regulation. This
documentation shall be kept for at least five years after the performance
evaluation of the device in question has ended.

Article 48

General
requirements regarding clinical performance studies

1.
Clinical performance studies shall be subject to
this Regulation if they are conducted for one or more of the following
purposes:

(a)
to verify that, under normal conditions of use,
the devices are designed, manufactured and packaged in such a way that they are
suitable for one or more of the specific purposes of an in vitro diagnostic
medical device referred to in number (2) of Article 2, and achieve the performance
intended as specified by the manufacturers;

(b)
to verify that devices achieve the intended
benefits to the patient as specified by the manufacturer;

(c)
to determine any limits to the performance of
the devices, under normal conditions of use.

2.
Clinical performance studies shall be performed
in circumstances similar to the normal conditions of use of the device.

3.
Where the sponsor is not
established in the Union, he shall ensure that a contact person is established
in the Union. That contact person shall be the addressee for all communications
with the sponsor provided for in this Regulation. Any communication to that
contact person shall be considered as communication to the sponsor.

4.
All clinical performance studies shall be
designed and conducted in a way that the rights, safety and well-being of the
subjects participating in such clinical performance studies are protected and
that the clinical data generated in the clinical performance study are going to
be reliable and robust.

5.
All clinical performance studies shall be
designed, conducted, recorded and reported in accordance with Section 2 of
Annex XII.

6.
For interventional clinical performance studies,
as defined in number (37) of Article 2, and for other clinical performance
studies, where the conduct of the study, including specimen collection,
involves invasive procedures or other risks for the subjects of the studies,
the requirements set out in Articles 49 to 58 and in Annex XIII shall apply, in
addition to the obligations laid down in this Article.

Article 49

Application for
interventional clinical performance studies and other clinical performance
studies involving risks for the subjects of the studies

1.
Before making the first application, the sponsor
shall procure from the electronic system referred to in Article 51 a single
identification number for a clinical performance study conducted in one site or
multiple sites, in one or more than one Member State. The sponsor shall use
this single identification number when registering the clinical performance
study in accordance with Article 50.

2.
The sponsor of a clinical performance study shall submit an application to the Member State(s) in which the study is to be conducted accompanied by the documentation
referred to in Annex XIII. Within six days after receipt of the application,
the Member State concerned shall notify the sponsor whether the clinical
performance study falls within the scope of this Regulation and whether the
application is complete.

Where the Member State has not notified the
sponsor within the time period referred to in the first subparagraph, the
clinical performance study shall be considered as falling within the scope of
this Regulation and the application shall be considered complete.

3.
Where the Member State finds that the clinical
performance study applied for does not fall within the scope of this Regulation
or that the application is not complete, it shall inform the sponsor thereof
and shall set a maximum of six days for the sponsor to comment or to complete
the application.

Where the sponsor has not provided comments nor
completed the application within the time-period referred to in the first
subparagraph, the application shall be considered as withdrawn.

Where the Member State has not notified the
sponsor according to paragraph 2 within three days following receipt of the
comments or of the completed application, the clinical performance study shall
be considered as falling within the scope of this Regulation and the
application shall be considered complete.

4.
For the purposes of this Chapter, the date on
which the sponsor is notified in accordance with paragraph 2 shall be the
validation date of the application. Where the sponsor is not notified, the
validation date shall be the last day of the time periods referred to in paragraphs
2 and 3.

5.
The sponsor may start the clinical performance
study in the following circumstances:

(a)
in the case of devices for performance
evaluation classified as class C or D, as soon as the Member State concerned
has notified the sponsor of its approval;

(b)
in the case of devices for performance
evaluation classified as class A or B immediately after the date of
application, provided that the Member State concerned has so decided and that
evidence is provided that the rights, safety and well-being of the subjects to
the clinical performance study are protected;

(c)
after the expiry of 35 days after the validation
date referred to in paragraph 4, unless the Member State concerned has notified
the sponsor within that period of its refusal based on considerations of public
health, patient safety or public policy.

6.
Member States shall ensure that the persons
assessing the application do not have conflicts of interest and that they are
independent of the sponsor, the institution of the study site(s) and the
investigators involved, as well as free of any other undue influence.

Member States shall ensure that the assessment
is done jointly by a reasonable number of persons who collectively have the
necessary qualifications and experience. In the assessment, the view of at least
one person whose primary area of interest is non-scientific shall be taken into
account. The view of at least one patient shall be taken into account.

7.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 amending or supplementing, in the
light of technical progress and global regulatory developments, the
requirements for the documentation to be submitted with the application for the
clinical performance study that is laid down in Chapter I of Annex XIII.

Article 50

Registration of
interventional clinical performance studies and other clinical performance
studies involving risks for the subjects of the studies

1.
Before commencing the clinical performance
study, the sponsor shall enter in the electronic system referred to in Article
51 the following information regarding the clinical performance study:

(a)
the single identification number of the clinical
performance study;

(b)
the name and contact details of the sponsor and,
if applicable, his contact person established in the Union;

(c)
the name and contact details of the natural or
legal person responsible for the manufacture of the device for performance
evaluation, if different from the sponsor;

(d)
the description of the device for performance
evaluation;

(e)
the description of the comparator(s), if
applicable;

(f)
the purpose of the clinical performance study;

(g)
the status of the clinical performance study.

2.
Within one week of any change occurring in
relation to the information referred to in paragraph 1, the sponsor shall
update the relevant data in the electronic system referred to in Article 51.

3.
The information shall be accessible to the
public, through the electronic system referred to in Article 51, unless, for
all or parts of that information, confidentiality of the information is
justified on any of the following grounds:

(a)
protection of personal data in accordance with
Regulation (EC) No 45/2001,

(b)
protection of commercially sensitive
information,

(c)
effective supervision of the conduct of the
clinical performance study by the Member State(s) concerned.

4.
No personal data of subjects participating in
the clinical performance study shall be accessible to the public.

Article 51

Electronic
system on interventional clinical performance studies and other clinical
performance studies involving risks for the subjects of the studies

1.
The Commission shall, in collaboration with the
Member States, set up and manage an electronic system on interventional
clinical performance studies and other clinical performance studies involving
risks for the subjects of the studies to create the single identification
numbers for such clinical performance studies referred to in Article 49(1) and
to collate and process the following information:

(a)
the registration of clinical performance studies
in accordance with Article 50;

(b)
the exchange of information between the Member
States and between them and the Commission in accordance with Article 54;

(c)
the information related to clinical performance
studies conducted in more than one Member State in case of a single application
in accordance with Article 56;

(d)
the reports on serious adverse events and device
deficiencies referred to in Article 57(2) in case of single application in
accordance with Article 56.

2.
When setting up the electronic system referred
in paragraph 1, the Commission shall ensure that it is interoperable with the
EU database for clinical trials on medicinal products for human use set up in
accordance with Article [...] of Regulation (EU) No [Ref. of future Regulation on
clinical trials]. With the exception of the information referred to in Article
50, the information collated and processed in the electronic system shall be
accessible only to the Member States and to the Commission.

3.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 determining which other
information regarding clinical performance studies collated and processed in
the electronic system shall be publicly accessible to allow interoperability
with the EU database for clinical trials on medicinal products for human use
set up by Regulation (EU) No [Ref. of future Regulation on clinical trials].
Article 50(3) and (4) shall apply.

Article 52

Interventional
clinical performance studies and other clinical performance studies involving
risks for the subjects of the studies with devices authorised to bear the CE
marking

1.
Where a clinical performance study is to be
conducted to further assess devices which are authorised in accordance with
Article 40 to bear the CE marking and within its intended purpose referred to
in the relevant conformity assessment procedure, hereinafter referred to as
‘post-market follow-up performance study’, the sponsor shall notify the Member
States concerned at least 30 days prior to their commencement if the study
would submit subjects to additionally invasive or burdensome procedures.
Articles 48(1) to (5), 50, 53, 54(1) and 55(1), the first subparagraph of
Article 55(2) and the relevant provisions of Annexes XII and XIII shall apply.

2.
If the aim of the clinical performance study
regarding a device which is authorised in accordance with Article 40 to bear
the CE marking is to assess such device for a purpose other than that referred
to in the information supplied by the manufacturer in accordance with Section
17 of Annex I and in the relevant conformity assessment procedure, Articles 48
to 58 shall apply.

Article 53

Substantial
modifications to interventional clinical performance studies and other clinical
performance studies involving risks for the subjects of the studies

1.
If the sponsor introduces modifications to a
clinical performance study that are likely to have a substantial impact on the
safety or rights of the subjects or on the robustness or reliability of the
clinical data generated by the study, he shall notify the Member State(s)
concerned of the reasons for and the content of those modifications. The
notification shall be accompanied by an updated version of the relevant
documentation referred to in Annex XIII.

2.
The sponsor may implement the modifications
referred to in paragraph 1 at the earliest 30 days after notification, unless
the Member State concerned has notified the sponsor of its refusal based on
considerations of public health, patient safety or public policy.

Article 54

Information
exchange between Member States on interventional clinical performance studies and
other clinical performance studies involving risks for the subjects of the
studies

1.
Where a Member State has refused, suspended or
terminated a clinical performance study, or has called for a substantial
modification or temporary halt of a clinical performance study, or has been
notified by the sponsor of the early termination of a clinical performance
study on safety grounds, that Member State shall communicate its decision and
the grounds therefor to all Member States and the Commission by means of the
electronic system referred to in Article 51.

2.
Where an application is withdrawn by the sponsor
prior to a decision by a Member State that Member State shall inform all the
other Member States and the Commission of that fact, by means of the electronic
system referred to in Article 51.

Article 55

Information by
the sponsor in the event of temporary halt or termination of interventional
clinical performance studies or of other clinical performance studies involving
risks for the subjects of the studies

1.
If the sponsor has temporarily halted a clinical
performance study on safety grounds, he shall inform the Member States
concerned within 15 days of the temporary halt.

2.
The sponsor shall notify each Member State concerned of the end of a clinical performance study in relation to that Member State, providing a justification in the event of early termination. That
notification shall be made within 15 days from the end of the clinical
performance study in relation to that Member State.

If the study is conducted in more than one Member State, the sponsor shall notify all Member States concerned of the overall end of
the clinical performance study. That notification shall be made within 15 days
from the overall end of the clinical performance study.

3.
Within one year from the
end of the clinical performance study, the sponsor shall submit to the Member
States concerned a summary of the results of the clinical performance study in
form of a clinical performance study report referred to in Section 2.3.3 of Part
A of Annex XII. Where, for scientific reasons, it is not possible to submit the
clinical performance study report within one year, it shall be submitted as
soon as it is available. In this case, the clinical performance study protocol
referred to in Section 2.3.2 of Part A of Annex XII shall specify when the
results of the clinical performance study are going to be submitted, together
with an explanation.

Article 56

Interventional
clinical performance studies and other clinical performance studies involving
risks for the subjects of the studies conducted in more than one Member State

1.
By means of the electronic system referred to in
Article 51, the sponsor of the clinical performance study to be conducted in
more than one Member State may submit, for the purpose of Article 49, a single
application that, upon receipt, is transmitted electronically to the Member
States concerned.

2.
In the single application, the sponsor shall
propose one of the Member States concerned as coordinating Member State. If that Member State does not wish to be the coordinating Member State, it shall agree, within six days of submission of the single application, with another Member State concerned that the latter shall be the coordinating Member State. If no other Member State accepts to be the coordinating Member State, the Member State proposed by the
sponsor shall be the coordinating Member State. If another Member State than
the one proposed by the sponsor becomes coordinating Member State, the deadlines referred to in Article 49(2) shall start on the day following the
acceptance.

3.
Under the direction of the coordinating Member
State referred to in paragraph 2, the Member States concerned shall coordinate
their assessment of the application, in particular of the documentation submitted
in accordance with Chapter I of Annex XIII, except for Sections 4.2, 4.3 and
4.4 thereof which shall be assessed separately by each Member State concerned.

The coordinating Member State shall:

(a)
within 6 days of receipt of the single
application notify the sponsor whether the clinical performance study falls
within the scope of this Regulation and whether the application is complete,
except for the documentation submitted in accordance with Sections 4.2, 4.3 and
4.4 of Chapter I of Annex XIII for which each Member State shall verify the
completeness. Article 49(2) to (4) shall apply to the coordinating Member State
in relation to the verification that the clinical performance study falls
within the scope of this Regulation and that the application is complete,
except for the documentation submitted in accordance with Sections 4.2, 4.3 and
4.4 of Chapter I of Annex XIII. Article 49(2) to (4) shall apply to each Member
State in relation to the verification that the documentation submitted in
accordance with Sections 4.2, 4.3 and 4.4 of Chapter I of Annex XIII is
complete;

(b)
establish the results of the coordinated
assessment in a report to be taken into account by the other Member States
concerned when deciding on the sponsor's application in accordance with Article
49(5).

4.
The substantial modifications referred to in
Article 53 shall be notified to the Member States concerned by means of the
electronic system referred to in Article 51. Any assessment as to whether there
are grounds for refusal as referred to in Article 53 shall be carried out under
the direction of the coordinating Member State.

5.
For the purpose of Article 55(3), the sponsor
shall submit the clinical performance study report to the Member States
concerned by means of the electronic system referred to in Article 51.

6.
The Commission shall provide secretarial support
to the coordinating Member State in the accomplishment of its tasks provided
for in this Chapter.

Article 57

Recording and
reporting of events occurring during interventional clinical performance
studies and other clinical performance studies involving risks for the subjects
of the studies

1.
The sponsor shall fully record any of the
following:

(a)
an adverse event identified in the clinical
performance study protocol as critical to the evaluation of the results of the
clinical performance study in view of the purposes referred to in Article
48(1);

(b)
a serious adverse event;

(c)
a device deficiency that might have led to a
serious adverse event if suitable action had not been taken, intervention had
not occurred, or circumstances had been less fortunate;

(d)
new findings in relation to any event referred
to in points (a) to (c).

2.
The sponsor shall report to all Member States
where a clinical performance study is conducted without delay any of the
following:

(a)
a serious adverse event that has a causal
relationship with the device for performance evaluation, the comparator or the
study procedure or where such causal relationship is reasonably possible;

(b)
a device deficiency that might have led to a
serious adverse event if suitable action had not been taken, intervention had
not occurred, or circumstances had been less fortunate;

(c)
new findings in relation to any event referred
to in points (a) to (b).

The time period for reporting shall take
account of the severity of the event. Where necessary to ensure timely
reporting, the sponsor may submit an initial incomplete report followed up by a
complete report.

3.
The sponsor shall also report to the Member
States concerned any event referred to in paragraph 2 occurring in third
countries in which a clinical performance study is performed under the same
clinical performance study protocol as the one applying to a clinical
performance study covered by this Regulation.

4.
In the case of a clinical performance study for
which the sponsor has used the single application referred to in Article 56,
the sponsor shall report any event as referred to in paragraph 2 by means of
the electronic system referred to in Article 51. Upon receipt, this report
shall be transmitted electronically to all Member States concerned.

Under the direction of the coordinating Member
State referred to in Article 56(2), the Member States shall coordinate their
assessment of serious adverse events and device deficiencies to determine
whether a clinical performance study needs to be terminated, suspended,
temporarily halted or modified.

This paragraph shall not affect the rights of
the other Member States to perform their own evaluation and to adopt measures
in accordance with this Regulation in order to ensure the protection of public
health and patient safety. The coordinating Member State and the Commission
shall be kept informed of the outcome of any such evaluation and the adoption
of any such measures.

5.
In the case of post-market follow-up performance
studies referred to in Article 52(1), the provisions on vigilance contained in
Articles 59 to 64 shall apply instead of this Article.

Article 58

Implementing
acts

The Commission may, by means of
implementing acts, adopt the modalities and procedural aspects necessary for
the implementation of this Chapter, as regards the following:

(a)
harmonised forms for the application for
clinical performance studies and their assessment as referred to in Articles 49
and 56, taking into account specific categories or groups of devices;

(b)
the functioning of the electronic system
referred to in Article 51;

(c)
harmonised forms for the notification of
post-market follow-up performance studies as referred to in Article 52(1), and
of substantial modifications as referred to in Article 53;

(d)
the exchange of information between Member
States as referred to in Article 54;

(e)
harmonised forms for the reporting of serious
adverse events and device deficiencies as referred to in Article 57;

(f)
the timelines for the reporting of serious
adverse events and device deficiencies, taking into account the severity of the
event to be reported as referred to in Article 57.

Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

Chapter VII

Vigilance and market surveillance

Section 1 —
Vigilance

Article 59

Reporting of
incidents and field safety corrective actions

1.
Manufacturers of devices, other than devices for
performance evaluation, shall report through the electronic system referred to
in Article 60 the following:

(a)
any serious incident in respect of devices made
available on the Union market;

(b)
any field safety corrective action in respect of
devices made available on the Union market, including any field safety
corrective action undertaken in a third country in relation to a device which
is also legally made available on the Union market if the reason for the field
safety corrective action is not limited to the device made available in the
third country.

Manufacturers shall make the report referred to
in the first subparagraph without delay, and no later than 15 days after they
have become aware of the event and the causal
relationship with their device or that such causal relationship is reasonably
possible. The time period for reporting shall take account of the severity of
the incident. Where necessary to ensure timely reporting, the manufacturer may
submit an initial incomplete report followed up by a complete report..

2.
For similar serious incidents occurring with the
same device or device type and for which the root cause has been identified or
the field safety corrective action implemented, manufacturers may provide
periodic summary reports instead of individual incident reports, on condition
that the competent authorities referred to in points (a), (b) and (c) of
Article 60(5) have agreed with the manufacturer on the format, content and
frequency of the periodic summary reporting.

3.
The Member States shall take all appropriate
measures to encourage healthcare professionals, users and patients to report to
their competent authorities suspected serious incidents referred to in point
(a) of paragraph 1. They shall record such reports centrally at national level.
Where a competent authority of a Member State obtains such reports, it shall
take the necessary steps to ensure that the manufacturer of the device
concerned is informed of the incident. The manufacturer shall ensure the
appropriate follow-up.

The Member States shall coordinate between them
the development of standard web-based structured forms for reporting of serious
incidents by healthcare professionals, users and patients.

4.
Health institutions manufacturing and using
devices referred to in Article 4(4) shall report any serious incidents and
field safety corrective actions referred to in paragraph 1 to the competent
authority of the Member State in which the health institution is located.

Article 60

Electronic
system on vigilance

1.
The Commission shall, in collaboration with the
Member States, set up and manage an electronic system to collate and process the
following information:

(a)
the reports by manufacturers on serious
incidents and field safety corrective actions referred to in Article 59(1);

(b)
the periodic summary reports by manufacturers
referred to in Article 59(2);

(c)
the reports by competent authorities on serious
incidents referred to in the second subparagraph of Article 61(1);

(d)
the reports by manufacturers on trends referred
to in Article 62;

(e)
the field safety notices by manufacturers
referred to in Article 61(4);

(f)
the information to be exchanged between the
competent authorities of the Member States and between them and the Commission
in accordance with Article 61(3) and (6).

2.
The information collated and processed by the
electronic system shall be accessible to the competent authorities of the
Member States, to the Commission and to the notified bodies.

3.
The Commission shall ensure that healthcare
professionals and the public have appropriate levels of access to the
electronic system.

4.
On the basis of arrangements between the
Commission and competent authorities of third countries or international
organisations, the Commission may grant those competent authorities or
international organisations access to the database at the appropriate level.
Those arrangements shall be based on reciprocity and make provision for
confidentiality and data protection equivalent to those applicable in the Union.

5.
The reports on serious incidents and field
safety corrective actions referred to in points (a) and (b) of Article 59(1),
the periodic summary reports referred to in Article 59(2), the reports on
serious incidents referred to in the second subparagraph of Article 61(1) and
the trend reports referred to in Article 62 shall be automatically transmitted
upon receipt via the electronic system to the competent authorities of the
following Member States

(a)
the Member State where the incident occurred;

(b)
the Member State where the field safety
corrective action is being or is to be undertaken;

(c)
the Member State where the manufacturer has his
registered place of business;

(d)
where applicable, the Member State where the
notified body, that issued a certificate in accordance with Article 43 for the
device in question, is established.

Article 61

Analysis of
serious incidents and field safety corrective action

1.
Member States shall take the necessary steps to
ensure that any information regarding a serious incident that has occurred
within their territory or a field safety corrective action that has been or is
to be undertaken within their territory, and that is brought to their knowledge
in accordance with Article 59 is, at national level, evaluated centrally by
their competent authority, if possible together with the manufacturer.

If in the case of reports received in
accordance with Article 59(3) the competent authority ascertains that the reports
relate to a serious incident it shall notify without delay those reports to the
electronic system referred to in Article 60, unless the same incident has
already been reported by the manufacturer.

2.
The national competent authorities shall carry
out a risk assessment with regard to reported serious incidents or field safety
corrective actions, taking into account criteria such as causality,
detectability and probability of recurrence of the problem, frequency of use of
the device, probability of occurrence of harm and severity of harm, clinical
benefit of the device, intended and potential users, and population affected.
They shall also evaluate the adequacy of the field safety corrective action
envisaged or undertaken by the manufacturer and the need for and kind of any other
corrective action. They shall monitor the manufacturer's investigation of the
incident.

3.
After carrying out the assessment, the
evaluating competent authority shall, through the electronic system referred to
in Article 60, inform without delay the other competent authorities of the
corrective action taken or envisaged by the manufacturer or imposed on him to
minimise the risk of recurrence of a serious incident, including information on
the underlying events and the outcome of its assessment.

4.
The manufacturer shall ensure that the users of
the device in question are informed without delay of the corrective action
taken by means of a field safety notice. Except in case of urgency, the content
of the draft field safety notice shall be submitted to the evaluating competent
authority or, in cases referred to in paragraph 5 of this Article, the
coordinating competent authority to allow them to make comments. Unless duly
justified by the situation of the individual Member State, the content of the
field safety notice shall be consistent in all Member States.

The manufacturer shall enter the field safety
notice in the electronic system referred to in Article 60 through which that
notice shall be accessible to the public.

5.
The competent authorities shall designate a
coordinating competent authority to coordinate their assessments referred to in
paragraph 2 in the following cases:

(a)
where similar serious incidents related to the
same device or type of device of the same manufacturer occur in more than one
Member State;

(b)
where the field safety corrective action is
being or is to be undertaken in more than one Member State.

Unless otherwise agreed between the competent
authorities, the coordinating competent authority shall be the one of the Member State where the manufacturer has his registered place of business.

The coordinating competent authority shall
inform the manufacturer, the other competent authorities and the Commission
that it has assumed the role of coordinating authority.

6.
The coordinating competent authority shall carry
out the following tasks:

(a)
to monitor the investigation of the serious
incident by the manufacturer and the corrective action to be taken;

(b)
to consult with the notified body that issued a
certificate in accordance with Article 43 for the device in question regarding
the impact of the serious incident on the certificate;

(c)
to agree with the manufacturer and the other
competent authorities referred to in points (a) to (c) of Article 60(5) on the
format, content and frequency of periodic summary reports in accordance with
Article 59(2);

(d)
to agree with the manufacturer and other
competent authorities concerned on the implementation of the appropriate field
safety corrective action;

(e)
to inform the other competent authorities and
the Commission, through the electronic system referred to in Article 60, of the
progress in and the outcome of its assessment.

The designation of a coordinating competent
authority shall not affect the rights of the other competent authorities to
perform their own assessment and to adopt measures in accordance with this
Regulation in order to ensure the protection of public health and patient
safety. The coordinating competent authority and the Commission shall be kept
informed of the outcome of any such assessment and the adoption of any such
measures.

7.
The Commission shall provide secretarial support
to the coordinating competent authority in the accomplishment of its tasks
under this Chapter.

Article 62

Trend reporting

Manufacturers of devices classified in
class C or D shall report to the electronic system referred to in Article 60
any statistically significant increase in the frequency or severity of
incidents that are not serious incidents or of expected undesirable effects
that have a significant impact on the risk-benefit analysis referred to in
Sections 1 and 5 of Annex I and which have led or may lead to unacceptable
risks to the health or safety of patients, users or other persons when weighted
against the intended benefits. The significant increase shall be established in
comparison to the foreseeable frequency or severity of such incidents or
expected undesirable effects in respect of the device, or category or group of
devices, in question during a specific time period as established in the
manufacturer’s conformity assessment. Article 61 shall apply.

Article 63

Documentation
of vigilance data

Manufacturers shall update their technical
documentation with information on incidents received from healthcare
professionals, patients and users, serious incidents, field safety corrective
actions, periodic summary reports referred to in Article 59, trend reports
referred to in Article 62 and field safety notices referred to in Article
61(4). They shall make this documentation available to their notified bodies,
which shall assess the impact of the vigilance data on the conformity
assessment and the certificate issued.

Article 64

Implementing
acts

The Commission may, by means of
implementing acts, adopt the modalities and procedural aspects necessary for
the implementation of Articles 59 to 63 as regards the following:

(a)
typology of serious incidents and field safety
corrective actions in relation to specific devices, or categories or groups of
devices;

(b)
harmonised forms for the reporting of serious
incidents and field safety corrective actions, periodic summary reports and
trend reports by manufacturers as referred to in Articles 59 and 62;

(c)
timelines for the reporting of serious incidents
and field safety corrective actions, periodic summary reports and trend reports
by manufacturers, taking into account the severity of the event to be reported
as referred to in Articles 59 and 62;

(d)
harmonised forms for the exchange of information
between competent authorities as referred to in Article 61.

Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 84(3).

Section 2 —
Market surveillance

Article 65

Market
surveillance activities

1.
The competent authorities shall perform
appropriate checks on the characteristics and performance of devices including,
where appropriate, review of documentation and physical or laboratory checks on
the basis of adequate samples. They shall take account of established
principles regarding risk assessment and risk management, vigilance data and
complaints. The competent authorities may require economic operators to make
available the documentation and information necessary for the purpose of
carrying out their activities, and, where necessary and justified, enter the
premises of economic operators and take the necessary samples of devices. They
may destroy or otherwise render inoperable devices presenting a serious risk
where they deem it necessary.

2.
The Member States shall periodically review and
assess the functioning of their surveillance activities. Such reviews and
assessments shall be carried out at least every four years and the results
thereof shall be communicated to the other Member States and the Commission.
The Member State concerned shall make a summary of the results accessible to
the public.

3.
The competent authorities of the Member States
shall coordinate their market surveillance activities, cooperate with each
other and share with each other and with the Commission the results thereof.
Where appropriate, the competent authorities of the Member States shall agree
on work-sharing and specialisation.

4.
Where more than one authority in a Member State is responsible for market surveillance and external border controls, those
authorities shall cooperate with each other, by sharing information relevant to
their role and functions.

5.
The competent authorities of the Member States
shall cooperate with the competent authorities of third countries with a view
to exchanging information and technical support and promoting activities
relating to market surveillance.

Article 66

Electronic
system on market surveillance

1.
The Commission, in collaboration with the Member
States, shall set up and manage an electronic system to collate and process the
following information:

(a)
information in relation to non-compliant devices
presenting a risk to health and safety referred to in Article 68(2), (4) and
(6);

(b)
information in relation to compliant devices
presenting a risk to health and safety referred to in Article 70(2);

(c)
information in relation to formal non-compliance
of products referred to in Article 71(2);

(d)
information in relation to preventive health
protection measures referred to in Article 72(2).

2.
The information mentioned in paragraph 1 shall
be immediately transmitted through the electronic system to all competent
authorities concerned and be accessible to the Member States and to the
Commission.

Article 67

Evaluation
regarding devices presenting a risk to health and safety at national level

Where the competent authorities of a Member
State, based on vigilance data or other information, have sufficient reason to
believe that a device presents a risk to the health or safety of patients,
users or other persons, they shall carry out an evaluation in relation to the
device concerned covering all the requirements laid down in this Regulation
that are relevant to the risk presented by the device. The relevant economic
operators shall cooperate as necessary with the competent authorities.

Article 68

Procedure for
dealing with non-compliant devices presenting a risk to health and safety

1.
Where, having performed an evaluation pursuant
to Article 67, the competent authorities find that the device, which presents a
risk to the health or safety of patients, users or other persons, does not
comply with the requirements laid down in this Regulation, they shall without
delay require the relevant economic operator to take all appropriate and duly
justified corrective action to bring the device into compliance with those
requirements, to prohibit or restrict the making available of the device on the
market, to subject the making available of the device
to specific requirements, to withdraw the device from
the market, or to recall it within a reasonable period, proportionate to the
nature of the risk.

2.
Where the competent authorities consider that non-compliance
is not restricted to their national territory, they shall inform the Commission
and the other Member States of the results of the evaluation and of the actions
which they have required the economic operators to take, by means of the
electronic system referred to in Article 66.

3.
The economic operators shall ensure that all
appropriate corrective action is taken in respect of all the devices concerned
that they have made available on the market throughout the Union.

4.
Where the relevant economic operator does not
take adequate corrective action within the period referred to in paragraph 1,
the competent authorities shall take all appropriate provisional measures to
prohibit or restrict the device's being made available on their national
market, to withdraw the device from that market or to recall it.

They shall notify the Commission and the other
Member States, without delay, of those measures, by means of the electronic
system referred to in Article 66.

5.
The notification referred to in paragraph 4 shall
include all available details, in particular the data necessary for the
identification of the non-compliant device, the origin of the device, the
nature of and the reasons for the non-compliance alleged and the risk involved,
the nature and duration of the national measures taken and the arguments put
forward by the relevant economic operator.

6.
Member States other than the Member State initiating the procedure shall without delay inform the Commission and the other Member States of any additional information at their disposal relating to the
non-compliance of the device concerned and of any
measures adopted by them in relation to the device concerned. In the event of disagreement with the notified national measure,
they shall without delay inform the Commission and the other Member States of
their objections, by means of the electronic system referred to in Article 66.

7.
Where, within two months of receipt of the
notification referred to in paragraph 4, no objection has been raised by either
a Member State or the Commission in respect of a provisional measure taken by a
Member State, that measure shall be deemed justified.

8.
All Member States shall ensure that appropriate
restrictive measures are taken without delay in respect of the device
concerned.

Article 69

Procedure at
Union level

1.
Where, within two months of receipt of the
notification referred to in Article 68(4), objections are raised by a Member
State against a provisional measure taken by another Member State, or where the
Commission considers the measure to be contrary to Union legislation, the
Commission shall evaluate the national measure. On the basis of the results of
that evaluation, the Commission shall decide, by means of implementing acts,
whether or not the national measure is justified. Those implementing acts shall
be adopted in accordance with the examination procedure referred to in Article
84(3).

2.
If the national measure is considered justified,
Article 68(8) shall apply. If the national measure is considered unjustified,
the Member State concerned shall withdraw the measure. Where, in the situations
referred to in Articles 68 and 70, a Member State or the Commission consider
that the risk to health and safety emanating from a device cannot be contained
satisfactorily by means of measures taken by the Member State(s) concerned, the
Commission, at the request of a Member State or on its own initiative, may
take, by means of implementing acts, the necessary and duly justified measures
to ensure the protection of health and safety, including measures restricting
or prohibiting the placing on the market and putting into service of the device
concerned. Those implementing acts shall be adopted in accordance with the
examination procedure referred to in Article 84(3).

3.
On duly justified imperative grounds of urgency
relating to the health and safety of humans, the Commission shall adopt
immediately applicable implementing acts referred to in paragraphs 1 and 2 in
accordance with the procedure referred to in Article 84(4).

Article 70

Procedure for dealing
with compliant devices presenting a risk to health and safety

1.
Where, having performed an evaluation pursuant
to Article 67, a Member State finds that although a device has been legally
placed on the market or put into service, it presents a risk to the health or
safety of patients, users or other persons or to other aspects of the
protection of public health, it shall require the relevant economic operator or
operators to take all appropriate provisional measures to ensure that the
device concerned, when placed on the market or put into
service, no longer presents that risk, to withdraw the
device from the market or to recall it within a reasonable period,
proportionate to the nature of the risk.

2.
The Member State shall immediately notify the
Commission and the other Member States of the measures taken, by means of the
electronic system referred to in Article 66. That information shall include the
data necessary for the identification of the device concerned, the origin and
the supply chain of the device, the findings of the Member State's evaluation specifying the nature of the risk
involved and the nature and duration of the national measures taken.

3.
The Commission shall evaluate the provisional
national measures taken. On the basis of the results of that evaluation, the
Commission shall decide, by means of implementing acts, whether or not the
measure is justified. Those implementing acts shall be adopted in accordance
with the examination procedure referred to in Article 84(3). On duly justified
imperative grounds of urgency relating to the health and safety of humans, the
Commission shall adopt immediately applicable implementing acts in accordance
with the procedure referred to in Article 84(4).

4.
Where the national measure is considered
justified, Article 68(8) shall apply. If the national measure is considered
unjustified, the Member State concerned shall withdraw the measure.

Article 71

Formal
non-compliance

1.
Without prejudice to Article 68, a Member State shall require the relevant economic operator to put an end to the
non-compliance concerned within a reasonable period that is proportionate to
the non-compliance where it makes one of the following
findings:

(a)
that the CE marking has been affixed in
violation of the formal requirements laid down in Article 16;

(b)
that the CE marking has not been affixed to a
device contrary to Article 16;

(c)
that the CE marking has been inappropriately
affixed in accordance with procedures in this Regulation on a product that is
not covered by this Regulation;

(d)
that the EU declaration of conformity has not
been drawn up or is not complete;

(e)
that the information to be supplied by the
manufacturer on the label or in the instructions for use is not available, not
complete, or not provided in the language(s) required;

(f)
that the technical documentation, including the
clinical evaluation, is not available or not complete.

2.
Where the economic
operator does not put an end to the non-compliance within the period referred
to in paragraph 1, the Member State concerned shall
take all appropriate measures to restrict or prohibit the product being made
available on the market or to ensure that it is recalled or withdrawn from the
market. That Member State shall inform the Commission and the other Member
States without delay of those measures, by means of the electronic system
referred to in Article 66.

Article 72

Preventive
health protection measures

1.
Where a Member State, after having performed an
evaluation which indicates a potential risk related to a device or a specific
category or group of devices considers that the making available on the market
or putting into service of such device or specific category or group of devices
should be prohibited, restricted or made subject to particular requirements or
that such device or, category or group of devices should be withdrawn from the
market or recalled in order to protect the health and safety of patients, users
or other persons or other aspects of public health, it may take any necessary
and justified provisional measures.

2.
The Member State shall immediately notify the
Commission and all other Member States, giving the reasons for its decision, by
means of the electronic system referred to in Article 66.

3.
The Commission shall
assess the provisional national measures taken. The Commission shall decide, by means of implementing acts,
whether the national measures are justified or not.
Those implementing acts shall be adopted in accordance with the examination
procedure referred to in Article 84(3).

On duly justified imperative grounds of urgency
relating to the health and safety of humans, the Commission may adopt
immediately applicable implementing acts in accordance with the procedure
referred to in Article 84(4).

4.
Where the assessment referred to in paragraph 3
demonstrates that the making available on the market or putting into service of
a device, specific category or group of devices should be prohibited,
restricted or made subject to particular requirements or that such device or
category or group of devices should be withdrawn from the market or recalled in
all Member States in order to protect the health and safety of patients, users or other persons or other
aspects of public health, the Commission shall be empowered to adopt delegated
acts in accordance with Article 85 to take the necessary and duly justified
measures.

Where in this case imperative grounds of
urgency so require, the procedure provided for in Article 86 shall apply to
delegated acts adopted pursuant to this paragraph.

Article 73

Good
administrative practice

1.
Any measure adopted by the competent authorities
of the Member States pursuant to Articles 68 to 72 shall state the exact
grounds on which it is based. Where it is addressed to a specific economic
operator, it shall be notified without delay to the economic operator concerned,
who shall at the same time be informed of the remedies available to him under
the law of the Member State concerned and of the time limits to which such
remedies are subject. Where the measure is of general scope, it shall be
appropriately published.

2.
Except in cases where immediate action is
necessary for reasons of serious risk to human health or safety, the economic
operator concerned shall be given the opportunity to make
submissions to the competent authority within an
appropriate period of time before any measure is adopted. If action has been
taken without the economic operator's being heard, he shall be given the
opportunity to make submissions as soon as possible and the action taken shall
be reviewed promptly thereafter.

3.
Any measure adopted shall be immediately
withdrawn or amended upon the economic operator's demonstrating that he has
taken effective corrective action.

4.
Where a measure adopted pursuant to Articles 68
to 72 concerns a product for which a notified body has been involved in the
conformity assessment, the competent authorities shall inform the relevant
notified body of the measure taken.

Chapter VIII

Cooperation between Member States, Medical Device Coordination
Group, EU reference laboratories, device registers

Article 74

Competent authorities

1.
The Member States shall designate the competent
authority or authorities responsible for the implementation of this Regulation.
They shall entrust their authorities with the powers, resources, equipment and
knowledge necessary for the proper performance of their tasks pursuant to this
Regulation. The Member States shall communicate the competent authorities to
the Commission which shall publish a list of competent authorities.

2.
For the implementation of Articles 48 to 58, the
Member States may designate a national contact point other than a national
authority. In this case, references to a competent authority in this Regulation
shall be understood as including the national contact point.

Article 75

Cooperation

1.
The competent authorities of the Member States
shall cooperate with each other and with the Commission and exchange with each
other the information necessary to enable this Regulation to be applied
uniformly.

2.
Member States and the Commission shall participate in initiatives developed at
international level with the aim of ensuring cooperation between regulatory
authorities in the field of medical devices.

Article 76

Medical Device
Coordination Group

The Medical Device Coordination Group
(MDCG) established in accordance with the conditions and modalities defined in
Article 78 of Regulation (EU) [Ref. of future Regulation on medical devices]
shall carry out, with the support of the Commission as provided in Article 79
of that Regulation, the tasks assigned to it by this Regulation.

Article 77

Tasks of the
MDCG

The MDCG shall have the following tasks:

(a)
to contribute to the assessment of applicant
conformity assessment bodies and notified bodies pursuant to the provisions set
out in Chapter IV;

(b)
to contribute to the scrutiny of certain
conformity assessments pursuant to Article 42;

(c)
to contribute to the development of guidance
aimed at ensuring effective and harmonised implementation of this Regulation,
in particular regarding the designation and monitoring of notified bodies,
application of the general safety and performance requirements and conduct of
the clinical evaluation by manufacturers and the assessment by notified bodies;

(d)
to assist the competent authorities of the
Member States in their coordination activities in the fields of clinical
performance studies, vigilance and market surveillance;

(e)
to provide advice and assist the Commission, at
its request, in its assessment of any issue related to the implementation of
this Regulation;

(f)
to contribute to harmonised administrative
practice with regard to in vitro diagnostic medical devices in the
Member States.

Article 78

European Union
reference laboratories

1.
For specific devices, or a category or group of
devices, or for specific hazards related to a category or group of devices, the
Commission may designate, by means of implementing acts, one or more European
Union reference laboratories, hereinafter referred to as 'EU reference
laboratories', that satisfy the criteria set out in paragraph 3. The Commission
shall only designate laboratories for which a Member State or the Commission's
Joint Research Centre have submitted an application for designation.

2.
Within the scope of their designation, the EU
reference laboratories shall, where appropriate, have the following tasks:

(a)
to verify compliance of class D devices with the
applicable CTS, when available, or with other solutions chosen by the
manufacturer to ensure a level of safety and performance that is at least
equivalent, as provided for in the second subparagraph of Article 40(2);

(b)
to carry out appropriate tests on samples of
manufactured class D devices or batches of class D devices, as provided for in
the Section 5.7 of Annex VIII and in Section 5.1 of Annex X;

(c)
to provide scientific and technical assistance
to the Commission, the Member States and notified bodies in relation to the
implementation of this Regulation;

(d)
to provide scientific advice regarding the state
of the art in relation to specific devices, or a category or group of devices;

(e)
to set up and manage a network of national
reference laboratories and publish a list of the participating national
reference laboratories and their respective tasks;

(f)
to contribute to the development of appropriate
testing and analysis methods to be applied for conformity assessment procedures
and market surveillance;

(g)
to collaborate with notified bodies in the
development of best practices for the performance of conformity assessment
procedures;

(h)
to provide recommendations on suitable reference
materials and reference measurement procedures of higher metrological order;

(i)
to contribute to the development of standards at
international level;

(j)
to provide scientific opinions in response to
consultations by notified bodies in accordance with this Regulation.

3.
EU reference laboratories shall satisfy the
following criteria:

(a)
to have appropriately qualified staff with
adequate knowledge and experience in the field of the in vitro
diagnostic medical devices for which they are designated;

(b)
to possess the necessary equipment and reference
material to carry out the tasks assigned to them;

(c)
to have the necessary knowledge of international
standards and best practices;

(d)
to have an appropriate administrative
organisation and structure;

(e)
to ensure that their staff observe the
confidentiality of the information and data obtained in carrying out their
tasks;

(f)
to act in the public interest and in an
independent manner;

(g)
to ensure that their staff do not have financial
or other interests in the in vitro diagnostic medical device industry
which could affect their impartiality, declare any other direct and indirect
interests they may have in the in vitro diagnostic medical device
industry and update this declaration whenever a relevant change occurs.

4.
EU reference laboratories may be granted a Union
financial contribution.

The Commission may adopt, by means of
implementing acts, the modalities and the amount of the grant of a Union
financial contribution to EU reference
laboratories, taking into account the objectives of protection of health and
safety, support of innovation and cost-effectiveness. Those implementing acts
shall be adopted in accordance with the examination procedure referred to in
Article 84(3).

5.
Where notified bodies or Member States request
scientific or technical assistance or a scientific opinion from an EU reference
laboratory, they may be required to pay fees to wholly or partially cover the
costs incurred by that laboratory in carrying out the requested task according
to a set of predetermined and transparent terms and conditions.

6.
The Commission shall be empowered to adopt
delegated acts in accordance with Article 85 for the following purposes:

(a)
amending or supplementing the tasks of EU
reference laboratories referred to in paragraph 2 and the criteria to be
satisfied by EU reference laboratories referred to in paragraph 3.

(b)
setting out the structure and the level of the
fees referred to in paragraph 5 which may be levied by an EU reference
laboratory for providing scientific opinions in response to consultations by
notified bodies in accordance with this Regulation, taking into account the
objectives of protection of human health and safety, support of innovation and
cost-effectiveness.

7.
EU reference laboratories shall be subject to
controls, including on-site visits and audits, by the Commission to verify
compliance with the requirements of this Regulation. If these controls find
that a laboratory is not complying with those requirements for which they have
been designated, the Commission, by means of implementing acts, shall take
appropriate measures, including the withdrawal of the designation.

Article 79

Device
registers

The Commission and the Member States shall take all appropriate measures to encourage the establishment of registers
for specific types of devices to gather post-market experience related to the
use of such devices. Such registers shall contribute to the independent
evaluation of the long-term safety and performance of devices.

Chapter IX

Confidentiality, data protection, funding, penalties

Article 80

Confidentiality

1.
Unless otherwise provided in this Regulation and
without prejudice to existing national provisions and practices in the Member
States on medical confidentiality, all parties involved in the application of
this Regulation shall respect the confidentiality of information and data
obtained in carrying out their tasks in order to protect the following:

(a)
personal data in compliance with Directive
95/46/EC and Regulation (EC) No 45/2001;

(b)
commercial interests of a natural or legal
person, including intellectual property rights;

(c)
the effective implementation of this Regulation,
in particular for the purpose of inspections, investigations or audits.

2.
Without prejudice to paragraph 1, information
exchanged between competent authorities and between competent authorities and
the Commission on condition of confidentiality shall remain confidential unless
the originating authority has agreed to its disclosure.

3.
Paragraphs 1 and 2 shall not affect the rights
and obligations of the Commission, Member States and notified bodies with
regard to exchange of information and the dissemination of warnings, nor the
obligations of the persons concerned to provide information under criminal law.

4.
The Commission and Member States may exchange
confidential information with regulatory authorities of third countries with
which they have concluded bilateral or multilateral confidentiality
arrangements.

Article 81

Data protection

1.
Member States shall apply Directive 95/46/EC to
the processing of personal data carried out in the
Member States pursuant to this Regulation.

2.
Regulation (EC) No 45/2001 shall apply to the
processing of personal data carried out by the Commission pursuant to this
Regulation.

Article 82

Levy of fees

This Regulation shall be without prejudice
to the possibility for Member States to levy fees for the activities set out in
this Regulation, provided that the level of the fees is set in a transparent
manner and on the basis of cost recovery principles. They shall inform the
Commission and the other Member States at least three months before the
structure and level of fees is to be adopted.

Article 83

Penalties

The Member States shall lay down the
provisions on penalties applicable for infringement of the provisions of this
Regulation and shall take all measures necessary to ensure that they are
implemented. The penalties provided for shall be effective, proportionate, and
dissuasive. The Member States shall notify those provisions to the Commission
by [3 months prior to the date of application of this Regulation] and shall
notify it without delay of any subsequent amendment affecting them.

Chapter X

Final provisions

Article 84

Committee
procedure

1.
The Commission shall be assisted by the
Committee on Medical Devices set up by Article 88 of Regulation (EU) [Ref. of
future Regulation on medical devices].

2.
Where reference is made to this paragraph,
Article 4 of Regulation (EU) No 182/2011 shall apply.

3.
Where reference is made to this paragraph,
Article 5 of Regulation (EU) No 182/2011 shall apply.

4.
Where reference is made to this paragraph,
Article 8 of Regulation (EU) No 182/2011, in conjunction with Article 4 or
Article 5, as appropriate, shall apply.

Article 85

Exercise of the
delegation

1.
The power to adopt the delegated acts referred
to in Articles 4(6), 8(2), 15(4), 22(7), 23(7), 27(2), 38(2), 39(4), 40(10),
43(5), 49(7), 51(3), 72(4) and 78(6) is conferred on the Commission subject to
the conditions laid down in this Article.

2.
The delegation of power referred to in Articles
4(6), 8(2), 15(4), 22(7), 23(7), 27(2), 38(2), 39(4), 40(10), 43(5), 49(7),
51(3), 72(4) and 78(6) shall be conferred on the Commission for an
indeterminate period of time from the date of entry into force of this
Regulation.

3.
The delegation of power referred to in Articles
4(6), 8(2), 15(4), 22(7), 23(7), 27(2), 38(2), 39(4), 40(10), 43(5), 49(7),
51(3), 72(4) and 78(6) may be revoked at any time by the European Parliament or
by the Council. A decision of revocation shall put an end to the delegation of
the power specified in that decision. It shall take effect the day following
its publication in the Official Journal of the European Union or at a
later date specified therein. It shall not affect the validity of any delegated
acts already in force.

4.
As soon as it adopts a delegated act, the
Commission shall notify it simultaneously to the European Parliament and to the
Council.

5.
A delegated act adopted pursuant to any of the
Articles listed in paragraph 1 shall enter into force only if no objection has
been expressed either by the European Parliament or by the Council within a
period of two months of notification of that act to the European Parliament and
the Council or if, before the expiry of that period, the European Parliament
and the Council have both informed the Commission that they will not object.
That period may be extended by two months at the initiative of the European
Parliament or the Council.

Article 86

Urgency
procedure for delegated acts

1.
Delegated acts adopted under this Article shall
enter into force without delay and shall apply as long as no objection is
expressed in accordance with paragraph 2. The notification of a delegated act
to the European Parliament and to the Council shall state the reasons for the
use of the urgency procedure.

2.
Either the European Parliament or the Council
may object to a delegated act in accordance with the procedure referred to in
Article 85. In such a case, the Commission shall repeal the act without delay
following the notification of the decision to object by the European Parliament
or the Council.

Article 87

Transitional
provisions

1.
From the date of application of this Regulation any
publication of a notification in respect of a notified body in accordance with
Directive 98/79/EC shall become void.

2.
Certificates issued by notified bodies in
accordance with Directive 98/79/EC prior to the entry into force of this
Regulation shall remain valid until the end of the period indicated on the
certificate, except for certificates issued in accordance with Annex VI of
Directive 98/79/EC which shall become void at the latest two years after the
date of application of this Regulation.

Certificates issued by notified bodies in
accordance with Directive 98/79/EC after the entry into force of this
Regulation shall become void at the latest two years after the date of
application of this Regulation.

3.
By way of derogation from Directive 98/79/EC, devices
which comply with this Regulation may be placed on the market before its date
of application.

4.
By way of derogation from Directive 98/79/EC,
conformity assessment bodies which comply with this Regulation may be
designated and notified before its date of application. Notified bodies which
are designated and notified in accordance with this Regulation may apply the
conformity assessment procedures laid down in this Regulation and issue
certificates in accordance with this Regulation before its date of application.

5.
By way of derogation from Article 10 and points
(a) and (b) of Article 12(1) of Directive 98/79/EC, manufacturers, authorised representatives, importers and notified
bodies who, during the period from [date of application] until [18 months after
date of application], comply with Article 23(2) and (3) and Article 43(4) of
this Regulation shall be considered to comply with the laws and regulations
adopted by Member States in accordance with Article 10 and points (a) and (b)
of Article 12(1) of Directive 98/79/EC as specified in Commission Decision 2010/227/EU.

6.
Authorisations granted by competent authorities
of the Member States in accordance with Article 9(12) of Directive 98/79/EC
shall keep the validity indicated in the authorisation.

Article 88

Evaluation

No later than five years after the date of
application, the Commission shall assess the application of this Regulation and
establish an evaluation report on the progress towards achievement of the
objectives of this Regulation including an assessment of resources required to
implement this Regulation.

Article 89

Repeal

Directive 98/79/EC of the European
Parliament and of the Council is repealed with effect from [date of application
of this Regulation] with the exception of Article 10
and points (a) and (b) of Article 12(1) of Directive 98/79/EC
which are repealed with effect from [18 months after date of application].

References to the repealed Directive shall
be understood as reference to this Regulation and shall be read in accordance
with the correlation table laid down in Annex XIV.

Article 90

Entry into
force and date of application

1.
This Regulation shall enter into force on the
twentieth day after its publication in the Official Journal of the
European Union.

2.
It shall apply from [five years after entry into
force].

3.
By way of derogation from paragraph 2, the
following shall apply:

(a)
Article 23(2) and (3) and Article 43(4) shall
apply from [18 months after date of application referred to in paragraph 2];

(b)
Articles 26 to 38 shall apply from [six months
after entry into force]. However, prior to [date of application as referred to
in paragraph 2], the obligations on notified bodies emanating from the
provisions in Articles 26 to 38 shall apply only to those bodies which submit
an application for notification in accordance with Article 29 of this
Regulation.

This Regulation shall be binding in its
entirety and directly applicable in all Member States.

Done at Brussels, 26.9.2012

For the European Parliament                       For
the Council

The President                                                 The
President

ANNEXES

I             General safety and performance
requirements

II            Technical documentation

III           EU Declaration of conformity

IV          CE marking of conformity

V            Information to be submitted with
the registration of devices and economic operators in accordance with Article
23 and data elements of the UDI device identifier in accordance with Article 22

VI          Minimum requirements to be met by
Notified Bodies

VII         Classification criteria

VIII        Conformity assessment based on
full quality assurance and design examination

IX          Conformity assessment based on
type examination

X            Conformity assessment based on
production quality assurance

XI          Minimum content of certificates
issued by a notified body

XII         Clinical evidence and post-market
follow-up

XIII        Interventional clinical performance
studies and other clinical performance studies involving risks for the subjects
of the studies

XIV        Correlation table

ANNEX I

GENERAL SAFETY AND PERFORMANCE REQUIREMENTS

I. General requirements

1.
The devices shall achieve the performance
intended by the manufacturer and be designed and manufactured in such a way
that, during normal conditions of use, they are suitable for their intended
purpose, taking into account the generally acknowledged state of the art. They
shall not compromise, directly or indirectly, the clinical condition or the
safety of the patients, or the safety or health of users or, where applicable,
other persons, provided that any risks or limits to performance which may be
associated with their use constitute acceptable risks when weighed against the
benefits to the patient and are compatible with a high level of protection of
health and safety.

This shall include:

–
reducing as far as possible the risk of error
due to ergonomic features of the device and the environment in which the device
is intended to be used (design for patient safety), and

–
consideration of the technical knowledge,
experience, education or training, and the medical and physical conditions of
intended users (design for lay, professional, disabled or other users).

2.
The solutions adopted by the manufacturer for
the design and manufacture of the devices shall conform to safety principles,
taking account of the generally acknowledged state of the art. To reduce risks,
the manufacturer shall manage the risks so that the residual risk associated
with each hazard as well as the overall residual risk is judged acceptable. The
manufacturer shall apply the following principles in the priority order listed:

(a)
identify known or foreseeable hazards and
estimate the associated risks arising from the intended use and foreseeable
misuse;

(b)
eliminate risks as far as possible through
inherently safe design and manufacture;

(c)
reduce as far as possible the remaining risks by
taking adequate protection measures, including alarms; and

(d)
provide training to users and/or inform users of
any residual risks.

3.
The characteristics and performances of the
device shall not be adversely affected to such a degree that the health or
safety of the patient or the user and, where applicable, of other persons are
compromised during the lifetime of the device, as indicated by the
manufacturer, when the device is subjected to the stresses which can occur
during normal conditions of use and has been properly maintained in accordance
with the manufacturer’s instructions. When no lifetime is stated, the same
applies for the lifetime reasonably to be expected of a device of that kind,
having regard to the intended purpose and the anticipated use of the device.

4.
The devices shall be designed, manufactured and
packaged in such a way that their characteristics and performance during their
intended use will not be adversely affected by transport and storage conditions
(for example, fluctuations of temperature and humidity) taking account of the
instructions and information provided by the manufacturer.

5.
All known and foreseeable risks, and any
undesirable effects, shall be minimised and be acceptable when weighed against
the benefits to the patients of the intended performance of the device during
normal conditions of use.

II. Requirements regarding design and construction

6.
Performance characteristics

6.1.
The devices shall be designed and manufactured
in such a way that the performance characteristics support the intended
purpose, based on appropriate scientific and technical methods. They shall
achieve the performances, as stated by the manufacturer and in particular,
where appropriate:

(a)
the analytical performance, such as accuracy
(trueness and precision), bias, analytical sensitivity, analytical specificity,
limits of detection and quantitation, measuring range, linearity, cut-off,
repeatability, reproducibility, including determination of appropriate criteria
for specimen collection and handling and control of known relevant endogenous
and exogenous interference, cross-reactions; and

(b)
the clinical performance, such as diagnostic
sensitivity, diagnostic specificity, positive and negative predictive value,
likelihood ratio, expected values in normal or affected populations.

6.2.
The performance characteristics of the device
need to be maintained during the lifetime of the device as indicated by the
manufacturer.

6.3.
Where the performance of devices depends on the
use of calibrators and/or control materials, the metrological traceability of
values assigned for a given analyte to such calibrators and/or control
materials shall be assured through available and suitable reference measurement
procedures and/or available and suitable reference materials of a higher
metrological order. The device shall be designed and manufactured to enable the
user to provide measurement results in patient specimens metrologically
traceable to available and suitable higher order reference materials and/or
reference measurement procedures following the instructions and information
provided by the manufacturer.

7.
Chemical, physical and biological
properties

7.1.
The devices shall be designed and manufactured
in such a way as to ensure the characteristics and performance referred to in
Chapter I 'General Requirements'.

Particular attention shall be paid to the
possibility of impairment of analytical performance due to incompatibility
between the materials used and the specimens and/or analyte to be detected
(such as biological tissues, cells, body fluids and micro-organisms), taking
account of the intended purpose of the device.

7.2.
The devices shall be designed, manufactured and
packaged in such a way as to minimise the risk posed by contaminants and
residues to patients, taking account of the intended purpose of the device, and
to the persons involved in the transport, storage and use of the devices.
Particular attention shall be paid to tissues exposed and to the duration and
frequency of exposure.

7.3.
The devices shall be designed and manufactured
in such a way as to reduce as far as possible the risks posed by substances
that may leach or leak from the device. Special attention shall be given to
substances which are carcinogenic, mutagenic or toxic to reproduction, in
accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the
European Parliament and of the Council of 16 December 2008 on classification,
labelling and packaging of substances and mixtures, amending and repealing
Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006[40], and to substances having endocrine disrupting properties for which there is
scientific evidence of probable serious effects to human health and which are
identified in accordance with the procedure set out in Article 59 of Regulation
(EC) No 1907/2006 of the European Parliament and of the Council of 18 December
2006 concerning the Registration, Evaluation, Authorisation and Restriction of
Chemicals (REACH)[41] .

7.4.
The devices shall be designed and manufactured
in such a way as to reduce as far as possible the risks posed by the
unintentional ingress or egress of substances into or from the device, taking
into account the device and the nature of the environment in which it is
intended to be used.

8.
Infection and microbial contamination

8.1.
The devices and their manufacturing processes
shall be designed in such a way as to eliminate or reduce as far as possible
the risk of infection to the user, professional or lay, or, where applicable,
other persons.

The design shall:

(a)
allow easy and safe handling;

and, where necessary

(b)
reduce as far as possible and appropriate any
microbial leakage from the device and/or microbial exposure during use;

(c)
prevent microbial contamination of the device or
specimen.

8.2.
The devices labelled either as sterile or as
having a special microbiological state shall be designed, manufactured and
packaged to ensure that they remain so when placed on the market, and remain so
under the transport and storage conditions specified by the manufacturer, until
the protective packaging is damaged or opened.

8.3.
The devices labelled either as sterile or as
having a special microbiological state shall have been processed, manufactured
and, if applicable, sterilised by appropriate validated methods.

8.4.
The devices intended to be sterilised shall be
manufactured in appropriately controlled (e.g. environmental) conditions.

8.5.
Packaging systems for non-sterile devices shall
maintain the integrity and cleanliness of the device indicated by the
manufacturer and, if the devices are to be sterilised prior to use, minimise
the risk of microbial contamination; the packaging system shall be suitable
taking account of the method of sterilisation indicated by the manufacturer.

8.6.
The labelling of the devices shall distinguish
between identical or similar products placed on the market in both sterile and
non‐sterile condition.

9.
Devices incorporating materials of biological
origin

9.1.
Where the devices include tissues, cells and
substances originating from animals, the processing, preservation, testing and
handling of tissues, cells and substances of such origin shall be carried out
so as to provide optimal safety for user, professional or lay, or other person.

In particular, safety with regard to viruses
and other transmissible agents shall be addressed by implementation of
validated methods of elimination or inactivation in the course of the
manufacturing process. This may not apply to certain devices if the activity of
the virus and other transmissible agent are integral to the intended purpose of
the device or when such elimination or inactivation process would compromise
the performance of the device.

9.2.
Where the devices include human tissues, cells
or substances, the selection of sources, donors and/or substances of human
origin, the processing, preservation, testing and handling of tissues, cells
and substances of such origin shall be carried out so as to provide optimal safety
for user, professional or lay, or other person.

In particular, safety with regard to viruses
and other transmissible agents shall be addressed by implementation of
validated methods of elimination or inactivation in the course of the
manufacturing process. This may not apply to certain devices if the activity of
the virus and other transmissible agent are integral to the intended purpose of
the device or when such elimination or inactivation process would compromise
the performance of the device.

9.3.
Where the devices include cells or substances of
microbial origin, the processing, preservation, testing and handling of cells
and substances shall be carried out so as to provide optimal safety for user,
professional or lay, or other person.

In particular, safety with regard to viruses
and other transmissible agents shall be addressed by implementation of
validated methods of elimination or inactivation in the course of the
manufacturing process. This may not apply to certain devices if the activity of
the virus and other transmissible agent are integral to the intended purpose of
the device or when such elimination or inactivation process would compromise
the performance of the device.

10.
Interaction of devices with their
environment

10.1.
If the device is intended for use in combination
with other devices or equipment, the whole combination, including the
connection system, shall be safe and shall not impair the specified
performances of the devices. Any restrictions on use applying to such
combinations shall be indicated on the label and/or in the instructions for
use. Connections which the user has to handle shall be designed and constructed
in such a way as to minimise all possible risks from incorrect connection.

10.2.
The devices shall be designed and manufactured
in such a way as to remove or reduce as far as possible and appropriate:

(a)
the risks of injury to user, professional or
lay, or other person in connection with their physical and ergonomic features;

(b)
the risks of use error due to the ergonomic
features, human factors and the environment in which the device is intended to
be used;

(c)
the risks connected with any foreseeable
external influences or environmental conditions, such as magnetic fields,
external electrical and electromagnetic effects, electrostatic discharge,
pressure, humidity, temperature variations or radio signal interferences;

(d)
the risks associated with the use of the device
when it comes into contact with materials, liquids, and substances, including
gases, to which it is exposed during normal conditions of use;

(e)
the risks associated with the possible negative
interaction between software and the environment within which it operates and
interacts;

(f)
the risks of accidental ingress of substances
into the device;

(g)
the risk of incorrect identification of specimens;

(h)
the risks of any foreseeable interference with
other devices.

10.3.
The devices shall be designed and manufactured
in such a way as to minimise the risks of fire or explosion during normal use
and in single fault condition. Particular attention shall be paid to devices
whose intended purpose includes exposure to or use in association with
flammable substances or substances which could cause combustion.

10.4.
The devices shall be designed and manufactured
in such a way that adjustment, calibration, and maintenance, where such is
necessary to achieve the performances intended, can be done safely.

10.5.
The devices that are intended to be operated
together with other devices or products shall be designed and manufactured in
such as way that the interoperability is reliable and safe.

10.6.
The devices shall be designed and manufactured
in such a way as to facilitate the safe disposal of the device and/or of any
waste substances by the user, professional or lay, or other person.

10.7.
The measuring, monitoring or display scale
(including colour change and other visual indicators) shall be designed and
manufactured in line with ergonomic principles, taking account of the intended
purpose of the device.

11.
Devices with a measuring function

11.1.
The devices having a primary analytical
measuring function shall be designed and manufactured in such a way as to
provide sufficient accuracy, precision and stability of measurement within
appropriate accuracy limits, taking into account the intended purpose of the
device and of available and appropriate reference measurement procedures and
materials. The accuracy limits shall be specified by the manufacturer.

11.2.
The measurements made by devices with a
measuring function and expressed in legal units shall conform to the provisions
of Council Directive 80/181/EEC[42].

12.
Protection against radiation

12.1.
The devices shall be designed, manufactured and
packaged in such a way that exposure of user, professional or lay, or other
persons to the emitted radiation (intended, unintended, stray or scattered) is
reduced as far as possible.

12.2.
When the devices are intended to emit
potentially hazardous, visible and/or invisible radiation, they shall as far as
possible be:

(a)
designed and manufactured in such a way as to
ensure that the characteristics and the quantity of radiation emitted can be
controlled and/or adjusted; and

(b)
fitted with visual displays and/or audible
warnings of such emissions.

12.3.
The operating instructions for devices emitting
radiation shall give detailed information as to the nature of the emitted
radiation, means of protecting the user, and on ways of avoiding misuse and of
eliminating the risks inherent in installation.

13.
Software incorporated in devices and
standalone software

13.1.
The devices that incorporate electronic
programmable systems, including software, or standalone software that are
devices in themselves, shall be designed to ensure repeatability, reliability
and performance according to the intended purpose. In the event of a single
fault condition, appropriate means shall be adopted to eliminate or reduce as
far as possible and appropriate consequent risks.

13.2.
For the devices that incorporate software or for
standalone software that are devices in themselves, the software shall be
developed and manufactured according to the state of the art taking into
account the principles of development life cycle, risk management, verification
and validation.

13.3.
Software referred to in this Section that are
intended to be used in combination with mobile computing platforms shall be
designed and manufactured taking into account the specific features of the
mobile platform (e.g. size and contrast ratio of the screen) and the external
factors related to their use (varying environment as regards to level of light
or noise).

14.
Devices connected to or equipped with an
energy source

14.1.
For the devices connected to or equipped with an
energy source, in the event of a single fault condition, appropriate means
shall be adopted to eliminate or reduce as far as possible and appropriate
consequent risks.

14.2.
The devices where the safety of the patient
depends on an internal power supply in the device shall be equipped with a
means of determining the state of the power supply.

14.3.
The devices shall be designed and manufactured
in such a way as to reduce as far as possible the risks of creating
electromagnetic interference which could impair the operation of this or other
devices or equipment in the intended environment.

14.4.
The devices shall be designed and manufactured
in such a way as to provide an adequate level of intrinsic immunity to
electromagnetic disturbance to enable them to operate as intended.

14.5.
The devices shall be designed and manufactured
in such a way as to avoid, as far as possible, the risk of accidental electric
shocks to the user, professional or lay, or other person both during normal use
of the device and in the event of a single fault condition in the device,
provided the device is installed and maintained as indicated by the
manufacturer.

15.
Protection against mechanical and thermal
risks

15.1.
The devices shall be designed and manufactured
in such a way as to protect the user, professional or lay, or other person
against mechanical risks.

15.2.
The devices shall be sufficiently stable under
the foreseen operating conditions. They shall be suitable to withstand stresses
inherent in the foreseen working environment, and to retain this resistance
during the expected lifetime of the devices, subject to any inspection and
maintenance requirements as indicated by the manufacturer.

15.3.
Where there are risks due to the presence of
moving parts, risks due to break-up or detachment, or leakage of substances,
then appropriate protection means shall be incorporated.

Any guards or other means included with the
device to provide protection, in particular against moving parts, shall be
secure and shall not interfere with access for the normal operation of the
device, or restrict routine maintenance of the device as intended by the
manufacturer.

15.4.
The devices shall be designed and manufactured
in such a way as to reduce to the lowest possible level the risks arising from
vibration generated by the devices, taking account of technical progress and of
the means available for limiting vibrations, particularly at source, unless the
vibrations are part of the specified performance.

15.5.
The devices shall be designed and manufactured
in such a way as to reduce to the lowest possible level the risks arising from
the noise emitted, taking account of technical progress and of the means
available to reduce noise, particularly at source, unless the noise emitted is
part of the specified performance.

15.6.
Terminals and connectors to the electricity, gas
or hydraulic and pneumatic energy supplies which the user, professional or lay,
or other person has to handle shall be designed and constructed in such a way
as to minimise all possible risks.

15.7.
Errors likely to be made when fitting or
refitting, or connecting or reconnecting, certain parts before or during use
which could be a source of risk must be made impossible by the design and
construction of such parts or, failing this, by information given on the parts
themselves and/or their housings.

The same information must be given on moving
parts and/or their housings where the direction of movement needs to be known
in order to avoid a risk.

15.8.
Accessible parts of the devices (excluding the
parts or areas intended to supply heat or reach given temperatures) and their
surroundings shall not attain potentially dangerous temperatures under normal
conditions of use.

16.
Protection against the risks posed by
devices intended by the manufacturer for self-testing or near-patient testing

16.1.
The devices intended for self-testing or
near-patient testing shall be designed and manufactured in such a way that they
perform appropriately for their intended purpose taking into account the skills
and the means available to the intended user and the influence resulting from
variation that can be reasonably anticipated in the intended user's technique
and environment. The information and instructions provided by the manufacturer
shall be easy for the intended user to understand and apply.

16.2.
The devices intended for self-testing or
near-patient testing shall be designed and manufactured in such a way as to

–
ensure that the device is easy to use by the
intended user at all stages of the procedure; and

–
reduce as far as possible the risk of error by
the intended user in the handling of the device and, if applicable, the
specimen, and also in the interpretation of the results.

16.3.
The devices intended for self-testing and
near-patient testing shall, where reasonably possible, include a procedure by
which the intended user can:

–
verify that, at the time of use, the device will
perform as intended by the manufacturer; and

–
be warned if the device has failed to provide a
valid result.

III. Requirements regarding information supplied with
the device

17.
Label and instructions for use

17.1.
General requirements regarding the
information supplied by the manufacturer

Each device shall be accompanied by the
information needed to identify the device and its manufacturer, and communicate
safety and performance related information to the user, professional or lay, or
other person, as appropriate. Such information may appear on the device itself,
on the packaging or in the instructions for use, taking into account the
following:

(i)           The medium, format, content,
legibility, and location of the label and instructions for use shall be
appropriate to the particular device, its intended purpose and the technical
knowledge, experience, education or training of the intended user(s). In
particular, instructions for use shall be written in terms readily understood
by the intended user and, where appropriate, supplemented with drawings and
diagrams. Some devices may include separate information for the professional
user and the lay person.

(ii)          The information required on the
label, shall be provided on the device itself. If this is not practicable or
appropriate, some or all of the information may appear on the packaging for
each unit, and/or on the packaging of multiple devices.

Where multiple devices are supplied to a single
user and/or location, a single copy of the instructions for use may be provided
if so agreed by the purchaser who in any case may request further copies to be
provided.

(iii)          In duly justified and
exceptional cases instructions for use may not be needed or may be abbreviated
if the device can be used safely and as intended by the manufacturer without
any such instructions for use.

(iv)         Labels shall be provided in a
human-readable format but may be supplemented by machine-readable forms, such
as radio-frequency identification (RFID) or bar codes.

(v)          When the device is intended for
professional use only , instructions for use may be provided to the user in
non-paper format (e.g. electronic), except when the device is intended for
near-patient testing.

(vi)         Residual risks which are required
to be communicated to the user and/or
other person shall be included as limitations, contraindications,
precautions or warnings in the information supplied by the manufacturer.

(vii)         Where appropriate, this
information should take the form of internationally recognised symbols. Any
symbol or identification colour used shall conform to the harmonised standards
or CTS. In areas for which no standards or CTS exist, the symbols and colours
shall be described in the documentation supplied with the device.

(viii)        In the case of devices
containing a substance or a mixture which may be considered as being dangerous,
taking account of the nature and quantity of its constituents and the form
under which they are present, relevant hazard pictograms and labelling
requirements of Regulation (EC) 1272/2008 shall apply. Where there is
insufficient space to put all the information on the device itself or on its
label, the relevant hazard pictograms shall be put on the label and the other
information required by that Regulation shall be given in the instructions for
use.

(ix)         The provisions of Regulation (EC)
1907/2006 on the safety data sheet shall apply, unless all relevant information
as appropriate is already made available by the instructions for use.

17.2.
Information on the label

The label shall bear the following particulars:

(i)           The name or trade name of the
device;

(ii)          The details strictly necessary
for the user to identify the device and, where it is not obvious for the user,
the intended purpose of the device;

(iii)          The name, registered trade name or registered trade mark of the
manufacturer and the address of his registered place of business at which he
can be contacted and his location be established;

(iv)         For imported devices, the name, registered trade name or registered
trade mark of the authorised representative established within the Union and
the address of his registered place of business at which he can be contacted and
his location be established;

(v)          An indication that the device is
for in vitro diagnostic use;

(vi)         The batch code/lot number or the
serial number of the device preceded by the word LOT or SERIAL NUMBER or an equivalent
symbol, as appropriate;

(vii)         Where applicable, the unique
device identification (UDI);

(viii)        An unambiguous indication of the
date until when the device may be used safely, without degradation of
performance, expressed at least as the year, the month and, where relevant, the
day, in that order;

(ix)         Where there is no indication of
the date until when it may be used safely, the year of manufacture. This year
of manufacture may be included as part of the batch or serial number, provided
the date is clearly identifiable;

(x)          Where
relevant, an indication of the net quantity of contents, expressed in terms of
weight or volume, numerical count, or any combination of these, or other terms
which accurately reflect the contents of the package;

(xi)         An indication of any special
storage and/or handling condition that applies;

(xii)         Where appropriate, an indication
of the sterile state of the device and the sterilisation method, or a statement
indicating any special microbiological state or state of cleanliness;

(xiii)        Warnings or precautions to be
taken that need to be brought to the immediate attention of the user, professional
or lay, or other person. This information may be kept to a minimum in which
case more detailed information shall appear in the instructions for use;

(xiv)        Where applicable, any particular
operating instructions;

(xv)        If the device is intended for single use, an indication of that
fact. A manufacturer's indication of single use shall be consistent across the Union;

(xvi)        If the device is intended for
self-testing or near-patient testing, an indication of that fact;

(xvii)       If the device is for performance
evaluation only, an indication of that fact;

(xviii)      Where device kits include
individual reagents and articles that may be made available as separate
devices, each of these devices shall comply with the labelling requirements
contained in this Section;

(xix)        Wherever reasonable and
practicable, the devices and separate components shall be identified, where
appropriate in terms of batches, to allow all appropriate action to detect any
potential risk posed by the devices and detachable components.

17.3.
Information in the instructions for use

17.3.1.
The instructions for use shall contain the
following particulars:

(i)           The name or trade name of the
device;

(ii)          The device’s intended purpose:

–
what is detected and/or measured;

–
its function (e.g. screening, monitoring,
diagnosis or aid to diagnosis);

–
the specific disorder, condition or risk factor
of interest that it is intended to detect, define or differentiate;

–
whether it is automated or not;

–
whether it is qualitative, semi-quantitative or
quantitative;

–
the type of specimen(s) required; and

–
where applicable, the testing population.

(iii)          An indication that the device
is for in vitro diagnostic use;

(iv)         The intended user, as appropriate
(e.g. healthcare professionals, lay person);

(v)          The test principle;

(vi)         A description of the reagents,
calibrators and controls and any limitation upon their use (e.g. suitable for a
dedicated instrument only);

(vii)         A list of materials provided and
a list of special materials required but not provided;

(viii)        For devices intended for use together
with other devices and/or general purpose equipment:

–
information to identify such devices or
equipment, in order to obtain a safe combination, and/or

–
information on any known restrictions to
combinations of devices and equipment.

(ix)         An indication of any special
storage (e.g. temperature, light, humidity, etc.) and/or handling conditions
which apply;

(x)          In-use stability which may
include the storage conditions, and shelf life following the first opening of
the primary container, together with the storage conditions and stability of
working solutions, where this is relevant;

(xi)         If the device is supplied as
sterile, an indication of its sterile state, the sterilisation method and
instructions in the event of the sterile packaging being damaged before use;

(xii)         Information that allows the user
to be informed of any warnings, precautions, measures to be taken and
limitations of use regarding the device. This information shall cover, where
appropriate:

–
warnings, precautions and/or measures to be taken
in the event of malfunction of the device or its degradation as suggested by
changes in its appearance that may affect performance;

–
warnings, precautions and/or measures to be
taken in regards to the exposure to reasonably foreseeable external influences
or environmental conditions, such as magnetic fields, external electrical and
electromagnetic effects, electrostatic discharge, radiation associated with
diagnostic or therapeutic procedures, pressure, humidity, or temperature;

–
warnings, precautions and/or measures to be
taken in regards to the risks of interference posed by the reasonably
foreseeable presence of the device during specific diagnostic investigations,
evaluations, therapeutic treatment or other procedures (e.g. electromagnetic
interference emitted by the device affecting other equipment);

–
precautions related to materials incorporated
into the device that are carcinogenic, mutagenic or toxic, or that have
endocrine disrupting properties or that could result in sensitisation or
allergic reaction of the patient or user;

–
if the device is intended for single use, an
indication of that fact. A manufacturer's indication of single use shall be
consistent across the Union;

–
if the device is reusable, information on the
appropriate processes to allow reuse, including cleaning, disinfection,
decontamination, packaging and, where appropriate, the validated method of
re-sterilization. Information shall be provided to identify when the device
should no longer be reused, e.g. signs of material degradation or the maximum
number of allowable reuses.

(xiii)        Any warnings and/or precautions
related to potentially infectious material that is included in the device;

(xiv)        Where relevant, requirements for
special facilities (e.g. clean room environment) or special training (e.g.
radiation safety), or particular qualifications of the device intended user;

(xv)        Conditions for collection,
handling, and preparation of the specimen;

(xvi)        Details of any preparatory
treatment or handling of the device before it is ready for use (e.g.
sterilisation, final assembly, calibration, etc.);

(xvii)       The information needed to verify
whether the device is properly installed and is ready to perform safely and as
intended by the manufacturer, together with, where relevant:

–
details of the nature, and frequency, of
preventative and regular maintenance, including cleaning and disinfection;

–
identification of any consumable components and
how to replace them;

–
information on any necessary calibration to
ensure that the device operates properly and safely during its intended lifetime;

–
methods of mitigating the risks encountered by
persons involved in installing, calibrating or servicing devices.

(xviii)      Where relevant, recommendations
for quality control procedures;

(xix)        The metrological traceability of
values assigned to calibrators and trueness-control materials, including
identification of applicable reference materials and/or reference measurement
procedures of higher order;

(xx)        Assay procedure including
calculations and interpretation of results and where relevant if any
confirmatory testing shall be considered;

(xxi)        Analytical performance
characteristics, such as sensitivity, specificity, and accuracy, repeatability,
reproducibility, limits of detection and measurement range, including
information needed for the control of known relevant interferences, limitations
of the method and information about the use of available reference measurement
procedures and materials by the user;

(xxii)       Where relevant, clinical
performance characteristics, such as diagnostic sensitivity and diagnostic
specificity;

(xxiii)      Where relevant, reference
intervals;

(xxiv)      Information on interfering
substances or limitations (e.g. visual evidence of hyperlipidaemia or
haemolysis, age of specimen) that may affect the performance of the device;

(xxv)       Warnings or precautions to be
taken in order to facilitate the safe disposal of the device, its accessories,
and the consumables used with it, if any. This information shall cover, where
appropriate:

–
infection or microbial hazards (e.g. consumables
contaminated with potentially infectious substances of human origin);

–
environmental hazards (e.g. batteries or
materials that emit potentially hazardous levels of radiation);

–
physical hazards (e.g. explosion).

(xxvi)      The name, registered trade name or
registered trade mark of the manufacturer and the address of his registered
place of business at which he can be contacted and his location be established,
together with a telephone number and/or fax number and/or website address to
obtain technical assistance;

(xxvii)     Date of issue of the instructions
for use or, if they have been revised, date of issue and identifier of the
latest revision of the instructions for use;

(xxviii)    A notice to the user, professional
or lay, that any serious incident that has occurred in relation to the device
should be reported to the manufacturer and the competent authority of the
Member State where the user and/or patient is established;

(xxix) Where device kits include individual
reagents and articles that may be made available as separate devices, each of
these devices shall comply with the instructions for use requirements contained
in this Section.

17.3.2.
In addition, the instructions for use for
devices intended for self-testing or near-patient testing shall comply with the
following principles:

(i)           Details of the test procedure
shall be given, including any reagent preparation, specimen collection and/or
preparation and information on how to run the test and read the results;

(ii)          The results need to be expressed
and presented in a way that is readily understood by the intended user;

(iii)          Information needs to be
provided with advice to the user on action to be taken (in case of positive,
negative or indeterminate result), on the test limitations and on the
possibility of false positive or false negative result. Information shall also
be provided as to any factors that can affect the test result (e.g. age,
gender, menstruation, infection, exercise, fasting, diet or medication);

(iv)         for devices intended for
self-testing, the information provided shall include a statement clearly
directing that the user should not take any decision of medical relevance
without first consulting the appropriate healthcare professional;

(v)          for devices intended for self-testing
used for the monitoring of an existing disease, the information shall specify
that the patient should only adapt the treatment if he has received the
appropriate training to do so.

ANNEX II

TECHNICAL DOCUMENTATION

The technical documentation and, if
applicable, the summary technical documentation (STED) to be drawn up by the
manufacturer shall include in particular the following elements:

1.
Device description and specification, including
variants and accessories
1.1.
Device description and specification

(a)
product or trade name and a general description
of the device, including its intended purpose;

(b)
the UDI device identifier as referred to in item
(i) of point (a) of Article 22(1) attributed by the manufacturer to the device
in question, as soon as identification of this device shall be based on a UDI
system, or otherwise clear identification by means of product code, catalogue
number or other unambiguous reference allowing traceability;

(c)
the intended purpose of the device which may
include:

(i)      what is detected and/or measured;

(ii)      its function (e.g. screening,
monitoring, diagnosis or aid to diagnosis);

(iii)     the specific disorder, condition or
risk factor of interest that it is intended to detect, define or differentiate;

(iv)     whether it is automated or not;

(v)     whether it is qualitative,
semi-quantitative or quantitative;

(vi)     the type of specimen(s) required;

(vii)    where
applicable, the testing population;

(viii)   the intended user.

(d)
the description of the principle of the assay
method or instrument principles of operation;

(e)
the risk class of the device and the applicable
classification rule according to Annex VII;

(f)
the description of the components and where
appropriate, the description of the reactive ingredients of relevant components
(such as antibodies, antigens, nucleic acid primers);

and where applicable:

(g)
the description of the
specimen collection and transport materials provided with the device or
descriptions of specifications recommended for use;

(h)
for instruments of automated
assays: the description of the appropriate assay characteristics or dedicated
assays;

(i)
for automated assays: a
description of the appropriate instrumentation characteristics or dedicated
instrumentation;

(j)
a description of any
software to be used with the device;

(k)
a description or complete
list of the various configurations/variants of the device that will be made
available;

(l)
a description of the accessories, other in
vitro diagnostic medical devices and other products, which are intended to
be used in combination with the device.

1.2.
Reference to previous and similar generations of
the device

(a)
an overview of the manufacturer’s previous
generation(s) of the device, if such exist;

(b)
an overview of the manufacturer’s similar
devices available on the EU or international markets, if such exist.

2.
Information supplied by the manufacturer

(a)
a complete set of

–
the label(s) on the device and on its packaging;

–
the instructions for use;

(b)
a list of the language variants for the Member
States where the device is envisaged to be marketed.

3.
Design and manufacturing information
3.1.
Design information

Information to
allow a general understanding of the design stages applied to the device.

This shall include:

(a)
the description of the critical ingredients of
the device such as antibodies, antigens, enzymes and nucleic acid primers
provided or recommended for use with the device;

(b)
for instruments, the description of major
subsystems, analytical technology (e.g. operating principles, control
mechanisms), dedicated computer hardware and software;

(c)
for instruments and software, the overview of
the entire system;

(d)
for standalone software, the description of the
data interpretation methodology (i.e. algorithm);

(e)
for devices intended for self-testing or
near-patient testing devices the description of the design aspects that make
them suitable for self-testing or near-patient testing.

3.2.
Manufacturing information

(a)
Information to allow a general understanding of
the manufacturing processes such as production, assembly, final product
testing, and packaging of the finished device. More detailed information needs
to be provided for the audit of the quality management system or other
applicable conformity assessment procedures;

(b)
identification of all sites, including suppliers
and sub-contractors, where manufacturing activities are performed.

4.
general safety and performance requirements

The documentation shall contain information
regarding the solutions adopted to meet the general safety and performance
requirements laid down in Annex I. This information may take the form of a
checklist identifying:

(a)
the general safety and performance requirements
that apply to the device and why others do not apply;

(b)
the method(s) used to demonstrate conformity
with each applicable general safety and performance requirement;

(c)
the harmonised standards or CTS applied or other
method(s) employed;

(d)
the precise identity of the controlled documents
offering evidence of conformity with each harmonised standard, CTS or other
method employed to demonstrate conformity with the general safety and performance
requirements. This information shall incorporate a cross-reference to the
location of such evidence within the full technical documentation and, if
applicable, the summary technical documentation.

5. Risk/benefit analysis and risk management

The documentation shall contain a summary
of

(a)
the risk/benefit analysis referred to in Section
1 and 5 of Annex I; and

(b)
the solutions adopted and the results of the
risk management referred to in Section 2 of Annex I.

6. Product verification and validation

The documentation shall contain the results
of verification and validation testing and/or studies undertaken to demonstrate
conformity of the device with the requirements of this Regulation and in
particular the applicable general safety and performance requirements.

This includes:

6.1 Information on analytical
performance

6.1.1
Specimen type

This section shall describe the different
specimen types that can be used, including their stability (e.g. storage and
where applicable transport conditions) and storage conditions (e.g. duration,
temperature limits and freeze/thaw cycles).

6.1.2
Analytical performance characteristics

6.1.2.1 Accuracy of measurement

(a)
Trueness of measurement

This section shall provide information on the
trueness of the measurement procedure and summarise the data in sufficient
detail to allow assessment of the adequacy of the means selected to establish
the trueness. Trueness measures apply to both quantitative and qualitative
assays only when a reference standard or method is available.

(b)
Precision of measurement

This section shall describe repeatability and
reproducibility studies.

6.1.2.2 Analytical sensitivity

This section shall include information
about the study design and results. It shall provide a description of specimen
type and preparation including matrix, analyte levels, and how levels were
established. The number of replicates tested at each concentration shall also
be provided as well as a description of the calculation used to determine assay
sensitivity.

6.1.2.3 Analytical specificity

This section shall describe interference
and cross reactivity studies to determine the analytical specificity in the
presence of other substances/agents in the specimen.

Information shall be provided on the
evaluation of potentially interfering and cross reacting substances/agents on
the assay, on the substance/agent type and concentration tested, specimen type,
analyte test concentration, and results.

Interferents and cross reacting
substances/agents, which vary greatly depending on the assay type and design,
could derive from exogenous or endogenous sources such as:

(a)
substances used for patient treatment (e.g.
medicinal products);

(b)
substances ingested by the patient (e.g.
alcohol, foods);

(c)
substances added during specimen preparation
(e.g. preservatives, stabilisers);

(d)
substances encountered in specific specimens
types (e.g. haemoglobin, lipids, bilirubin, proteins);

(e)
analytes of similar structure (e.g. precursors,
metabolites) or medical conditions unrelated to the test condition including
specimens negative for the assay but positive for a condition that may mimic
the test condition.

6.1.2.4 Metrological traceability of
calibrator and control material values

6.1.2.5 Measuring range of the assay

This section shall include information on
the measuring range (linear and non-linear measuring systems) including the
limit of detection and describe information on how these were established.

This information shall include a
description of specimen type, number of specimen, number of replicates, and
preparation including information on matrix, analyte levels and how levels were
established. If applicable, a description of high dose hook effect and the data
supporting the mitigation (e.g. dilution) steps shall be added.

6.1.2.6 Definition of assay cut-off

This
section shall provide a summary of analytical data with a description of the
study design including methods for determining the assay cut-off, including:

(a)
the population(s) studied (demographics /
selection / inclusion and exclusion criteria / number of individuals included);

(b)
method or mode of characterisation of specimens;
and

(c)
statistical methods e.g. Receiver Operator
Characteristic (ROC) to generate results and if applicable, define grey-zone/equivocal
zone.

6.2 Information on clinical
performance

Where applicable, the documentation shall
contain data on the clinical performance of the device.

The clinical evidence report referred to in
Section 3 of Annex XII shall be included and/or fully referenced in the
technical documentation.

6.3 Stability (excluding specimen
stability)

This section shall describe claimed shelf
life, in use stability and shipping stability studies.

6.3.1 Claimed shelf life

This section shall provide information on stability testing
studies to support the claimed shelf life. Testing shall be performed on at
least three different lots manufactured under conditions that are essentially
equivalent to routine production conditions (these lots do not need to be
consecutive lots). Accelerated studies or extrapolated data from real time data
are acceptable for initial shelf life claim but need to be followed up with
real time stability studies.

Such detailed information shall describe:

(a)
the study report (including the protocol, number
of lots, acceptance criteria and testing intervals);

(b)
when accelerated studies have been performed in
anticipation of the real time studies, the method used for accelerated studies;

(c)
the conclusions and claimed shelf life.

6.3.2 In-use
stability

This section shall provide information on in-use stability
studies for one lot reflecting actual routine use of the device (real or
simulated). This may include open vial stability and/or, for automated
instruments, on board stability.

In the case of automated instrumentation if calibration
stability is claimed, supporting data shall be included.

Such detailed information shall describe:

(a)
the study report (including the protocol,
acceptance criteria and testing intervals);

(b)
the conclusions and claimed in-use stability.

6.3.3 Shipping
stability

This section shall provide information on shipping
stability studies for one lot to evaluate the tolerance of products to the
anticipated shipping conditions.

Shipping studies can be done under real and/or simulated
conditions and shall include variable shipping conditions such as extreme heat
and/or cold.

Such information shall describe:

(a)
the study report (including the protocol,
acceptance criteria);

(b)
the method used for simulated conditions;

(c)
the conclusion and recommended shipping
conditions.

6.4 Software verification and validation

The documentation shall
contain evidence of the validation of the software, as used in the finished
device. This information shall typically include the summary results of all
verification, validation and testing performed in-house and as applicable in an
actual user environment prior to final release. It shall also address all of
the different hardware configurations and, where applicable, operating systems
identified in the labelling.

6.5 Additional information in specific
cases

(a)
In the case of devices placed on the market in a
sterile or defined microbiological condition, a description of the
environmental conditions for the relevant manufacturing steps. In the case of
devices placed on the market in a sterile condition, a description of the methods
used, including the validation reports, with respect to packaging,
sterilisation and maintenance of sterility. The validation report shall address
bioburden testing, pyrogen testing and, if applicable, testing for sterilant
residues.

(b)
In the case of devices containing tissues, cells
and substances of animal, human or microbial origin, information on the origin
of such material and on the conditions in which it was collected.

(c)
In the case of devices placed on the market with
a measuring function, a description of the methods used in order to ensure the
accuracy as given in the specifications.

(d)
If the device is to be connected to other equipment
in order to operate as intended, a description of this combination including
proof that it conforms to the general safety and performance requirements when
connected to any such equipment having regard to the characteristics specified
by the manufacturer.

ANNEX III

EU DECLARATION OF CONFORMITY

1.
Name, registered trade name or registered trade
mark of the manufacturer and, if applicable, his authorised representative, and
the address of their registered place of business where they can be contacted
and their location be established;

2.
A statement that the declaration of conformity
is issued under the sole responsibility of the manufacturer;

3.
The UDI device identifier as referred to in item
(i) of point (a) of Article 22(1) as soon as identification of the device that
is covered by the declaration shall be based on a UDI system;

4.
Product or trade name, product code, catalogue
number or other unambiguous reference allowing identification and traceability
of the device that is covered by the declaration (it may include a photograph,
where appropriate). Except for the product or trade name, the information
allowing identification and traceability may be provided by the device
identifier referred to in point 3;

5.
Risk class of the device in accordance with the
rules set out in Annex VII;

6.
A statement that the device that is covered by
the present declaration is in conformity with this Regulation and, if
applicable, with other relevant Union legislation that make provision for the
issuing of a declaration of conformity;

7.
References to the relevant harmonised standards
or CTS used in relation to which conformity is declared;

8.
Where applicable, name and identification number
of the notified body, description of the conformity assessment procedure
performed and identification of the certificate(s) issued;

9.
Where applicable, additional information;

10.
Place and date of issue, name and function of
the person who signs as well as indication for and on behalf of whom he/she
signs, signature.

ANNEX IV

CE MARKING OF CONFORMITY

1.
The CE marking shall consist of the initials
‘CE’ taking the following form:

2.
If the CE marking is reduced or enlarged, the
proportions given in the above graduated drawing shall be respected.

3.
The various components of the CE marking shall
have substantially the same vertical dimension, which may not be less than 5
mm. This minimum dimension may be waived for small-scale devices.

ANNEX V

INFORMATION TO BE SUBMITTED WITH THE REGISTRATION OF
DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLE 23

AND

DATA ELEMENTS OF THE UDI DEVICE IDENTIFIER IN
ACCORDANCE WITH ARTICLE 22

Part
A

Information
to be submitted with the registration of devices in accordance with Article 23

Manufacturers
or, when applicable, authorised representatives, and, when applicable,
importers shall submit the following information:

1.
economic operator's role (manufacturer,
authorised representative, or importer),

2.
name, address and contact details of the
economic operator,

3.
where submission of information is completed by
another person on behalf of any of the economic operators mentioned under point
1, the name, address and contact details of this person,

4.
UDI device identifier, or where identification
of the device is not yet based on a UDI system, the data elements laid down in
points 5 to 18 of Part B of this Annex,

5.
type, number and expiry date of certificate and
name or identification number of the notified body that has issued the
certificate (and link to the information on the certificate entered by the
notified body in the electronic system on certificates),

6.
Member State where the device shall or has been placed on the market in the Union,

7.
in case of devices classified as classes B, C or
D: Member States where the device is or shall be made available,

8.
in case of imported device: country of origin,

9.
presence of tissues, cells or substances of
human origin (y/n),

10.
presence of tissues, cells or substances of
animal origin (y/n),

11.
presence of cells or substances of microbial
origin (y/n),

12.
risk class of the device according to the rules
set out in Annex VII,

13.
where applicable, single identification number
of the interventional clinical performance study and other clinical performance
study involving risks for the subjects of the study conducted in relation to
the device (or link to the clinical performance study registration in the
electronic system regarding clinical performance studies),

14.
in case of devices designed and manufactured by
another legal or natural person as referred in Article 8(10), the name, address
and contact details of that legal or natural person,

15.
in case of devices classified as class C or D,
the summary of safety and performance,

16.
status of the device (on the market, no longer
manufactured, withdrawn from the market, recalled),

17.
indication when the device is a 'new' device.

A device shall be considered as 'new' if:

(a)
there has been no such device continuously
available on the Union market during the previous three years for the relevant
analyte or other parameter;

(b)
the procedure involves analytical technology not
continuously used in connection with a given analyte or other parameter on the
Union market during the previous three years.

18.
Indication if the device is intended for
self-testing or near-patient testing.

Part B

Data elements of the UDI device identifier in accordance with
Article 22

The UDI device identifier shall provide
access to the following information related to the manufacturer and the device
model:

1.
quantity per package configuration,

2.
if applicable, alternative or additional
identifier(s),

3.
the way how the device production is controlled
(expiration date or manufacturing date, lot or batch number, serialisation
number),

4.
if applicable, the 'unit of use' device
identifier (when a UDI is not assigned to the device at the level of its 'unit
of use', a 'unit of use' device identifier shall be assigned to associate the
use of a device with a patient),

5.
name and address of the manufacturer (as indicated
on the label),

6.
if applicable, name and address of the
authorised representative (as indicated on the label),

7.
Global Medical Device Nomenclature (GMDN) code
or internationally recognised nomenclature code,

8.
if applicable, trade/brand name,

9.
if applicable, device model, reference, or
catalogue number,

10.
additional product description (optional),

11.
if applicable, storage and/or handling
conditions (as indicated on the label or in the instructions for use),

12.
if applicable, additional trade names of the
device,

13.
labelled as single use device (y/n),

14.
if applicable, restricted number of reuses,

15.
device packaged sterile (y/n),

16.
need for sterilisation before use (y/n),

17.
URL for additional information, e.g. electronic
instructions for use (optional),

18.
if applicable, critical warnings or
contraindications.

ANNEX VI

MINIMUM REQUIREMENTS TO BE MET BY NOTIFIED BODIES

1.
Organisational and general requirements
1.1.
Legal status and organisational structure
1.1.1.
A notified body shall be established under the national law of a
Member State, or under the law of a third country with which the Union has
concluded an agreement in this respect, and shall have full documentation of
its legal personality and status. This shall include information about ownership and the legal or natural
persons exercising control over the notified body.
1.1.2.
If the notified body
is a legal entity that is part of a larger organisation, the activities of this
organisation as well as its organisational structure and governance, and the
relationship with the notified body shall be clearly documented.
1.1.3.
If the notified body
wholly or partly owns legal entities established in a Member State or in a third country, the activities and responsibilities of those entities, as well as
their legal and operational relationships with the notified body, shall be
clearly defined and documented.
1.1.4.
The organisational
structure, distribution of responsibilities and operation of the notified body
shall be such that it assures confidence in the performance and results of the
conformity assessment activities conducted.

The organisational structure and the functions,
responsibilities and authority of its top-level management and of other
personnel with influence upon the performance and results of the conformity
assessment activities shall be clearly documented.

1.2.
Independence and
impartiality
1.2.1.
The notified body
shall be a third-party body that is independent of the manufacturer of the
product in relation to which it performs conformity assessment activities. The
notified body shall also be independent of any other economic operator having
an interest in the product as well as of any competitor of the manufacturer.
1.2.2.
The notified body
shall be organised and operated so as to safeguard the independence,
objectivity and impartiality of its activities. The notified body shall have
procedures in place that effectively ensure identification, investigation and
resolution of any case in which a conflict of interests may arise, including
involvement in consultancy services in the field of in
vitro diagnostic medical
devices prior to taking up employment with the notified body.
1.2.3.
The notified body, its
top-level management and the personnel responsible for carrying out the
conformity assessment tasks shall not

–
be the designer, manufacturer, supplier,
installer, purchaser, owner, user or maintainer of the products, nor the
authorised representative of any of those parties. This shall not preclude the
purchase and use of assessed products that are necessary for the operations of
the notified body (e.g. measuring equipment), the conduct of the conformity
assessment or the use of such products for personal purposes;

–
be directly involved in the design, manufacture
or construction, the marketing, installation, use or maintenance of the
products which they assess, or represent the parties engaged in those
activities. They shall not engage in any activity that may conflict with their
independence of judgement or integrity in relation to conformity assessment
activities for which they are notified;

–
offer or provide any service which may
jeopardise the confidence in their independence, impartiality or objectivity.
In particular, they shall not offer or provide consultancy services to the
manufacturer, his authorised representative, a supplier or a commercial
competitor as regards the design, construction, marketing or maintenance of the
products or processes under assessment. This does not preclude general training
activities relating to medical device regulations or related standards that are
not client specific.

1.2.4.
The impartiality of
the notified bodies, of their top level management and of the assessment
personnel shall be guaranteed. The remuneration of the top level management and
assessment personnel of a notified body shall not depend on the results of the
assessments.
1.2.5.
If a notified body is
owned by a public entity or institution, independence and absence of any
conflict of interests shall be ensured and documented between, on the one hand,
the national authority responsible for notified bodies and/or competent
authority and, on the other hand, the notified body.
1.2.6.
The notified body
shall ensure and document that the activities of its subsidiaries or
subcontractors, or of any associated body, do not affect its independence,
impartiality or objectivity of its conformity assessment activities.
1.2.7.
The notified body
shall operate in accordance with a set of consistent, fair and reasonable terms
and conditions, taking into account the interests of small and medium-sized
enterprises as defined by Commission Recommendation 2003/361/EC.
1.2.8.
The requirements of
this section in no way preclude exchanges of technical information and
regulatory guidance between a notified body and a manufacturer seeking their
conformity assessment.
1.3.
Confidentiality

The personnel of a notified body shall
observe professional secrecy with regard to all information obtained in
carrying out their tasks under this Regulation, except in relation to the
national authorities responsible for notified bodies, competent authorities or
the Commission. Proprietary rights shall be protected. To this end, the
notified body shall have documented procedures in place.

1.4.
Liability

The notified body shall take out
appropriate liability insurance that corresponds to the conformity assessment
activities for which it is notified, including the possible suspension,
restriction or withdrawal of certificates, and the geographic scope of its
activities, unless liability is assumed by the State in accordance with
national law, or the Member State itself is directly responsible for the
conformity assessment.

1.5.
Financial requirements

The notified body shall have at its
disposal the financial resources required to conduct its conformity assessment
activities and related business operations. It shall document and provide
evidence of its financial capacity and its sustainable economic viability,
taking into account specific circumstances during an initial start-up phase.

1.6.
Participation in coordination activities
1.6.1.
The notified body
shall participate in, or ensure that its assessment personnel is informed of the
relevant standardisation activities and the activities of the notified body
coordination group and that its assessment and decision making personnel are
informed of all relevant legislation, guidance and best practice documents
adopted in the framework of this Regulation.
1.6.2.
The notified body
shall adhere to a code of conduct, addressing among other things, ethical
business practices for notified bodies in the field of in
vitro diagnostic medical
devices that is accepted by the national authorities responsible for notified
bodies. The code of conduct shall provide for a mechanism of monitoring and
verification of its implementation by notified bodies.
2.
Quality management requirements
2.1.
The notified body
shall establish, document, implement, maintain and operate a quality management
system that is appropriate to the nature, area and scale of its conformity
assessment activities and capable of supporting and demonstrating the
consistent achievement of the requirements of this Regulation.
2.2.
The quality
management system of the notified body shall at least address the following:

–
policies for assignment of personnel to
activities and their responsibilities;

–
decision-making process in accordance with the tasks, responsibilities and role of the top-level management and
other notified body personnel;

–
control of documents;

–
control of records;

–
management review;

–
internal audits;

–
corrective and preventive actions;

–
complaints and appeals.

3.
Resource requirements
3.1.
General
3.1.1.
A notified body shall
be capable of carrying out all the tasks assigned to it by this Regulation with
the highest degree of professional integrity and the requisite technical
competence in the specific field, whether those tasks are carried out by the
notified body itself or on its behalf and under its responsibility.

In particular, it shall have the necessary
personnel and shall possess or have access to all equipment and facilities
needed to perform properly the technical and administrative tasks entailed in
the conformity assessment activities in relation to which it has been notified.

This presupposes the availability within its
organisation of sufficient scientific personnel who possess experience and
knowledge sufficient to assess the medical functionality and performance of
devices for which it has been notified, having regard to the requirements of
this Regulation and, in particular, those set out in Annex I.

3.1.2.
At all times and for
each conformity assessment procedure and each kind or category of products in
relation to which it has been notified, a notified body shall have within its
organisation the necessary administrative, technical and scientific personnel
with technical knowledge and sufficient and appropriate experience relating to in vitro
diagnostic medical devices and the corresponding technologies to perform the
conformity assessment tasks, including the assessment of clinical data.
3.1.3.
The notified body
shall clearly document the extent and the limits of the duties,
responsibilities and authorities in relation of the personnel involved in
conformity assessment activities and inform the personnel concerned about it.
3.2.
Qualification criteria in relation to personnel
3.2.1.
The notified body
shall establish and document qualification criteria and procedures for
selection and authorisation of persons involved in conformity assessment
activities (knowledge, experience and other competence required) and the
required training (initial and ongoing training). The qualification criteria
shall address the various functions within the conformity assessment process (e.g.
auditing, product evaluation/testing, design dossier/file review,
decision-making) as well as the devices, technologies and areas covered by the
scope of designation.
3.2.2.
The qualification
criteria shall refer to the scope of the notified body's designation in
accordance with the scope description used by the Member State for the notification referred to in Article 31, providing sufficient level of
detail for the required qualification within the subdivisions of the scope
description.

Specific qualification criteria shall be
defined for the assessment of biocompatibility aspects, clinical evaluation
and the different types of sterilisation processes.

3.2.3.
The personnel
responsible for authorising other personnel to perform specific conformity
assessment activities and the personnel with overall responsibility for the
final review and decision-making on certification shall be employed by the
notified body itself and shall not be subcontracted. This personnel altogether
shall have proven knowledge and experience in the following:

–
Union in vitro diagnostic medical devices
legislation and relevant guidance documents;

–
the conformity assessment procedures in
accordance with this Regulation;

–
a broad base of in vitro diagnostic
medical device technologies, the in vitro diagnostic medical device
industry and the design and manufacture of in vitro diagnostic medical
devices;

–
the notified body’s quality management system
and related procedures;

–
the types of qualifications (knowledge,
experience and other competence) required for carrying out conformity
assessments in relation to in vitro diagnostic medical devices as well
as the relevant qualification criteria;

–
training relevant to personnel involved in
conformity assessment activities in relation to in vitro diagnostic
medical devices;

–
the ability to draw up certificates, records and
reports demonstrating that the conformity assessments
have been appropriately carried out.

3.2.4.
Notified bodies shall
have available personnel with clinical expertise. This personnel shall be
integrated in the notified body's decision-making process in a steady way in
order to:

–
identify when specialist input is required for
the assessment of the clinical evaluation conducted by the manufacturer and
identify appropriately qualified experts;

–
appropriately train external clinical experts in
the relevant requirements of this Regulation, delegated and/or implementing
acts, harmonised standards, CTS and guidance documents and ensure that the
external clinical experts are fully aware of the context and implication of
their assessment and advice provided;

–
be able to discuss the clinical data contained
within the manufacturer's clinical evaluation with the manufacturer and with
external clinical experts and to appropriately guide external clinical experts
in the assessment of the clinical evaluation;

–
be able to scientifically challenge the clinical
data presented, and the results of the external clinical experts' assessment of
the manufacturer's clinical evaluation;

–
be able to ascertain the comparability and consistency
of the clinical assessments conducted by clinical experts;

–
be able to make an objective clinical judgement
about the assessment of the manufacturer's clinical evaluation and make a
recommendation to the notified body's decision maker.

3.2.5.
The personnel responsible
for carrying out product related review (e.g. design dossier review, technical
documentation review or type examination including aspects such as clinical
evaluation, sterilisation, software validation) shall have the following proven
qualification:

–
successful completion of a university or a
technical college degree or equivalent qualification in relevant studies, e.g.
medicine, natural science or engineering;

–
four years professional experience in the field
of healthcare products or related sectors (e.g. industry, audit, healthcare,
research experience) whilst two years of this experience shall be in the
design, manufacture, testing or use of the device or technology to be assessed
or related to the scientific aspects to be assessed;

–
appropriate knowledge of the general safety and
performance requirements laid down in Annex I as well as related delegated
and/or implementing acts, harmonised standards, CTS and guidance documents;

–
appropriate knowledge and experience of risk
management and related in vitro diagnostic medical device standards and
guidance documents;

–
appropriate knowledge and experience of the
conformity assessment procedures laid down in Annexes VIII to X, in particular
of those aspects for which they are authorised, and adequate authority to carry
out those assessments.

3.2.6.
The personnel
responsible for carrying out audits of the manufacturer's quality management
system shall have the following proven qualification:

–
successful completion of a university or a
technical college degree or equivalent qualification in relevant studies, e.g.
medicine, natural sciences or engineering;

–
four years professional experience in the field
of healthcare products or related sectors (e.g. industry, audit, healthcare,
research experience) whilst two years of this experience shall be in the area
of quality management;

–
appropriate knowledge of the in vitro diagnostic
medical devices legislation as well as related delegated and/or implementing
acts, harmonised standards, CTS and guidance documents;

–
appropriate knowledge and experience of risk
management and related in vitro diagnostic medical device standards and
guidance documents;

–
appropriate knowledge of quality management
systems and related standards and guidance documents;

–
appropriate knowledge and experience of the
conformity assessment procedures laid down in Annexes VIII to X, in particular
of those aspects for which they are authorised, and adequate authority to carry
out the audits;

–
training in auditing techniques enabling them to
challenge quality management systems.

3.3.
Documentation of qualification, training and
authorisation of personnel
3.3.1.
The notified body
shall have a process in place to fully document the qualification of each
personnel involved in conformity assessment activities and the satisfaction of
the qualification criteria referred to in Section 3.2. Where in exceptional
circumstances the fulfilment of the qualification criteria set out in Section
3.2 cannot be fully demonstrated, the notified body shall appropriately justify
the authorisation of this personnel to carry out specific conformity assessment
activities.
3.3.2.
For its personnel
referred to in Sections 3.2.3 to 3.2.6, the notified body shall establish and
maintain up to date:

–
a matrix detailing the responsibilities of the
personnel in respect of the conformity assessment activities;

–
records demonstrating the required knowledge and
experience for the conformity assessment activity for which they are
authorised.

3.4.
Subcontractors and external experts
3.4.1.
Without prejudice to
the limitations emanating from Section 3.2., the notified bodies may
subcontract clearly defined parts of the conformity assessment activities. The
subcontracting of the auditing of quality management systems or of product
related reviews as a whole is not allowed.
3.4.2.
Where a notified body
subcontracts conformity assessment activities either to an organisation or an
individual, it shall have a policy describing the conditions under which
subcontracting may take place. Any subcontracting or consultation of external
experts shall be properly documented and be subject to a written agreement
covering, among others, confidentiality and conflict of interests.
3.4.3.
Where subcontractors
or external experts are used in the context of the conformity assessment, the
notified body shall have adequate own competence in each product area for which
it is designated to lead the conformity assessment, to verify the
appropriateness and validity of expert opinions and make the decision on the
certification.
3.4.4.
The notified body
shall establish procedures for assessing and monitoring the competence of all
subcontractors and external experts used.
3.5.
Monitoring of competences and training
3.5.1.
The notified body
shall appropriately monitor the satisfactory performance of the conformity
assessment activities by its personnel.
3.5.2.
It shall review the
competence of its personnel and identify training needs in order to maintain
the required level of qualification and knowledge.
4.
Process requirements
4.1.
The notified body's
decision-making process shall be clearly documented, including the process for
the issue, suspension, reinstatement, withdrawal or refusal of conformity
assessment certificates, their modification or restriction and the issue of
supplements.
4.2.
The notified body
shall have in place a documented process for the conduct of the conformity
assessment procedures for which it is designated taking into account their
respective specificities, including legally required consultations, in respect
of the different categories
of devices covered by the scope of notification, ensuring transparency and the ability of
reproduction of those procedures.
4.3.
The notified body
shall have in place documented procedures covering at least:

–
the application for conformity assessment by a
manufacturer or by an authorised representative,

–
the processing of the application, including the
verification of the completeness of the documentation, the qualification of the
product as in vitro diagnostic
medical device and its classification,

–
the language of the application, of the
correspondence and of the documentation to be submitted,

–
the terms of the agreement with the manufacturer
or authorised representative,

–
the fees to be charged for conformity assessment
activities,

–
the assessment of relevant changes to be
submitted for prior approval,

–
the planning of surveillance,

–
the renewal of certificates.

ANNEX VII

CLASSIFICATION CRITERIA

1.
Implementing rules for the classification rules
1.1.
Application of the
classification rules shall be governed by the intended purpose of the devices.
1.2.
If the device is
intended to be used in combination with another device, the classification
rules shall apply separately to each of the devices.
1.3.
Accessories are
classified in their own right separately from the device with which they are
used.
1.4.
Standalone software,
which drives a device or influences the use of a device, falls automatically in
the same class as the device. If standalone software is independent of any
other device, it is classified in its own right.
1.5.
Calibrators intended
to be used with a device shall be classified in the same class as the device.
1.6.
Standalone control
materials with quantitative or qualitative assigned values intended for one
specific analyte or multiple analytes shall be classified in the same class as
the device.
1.7.
The manufacturer
shall take into consideration all the rules in order to establish the proper
classification for the device.
1.8.
Where a device has
multiple intended purposes stated by the manufacturer, which place the device
into more than one class, it shall be classified in the higher class.
1.9.
If several
classification rules apply to the same device the rule resulting in the higher
classification shall apply.
2.
Classification Rules
2.1.
Rule 1

Devices intended for the following purposes
are classified as class D:

–
Devices intended to be used to detect the
presence of, or exposure to, a transmissible agent in blood, blood components,
cells, tissues or organs, or in any of their derivatives, in order to assess
their suitability for transfusion or transplantation.

–
Devices intended to be used to detect the
presence of, or exposure to, a transmissible agent that causes a
life-threatening disease with a high or currently undefined risk of
propagation.

This rule applies to first line assays,
confirmatory assays and supplemental assays.

2.2.
Rule 2

Devices intended to be used for blood
grouping, or tissue typing to ensure the immunological compatibility of blood,
blood components, cells, tissue or organs that are intended for transfusion or
transplantation, are classified as class C, except when intended to
determine any of the following markers:

–
ABO system [A (ABO1), B (ABO2), AB (ABO3)];

–
Rhesus system [RH1 (D), RH2 (C), RH3 (E), RH4 (c),
RH5 (e)];

–
Kell system [Kel1 (K)];

–
Kidd system [JK1 (Jka), JK2 (Jkb)];

–
Duffy system [FY1 (Fya), FY2 (Fyb)]

in which case they are classified as class
D.

2.3.
Rule 3

Devices are classified as class C if
they are intended for:

(a)
detecting the presence of, or exposure to, a
sexually transmitted agent;

(b)
detecting the presence in cerebrospinal fluid or
blood of an infectious agent with a risk of limited propagation;

(c)
detecting the presence of an infectious agent,
if there is a significant risk that an erroneous result would cause death or
severe disability to the individual or foetus being tested, or to the
individual's offspring;

(d)
pre-natal screening of women in order to
determine their immune status towards transmissible agents;

(e)
determining infective disease status or immune
status, if there is a risk that an erroneous result would lead to a patient
management decision resulting in an imminent life-threatening situation for the
patient or for the patient's offspring;

(f)
selection of patients, i.e.

(i)      Devices intended to be used as
companion diagnostics; or

(ii)      Devices intended to be used for
disease staging; or

(iii)     Devices intended to be used in
screening for or in the diagnosis of cancer.

(g)
human genetic testing;

(h)
monitoring of levels of medicinal products,
substances or biological components, when there is a risk that an erroneous
result will lead to a patient management decision resulting in an imminent
life-threatening situation for the patient or for the patient's offspring;

(i)
management of patients suffering from a
life-threatening infectious disease;

(j)
screening for congenital disorders in the
foetus.

2.4.
Rule 4

(a)
Devices intended for self-testing are classified
as class C, except those devices from which the result is not determining a
medically critical status, or is preliminary and requires follow-up with the
appropriate laboratory test in which case they are Class B.

(b)
Devices intended for blood gases and blood
glucose determinations for near-patient testing are class C. Other devices that
are intended for near-patient testing shall be classified in their own right.

2.5.
Rule 5

The following devices are classified as class
A:

(a)
reagents or other articles which possess
specific characteristics, intended by the manufacturer to make them suitable
for in vitro diagnostic procedures related to a specific examination;

(b)
instruments intended by the manufacturer
specifically to be used for in vitro diagnostic procedures;

(c)
specimen receptacles.

2.6.
Rule 6

Devices not covered by the above-mentioned
classification rules are classified as class B.

2.7.
Rule 7

Devices which are controls without a
quantitative or qualitative assigned value are classified as class B.

ANNEX VIII

CONFORMITY ASSESSMENT BASED ON FULL QUALITY ASSURANCE
AND DESIGN EXAMINATION

Chapter I: Full Quality Assurance System

1.
The manufacturer shall ensure application of the
quality management system approved for the design, manufacture and final
inspection of the devices concerned, as specified in Section 3, and is subject
to audit as laid down in Sections 3.3 and 3.4 and to the surveillance as
specified in Section 4.

2.
The manufacturer who fulfils the obligations
imposed by Section 1 shall draw up and keep an EU declaration of conformity in
accordance with Article 15 and Annex III for the device model covered by the
conformity assessment procedure. By issuing a declaration of conformity, the
manufacturer ensures and declares that the devices concerned meet the provisions
of this Regulation which apply to them.

3.
Quality management system

3.1.
The manufacturer shall lodge an application for
assessment of his quality management system with a notified body. The
application shall include:

–
the name and address of the manufacturer and any
additional manufacturing site covered by the quality management system, and, if
the application is lodged by the authorised representative, his name and
address as well,

–
all the relevant information on the device or
device category covered by the procedure,

–
a written declaration that no application has
been lodged with any other notified body for the same device-related quality
management system, or information about any previous application for the same
device-related quality management system that has been refused by another
notified body,

–
the documentation on the quality management
system,

–
a description of the procedures in place to
fulfil the obligations imposed by the quality management system approved and the
undertaking by the manufacturer to apply these procedures,

–
a description of the procedures in place to keep
the approved quality management system adequate and efficacious and an
undertaking by the manufacturer to apply these procedures,

–
the documentation on the post-market surveillance
plan, including, when applicable, a plan for the post-market follow-up, and the
procedures put in place to ensure compliance with the obligations emanating
from the provisions on vigilance set out in Articles 59 to 64,

–
a description of the procedures in place to keep
up to date the post-market surveillance plan, including, when applicable, a
plan for the post-market follow-up, and the procedures ensuring compliance with
the obligations emanating from the provisions on vigilance set out in Articles
59 to 64, as well as the undertaking by the manufacturer to apply these
procedures.

3.2.
Application of the quality management system
shall ensure that the devices conform to the provisions of this Regulation
which apply to them at every stage, from design to final inspection. All the
elements, requirements and provisions adopted by the manufacturer for his
quality management system shall be documented in a systematic and orderly
manner in the form of written policies and procedures, such as quality
programmes, quality plans, quality manuals and quality records.

Moreover, the documentation to be submitted for
the assessment of the quality management system shall include an adequate
description of, in particular:

(a)
the manufacturer's quality objectives;

(b)
the organisation of the business and in
particular:

–
the organisational structures, the
responsibilities of the managerial staff and their organisational authority
where quality of design and manufacture of the products is concerned,

–
the methods of monitoring the efficient operation
of the quality management system and in particular its ability to achieve the
desired quality of design and of product, including control of products which
fail to conform,

–
where the design, manufacture and/or final
inspection and testing of the products, or elements thereof, is carried out by
another party, the methods of monitoring the efficient operation of the quality
management system and in particular the type and extent of control applied to
the other party,

–
where the manufacturer does not have a
registered place of business in a Member State, the draft mandate for the
designation of an authorised representative and a letter of intention of the
authorised representative to accept the mandate;

(c)
the procedures and techniques for monitoring,
verifying, validating and controlling the design of the devices, including the
corresponding documentation as well as the data and records arising from those
procedures and techniques;

(d)
the inspection and quality assurance techniques
at the manufacturing stage and in particular:

–
the processes and procedures which will be used,
particularly as regards sterilisation, purchasing and the relevant documents,

–
the product identification procedures drawn up
and kept up to date from drawings, specifications or other relevant documents
at every stage of manufacture;

(e)
the appropriate tests and trials which will be
carried out before, during and after manufacture, the frequency with which they
will take place, and the test equipment used; it shall be possible to trace
back the calibration of the test equipment adequately.

In addition, the manufacturer shall grant the
notified body access to the technical documentation referred to in Annex II.

3.3.
Audit

(a)
The notified body shall audit the quality system
to determine whether it meets the requirements referred to in Section 3.2.
Unless duly substantiated, it shall presume that quality management systems
which satisfy the relevant harmonised standards or CTS conform to the
requirements covered by the standards or CTS.

(b)
The assessment team shall include at least one
member with past experience of assessments of the technology concerned. The
assessment procedure shall include an audit on the manufacturer's premises and,
if appropriate, on the premises of the manufacturer's suppliers and/or
subcontractors to inspect the manufacturing and other relevant processes.

(c)
Moreover, in the case of devices classified as
class C, the audit procedure shall include an assessment, on a representative
basis, of the design documentation within the technical documentation as
referred to in Annex II of the device(s) concerned. In choosing representative
sample(s) the notified body shall take into account the novelty of the
technology, similarities in design, technology, manufacturing and sterilisation
methods, the intended purpose and the results of any previous relevant
assessments that have been carried out in accordance with this Regulation. The
notified body shall document its rationale for the sample(s) taken.

(d)
If the quality management system conforms to the
relevant provisions of this Regulation, the notified body shall issue an EU
full quality assurance certificate. The decision shall be notified to the
manufacturer. It shall contain the conclusions of the audit and a reasoned
assessment.

3.4.
The manufacturer shall inform the notified body
which approved the quality management system of any plan for substantial
changes to the quality management system or the product-range covered. The
notified body shall assess the changes proposed and verify whether after these
changes the quality management system still meets the requirements referred to
in Section 3.2. It shall notify the manufacturer of its decision which shall
contain the conclusions of the audit and a reasoned assessment. The approval of
any substantial change to the quality management system or the product-range
covered shall take the form of a supplement to the EU full quality assurance
certificate.

4.
Surveillance assessment applicable to
devices classified as class C and D

4.1.
The aim of surveillance is to ensure that the
manufacturer duly fulfils the obligations imposed by the approved quality
management system.

4.2.
The manufacturer shall authorise the notified
body to carry out all the necessary audits, including inspections, and supply
it with all relevant information, in particular:

–
the documentation on the quality management
system,

–
the documentation on the post-market
surveillance plan, including a post-market follow-up, as well as, if
applicable, any findings resulting from the application of the post-market surveillance
plan, including the post-market follow-up, and of the provisions on vigilance
set out in Articles 59 to 64,

–
the data stipulated in the part of the quality
management system relating to design, such as the results of analyses,
calculations, tests and the solutions adopted regarding the risk-management as
referred to in Section 2 of Annex I,

–
the data stipulated in the part of the quality
management system relating to manufacture, such as inspection reports and test
data, calibration data, qualification reports of the personnel concerned, etc.

4.3.
The notified body shall periodically, at least
every 12 months, carry out appropriate audits and assessments to make sure that
the manufacturer applies the approved quality management system and the
post-market surveillance plan, and shall supply the manufacturer with an
assessment report. This shall include inspections on the premises of the
manufacturer and, if appropriate, of the manufacturer’s suppliers and/or
subcontractors. At the time of such inspections, the notified body shall, where
necessary, carry out or ask for tests in order to check that the quality
management system is working properly. It shall provide the manufacturer with
an inspection report and, if a test has been carried out, with a test report.

4.4.
The notified body shall randomly perform
unannounced factory inspections to the manufacturer and, if appropriate, of the
manufacturer's suppliers and/or subcontractors, which may be combined with the
periodic surveillance assessment referred to in Section 4.3. or be performed in
addition to this surveillance assessment. The notified body shall establish a
plan for the unannounced inspections which shall not be disclosed to the
manufacturer.

Within the context of such unannounced
inspections, the notified body shall check an adequate sample from the
production or the manufacturing process to verify that the manufactured device
is in conformity with the technical documentation and/or design dossier. Prior
to the unannounced inspection, the notified body shall specify the relevant
sampling criteria and testing procedure.

Instead of, or in addition to, the sampling
from the production, the notified body shall take samples of devices from the
market to verify that the manufactured device is in conformity with the
technical documentation and/or design dossier. Prior to the sampling, the
notified body shall specify the relevant sampling criteria and testing
procedure.

The notified body shall provide the
manufacturer with an inspection report which shall include, if applicable, the
result of the sample check.

4.5.
In the case of devices classified as class C,
the surveillance assessment shall also include the assessment of the design
documentation within the technical documentation of the device(s) concerned on
the basis of further representative sample(s) chosen in accordance with the
rationale documented by the notified body in accordance with point (c) of
Section 3.3.

4.6.
The notified body shall ensure that the
composition of the assessment team assures experience with the technology
concerned, continuous objectivity and neutrality; this shall include a rotation
of the members of the assessment team at appropriate intervals. As a general
rule, a lead auditor shall not lead and attend an audit for more than three consecutive
years in respect to the same manufacturer.

4.7.
If the notified body establishes a divergence
between the sample taken from the production or from the market and the
specifications laid down in the technical documentation or the approved design,
it shall suspend or withdraw the relevant certificate or impose restrictions on
it.

Chapter
II: Design dossier examination

5.
Examination of the design of the device
and batch verification applicable to devices in class D

5.1.
In addition to the obligation imposed by Section
3, the manufacturer of devices classified as class D shall lodge with the
notified body referred to in Section 3.1 an application for the examination of
the design dossier relating to the device which he plans to manufacture and
which falls into the device category covered by the quality management system
referred to in Section 3.

5.2.
The application shall describe the design,
manufacture and performances of the device in question. It shall include the
technical documentation as referred to in Annex II; where the technical
documentation is voluminous and/or held in different locations, the
manufacturer shall submit a summary technical documentation (STED) and grant
access to the full technical documentation upon request.

In the case of devices for self-testing or
near-patient testing, the application shall also include the aspects referred
to in Section 6.1, point b).

5.3.
The notified body shall examine the application
employing staff with proven knowledge and experience regarding the technology
concerned. The notified body may require the application to be completed by
further tests or other evidence to allow assessment of conformity with the
requirements of this Regulation. The notified body shall carry out adequate
physical or laboratory tests in relation to the device or request the
manufacturer to carry out such tests.

5.4.
Before issuing an EU design-examination
certificate, the notified body shall request a reference laboratory, where
designated in accordance with Article 78, to verify compliance of the device
with the CTS, when available, or with other solutions chosen by the
manufacturer to ensure a level of safety and performance that is at least
equivalent.

The reference laboratory shall provide a
scientific opinion within 30 days.

The scientific opinion of the reference
laboratory and any possible updates shall be included in the documentation of
the notified body concerning the device. The notified body shall give due
consideration to the views expressed in the scientific opinion when making its
decision. The notified body shall not deliver the certificate if the scientific
opinion is unfavourable.

5.5.
The notified body shall provide the manufacturer
with an EU design-examination report.

If the device conforms to the relevant
provisions of this Regulation, the notified body shall issue an EU
design-examination certificate. The certificate shall contain the conclusions
of the examination, the conditions of validity, the data needed for
identification of the approved design, where appropriate, a description of the
intended purpose of the device.

5.6.
Changes to the approved design shall receive
further approval from the notified body which issued the EU design-examination
certificate, wherever the changes could affect conformity with the general
safety and performance requirements of this Regulation or with the conditions
prescribed for use of the device. The applicant shall inform the notified body
which issued the EU design-examination certificate of any planned changes to
the approved design. The notified body shall examine the planned changes,
notify the manufacturer of its decision and provide him with a supplement to
the EU design-examination report.

Where the changes could affect compliance with
the CTS or with other solutions chosen by the manufacturer which were approved
through the EU design-examination certificate, the notified body shall consult
the reference laboratory that was involved in the initial consultation, in
order to confirm that compliance with the CTS or with other solutions chosen by
the manufacturer to ensure a level of safety and performance that is at least
equivalent are maintained.

The reference laboratory shall provide a
scientific opinion within 30 days.

The approval of any change to the approved
design shall take the form of a supplement to the EU design-examination
certificate.

5.7.
To verify conformity of manufactured devices
classified as class D, the manufacturer shall carry out tests on the
manufactured devices or each batch of devices. After the conclusion of the
controls and tests he shall forward to the notified body without delay the
relevant reports on these tests. Furthermore, the manufacturer shall make the
samples of manufactured devices or batches of devices available to the notified
body in accordance with pre-agreed conditions and modalities which shall
include that the notified body or the manufacturer, in regular intervals, shall
send samples of the manufactured devices or batches of devices to a reference
laboratory, where designated in accordance with Article 78, to carry out
appropriate tests. The reference laboratory shall inform the notified body
about its findings.

5.8.
The manufacturer may place the devices on the
market, unless the notified body communicates to the manufacturer within the
agreed time-frame, but not later than 30 days after reception of the samples,
any other decision, including in particular any condition of validity of
delivered certificates.

6.
Examination of the design of specific
types of devices

6.1.
Examination of the design of devices for
self-testing and near-patient testing classified as class A, B or C

(a)
The manufacturer of devices for self-testing or
near-patient testing classified as class A, B and C shall lodge with the
notified body referred to in Section 3.1 an application for the examination of
the design.

(b)
The application shall enable the design of the
device to be understood and shall enable conformity with the design-related
requirements of this Regulation to be assessed. It shall include:

–
test reports, including results of studies
carried out with intended users;

–
where practicable, an example of the device; if
required, the device shall be returned on completion of the design examination;

–
data showing the handling suitability of the
device in view of its intended purpose for self-testing or near patient-testing;

–
the information to be provided with the device
on its label and its instructions for use.

The notified body may require the application
to be completed by further tests or proof to allow assessment of conformity
with the requirements of this Regulation.

(c)
The notified body shall examine the application
employing staff with proven knowledge and experience regarding the technology
concerned and provide the manufacturer with an EU design-examination report.

(d)
If the device conforms to the relevant
provisions of this Regulation, the notified body shall issue an EU
design-examination certificate. The certificate shall contain the conclusions
of the examination, the conditions of validity, the data needed for the
identification of the approved design and, where appropriate, a description of
the intended purpose of the device.

(e)
Changes to the approved design shall receive
further approval from the notified body which issued the EU design-examination
certificate, wherever the changes could affect conformity with the general
safety and performance requirements of this Regulation or with the conditions
prescribed for use of the device. The applicant shall inform the notified body
which issued the EU design-examination certificate of any planned changes to
the approved design. The notified body shall examine the planned changes,
notify the manufacturer of its decision and provide him with a supplement to
the EU design-examination report. The approval of any change to the approved
design shall take the form of a supplement to the EU design-examination
certificate.

6.2.
Examination of the design of companion
diagnostics

(a)
The manufacturer of a companion diagnostic shall
lodge with the notified body referred to in Section 3.1 an application for the
examination of the design.

(b)
The application shall enable the design of the
device to be understood and shall enable conformity with the design-related
requirements of this Regulation to be assessed, in particular, with regard to
the suitability of the device in relation to the medicinal product concerned.

(c)
For companion diagnostic intended to be used to
assess the patient eligibility to a treatment with a specific medicinal
product, the notified body shall consult before issuing an EU
design-examination certificate and on the basis of the draft summary of safety
and performance and the draft instructions for use, one of the competent
authorities designated by the Member States in accordance with Directive
2001/83/EC (hereinafter referred to as 'medicinal products competent authority')
or the European Medicines Agency (hereinafter referred to as ‘EMA’) established
by the Regulation (EC) No 726/2004 laying down Community procedures for the
authorisation and supervision of medicinal products for human and veterinary
use and establishing a European Medicines Agency[43], regarding the suitability of
the device in relation to the medicinal product concerned. Where the medicinal
product falls exclusively within the scope of the Annex of Regulation (EC) No
726/2004, the notified body shall consult the EMA.

(d)
The medicinal products competent authority or
the EMA shall give its opinion, if any, within 60 days after receipt of valid
documentation. This 60-day period may be extended only once for a further 60
days on scientifically valid grounds. The opinion of the medicinal products
authority or of the EMA and any possible update shall be included in the
documentation of the notified body concerning the device.

(e)
The notified body shall give due consideration
to the opinion, if any, expressed by the medicinal products competent authority
concerned or the EMA when making its decision. It shall convey its final
decision to the medicinal products competent authority concerned or to the EMA.
The design-examination certificate shall be delivered in accordance with point
(d) of Section 6.1.

(f)
Before changes affecting the suitability of the
device in relation to the medicinal product concerned are made, the
manufacturer shall inform the notified body of the changes, which shall consult
the medicinal products competent authority that was involved in the initial
consultation or the EMA. The medicinal products competent authority or the EMA
shall give its opinion, if any, within 30 days after receipt of the valid
documentation regarding the changes. A supplement to the EU design-examination
certificate shall be issued in accordance with point (e) of Section 6.1.

Chapter
III: Administrative provisions

7.
The manufacturer or his authorised
representative shall, for a period ending at least five years after the last
device has been placed on the market, keep at the disposal of the competent
authorities:

–
the declaration of conformity,

–
the documentation referred to in the fourth
indent of Section 3.1 and in particular the data and records arising from the
procedures referred to in point (c) of Section 3.2.,

–
the changes referred to in Section 3.4,

–
the documentation referred to in Sections 5.2
and point (b) of Section 6.1, and

–
the decisions and reports from the notified body
as referred to in Sections 3.3, 4.3, 4.4, 5.5, 5.6, 5.8, points (c), (d) and
(e) of Section 6.1, point (e) of Section 6.2 and point (f) of Section 6.2.

8.
Each Member State shall make provision that this
documentation is kept at the disposal of the competent authorities for the
period indicated in the first sentence of the preceding paragraph in case the
manufacturer, or his authorised representative, established within its
territory goes bankrupt or ceases its business activity prior to the end of
this period.

ANNEX IX

CONFORMITY ASSESSMENT BASED ON TYPE EXAMINATION

1.
EU type-examination is the procedure whereby a
notified body ascertains and certifies that a representative sample of the
production covered fulfils the relevant provisions of this Regulation.

2.
Application

The application shall include:

–
the name and address of the manufacturer and, if
the application is lodged by the authorised representative, the name and
address of the authorised representative,

–
the technical documentation referred to in Annex
II needed to assess the conformity of the representative sample of the
production in question, hereinafter referred to as the ‘type’, with the
requirements of this Regulation; where the technical documentation is voluminous and/or held in different locations, the manufacturer
shall submit a summary technical documentation (STED) and
grant access to the full technical documentation upon request. The applicant
shall make a ‘type’ available to the notified body. The notified body may
request other samples as necessary,

–
in the case of devices for self-testing or
near-patient testing, test reports, including results of studies carried out
with intended users, and data showing the handling suitability of the device in
view of its intended purpose for self-testing or near patient-testing,

–
a written declaration that no application has
been lodged with any other notified body for the same type, or information
about any previous application for the same type that has been refused by
another notified body.

3.
Assessment

The notified body shall:

3.1.
examine and assess the technical documentation
and verify that the type has been manufactured in conformity with that
documentation; it shall also record the items designed in conformity with the
applicable specifications of the standards referred to in Article 6 or CTS, as
well as the items not designed on the basis of the relevant provisions of the
abovementioned standards;

3.2.
carry out or arrange for the appropriate
assessments and the physical or laboratory tests necessary to verify whether
the solutions adopted by the manufacturer meet the general safety and
performance requirements of this Regulation if the standards referred to in
Article 6 or CTS have not been applied; if the device is to be connected to
other equipment in order to operate as intended, proof shall be provided that
it conforms to the general safety and performance requirements when connected
to any such equipment having the characteristics specified by the manufacturer;

3.3.
carry out or arrange for the appropriate
assessments and the physical or laboratory tests necessary to verify whether,
if the manufacturer has chosen to apply the relevant standards, these have
actually been applied;

3.4.
agree with the applicant on the place where the
necessary assessments and tests will be carried out;

3.5.
in the case of devices classified as class D,
request a reference laboratory, where designated in accordance with Article 78,
to verify compliance of the device with the CTS or with other solutions chosen
by the manufacturer to ensure a level of safety and performance that is at least
equivalent. The reference laboratory shall provide a scientific opinion within
30 days. The scientific opinion of the reference laboratory and any possible
update shall be included in the documentation of the notified body concerning
the device. The notified body shall give due consideration to the views
expressed in the scientific opinion when making its decision. The notified body
shall not deliver the certificate if the scientific opinion is unfavourable;

3.6.
For companion diagnostic intended to be used to assess
the patient eligibility to a treatment with a specific medicinal product, seek
the opinion, on the basis of the draft summary of safety and performance and
the draft instructions for use, of a one of the competent authorities
designated by the Member States in accordance with Directive 2001/83/EC (hereinafter
referred to as 'medicinal products competent authority') or the European
Medicines Agency (hereinafter referred to as ‘EMA’) on the suitability of the
device in relation to the medicinal product concerned. Where the medicinal
product falls exclusively within the scope of the Annex of Regulation (EC) No
726/2004, the notified body shall consult the EMA. The medicinal products
authority or the European Medicines Agency shall deliver its opinion, if any,
within 60 days upon receipt of the valid documentation. This 60-day period may
be extended only once for a further 60 days on scientifically valid grounds.
The opinion of the medicinal products authority or of the EMA and any possible
update shall be included in the documentation of the notified body concerning
the device. The notified body shall give due consideration to the opinion, if
any, expressed by the medicinal products competent authority concerned or the
EMA when making its decision. It shall convey its final decision to the
medicinal products competent authority concerned or to the EMA.

4.
Certificate

If the type conforms to the provisions of
this Regulation, the notified body shall issue an EU type-examination
certificate. The certificate shall contain the name and address of the
manufacturer, the conclusions of the assessment, the conditions of validity and
the data needed for identification of the type approved. The relevant parts of
the documentation shall be annexed to the certificate and a copy kept by the
notified body.

5.
Changes to the type

5.1.
The applicant shall inform the notified body
which issued the EU type-examination certificate of any planned change to the
approved type.

5.2.
Changes to the approved product shall receive
further approval from the notified body which issued the EU type-examination
certificate wherever the changes may affect conformity with the general safety
and performance requirements or with the conditions prescribed for use of the
product. The notified body shall examine the planned changes, notify the
manufacturer of its decision and provide him with a supplement to the EU
type-examination report. The approval of any change to the approved type shall
take the form of a supplement to the initial EU type-examination certificate.

5.3.
Where the changes could affect compliance with
the CTS or with other solutions chosen by the manufacturer which were approved
through the EU type-examination certificate, the notified body shall consult
the reference laboratory that was involved in the initial consultation, in
order to confirm that compliance with the CTS, when available, or with other
solutions chosen by the manufacturer to ensure a level of safety and
performance that is at least equivalent are maintained.

The reference laboratory shall provide a
scientific opinion within 30 days.

5.4.
Where the changes affect a companion diagnostic
approved through the EU type-examination certificate with regard to its
suitability in relation to a medicinal product, the notified body shall consult
the medicinal products competent authority that was involved in the initial
consultation or the EMA. The medicinal products competent authority or the EMA
shall give its opinion, if any, within 30 days after receipt of the valid
documentation regarding the changes. The approval of any change to the approved
type shall take the form of a supplement to the initial EU type-examination
certificate.

6.
Administrative provisions

The manufacturer or his authorised
representative shall, for a period ending at least five years, after the last
device has been placed on the market, keep at the disposal of the competent
authorities:

–
the documentation referred to in the second
indent of Section 2,

–
the changes referred to in Section 5,

–
copies of EU type-examination certificates and
their additions.

Section 8 of Annex VIII shall apply.

ANNEX X

CONFORMITY ASSESSMENT BASED ON PRODUCTION QUALITY
ASSURANCE

1.
The manufacturer shall ensure application of the
quality management system approved for the manufacture of the devices concerned
and carry out the final inspection, as specified in Section 3, and is subject
to the surveillance referred to in Section 4.

2.
The manufacturer who fulfils the obligations
imposed by Section 1 shall draw up and keep an EU declaration of conformity in
accordance with Article 15 and Annex III for the device model covered by the
conformity assessment procedure. By issuing an EU declaration of conformity,
the manufacturer ensures and declares that the devices concerned conform to the
type described in the EU type-examination certificate and meet the provisions
of this Regulation which apply to them.

3.
Quality management system

3.1.
The manufacturer shall lodge an application for
assessment of his quality management system with a notified body.

The application shall include:

–
all elements listed in Section 3.1 of Annex
VIII,

–
the technical documentation as referred to in
Annex II for the types approved; where the technical documentation is
voluminous and/or held in different locations, the manufacturer shall submit a
summary technical documentation (STED) and grant access to the full technical
documentation upon request;

–
a copy of the EU-type examination certificates
referred to in Section 4 of Annex IX; if the EU-type examination certificates
have been issued by the same notified body with which the application is
lodged, a reference to the technical documentation and the certificates issued
is sufficient.

3.2.
Application of the quality management system
shall ensure that the devices conform to the type described in the EU
type-examination certificate and to the provisions of this Regulation which
apply to them at every stage. All the elements, requirements and provisions
adopted by the manufacturer for his quality management system shall be
documented in a systematic and orderly manner in the form of written policies
and procedures such as quality programmes, quality plans, quality manuals and
quality records.

It shall, in particular, include an adequate
description of all elements listed in points (a), (b), (d) and (e) of Section
3.2 of Annex VIII.

3.3.
The provisions of points (a) and (b) of Section
3.3 of Annex VIII, apply.

If the quality system ensures that the devices
conform to the type described in the in the EU type-examination certificate and
conforms to the relevant provisions of this Regulation, the notified body shall
issue an EU quality assurance certificate. The decision shall be notified to
the manufacturer. It shall contain the conclusions of the inspection and a
reasoned assessment.

3.4.
The provisions of the Section 3.4 of Annex VIII
apply.

4.
Surveillance

The provisions of Section 4.1, the first,
second and fourth indents of Section 4.2, Section 4.3, Section 4.4, Section 4.6
and Section 4.7 of Annex VIII apply.

5.
Verification of manufactured devices
classified as class D

5.1.
In the case of devices classified as class D,
the manufacturer shall carry out tests on the manufactured devices or each
batch of devices. After the conclusion of the controls and tests he shall
forward to the notified body without delay the relevant reports on these tests.
Furthermore, the manufacturer shall make the samples of manufactured devices or
batches of devices available to the notified body in accordance with pre-agreed
conditions and modalities which shall include that the notified body or the manufacturer,
in regular intervals, shall send samples of the manufactured devices or batches
of devices to a reference laboratory, where designated in accordance with
Article 78, to carry out appropriate tests. The reference laboratory shall
inform the notified body about its findings

5.2.
The manufacturer may place the devices on the
market, unless the notified body communicates to the manufacturer within the
agreed time-frame, but not later than 30 days after reception of the samples,
any other decision, including in particular any condition of validity of
delivered certificates.

6.
Administrative provisions

The manufacturer or his authorised
representative shall, for a period ending at least five years after the last
device has been placed on the market, keep at the disposal of the competent
authorities:

–
the declaration of conformity,

–
the documentation referred to in the fourth
indent of Section 3.1 of Annex VIII,

–
the documentation referred to in the seventh
indent of Section 3.1 of Annex VIII, including the EU type-examination
certificate referred to in Annex IX,

–
the changes referred to in Section 3.4 of Annex
VIII and

–
the decisions and reports from the notified body
as referred to in Sections 3.3, 4.3 and 4.4 of Annex VIII.

Section 8 of Annex VIII shall apply.

ANNEX XI

MINIMUM CONTENT OF CERTIFICATES ISSUED BY A NOTIFIED
BODY

1.
Name, address and identification number of the
notified body;

2.
name and address of the manufacturer and, if
applicable, of the authorised representative;

3.
unique number identifying the certificate;

4.
date of issue;

5.
date of expiry;

6.
data needed for the identification of the
device(s) or categories of devices covered by the certificate, including the
intended purpose of the device(s) and the GMDN code(s) or internationally
recognised nomenclature code(s);

7.
if applicable, the manufacturing facilities
covered by the certificate;

8.
reference to this Regulation and the relevant
Annex according to which the conformity assessment has been carried out;

9.
examinations and tests performed, e.g. reference
to relevant standards / test reports / audit report(s);

10.
if applicable, reference to the relevant parts
of the technical documentation or other certificates required for the placing
on the market of the device(s) covered;

11.
if applicable, information about the surveillance
by the notified body;

12.
conclusions of the notified body's assessment,
examination or inspection;

13.
conditions for or limitations to the validity of
the certificate;

14.
legally binding signature of the notified body
according to the applicable national law.

ANNEX XII

CLINICAL EVIDENCE AND POST-MARKET FOLLOW-UP

Part
A: Clinical evidence

The
demonstration of conformity with the general safety and performance
requirements set out in Annex I, under the normal conditions of use of the
device, shall be based on clinical evidence.

The clinical
evidence includes all the information supporting the scientific validity of the
analyte, the analytical performance and, where applicable, the clinical
performance of the device for its intended purpose as stated by the
manufacturer.

1.
Scientific validity determination and performance
evaluation
1.1.
Scientific validity determination
1.1.1.
The scientific
validity refers to the association of the analyte to a clinical condition or a
physiological state.
1.1.2.
The determination of
the scientific validity may not be necessary where the association of the
analyte to a clinical condition or a physiological state is well known, based
on available information, such as peer reviewed literature, historical data and
experience.
1.1.3.
For a new analyte and/or
a new intended purpose, the scientific validity shall be demonstrated based on
one or a combination of the following sources:

–
information on devices measuring the same
analyte with the same intended purpose that have marketing history;

–
literature;

–
expert opinions;

–
results from proof of concept studies;

–
results from clinical performance studies.

1.1.4.
The information
supporting the scientific validity of the analyte shall be summarised as part
of the clinical evidence report.
1.2.
Performance evaluation

The performance
evaluation of a device is the process by which generated data are assessed and
analysed to demonstrate the analytical performance, and where applicable the
clinical performance of that device for its intended purpose as stated by the
manufacturer.

Interventional
performance studies and other clinical performance studies involving risks for
the subjects of the studies shall only be performed once the analytical
performance of the device has been established and determined to be acceptable.

1.2.1.
Analytical performance

1.2.1.1 The analytical performance
characteristics are described in point (a) of Section 6(1) of Annex I.

1.2.1.2 As a general rule, the analytical
performance shall always be demonstrated on the basis of analytical performance
studies.

1.2.1.3 For novel devices, it may not be
possible to demonstrate trueness since suitable higher order reference
materials or a suitable comparative method may not be available. If there are
no comparative methods, different approaches may be used (e.g. comparison to
some other well-documented method, comparison to the composite reference
method). In the absence of such approaches, a clinical performance study
comparing test performance to the current clinical standard practice would be
needed.

1.2.1.4 The analytical performance data
shall be summarised as part of the clinical evidence report.

1.2.2.
Clinical
performance

1.2.2.1 The
clinical performance characteristics are described in point (b) of Section 6(1)
of Annex I.

1.2.2.2
Clinical performance data may not be required for established and standardised
devices and for devices classified as class A according to the rules set out in
Annex VII.

1.2.2.3 Clinical performance of a device
shall be demonstrated based on one or a combination of the following sources

–
clinical performance studies;

–
literature;

–
experience gained by routine diagnostic testing.

1.2.2.4 Clinical performance studies shall
be performed unless it is duly justified to rely on other sources of clinical
performance data.

1.2.2.5
Clinical performance data shall be summarised as part of the clinical evidence
report.

1.2.2.6 When
the clinical performance evaluation includes a clinical performance study, the
level of detail of the clinical performance study report referred to in Section
2.3.3 of this Annex will vary based on the risk class of the device determined
according to the rules set out in Annex VII:

–
For devices classified as class B according to the rules set out in Annex VII,
the clinical performance study report may be limited to a summary of the study protocol, results and
conclusion;

–
For devices classified as class C according to the rules set out in Annex VII,
the clinical performance study report shall include the method of data analysis, the study conclusion and the
relevant details of the study protocol;

–
For devices classified as class D according to the rules set out in Annex VII,
the clinical performance study report shall include the method of data analysis, the study conclusion, the
relevant details of the study protocol and the individual data points.

2.
Clinical performance studies
2.1.
Purpose of clinical performance studies

The purpose of
clinical performance studies is to establish or confirm aspects of device
performance which cannot be determined by analytical performance studies,
literature and/or previous experience gained by routine diagnostic testing.
This information is used to demonstrate compliance with the relevant general safety
and performance requirements with respect to clinical performance. When
clinical performance studies are conducted, the data obtained shall be used in
the performance evaluation process and be part of the clinical evidence for the
device.

2.2.
Ethical considerations for clinical performance
studies

Every step in
the clinical performance study, from first consideration
of the need and justification of the study to the publication of the results, shall
be carried out in accordance with recognised ethical principles, as for example
those laid down in the World Medical Association Declaration of Helsinki on
Ethical Principles for Medical Research Involving Human Subjects adopted by the
18th World Medical Assembly in Helsinki, Finland, in 1964 and last
amended by the 59th World Medical Association General Assembly in
Seoul, Korea, in 2008.

2.3.
Methods for clinical performance studies
2.3.1.
Clinical performance
study design type

Clinical
performance studies shall be designed in such a way as to maximize the
relevance of the data while minimising potential biases. The design of the study shall provide the data necessary to address the
clinical performance of the device.

2.3.2.
Clinical performance
study protocol

Clinical
performance studies shall be performed on the basis of an appropriate 'clinical
performance study protocol'.

The clinical
performance study protocol shall set out how the study is intended to be
conducted. It shall contain information about the study design such as the
purpose, objectives, study population, description of test method(s) and
interpretation of results, site training and monitoring, specimen type,
specimen collection, preparation, handling and storage, inclusion and exclusion
criteria, limitations, warning and precautions, data collection/management,
data analysis, required materials, number of study sites and if applicable,
clinical endpoints/outcomes, and requirements for patient follow-up.

In addition,
the clinical performance study protocol shall identify the key factors which
may impact the completeness and significance of results, such as intended
participant follow-up procedures, decision algorithms, discrepancy resolution
process, masking/blinding, approaches to statistical analyses, and methods for
recording endpoints/outcomes and, where appropriate, communication of test
results.

2.3.3.
Clinical performance
study report

A 'clinical performance study
report', signed by a medical practitioner or any other authorised person
responsible, shall contain documented information on the clinical performance
study protocol, results and conclusions of the clinical performance study,
including negative findings. The results and conclusions shall be transparent,
free of bias and clinically relevant. The report shall contain sufficient
information to enable it to be understood by an independent party without
reference to other documents. The report shall also include as appropriate any
protocol amendments or deviations, and data exclusions with the appropriate
rationale.

3.
Clinical evidence report

3.1 The
clinical evidence report shall contain the scientific validity data, the
analytical performance data and, where applicable, the clinical performance
data. If the analytical
performance data is determined to be sufficient to declare conformity with the general safety and performance requirements set out to in Annex I without the need for clinical performance
data, a rationale should be documented and included in the clinical evidence report.

3.2 The
clinical evidence report shall in particular outline:

–
the justification for the approach taken to
gather the clinical evidence;

–
the technology on which the device is based, the
intended purpose of the device and any claims made about the device’s clinical
performance or safety;

–
the nature and extent of the scientific validity
and the performance data that has been evaluated;

–
how the referenced information demonstrate the
clinical performance and safety of the device in question;

–
the literature search methodology, if a
literature review is the approach taken to gathering clinical evidence.

3.3 The
clinical evidence and its documentation shall be updated throughout the life cycle of the device
concerned with data obtained from the implementation of
the manufacturer's post-market surveillance plan referred to in Article 8(5)
which shall include a plan for the device post-market follow-up in accordance with Part B of this Annex.

Part
B: Post-market follow-up

1.
Manufacturers shall put in place procedures to
enable them to collect and evaluate information relating to the scientific
validity, as well as the analytical and clinical performance of their devices
on the basis of data obtained from post-market follow-up.

2.
Where such information becomes available to the
manufacturer, an appropriate risk assessment shall be conducted and the
clinical evidence report shall be amended accordingly.

3.
Where changes to devices are necessary, the
conclusion of the post market follow-up shall be taken into account for the
clinical evidence referred to in Part A of this Annex and for the risk
assessment referred to in Section 2 of Annex I. If
necessary, the clinical evidence or risk management shall be updated and/or
corrective actions be implemented.

4.
Any new intended purpose of a device shall be
supported by an updated clinical evidence report.

ANNEX XIII

INTERVENTIONAL CLINICAL PERFORMANCE STUDIES AND OTHER
CLINICAL PERFORMANCE STUDIES INVOLVING RISKS FOR THE SUBJECTS OF THE STUDIES

I.            Documentation regarding the
application for interventional clinical performance studies and other clinical
performance studies involving risks for the subjects of the studies

For devices for performance evaluation
intended to be used in the context of interventional clinical performance
studies or other clinical performance studies involving risks for the subjects
of the studies the sponsor shall draw up and submit the application in
accordance with Article 49 accompanied by the documentation as laid down below:

1.         Application form

The application form shall be duly filled
out containing the following information:

1.1.   Name, address and contact details of
the sponsor and, if applicable, name, address and contact details of his contact
person established in the Union.

1.2.   If different from the above, name,
address and contact details of the manufacturer of the device intended for
performance evaluation and, if applicable, of his authorised representative.

1.3.   Title of the clinical performance
study.

1.4.   Single identification number in
accordance with Article 49(1).

1.5.   Status of the clinical performance
study (e.g. first submission, resubmission, significant amendment).

1.6.   If resubmission with regard to same
device, previous date(s) and reference number(s) of earlier submission(s) or in
the case of significant amendment, reference to the original submission.

1.7.   If parallel submission for a clinical
trial on a medicinal product in accordance with Regulation (EU) No [Ref. of future
Regulation on clinical trials], reference to the official registration number
of the clinical trial.

1.8.   Identification of the Member States,
EFTA countries, Turkey and third countries in which the clinical performance
study shall be conducted as part of a multicentre/ multinational study at the
time of application.

1.9.   Brief description of the device for
performance evaluation (e.g. name, GMDN code or internationally recognised
nomenclature code, intended purpose, risk class and applicable classification
rule according to Annex VII).

1.10  Summary of the clinical performance
study protocol.

1.11. If applicable, information regarding a
comparator.

2.         Investigator's Brochure

The investigator's brochure (IB) shall
contain the information on the device for performance evaluation that is
relevant for the study and available at the time of application. It shall be
clearly identified and contain in particular the following information:

2.1.   Identification and description of the
device, including information on the intended purpose, the risk classification
and applicable classification rule according to Annex VII, design and
manufacturing of the device and reference to previous and similar generations
of the device.

2.2.   Manufacturer's instructions for installation,
and use, including storage and handling requirements, as well as the label and
instructions for use to the extent that this information is available.

2.3.   Pre-clinical testing and experimental
data.

2.4.   Existing clinical data, in particular
the following:

–
relevant scientific literature available
relating to the safety, performance, design characteristics and intended
purpose of the device and/or of equivalent or similar devices;

–
other relevant clinical data available relating
to the safety, performance, design characteristics and intended purpose of
equivalent or similar devices of the same manufacturer, including length of
time on the market and a review of performance and safety related issues and
any corrective actions taken.

2.5.   Summary of the risk/benefit analysis
and the risk management, including information regarding known or foreseeable
risks and warnings.

2.6.   In the case of devices that include
tissues, cells and substances of human, animal or microbial origins detailed
information on the tissues, cells and substances, and on the compliance with
the relevant general safety and performance requirements and the specific risk
management in relation to the tissues, cells and substances.

2.7.   Reference to harmonised or other
internationally recognised standards complied with in full or in part.

2.8.   A clause that any updates to the IB or
any other relevant information that is newly available shall be brought to the
attention of the investigators.

3.         Clinical
performance study protocol, as referred to in Section 2.3.2 of Annex XII.

4.         Other information

4.1.   A signed statement by the natural or
legal person responsible for the manufacture of the device for performance
evaluation that the device in question conforms to the general safety and performance
requirements apart from the aspects covered by the clinical performance study
and that, with regard to these aspects, every precaution has been taken to
protect the health and safety of the subject. This statement may be supported
by an attestation issued by a notified body.

4.2.   Where applicable according to national
law, a copy of the opinion(s) of the ethics committee(s) concerned as soon as
available.

4.3.   Proof of insurance cover or
indemnification of subjects in case of injury, according to the national law

4.4.   Documents and procedures to be used to
obtain informed consent.

4.5    Description of the arrangements to
comply with the applicable rules on the protection and confidentiality of
personal data, in particular:

–
organisational and technical arrangements that
will be implemented to avoid unauthorised access, disclosure, dissemination,
alteration or loss of information and personal data processed;

–
a description of measures that will be
implemented to ensure confidentiality of records and personal data of subjects
concerned in clinical performance studies;

–
a description of measures that will be
implemented in case of data security breach in order to mitigate the possible
adverse effects.

II.          Other sponsor's obligations

1. The sponsor shall undertake to keep
available for the competent national authorities any documentation necessary to
provide evidence for the documentation referred to in Chapter I of this Annex.
If the sponsor is not the natural or legal person responsible for the manufacture
of the device intended for performance evaluation, this obligation may be
fulfilled by that person on behalf of the sponsor.

2. The reportable events shall be provided
by the investigator(s) in timely conditions.

3. The documentation mentioned in this Annex
shall be kept for a period of time of at least five years after the clinical
performance study with the device in question has ended, or, when the device is
subsequently placed on the market, at least five years after the last device
has been placed on the market.

Each Member State shall make provision that
this documentation is kept at the disposal of the competent authorities for the
period indicated in the preceding paragraph in case the sponsor, or his contact
person, established within its territory goes bankrupt or ceases its activity
prior to the end of this period.

ANNEX XIV

CORRELATION TABLE

Directive 98/79/EC || This Regulation

Article 1(1) || Article 1(1)

Article 1(2) || Article 2

Article 1(3) || Number (36) of Article 2

Article 1(4) || -

Article 1(5) || Article 4(4) and (5)

Article 1(6) || Article 1(6)

Article 1(7) || Article 1(4)

Article 2 || Article 4(1)

Article 3 || Article 4(2)

Article 4(1) || Article 20

Article 4(2) || Article 17(1)

Article 4(3) || Article 17(3)

Article 4(4) || Article 8(7)

Article 4(5) || Article 16(6)

Article 5(1) || Article 6(1)

Article 5(2) || -

Article 5(3) || Article 7

Article 6 || -

Article 7 || Article 84

Article 8 || Articles 67 to 70

Article 9(1) 1st subparagraph || Article 40(5) 1st subparagraph

Article 9(1) 2nd subparagraph || Article 40(3) 2nd subparagraph and (4) 2nd subparagraph

Article 9(2) || Article 40(2)

Article 9(3) || Article 40(3)

Article 9(4) || Article 40(7)

Article 9(5) || -

Article 9(6) || Article 9(3)

Article 9(7) || Article 8(4)

Article 9(8) || Article 41(1)

Article 9(9) || Article 41(3)

Article 9(10) || Article 43(2)

Article 9(11) || Article 40(8)

Article 9(12) || Article 45(1)

Article 9(13) || Article 5(2)

Article 10 || Article 23

Article 11(1) || Numbers (43) and (44) of Article 2, Article 59(1) and Article 61(1)

Article 11(2) || Article 59(3) and Article 61(1) 2nd subparagraph

Article 11(3) || Article 61(2) and (3)

Article 11(4) || -

Article 11(5) || Article 61(3) and Article 64

Article 12 || Article 25

Article 13 || Article 72

Article 14(1)(a) || Article 39(4)

Article 14(1)(b) || -

Article 14(2) || -

Article 14(3) || -

Article 15(1) || Article 31 and Article 32

Article 15(2) || Article 27

Article 15(3) || Article 33(1) and Article 34(2)

Article 15(4) || -

Article 15(5) || Article 43(4)

Article 15(6) || Article 43 (3)

Article 15(7) || Articles 29(2) and Article 33(1)

Article 16 || Article 16

Article 17 || Article 71

Article 18 || Article 73

Article 19 || Article 80

Article 20 || Article 75

Article 21 || -

Article 22 || -

Article 23 || Article 90

Article 24 || -

[1]               OJ L 331, 7.12.1998, p. 1.

[2]               OJ L 189, 20.7.1990, p. 17.

[3]               OJ L 169, 12.7.1993, p. 1.

[4]               EU Member States, EFTA countries and Turkey.

[5]               See http://ec.europa.eu/health/medical-devices/documents/revision/index_en.htm.

[6]               OJ L 247, 21.9.2007, p. 21.

[7]               OJ C 202, 8.7.2011, p. 7.

[8]               Resolution of 14 June 2012 (2012/2621(RSP));
P7_TA-PROV(2012)0262, http://www.europarl.europa.eu/plenary/en/texts-adopted.html

[9]               Communication from the President to the Commission of
10.11.2010, Framework for Commission Expert Groups: Horizontal Rules and Public
Registers, C(2010)7649 final.

[10]             Consisting of Regulation (EC)
No 765/2008 of the European Parliament and of the Council setting out the requirements for accreditation and market
surveillance relating to the marketing of products and repealing Regulation
(EEC) No 339/93, OJ L 218, 13.8.2008, p. 30, and
Decision No 768/2008/EC of the European Parliament and of the Council on a
common framework for the marketing of products, and repealing Council Decision
93/465/EEC, OJ L 218, 13.8.2008, p. 82.

[11]             http://www.ghtf.org/

[12]             OJ L 102, 23.4.2010, p. 45.

[13]             In accordance with Article 3(3) of Regulation (EEC,
EURATOM) No 1182/71 of the Council of 3 June 1971 determining the rules applicable
to periods, dates and time limits, (OJ L 124, 8.6.1971, p. 1) days referred to
in this Regulation mean calendar days.

[14]             OJ L 105, 26.4.2003, p. 18. This directive will be
replaced by a Commission Regulation (EU) No 722/2012 (OJ L 212, 9.8.2012, p. 3)
with effect from 29 August 2013.

[15]             COM(2012)369.

[16]             OJ L [...], [...], p. [...]

[17]             OJ C [...], [...], p. [...].

[18]             OJ C [...], [...], p. [...].

[19]             OJ C [...], [...], p. [...].

[20]             OJ L 331, 7.12.1998, p.1

[21]             OJ L 390, 31.12.2004, p. 24

[22]             OJ L 157, 9.6.2006, p. 24.

[23]             OJ L 159, 29.6.1996, p. 1.

[24]             OJ L 180, 9.7.1997, p. 22.

[25]             OJ L 1, 3.1.1994, p. 3.

[26]             OJ L 114, 30.4.2002, p. 369.

[27]             OJ 217, 29.12.1964, p. 3687

[28]             OJ L 204, 21.7.1998, p. 37, as amended by Directive
98/48/EC of the European Parliament and of the Council of 20 July 1998, OJ L
217, 5.8.1998, p. 18.

[29]             OJ C [...], [...], p. [...].

[30]             OJ L 218, 13.8.2008, p.30.

[31]             OJ L 218, 13.8.2008, p. 82.

[32]             Judgment of the Court of 28 July 2011 in joined cases
C-400/09 and C-207/10

[33]             OJ L 102, 23.4.2010, p. 45.

[34]             OJ L 281, 23.11.1995, p. 31.

[35]             OJ L 8, 12.1.2001, p. 1.

[36]             OJ L [...], [...], p. [...]

[37]             OJ L 55, 28.2.2011, p. 13.

[38]             OJ L 124, 20.5.2003, p. 36

[39]             OJ L 311, 28.11.2001, p. 67.

[40]             OJ L 353, 31.12.2008, p. 1.

[41]             OJ L 136, 29.5.2007, p.3.

[42]             OJ L 39, 15.2.1980.

[43]             OJ L 136, 30.4.2004, p. 1