Day 1 of 2 SHD

Capacity building Initiative for Trade
Development (CITD) in India
Capacity Building Initiative for

Trade Development in India (CITD)
Two Days Training on

EU Medical Device Directives and
Related Regulations for Accreditation
and Certification Bodies
How medical devices and in vitro
diagnostics are regulated
in the European Union (EU)
Capacity Building Initiative for Trade Development in India (CITD) Lot 1 SPS/TBT/Customs
INTRODUCTIONS
National Accreditation Board for

Collaboration Bodies (NABCB).
Honourable Invited Speakers.
Capacity Building Initiative for Trade

Development in India (CITD)
Mr. Nicola Antonopoulos,
Key Expert for Technical Regulations.
MAIN AIMS
To provide support to India in strengthening its capacity to
achieve economic growth and sustainable development,
through further integration into the global trading system.
To enhance the capacity of Indias trade-related regulatory
institutions and enforcement systems in order to meet
international standards, requirements and business needs.
To support Indias trade-related training institutions in
strengthening their capacities.
To learn specifically about the current New Approach
medical device directives and how the system works,
especially in regard to the use of standards.
To learn about the emerging new regulations for medical
devices and in vitro diagnostics.
This includes learning about Competent Authorities and
Notified Bodies, how they work and achieve certification.
3
Two Days Training on EU Medical Device Directives and

Related Regulations for Accreditation and Certification
Bodies, Mumbai, India, 29-30 August 2016 1
CONTENT
A. Day 1 morning
What is a medical device or diagnostic?
The key actors, Directives and Blue Guide.
Device classification, with interaction/examples.
Conformity Assessment Procedures (CAPs).
How it works in the European Union (EU).
The Essential Requirements (ERs).
Technical Documentation and Standards.
CONTENT
B. Day 1 afternoon
Specific In Vitro Diagnostic (IVD) considerations.
Quality Management System and ISO 13845.
Risk Management and ISO 14971.
Labelling, including practical exercise.
Clinical Evaluation and ISO 14155.
The Indian Certification of Medical Devices
Scheme (ICMED) presented by NABCB.
Questions and answers.
CONTENT
A. Day 2 morning
Review of Day 1.
Commission Recommendation on the Audits and
Assessment performed by Notified Bodies (NBs).
The International Medical Device Regulators
Forum (IMDRF) and the Medical Device Single
Audit Program (MDSAP).
Post-Market Surveillance (PMS) and Vigilance.

CONTENT
B. Day 2 afternoon
Combination Devices.
Regulation of Software, including ISO 62304.
Usability and Human Factors Engineering (HFE),
including comments on the design process.
The Designating Handbook and related MEDDEV.
Other Directives and Regulations to consider.
Introduction to the emerging Medical Device
Regulations (MDR) and In Vitro Diagnostic
Regulations (IVDR).
Closing remarks.
If in doubt please ask a question?

and always work as a team!
Please make your questions

short, helpful and of a general
nature wherever you can.
What is a medical device and

what is not

Common view of medical devices
Stethoscope
Needles
Syringes
Wound Dressings
Surgical scalpels
Sutures
X-Ray machines
Prosthetic legs
Heart valves
Joint replacements
but also includes the less obvious:
Standalone software
Medical Apps that meet the definition
of a medical device
Condoms, including those with a
medicinal component with an
ancillary action
Bone cement
Ostomy pouches
Fridges for storing blood
Surgical robots
Over The Counter self-diagnostics that
meet the definition of a medical device
Medical devices are diverse, from contact lenses to condoms, from

pregnancy test kits to MRI machines, and a wide assortment of
radiological devices.
Patient Blood Pressure Cuff Heart Valve
Examination
Table
Contact Lens
Infusion pump
Stethoscope
Pacemaker
Hip Implant
Biopsy Device
Test Strips

Examples of medical devices
14
15

What are NOT medical devices
Medicines Directive 2001/83/EC and

amendments.
Cosmetics EU Regulation 1223/2009.
Pure sports and leisure products with NO
medical intended purpose.
Note if a product sold to consumers does not fall
into medical device category, nor is a medicine,
nor a cosmetic then it will still be subject to the
General Product Safety Directive (GPSD)
Directive 2001/95/EC, e.g. a hot water bottle.
17
Examples of High Risk

Active Implantable Medical Devices
(AIMDs)
Pacemaker.
Cardioverter defibrillator.
Implantable muscle stimulator.
Implantable subthalamic
nucleus stimulator for the
treatment of Parkinsons
Disease.
18


Active Implantable Medical Devices
(AIMDs)
19

In Vitro Diagnostic Devices (IVDs)
List A blood grouping tests

List A HIV and hepatitis tests
List B blood grouping tests
Reagents for rubella testing
Reagents for toxoplasmosis
Reagents for prostate-specific antigen
(PSA) test
Self-diagnosis of blood-sugar
20
Examples of Low to Moderate Risk

In Vitro Diagnostic (IVD) Devices
Most tests not List A or List B

Most tests for self-diagnosis except for those
on List A or List B and for blood-sugar /
glucose for diabetic disease management
Pregnancy test
Molecular diagnostic tests for infectious
diseases on List A or List B but note these
can still have high consequences if incorrect
test results are provided to clinicians or
patients that influence the treatment provided
21

Medical Device Definition

means any instrument, apparatus, appliance,
software, material or other article, used on
human beings for the purpose of:
diagnosis, prevention, monitoring, treatment,
alleviation of disease
diagnosis, monitoring, treatment, alleviation of
or compensation for an injury or handicap
investigation, replacement or modification of
the anatomy or of a physiological process,
control of conception,
and does not achieve principal action by
pharmacological, immunological, or metabolic
means, but which may be assisted in its function
by such means.
22
Definition of an Accessory
means an article which whilst not being a device

is intended specifically by its manufacturer to be
used together with a device to enable it to be used
in accordance with the use of the device intended
by the manufacturer of the device.
Examples:
Steriliser for use in the medical environment
Water treatment device specifically for use with a
dialysis machine
Please note that accessories are treated exactly the

same as medical devices with regard to
classification, conformity assessment etc.
23
Definition of Pharmaceutical, i.e. Drug
Primary intended purpose is achieved by

physiological, metabolic or immunological means, i.e.
drug mode of action.
Expensive and lengthy regulatory process, generally

much longer and more expensive than even very
complex and novel devices.
Note a medical syringe intended for use in humans

without a drug is a medical device. BUT the same
product filled with a drug is regulated as a drug.
24

What is CE Marking?
CE Marking is an indication that a

manufacturer has declared the product
meets all the applicable Directives and
Regulations.
At the heart of this is the Manufacturer's
claim that the product meets the essential
requirements of all relevant European
Directives and related Regulations.
Directives define its size and appearance.
If a Notified Body is involved, then its
number appears under the CE Mark.
25
CE Marking is not a voluntary mark of

quality
26
CE marked products can be sold throughout

the European Economic Area
European Union (EU) Member States
EFTA: Norway, Iceland, Switzerland, Liechtenstein
.plus Turkey
27

Today:
[in theory if not real world practice]
a Single Market Authorization
28
How it works in one slide

European Commission and
Member States
Registrations Certification
Manufacturer and Audits
Surveillance
Enforcement (Inspections)
Competent Notified
Designation
Authority Surveillance Body
Enforcement
29
Competent Authorities and Notified Bodies
Role of Competent Authorities (CAs) and

Notified Bodies (NBs).
Designation of NBs and related guidance.
How the system works in the UK as an
example: the Medicines and Healthcare
products Regulatory Agency (MHRA).
30

The Role of Competent Authorities
The Competent Authority is the body authorised to act on

behalf of the government of an EC Member State to ensure
that the requirements of the medical devices directives are
carried out. They have responsibility for:
Working with the Commission on issues concerning the
directives on behalf of their Member State. This includes
working parties and items like global harmonisation.
Implementing the directives in their Member State and
ensuring products placed on the market are safe.
The appointment and monitoring of notified bodies, this
includes removing them, if necessary.
Monitoring of compliance. This includes resolving disputes
between manufacturers and notified bodies.
31
The Role of Competent Authorities
Operation of a vigilance system for the reporting of

adverse incidents by manufacturers.
Review and authorise applications from
manufacturers for clinical investigations of new
devices.
Decisions of doubt about product classifications or
referral of issues to the Commission.
For low risk IVDs, Class I devices, custom made
devices, or procedure packs receive notifications of
addresses of those placing them on the market.
They will inform other EU Member States and the
Commission.
Enforcement of the regulations.
32
The Role of Notified Bodies

A NB is a certification organisation which the Member
State CA designates to carry out one or more of the
conformity assessment procedures described in the
Annexes of the Directives. Key activities of a Notified
Body (NB) include:
Assessment and audit of manufacturers chosen
conformity assessment route, including discussion
with manufacturers about device classification, risk
analysis, validation methodology and of course the
essential requirements to an agreed time scale.
Notified body assessment will involve an audit of the
manufacturers quality system if this route is chosen
and can also involve type examination of the device
using harmonized and others standards to ensure
the essential requirements have been met. 33

The Role of Notified Bodies

Review of design dossiers for Class III devices and
high risk List A In Vitro Diagnostic (IVD) devices.
Checking manufacturers apply the CE mark correctly.
Checking manufacturers declared procedures,
including market surveillance activities, and significant
changes are maintained in a suitable manner.
Referral to the Competent Authority when trial
protocols are not followed correctly.
Manufacturers have to pay Notified Bodies for their
services.
A register of all Notified Bodies is available at:
http://ec.europa.eu/enterprise/newapproach/nando/
34
Notified Bodies Operation Group - NBOG
NBOG set up in 2000 by Member States & EC to

help improve the overall performance of NBs.
Primary function to identify and encourage best
practice by both NBs and CAs controlling them.
Aims to ensure a consistent level of expertise and
decision making across all NBs.
Please see http://www.nbog.eu
Do use NBOGs Best Practice Guides that indicate
what and how NBs should operate.
Do recommend NBOG guidance to manufacturers.
NBOG and guidance helps to establish the direction of
travel in compliance.
35
Notified Bodies Operation Group - NBOG
CAs & NBs / NBOG

do provide a peer group for review of good
performance and practice;
aim to ensure consistency of approach in the
designation and control of NBs;
detect common problems and issues;
encourage skills transfer between Member
States, CAs and NBs; and
promote best practice, especially via guidance
documents.
36

European Commission MEDDEV

Important Reference Guide
MEDDEV 2.10/2 Designation and

Monitoring of Notified Bodies within
the Framework of EC Directives on
Medical Devices (April 2001) is EC
level guidance for CAs designating
and controlling medical device NBs.
http://ec.europa.eu/growth/sectors/medical-
devices/documents/guidelines/files/meddev/2_10_2date04
_2001_en.pdf
37
NBOG Key Reference Guide

Designating Authorities Handbook
NBOG produced this very useful guide that is
strongly recommended when
appointing/designating and monitoring NBs.
It does provide manufacturers with useful
background and insights (113 pages).
It (including several Appendices) does cover the
whole process from setting designation criteria,
assessing and selecting NB candidates, initial
assessments, surveillance assessments and
related follow-up.
http://www.nbog.eu/resources/da_handbook.pdf
38
NB-MED Documents
NB-MED are guidance documents produced by

TEAM-NB (The European Association Medical
devices - Notified Bodies) please see:
http://www.team-nb.org/ and click on
Documents.
These guidance documents are vital reading for
both prospective notified bodies and important
for manufacturers (useful background).
BUT please note many of these are now very
dated and it is more important to pay attention
to current MEDDEVs, NBOG and CA guidance
documents and harmonised standards.
39

How the system works in the EU
Key focus on manufacturers responsibilities.

Centres on compliance with The Essential Requirements
(ERs) of the New Approach directives.
Voluntary use of harmonized standards encouraged and
proof of compliance provides a presumption of
compliance with the relevant ERs.
Labelling is very important for compliance.
Post market surveillance is vital and acting upon
complaints / information from competitors, users, other
regulators and the public is all a part of this.
40
Manufacturers in the UK have to pay for registering

Class I devices (GBP70).
Notified Bodies (NBs) are commercial organisations and
requiring paying for their services ranging from GBP low
thousands for low risk devices to many thousands for
high risk devices. Larger product ranges and more
complex devices tend to cost more.
Competent Authorities (CAs) are generally funded by
Member State governments.
In some Member States there are some small additional
fees for local registration requirements. 41
Manufacturers in the UK have to the CA, The Medicines

and Healthcare product Regulatory Agency (MHRA) for
reviewing clinical investigation submissions ranging
from GBP3820 for Class I, IIa or IIb other than an
implantable or long-term invasive device to GBP5040
for implantable, long-term invasive and Class III
devices.
Drug device combination GBP4136 with a known
substance up to GBP42296 for a device incorporating a
new active substance.
Please see https://www.gov.uk/notify-mhra-about-a-
clinical-investigation-for-a-medical-device
42

How the system works in the UK
The UK Competent Authority (CA) for both

pharmaceutical and medical device regulation is
the Medicines and Healthcare products
Regulatory Agency (MHRA).
The MHRA is one of the leading CAs in Europe
with an excellent web site that has lots of
guidance - all in English. Please do use
www.mhra.gov.uk
Check when needed with the Europa web site:
http://ec.europa.eu/growth/sectors/medical-
devices/index_en.htm
43
The MHRA is an agency of the Department of

Health that is responsible for public health.
We enhance and safeguard the health of
the public by ensuring that medicines and
medical devices work and are acceptably
safe. No product is risk free.
Underpinning all our work lie robust and
fact-based judgements to ensure that the
benefits to patients and the public justify the
risks.
44
GMP and GDP!
The MHRA provides guidance does

include DISTRIBUTION:
Comply with good manufacturing
practice (GMP) and good
distribution practice (GDP), and
prepare for an inspection.
https://www.gov.uk/good-
manufacturing-practice-and-good-
45 distribution-practice

Corporate Governance
The MHRAs corporate governance is achieved via
structures and processes that are designed to ensure
accountability and a framework for risk management:
The Agency Board is made up of a non-executive Chairman,
non-executive members and the Agency's Chief Executive
Officer.
The Agency's Chief Executive is responsible for service
delivery and resources.
The Executive Board, consisting of the Agency's directors,
takes overall responsibility for day-to-day management,
strategic decision-making, line management, and all financial,
policy, operational and resource management issues.
The Risk and Audit Committee provides independent feedback
to the Chief Executive, who is also the Accounting Officer, and
the Management Board on the effectiveness of the risk
management processes. The Committee is supported by the
Agency's Risk Management Team. 46
The Directives are transposed in National

Law through Statutory Instruments 2002
No. 618 (consolidated legislation) and
subsequent amendments.
The latest is Medical Devices
(Amendment) Regulations 2008 No 2936
which transposes Directive 2007/47/EC
the Revision.
These Statutory Instruments are issued
under the Consumer Protection Act.
For more and relevant links please see:
http://www.mhra.gov.uk/Howweregulate/Devices/index.htm 47
MHRA Guidance on
Designating and Monitoring NBs
MHRA is the UK designating authority for medical

device NBs and has produced Guidance on
legislation Requirements for UK Notified Bodies
(November 2013):
https://www.gov.uk/government/uploads/system/uploads/at
tachment_data/file/377799/Requirements_for_UK_notified
_bodies.pdf
MHRA assess the suitability of NBs to ensure they

are impartial and have the appropriate expertise,
i.e. people to undertake quality system audits;
product verification; type and design examination.
It is effectively a succinct summary of the other
extensive guidance already indicated.

Competent Authorities and Notified Bodies
Key focus on public health and market

surveillance both pre- and post- market.
Increasingly sensitive to Public and Political
Pressure.
Knowing who to contact is vital both ways.
Will work with you if you work with them,
with respect and consideration to their
demanding role in our society.
Succinct philosophic summary:
First do no harm
49
What is CE Marking?
CE Marking is an indication that a manufacturer

has declared the product meets all the
applicable Directives and Regulations.
At the heart of this is the Manufacturer's
claim that the product meets the
essential requirements of all relevant
European Directives and related
Regulations.
Directives define its size and appearance.
If a Notified Body is involved, then its
number appears under the CE Mark.
50
Transposition of Directives always raises

the need for National Language use
Icelandic:
Iceland* Swedish:
Norwegian:
Sweden
Norway*
English:
UK
Ireland Danish: Finnish: Finland
Denmark Estonian: Estonia
Dutch:
Netherlands Latvian: Latvia
Belgium Lithuanian: Lithuania
German:
French: Belgium Germany,
France Liechtenstein*,
Luxembourg Luxembourg
Austria
Czech: Czech Republic Polish: Poland
Letzeburgish:Luxembourg
Hungarian: Hungary
Portuguese: Portugal
Spanish: Italian:
Slovene: Slovenia Spain
Italy
English/(Maltese): Malta
Non-EEA countries that recognise CE-marking: Switzerland
Slovak: Slovakia
(German, French, Italian)
Greek: Greece - Cyprus

Europe
EC Medical Device Homepage
The European Commission home page for medical

devices of all kinds, including IVDs with useful links
to the directives and other relevant documents is:
https://ec.europa.eu/growth/sectors/medical-devices_en
MEDDEV and Notified Body Recommendations,

Consensus Statements, interpretative documents,
links to harmonised standards, the New Approach
Revision and more is available from the regulatory
framework page:
http://ec.europa.eu/growth/sectors/medical-devices/regulatory-
framework_en
53
Three Main Medical Device Directives
Active Implantable Medical Devices (AIMDD),

90/385/EEC, published on June 20, 1990.
Medical Devices Directive (MDD), 93/42/EEC,

published June 14, 1993 (MDD).
IVD Directive (IVDD), 98/79/EC, published on 27

October 1998.
Plus Commission Decision of 7 May 2002 on common
technical specifications for in vitro-diagnostic medical
devices (CTS, 2002/364/EC) for Annex II, List A IVDs.
Each had a transition period of 3-5 years, compliance

is now mandatory. Each has undergone various
amendments.
54

Other Amendments
Classification Directives
Breast implants (2003/12/EC)
Hip, knee and shoulder prostheses
(2005/50/EC)
Devices manufactured using animal origin tissues
Directive 2003/32/EC
Commission Regulation (EU) 722/2012
Commission Decisions
EUDAMED (2010/227/EU)
IVD Common Technical Specifications
(2002/364/EC etc.)
Commission Regulation (EU) 207/2012 on
electronic Instructions for Use 55
Custom-Made Devices
Any device specifically made in accordance with a

duly qualified medical practitioners written
prescription which gives under his responsibility,
specific design characteristics and,
Is intended for the sole use on a particular
patient
The abovementioned prescription may also be
made out by any other person authorized by
virtue of his professional qualifications to do so
Mass-produced devices which need to be adapted
to meet specific requirements of the medical
practitioner or any other professional user shall
not be considered to be custom-made devices
56
Humanitarian Use
The Competent Authorities may authorise, on

a duly justified request, the placing on the
market and putting into service, within the
territory of the Member State concerned, of
individual devices for which the (conformity
assessment) procedures have not been carried
out and the use of which is in the interest of
protection of health.
Please note this is only ever granted in rare,

very exceptional circumstances.
57

What is important to those seeking

the CE marking?
Manufacturers need to address the following:

Obtain, read and understand the appropriate
medical device directives plus any other applicable
directives and regulations. This includes such
things as the Packaging and Packaging Waste
Directive (PPWD).
Classify their products based on the intended use
and classification criteria given in the directives.

the CE marking?

Decide on their Conformity Assessment Procedure
and the need for a Notified Body, European
Authorised Representative (EC REP) and any
registrations with Competent Authorities.
Search, locate, review and obtain relevant
standards, especially those harmonised to the
directives and use them to demonstrate how the
Essential Requirements (ERs) are complied with.

the CE marking?
Complete Clinical Evaluation, i.e. both clinical
literature review and any clinical investigations
(trials) or performance evaluations for In Vitro
Diagnostics (IVDs).
Set up a basic Quality Management System (QMS)
to ensure the requirements of the Conformity
Assessment Procedure is met in full. It is
recommended that the manufacturer works
towards ISO 13485: 2012 Medical devices. Quality
management systems Requirements for
regulatory purposes which has become the world
standard for medical device quality systems.


the CE marking?
The QMS should incorporate procedures for
design; development; manufacturing;
distribution; post market surveillance, including
customer complaints and vigilance; post market
clinical follow-up; and translations.
Guidance and Direction
The European Commission does publish helpful

regulatory guidance in the form of MEDDEVs these
need to be followed wherever possible.
Recommendations provide insights on specific topics like
Unique Device Identification (UDI) and audits.
Consensus statements and interpretative documents provide
insights on regulatory process and demarcation between
directives.
Lists of harmonised standards applicable to each main
directive are published in the Official Journal (OJ) and should
be implemented wherever possible.
International standards are encouraged to be used and
Notified Body guidance (NBOG & NB-MEDs) help with
understanding what is expected.
Harmonised Standards and ERs
Harmonised standards help all stakeholders

understand what is required to meet the Essential
Requirements (ERs) given in the first annex of each
directive.
The use of such standards is voluntary but when

used can provide a presumption of conformity to
the scope of the standard against specific ERs.
Any other standard or method has to be at least as

comprehensive as the harmonised standard.

European Commission working committees provide

useful insights and guidance that helps to define the
state-of-the-art and regulator expectations, these
include:
MDEG - Medical Device Experts Group.
NBOG Notified Body Operations Group.
CIE Working Group on Clinical Investigations and
Evaluations.
NET New and Emerging Technologies working
group.
Plus there are groups for vigilance; classification and
borderline; compliance and enforcement; IVDs;
electronic labelling; and the Eudamed database.
http://ec.europa.eu/growth/sectors/medical-devices_en
Other Sources of Guidance

include:
National Trade Associations such as ABHI, BIVDA,
BVMed, SNITEM, Assobiomedica, Swedish Medtech,
etc.
European Trade Associations such as EUCOMED,
EDMA, COCIR etc.
Product or regionally specific industry groups.
Consultants, lawyers, and product testing
organisations.
Legal Status of Directives and Guidance

Directives are not in themselves law and only
become so by National Law implemented in each
and every Member State.
Regulations are directly applicable to all Member
States without implementing legislation and are
binding. The use of regulations is increasing for
medical devices.
Decisions are directly applicable to all Member
States, enterprises and individuals without
implementing legislation and are binding.
Recommendations and Opinions are not binding
but do help define the state-of-the-art that is
expected from those skilled in the art. Useful to
follow for strict liability considerations where
relevant and reasonable to do so.

Content and Structure of

Directive 93/42/EEC (MDD)
Recitals set the context sat the time of

publication to assist with interpretation.
Articles sets out what to do and becomes the

foundation for national law.
Annexes sets out how the manufacturer can

comply.
Articles of MDD
1. Definitions, scope 13. Decisions with regard to
2. Placing on the market and classification and derogation
putting into service clause
3. Essential requirements 14. Registration of persons
4. Free movement, devices intended responsible for placing devices on
for special purposes the market 14a. European
databank 14b. Particular health
5. Reference to standards monitoring measures
6. Committee on Standards and 15. Clinical investigation
Technical Regulations
16. Notified bodies
7. Article 7 Committee
17. CE marking
8. Safeguard clause
18. Wrongly affixed CE marking
9. Classification
19. Decision in respect of refusal or
10. Information on incidents restriction
occurring following placing of
devices on the market 20. Confidentiality 20a. Cooperation
11. Conformity assessment 21. Repeal and amendment of
procedures Directives
12. Particular procedure for systems 22. Implementation, transitional
and procedure packs and provisions
procedure for sterilisation 12a. 23. Addressed to Member States
Reprocessing of medical devices
Annexes of MDD 93/42/EEC

Annex I Essential Requirements
Annexes II to VI cover the possible Conformity Assessment
Procedures to CE marking
Annex II Full quality assurance system
Annex III EC Type-Examination
Annex IV EC Verification
Annex V Production quality assurance
Annex VI Product quality assurance
Annex VII EC Declaration of Conformity
Annex VIII Statement concerning devices for Special
Purposes
Annex IX Classification Criteria
Annex X Clinical Evaluation
Annex XI Criteria to be met for the Designation of Notified
Bodies
Annex XII CE Marking of Conformity

Directive 93/42/EEC Amendments
M1 98/79/EC In Vitro Diagnostic Medical Devices.

M2 2000/70/EC Amendment concerning Medical
Devices containing human blood or plasma
derivatives.
M3 2001/104/EC Corrigendum concerning Medical
derivatives.
M4 Regulation 1882/2003 Regulation for
Committees assisting the EU Commission.
M5 2007/47/EC amending 90/385/EEC and
93/42/EEC.
70
Scope of Directives
Medical Device Directives regulate, via National

Law, the placing on the market and putting into
service of medical devices.
Directives do NOT cover:
Reimbursement
Distribution
Health Technology Assessment (HTA)
So where do Economic Operators fit in?
Surveillance
Competent Notified
Designation
Enforcement
72

EU Blue Guide 2014 and 2016

http://ec.europa.eu/DocsRoom/documents/18027 for latest 26th July 2016 version.
Please read this to fully

understand the Directives!
It describes the operation of

the framework within which
all EU Directives, including
those for Medical Devices
operate.
Latest version has a plain

cover and was published in
the Official Journal of the
European Union (OJ) on the
26th July 2016.
Economic Operators
P28-38 of the Blue Guide covers:

3. THE ACTORS IN THE PRODUCT SUPPLY
CHAIN AND THEIR OBLIGATIONS
3.1 Manufacturer
3.2 Authorised Representative
3.3 Importer
3.4 Distributor
The following are not defined as

Economic Operators:
3.5 Other Intermediaries: Intermediary
Service Providers under the E-Commerce
Directive.
3.6 End-User
Economic Operators
3.4. DISTRIBUTOR
The distributor is a natural or a legal person in the supply
chain, other than the manufacturer or the importer, who
makes a product available on the market.
Distributors are subject to specific obligations and have a
key role to play in the context of market surveillance.
Along with manufacturers and importers, distributors are the
third category of economic operators who are subject to
specific obligations. The distributor is a natural or a legal
person in the supply chain, other than the manufacturer or
the importer, who makes a product available on the
market.

Economic Operators
Only manufacturer and authorised representative

(EC REP) defined in the current Medical Directives
and both are considered to be Economic
Operators.
P15 of the Blue Guide 2014, note 35, states:This

implies that the economic operator that offers the
product has to be in a position to provide the
evidence that the product complies with the
applicable requirements i.e. by providing the
technical file on request of a market surveillance
authority.
Economic Operators
The manufacturer, EC REP, distributor,

Economic Operators are defined in the New
Legislative Framework and the Blue Guide.
P99 of the latest 2016 Blue Guide states:
All economic operators have a role and

obligations in market surveillance.
Device Classification
78

Risk Based Classification System
Most stringent ERs and Class III, few devices

regulations highest risk
Most ERs apply, Class II, most devices

modest touch modest risk
Minimum ERs and Class I, many devices

documentation, low risk
light touch
Device Classification Annex IX
18 rules to classify devices based on:

Intended use
Duration of use
Combination of devices used
Level of invasiveness
Transference of power
Special rules
Class I (lowest), IIa, IIb, III (highest)
Classes
Class I - low risk

Class I Sterile
Class I with a Measuring Function
Class IIa - medium risk
Classes IIb & III - high risk

Examples of Low Risk

Class I Medical Devices
Tongue depressor
Stethoscope
Examination gloves (not surgical)
Reusable surgical instruments, including dental
instruments and items like forceps
Absorbent pads for use on intact skin
Dressings specifically for nose bleeds
Non-invasive electrodes
Syringe without needle
Wheelchair
Patient hoist
Simple orthotic products for use on intact skin
82

Class IIa Medical Devices
Surgical gloves
Tubing for use with an infusion pump or blood
Simple wound dressings (without an ancillary medicine and
not made from animal products) that are primarily
designed to manage the micro-environment
Fixed dental prostheses such as bridges and crowns
Suction catheters or tubes for stomach drainage
Surgical needles for suturing
Surgical staplers
TENS device or similar muscle stimulator
Phototherapy device, ideally for neonatal jaundice
Hearing aid
Physiotherapy equipment
83
Examples of Moderate Risk

Class IIb Medical Devices
Condom; Blood bag; Apnoea Monitor
Advanced wound dressings (without an ancillary
medicine and not made from animal products) that
are primarily designed to be used on wounds that
have breached the dermis and can only heal by
secondary intent
Contact lens cleaning solutions
Denture disinfecting solutions
Hemodialyser filter
Prosthetic joint replacement (not covered by Directive
2005/50/EC)
Surgical laser; Incubator for babies; Warming
blankets
Blood warmers; Therapeutic radiation sources 84


Class III Medical Devices
Absorbable sutures; Implantable replacement joint
Contraceptive intrauterine devices (IUDs)
Catheters intended for use in the central circulatory
system
Neuro-endoscopes that come into direct contact with
the central nervous system (CNS); CNS electrodes
Brain spatulas; Spinal cord retractors; Spinal needles
Wound dressings with an ancillary medicine
incorporated into them, such as silver
Wound dressing or other device using animal derived
products that require special controls, such as
products containing collagen, porcine xenograft
dressings or utilizing hyaluronic acid of animal origin
Duration of Contact
Up to 60 minutes - transient
Up to 30 days --- short term
Beyond 30 days ----- long term

In calculating the duration referred to in Section 1.1 of Chapter I,
continuous use means an uninterrupted actual use of the device for
the intended purpose. However where usage of a device is
discontinued in order for the device to be replaced immediately by
the same or an identical device this shall be considered an
extension of the continuous use of the device.
Degree of Invasiveness
Application to body surface or into

body orifice (mouth as far as pharynx)
Surgically invasive
Implantable

The Central circulatory system

For the purposes of this Directive, central
circulatory system means the following vessels:
arteriae pulmonales, aorta ascendens, arcus
aorta, aorta descendens to the bifurcatio aortae,
arteriae coronariae, arteria carotis communis,
arteria carotis externa, arteria carotis interna,
arteriae cerebrales, truncus brachiocephalicus,
venae cordis, venae pulmonales, vena cav
superior, vena cava inferior.
The Central nervous system

For the purposes of this Directive,
central nervous system means brain,
meninges and spinal cord.
Non-Invasive Devices Rules 1 to 4
Class I unless other Rules apply, e.g.

administration, filtration of blood etc. are Class IIa.
Highest rule applicable determines classification.
All non-invasive devices intended for modifying the
biological or chemical composition of blood, other
body liquids or other liquids intended for infusion
into the body are in Class IIb, unless the treatment
consists of filtration, centrifugation or exchanges
of gas, heat, in which case they are in Class IIa.
Contact with injured skin Class I, IIa or IIb.

Invasive Devices Rule 5
All invasive devices with respect to body orifices, other than

surgically invasive devices and which are not intended for
connection to an active medical device or which are intended
for connection to an active medical device in Class I:
are in Class I if they are intended for transient use,
are in Class IIa if they are intended for short-term use,
except if they are used in the oral cavity as far as the pharynx,
in an ear canal up to the ear drum or in a nasal cavity, in which
case they are in Class I,
are in Class IIb if they are intended for long-term use,
in an ear canal up to the ear drum or in a nasal cavity and are
not liable to be absorbed by the mucous membrane, in which
case they are in Class IIa. All invasive devices with respect to
body orifices, other than surgically invasive devices, intended
for connection to an active medical device in Class IIa or a
higher class, are in Class IIa.
Transient Invasive, Rule 6
All surgically invasive devices intended for

transient use are in Class IIa unless they are:
intended specifically to control, diagnose,
monitor or correct a defect of the heart or of
the central circulatory system through direct
contact with these parts of the body, in which
case they are in Class III,
reusable surgical instruments, in which case
they are in Class I,
intended specifically for use in direct
contact with the central nervous system, in
which case they are in Class III,
intended to supply energy in the form of

ionising radiation in which case they are in
Class IIb,
intended to have a biological effect or to be
wholly or mainly absorbed in which case they
are in Class IIb,
intended to administer medicines by means of

a delivery system, if this is done in a manner
that is potentially hazardous taking account of
the mode of application, in which case they are
in Class IIb.

Short Term Invasive, Rule 7
All surgically invasive devices

intended for short-term use are in
Class IIa unless they are intended:
either specifically to control,
diagnose, monitor or correct a defect
of the heart or of the central
circulatory system through direct
contact with these parts of the body,
in which case they are in Class III,
or specifically for use in direct contact with the

central nervous system, in which case they are
in Class III,
or to supply energy in the form of ionizing
radiation in which case they are in Class IIb,
or to have a biological effect or to be wholly or
mainly absorbed in which case they are in
Class III,
or to undergo chemical change in the body,
except if the devices are placed in the teeth, or
to administer medicines, in which case they are
in Class IIb.
Long Term Invasive, Rule 8
All implantable devices and long-term surgically invasive

devices are in Class IIb unless they are intended:
to be placed in the teeth, in which case they are in
Class IIa,
to be used in direct contact with the heart, the central
circulatory system or the central nervous system, in
to have a biological effect or to be wholly or mainly
absorbed, in which case they are in Class III,
or to undergo chemical change in the body, except if
the devices are placed in the teeth, or to administer
medicines, in which case they are in Class III.

Active Devices Rule 9
All active therapeutic devices intended to administer

or exchange energy are in Class IIa unless their
characteristics are such that they may administer or
exchange energy to or from the human body in a
potentially hazardous way, taking account of the
nature, the density and site of application of the
energy, in which case they are in Class IIb.
All active devices intended to control or monitor the

performance of active therapeutic devices in Class IIb,
or intended directly to influence the performance of
such devices are in Class IIb.
Active devices intended for diagnosis are in Class IIa:

if they are intended to supply energy which will be
absorbed by the human body, except for devices
used to illuminate the patient's body, in the visible
spectrum,
if they are intended to image in vivo distribution of
radiopharmaceuticals,
Note:Stand alone software is considered to be

an active medical device
if they are intended to allow direct diagnosis or

monitoring of vital physiological processes, unless
they are specifically intended for monitoring of vital
physiological parameters, where the nature of
variations is such that it could result in immediate
danger to the patient, for instance variations in
cardiac performance, respiration, activity of CNS in
which case they are in Class IIb. Active devices
intended to emit ionizing radiation and intended for
diagnostic and therapeutic interventional radiology
including devices which control or monitor such
devices, or which directly influence their performance,
are in Class IIb.

All active devices intended to administer and/or

remove medicines, body liquids or other substances
to or from the body are in Class IIa, unless this is
done in a manner:
that is potentially hazardous, taking account of
the nature of the substances involved, of the part
of the body concerned and of the mode of
application in which case they are in Class IIb.
All other active devices are in Class I.
Special Rules Rule 13
All devices incorporating, as an integral part, a

substance which, if used separately, can be
considered to be a medicinal product, as
defined in Article 1 of Directive 2001/83/EC,
and which is liable to act on the human body
with action ancillary to that of the devices, are
in Class III.
human blood derivative are in Class III.

All devices used for contraception or the

prevention of the transmission of sexually
transmitted diseases are in Class IIb, unless
they are implantable or long term invasive
devices, in which case they are in Class III.
All devices intended specifically to be used for

disinfecting, cleaning, rinsing or, when appropriate,
hydrating contact lenses are in Class IIb.
disinfecting medical devices are in Class IIa. Unless
they are specifically to be used for disinfecting
invasive devices in which case they are in Class IIb.
This rule does not apply to products that are intended

to clean medical devices other than contact lenses by
means of physical action.
Devices specifically intended for recording

of X-ray diagnostic images are in Class IIa.

Special Rules Rules 17 and 18
Rule 17: All devices manufactured utilizing

animal tissues or derivatives rendered non-viable
are Class III except where such devices are
intended to come into contact with intact skin
only.
Rule 18: By derogation from other rules, blood

bags are in Class IIb.
Classification More Guidance

The key classification guidance is
MEDDEV 2. 4/1 Rev. 9, June 2010 please see the
flow charts in it!
and for stand alone software is

MEDDEV 2.1/6, January 2012.
and for Borderline products, drug-delivery

products and medical devices incorporating, as
an integral part, an ancillary medicinal substance
or an ancillary human blood derivative is
MEDDEV 2.1/3 rev 3
If any doubt then discuss with your Notified Body

and/or Competent Authority.

Please note it is always important to double check with the:
MANUAL ON BORDERLINE AND
CLASSIFICATION IN THE COMMUNITY
REGULATORY FRAMEWORK FOR MEDICAL
DEVICES Version 1.17 (09-2015)
It does provide specific example rulings
that can help you with the same and
similar devices.
Best to search on title to find the location
at the Europa web site and make sure you
have the latest version. It does get
updated periodically with new rulings.

Since 2007 Directive 2005/50/EC on the

reclassification of hip, knee and
shoulder joint replacements applies to
total joint replacement systems (not
ancillary components like screws, wedges,
plates or instruments) has made such
systems Class III.

reclassification of breast implants has
made such devices Class III.
Combination Products
There are extra requirements for devices incorporating

a medicine (as per MDD Annex IX Rule 13 & Annex I
paragraph 7.4; and AIMDD Annex 1 paragraph 10) and
the manufacturer must demonstrate the usefulness of
the substance as part of the medical device and
taking account of the intended purpose of the
Device to the Notified Body (NB) who then seeks a
scientific opinion from one of the competent authorities
designated by the Member States or the European
Medicines Agency (EMEA).
When issuing its opinion, the competent authority or the

EMEA shall take into account the manufacturing process
and the data related to the usefulness of incorporation of
the substance into the device as determined by the
notified body.
Pharmaceutical, i.e. Drug
Primary intended purpose is achieved by

physiological, metabolic or immunological means, i.e.
drug mode of action.
Expensive and lengthy regulatory process, generally

much longer and more expensive than even very
complex and novel devices.
Note a medical syringe intended for use in humans

without a drug is a medical device. BUT the same
product filled with a drug is regulated as a drug.
111

Combination Products
There are extra requirements for devices incorporating a

human blood derivative product (as per MDD Annex
IX Rule 13 & Annex I paragraph 7.4; and AIMDD Annex 1
paragraph 10) and the manufacturer must demonstrate
the usefulness of the substance as part of the
medical device and taking account of the intended
purpose of the Device to the Notified Body (NB) who
then seeks a scientific opinion from one the European
Medicines Agency (EMEA).
When issuing its opinion, the EMEA shall take into account
the manufacturing process and the data related to the
usefulness of incorporation of the substance into the
device as determined by the notified body.
Combination Products Review Time
For combination products, either incorporating a medicine

or a human blood derivative product (as per MDD Annex
IX Rule 13 & Annex I paragraph 7.4; and AIMDD Annex 1
paragraph 10) the relevant and appropriate Competent
Authority (CA) / EMEA can take up to 210 days to provide
an opinion.
210 days is around 7 months!
Combination Products - Classification
Combination products are Class III under Annex IX,

Rule 13 for ancillary medicines and blood;
Rule 17 for animal tissues.

Devices incorporating Animal Products

For combination products incorporating animal derived
tissues then the requirements of Commission
Regulation (EU) No. 722/2012 concerning particular
requirements as regards the requirements laid down
in Council Directives 90/385/EEC with respect to
active implantable medical devices and medical
devices manufactured utilizing tissues of animal
origin will apply. All requirements provided in MDD Annex
I para 8 must be fully complied with.
The standards associated with animal tissues, that
is the EN ISO 22442 series should be treated as de
facto mandatory.
The sourcing and control of the animal origins must be
rigorous and designed to minimise the risk of any possible
infection for humans.
Vital Standards to use when considering

devices incorporating Animal Products
EN ISO 22442-1:2015 Medical devices utilizing animal tissues

and their derivatives. Application of risk management.
and their derivatives. Controls on sourcing, collection and
handling.
and their derivatives. Validation of the elimination and/or
inactivation of viruses and transmissible spongiform
encephalopathy (TSE) agents.
PD ISO/TR 22442-4:2010 Medical devices utilizing animal
tissues and their derivatives. Principles for elimination and/or
inactivation of transmissible spongiform encephalopathy (TSE)
agents and validation assays for those processes.

For combination products incorporating animal derived
tissues then the requirements of Commission
Regulation (EU) No. 722/2012 concerning particular
requirements as regards the requirements laid down
in Council Directives 90/385/EEC with respect to
active implantable medical devices and medical
devices manufactured utilizing tissues of animal
origin will apply. All requirements provided in MDD Annex
I para 8 must be fully complied with.
The standards associated with animal tissues, that
is the EN ISO 22442 series should be treated as de
facto mandatory.
The sourcing and control of the animal origins must be
rigorous and designed to minimise the risk of any possible
infection for humans.

Article 5 of Commission Regulation 722/2012 makes

it clear what the Notified Body (NB) should examine
very carefully:
(a) the manufacturers risk analysis and risk
management process;
(b) the justification for the use of animal tissues or
derivatives, taking into consideration lower risk
tissues or synthetic alternatives;
(c) the results of elimination and inactivation studies
or results of the analysis of relevant literature;

Article 5 of Commission Regulation 722/2012 makes
it clear what the Notified Body (NB) should examine
very carefully:
(d) the manufacturers control of the sources of raw
materials, finished products, production process,
testing, and subcontractors;
(e) the need to audit matters related to the sourcing
and processing of animal tissues and derivatives,
processes to eliminate or inactivate pathogens,
including those activities carried out by suppliers.
Any changes to such devices needs to be fully
discussed with the NB and where applicable needs to
be approved by the NB prior to implementation.

the CE marking?

Obtain, read and understand the appropriate
medical device directives plus any other applicable
directives and regulations. This includes such
things as the Packaging and Packaging Waste
Directive (PPWD).
Classify their products based on the intended use
and classification criteria given in the directives.


the CE marking?

Decide on their Conformity Assessment Procedure
and the need for a Notified Body, European
Authorised Representative (EC REP) and any
registrations with Competent Authorities.
Search, locate, review and obtain relevant
standards, especially those harmonised to the
directives and use them to demonstrate how the
Essential Requirements (ERs) are complied with.

the CE marking?
Complete Clinical Evaluation, i.e. both clinical
literature review and any clinical investigations
(trials) or performance evaluations for In Vitro
Diagnostics (IVDs).
Set up a basic Quality Management System (QMS)
to ensure the requirements of the Conformity
Assessment Procedure is met in full. It is
recommended that the manufacturer works
towards ISO 13485: 2012 Medical devices. Quality
management systems Requirements for
regulatory purposes which has become the world

the CE marking?
The QMS should incorporate procedures for
design; development; manufacturing;
distribution; post market surveillance, including
customer complaints and vigilance; post market
clinical follow-up; and translations.

The European Commission does publish helpful

regulatory guidance in the form of MEDDEVs these
need to be followed wherever possible.
Recommendations provide insights on specific topics like
Unique Device Identification (UDI) and audits.
Consensus statements and interpretative documents provide
insights on regulatory process and demarcation between
directives.
Lists of harmonised standards applicable to each main
directive are published in the Official Journal (OJ) and should
be implemented wherever possible.
International standards are encouraged to be used and
Notified Body guidance (NBOG & NB-MEDs) help with
understanding what is expected.
Harmonised Standards and ERs
Harmonised standards help all stakeholders

understand what is required to meet the Essential
Requirements (ERs) given in the first annex of each
directive.
The use of such standards is voluntary but when

used can provide a presumption of conformity to
the scope of the standard against specific ERs.
Any other standard or method has to be at least as

comprehensive as the harmonised standard.

include:
MDEG - Medical Device Experts Group.
NBOG Notified Body Operations Group.
CIE Working Group on Clinical Investigations and
Evaluations.
NET New and Emerging Technologies working
group.
Plus there are groups for vigilance; classification and
borderline; compliance and enforcement; IVDs;
electronic labelling; and the Eudamed database.
http://ec.europa.eu/growth/sectors/medical-devices_en

Other Sources of Guidance

include:
National Trade Associations such as ABHI, BIVDA,
BVMed, SNITEM, Assobiomedica, Swedish Medtech,
etc.
European Trade Associations such as EUCOMED,
EDMA, COCIR etc.
Product or regionally specific industry groups.
Consultants, lawyers, and product testing
organisations.
Legal Status of Directives and Guidance

Directives are not in themselves law and only
become so by National Law implemented in each
and every Member State.
Regulations are directly applicable to all Member
States without implementing legislation and are
binding. The use of regulations is increasing for
medical devices.
Decisions are directly applicable to all Member
States, enterprises and individuals without
implementing legislation and are binding.
Recommendations and Opinions are not binding
but do help define the state-of-the-art that is
expected from those skilled in the art. Useful to
follow for strict liability considerations where
relevant and reasonable to do so.
Content and Structure of

Directive 93/42/EEC (MDD)
Recitals set the context sat the time of

publication to assist with interpretation.
Articles sets out what to do and becomes the

foundation for national law.
Annexes sets out how the manufacturer can

comply.

Articles of MDD
1. Definitions, scope 13. Decisions with regard to
2. Placing on the market and classification and derogation
putting into service clause
3. Essential requirements 14. Registration of persons
4. Free movement, devices intended responsible for placing devices on
for special purposes the market 14a. European
databank 14b. Particular health
5. Reference to standards monitoring measures
6. Committee on Standards and 15. Clinical investigation
Technical Regulations
16. Notified bodies
7. Article 7 Committee
17. CE marking
8. Safeguard clause
18. Wrongly affixed CE marking
9. Classification
19. Decision in respect of refusal or
10. Information on incidents restriction
occurring following placing of
devices on the market 20. Confidentiality 20a. Cooperation
11. Conformity assessment 21. Repeal and amendment of
procedures Directives
12. Particular procedure for systems 22. Implementation, transitional
and procedure packs and provisions
procedure for sterilisation 12a. 23. Addressed to Member States
Reprocessing of medical devices
Annexes of MDD 93/42/EEC

Annex I Essential Requirements
Annexes II to VI cover the possible Conformity Assessment
Procedures to CE marking
Annex II Full quality assurance system
Annex III EC Type-Examination
Annex IV EC Verification
Annex VI Product quality assurance
Annex VII EC Declaration of Conformity
Annex VIII Statement concerning devices for Special
Purposes
Annex IX Classification Criteria
Annex X Clinical Evaluation
Annex XI Criteria to be met for the Designation of Notified
Bodies
Annex XII CE Marking of Conformity
Directive 93/42/EEC Amendments
M1 98/79/EC In Vitro Diagnostic Medical Devices.

M2 2000/70/EC Amendment concerning Medical
derivatives.
M3 2001/104/EC Corrigendum concerning Medical
derivatives.
M4 Regulation 1882/2003 Regulation for
Committees assisting the EU Commission.
M5 2007/47/EC amending 90/385/EEC and
93/42/EEC.
132

Scope of Directives
Medical Device Directives regulate, via National

Law, the placing on the market and putting into
service of medical devices.
Directives do NOT cover:
Reimbursement
Distribution
Health Technology Assessment (HTA)
So where do Economic Operators fit in?
Surveillance
Competent Notified
Designation
Enforcement
134



operate.

26th July 2016.

Economic Operators
P28-38 of the Blue Guide covers:

3. THE ACTORS IN THE PRODUCT SUPPLY
CHAIN AND THEIR OBLIGATIONS
3.1 Manufacturer
3.2 Authorised Representative
3.3 Importer
3.4 Distributor
The following are not defined as

Economic Operators:
3.5 Other Intermediaries: Intermediary
Service Providers under the E-Commerce
Directive.
3.6 End-User
Economic Operators
3.4. DISTRIBUTOR
The distributor is a natural or a legal person in the supply
chain, other than the manufacturer or the importer, who
makes a product available on the market.
Distributors are subject to specific obligations and have a
key role to play in the context of market surveillance.
Along with manufacturers and importers, distributors are the
third category of economic operators who are subject to
specific obligations. The distributor is a natural or a legal
person in the supply chain, other than the manufacturer or
the importer, who makes a product available on the
market.
Economic Operators
Only manufacturer and authorised representative

(EC REP) defined in the current Medical Directives
and both are considered to be Economic
Operators.
P15 of the Blue Guide 2014, note 35, states:This

implies that the economic operator that offers the
product has to be in a position to provide the
evidence that the product complies with the
applicable requirements i.e. by providing the
technical file on request of a market surveillance
authority.

Economic Operators
The manufacturer, EC REP, distributor,

Economic Operators are defined in the New
Legislative Framework and the Blue Guide.
P99 of the latest 2016 Blue Guide states:
All economic operators have a role and

obligations in market surveillance.
140



light touch


Intended use
Duration of use
Special rules
Classes
Class I - low risk

Class I Sterile
Class I with a Measuring Function
Examples of Low Risk

Class I Medical Devices
Tongue depressor
Stethoscope
Examination gloves (not surgical)
Reusable surgical instruments, including dental
instruments and items like forceps
Absorbent pads for use on intact skin
Dressings specifically for nose bleeds
Non-invasive electrodes
Syringe without needle
Wheelchair
Patient hoist
Simple orthotic products for use on intact skin
144


Class IIa Medical Devices
Surgical gloves
Tubing for use with an infusion pump or blood
Simple wound dressings (without an ancillary medicine and
not made from animal products) that are primarily
designed to manage the micro-environment
Fixed dental prostheses such as bridges and crowns
Suction catheters or tubes for stomach drainage
Surgical needles for suturing
Surgical staplers
TENS device or similar muscle stimulator
Phototherapy device, ideally for neonatal jaundice
Hearing aid
Physiotherapy equipment
145
Examples of Moderate Risk

Class IIb Medical Devices
Condom; Blood bag; Apnoea Monitor
Advanced wound dressings (without an ancillary
medicine and not made from animal products) that
are primarily designed to be used on wounds that
have breached the dermis and can only heal by
secondary intent
Contact lens cleaning solutions
Denture disinfecting solutions
Hemodialyser filter
Prosthetic joint replacement (not covered by Directive
2005/50/EC)
Surgical laser; Incubator for babies; Warming
blankets
Blood warmers; Therapeutic radiation sources 146

Class III Medical Devices
Absorbable sutures; Implantable replacement joint
Contraceptive intrauterine devices (IUDs)
Catheters intended for use in the central circulatory
system
Neuro-endoscopes that come into direct contact with
the central nervous system (CNS); CNS electrodes
Brain spatulas; Spinal cord retractors; Spinal needles
Wound dressings with an ancillary medicine
incorporated into them, such as silver
Wound dressing or other device using animal derived
products that require special controls, such as
products containing collagen, porcine xenograft
dressings or utilizing hyaluronic acid of animal origin

Duration of Contact
Up to 60 minutes - transient
Up to 30 days --- short term
Beyond 30 days ----- long term

In calculating the duration referred to in Section 1.1 of Chapter I,
continuous use means an uninterrupted actual use of the device for
the intended purpose. However where usage of a device is
discontinued in order for the device to be replaced immediately by
the same or an identical device this shall be considered an
extension of the continuous use of the device.
Degree of Invasiveness
Application to body surface or into

body orifice (mouth as far as pharynx)
Surgically invasive
Implantable
The Central circulatory system

For the purposes of this Directive, central
circulatory system means the following vessels:
arteriae pulmonales, aorta ascendens, arcus
aorta, aorta descendens to the bifurcatio aortae,
arteriae coronariae, arteria carotis communis,
arteria carotis externa, arteria carotis interna,
arteriae cerebrales, truncus brachiocephalicus,
venae cordis, venae pulmonales, vena cav
superior, vena cava inferior.

The Central nervous system

For the purposes of this Directive,
central nervous system means brain,
meninges and spinal cord.
Non-Invasive Devices Rules 1 to 4
Class I unless other Rules apply, e.g.

administration, filtration of blood etc. are Class IIa.
Highest rule applicable determines classification.
All non-invasive devices intended for modifying the
biological or chemical composition of blood, other
body liquids or other liquids intended for infusion
into the body are in Class IIb, unless the treatment
consists of filtration, centrifugation or exchanges
of gas, heat, in which case they are in Class IIa.
Contact with injured skin Class I, IIa or IIb.
Invasive Devices Rule 5
All invasive devices with respect to body orifices, other than

surgically invasive devices and which are not intended for
connection to an active medical device or which are intended
for connection to an active medical device in Class I:
are in Class I if they are intended for transient use,
are in Class IIa if they are intended for short-term use,
in an ear canal up to the ear drum or in a nasal cavity, in which
case they are in Class I,
are in Class IIb if they are intended for long-term use,
in an ear canal up to the ear drum or in a nasal cavity and are
not liable to be absorbed by the mucous membrane, in which
case they are in Class IIa. All invasive devices with respect to
body orifices, other than surgically invasive devices, intended
for connection to an active medical device in Class IIa or a
higher class, are in Class IIa.

All surgically invasive devices intended for

transient use are in Class IIa unless they are:
intended specifically to control, diagnose,
monitor or correct a defect of the heart or of
the central circulatory system through direct
contact with these parts of the body, in which
case they are in Class III,
reusable surgical instruments, in which case
they are in Class I,
intended specifically for use in direct
contact with the central nervous system, in
intended to supply energy in the form of

ionising radiation in which case they are in
Class IIb,
intended to have a biological effect or to be
wholly or mainly absorbed in which case they
are in Class IIb,
intended to administer medicines by means of

a delivery system, if this is done in a manner
that is potentially hazardous taking account of
the mode of application, in which case they are
in Class IIb.
All surgically invasive devices

intended for short-term use are in
Class IIa unless they are intended:
either specifically to control,
diagnose, monitor or correct a defect
of the heart or of the central
circulatory system through direct
contact with these parts of the body,
in which case they are in Class III,

or specifically for use in direct contact with the

central nervous system, in which case they are
in Class III,
or to supply energy in the form of ionizing
radiation in which case they are in Class IIb,
or to have a biological effect or to be wholly or
mainly absorbed in which case they are in
Class III,
or to undergo chemical change in the body,
except if the devices are placed in the teeth, or
to administer medicines, in which case they are
in Class IIb.
Long Term Invasive, Rule 8
All implantable devices and long-term surgically invasive

devices are in Class IIb unless they are intended:
to be placed in the teeth, in which case they are in
Class IIa,
to be used in direct contact with the heart, the central
circulatory system or the central nervous system, in
to have a biological effect or to be wholly or mainly
absorbed, in which case they are in Class III,
or to undergo chemical change in the body, except if
the devices are placed in the teeth, or to administer
medicines, in which case they are in Class III.
All active therapeutic devices intended to administer

or exchange energy are in Class IIa unless their
characteristics are such that they may administer or
exchange energy to or from the human body in a
potentially hazardous way, taking account of the
nature, the density and site of application of the
energy, in which case they are in Class IIb.
All active devices intended to control or monitor the

performance of active therapeutic devices in Class IIb,
or intended directly to influence the performance of
such devices are in Class IIb.

Active devices intended for diagnosis are in Class IIa:

if they are intended to supply energy which will be
absorbed by the human body, except for devices
used to illuminate the patient's body, in the visible
spectrum,
if they are intended to image in vivo distribution of
radiopharmaceuticals,
Note:Stand alone software is considered to be

an active medical device
if they are intended to allow direct diagnosis or

monitoring of vital physiological processes, unless
they are specifically intended for monitoring of vital
physiological parameters, where the nature of
variations is such that it could result in immediate
danger to the patient, for instance variations in
cardiac performance, respiration, activity of CNS in
which case they are in Class IIb. Active devices
intended to emit ionizing radiation and intended for
diagnostic and therapeutic interventional radiology
including devices which control or monitor such
devices, or which directly influence their performance,
are in Class IIb.
All active devices intended to administer and/or

remove medicines, body liquids or other substances
to or from the body are in Class IIa, unless this is
done in a manner:
that is potentially hazardous, taking account of
the nature of the substances involved, of the part
of the body concerned and of the mode of
application in which case they are in Class IIb.

All other active devices are in Class I.

substance which, if used separately, can be
considered to be a medicinal product, as
defined in Article 1 of Directive 2001/83/EC,
and which is liable to act on the human body
with action ancillary to that of the devices, are
in Class III.
human blood derivative are in Class III.
All devices used for contraception or the

prevention of the transmission of sexually
transmitted diseases are in Class IIb, unless
they are implantable or long term invasive
devices, in which case they are in Class III.


disinfecting, cleaning, rinsing or, when appropriate,
hydrating contact lenses are in Class IIb.
disinfecting medical devices are in Class IIa. Unless
they are specifically to be used for disinfecting
invasive devices in which case they are in Class IIb.
This rule does not apply to products that are intended

to clean medical devices other than contact lenses by
means of physical action.
Devices specifically intended for recording

of X-ray diagnostic images are in Class IIa.
Special Rules Rules 17 and 18
Rule 17: All devices manufactured utilizing

animal tissues or derivatives rendered non-viable
are Class III except where such devices are
intended to come into contact with intact skin
only.
Rule 18: By derogation from other rules, blood

bags are in Class IIb.


The key classification guidance is
MEDDEV 2. 4/1 Rev. 9, June 2010 please see the
flow charts in it!
and for stand alone software is

and for Borderline products, drug-delivery

products and medical devices incorporating, as
an integral part, an ancillary medicinal substance
or an ancillary human blood derivative is
MEDDEV 2.1/3 rev 3
If any doubt then discuss with your Notified Body

and/or Competent Authority.

Please note it is always important to double check with the:
MANUAL ON BORDERLINE AND
CLASSIFICATION IN THE COMMUNITY
REGULATORY FRAMEWORK FOR MEDICAL
DEVICES Version 1.17 (09-2015)
It does provide specific example rulings
that can help you with the same and
similar devices.
Best to search on title to find the location
at the Europa web site and make sure you
have the latest version. It does get
updated periodically with new rulings.

reclassification of hip, knee and
shoulder joint replacements applies to
total joint replacement systems (not
ancillary components like screws, wedges,
plates or instruments) has made such
systems Class III.

reclassification of breast implants has
made such devices Class III.

Breast Implant Reclassification
Commission Directive 2003/12/EC of 3

February 2003 on the reclassification of
breast implants in the framework of
Directive 93/42/EEC concerning medical
devices.
Brief document reclassifying breast implants from
Class IIb to Class III.
Breast implants now require a NB review of
Design Dossiers and Design Examination
Certificates.
172
Joint Replacement Reclassification
Commission Directive 2005/50/EC of 11

August 2005 on the reclassification of hip,
knee and shoulder joint replacements in the
framework of Council Directive 93/42/EEC
concerning medical devices.
Brief document reclassifying such medical devices
from Class IIb to Class III from 1Sep07.
A NB review of Design Dossiers and Design
Examination Certificates are now required by
1Sep09 for Annex II and 1Sep10 for Type-
Examination + Product Quality Assurance
conformity assessment procedures.
173
Medical Device Regulation (MDR)

Classification
Annex VII Classification Criteria very similar in
format to MDD but with additional definitions,
qualifications and rules.
Rule 10a for software based devices which is
risk-based.
Rule 18 for blood bags deleted.
Rule 20 for aphaeresis machines deleted.
New rules:
Rule 19 for nanomaterial.
Rule 21 for some types of combination
products.
Rule 22 inhalation devices.
Rule 23 for active therapeutic devices.

MDR Classification Rule 21

including amendments
6.9. Rule 21
Devices that are composed of substances or combinations of substances
that are intended to be ingested, inhaled or administered rectally or
vaginally introduced into the human body via a body orifice, or
applied on skin and that are absorbed by or locally dispersed in the
human body are:
- in class III if they, or their products of metabolism, are
systemically absorbed by the human body in order to achieve the
intended purpose,
- in class III if they are achieve their intended purpose to be
introduced into in the stomach or lower gastrointestinal tract and
they, or their products of metabolism, are systemically absorbed by
the human body,
- in class IIb in all other cases, except if they are applied on skin, in
which case they are in class IIa, or
- if they are applied in the nasal or oral cavity as far as the pharynx,
and achieve their intended purpose on those cavities, in which case
they are in class IIa.
Practical Session Classification
Your chance to work together

on the current Directives.
Please classify the following:
Bandage for intact skin.
Apnoea Monitor.
Tongue Depressor.
Implantable Defibrillator.
Wound Dressing with added silver.
Pregnancy test for use at home.
176
Conformity Assessment Procedures

(CAPs
CAPs))
or regulatory routes to market
177

Device Classification drives the process
Classes
Class I - low risk



light touch

Intended use
Duration of use
Special rules

An important guidance reference point

is the MEDDEV 2. 4/1 Rev. 9, June 2010
and for stand alone software:
Class I Device
Annex VII MDD

Declaration of Conformity
No Sterile or measuring function? Yes
Verification by notified body

for sterile and/or measuring
features.
Affix CE marking Affix CE marking
MDD Conformity Assessment Procedure
Recommended Class IIa Device
Annex II MDD
Annex VII MDD
full quality audit
Declaration of Conformity
by notified body
Manufacturers choice between Annexes IV, V & VI
Annex IV MDD Annex V MDD Annex VI MDD

product verification production quality audit product quality audit
by notified body by notified body by notified body
Affix CE marking Affix CE marking Affix CE marking

Recommended Class IIb Device
Annex II MDD Annex III MDD

full quality audit type-examination
by notified body by notified body
Manufacturers choice between Annexes IV, V & VI
Annex IV MDD Annex V MDD Annex VI MDD

product verification production quality audit product quality audit
Recommended Class III Device
Annex II MDD Annex III MDD

Design dossier
examination
by notified body Manufacturers choice between Annexes IV & V
Annex IV MDD Annex V MDD

product verification production quality audit
Annex II List A
Reagents & related for

blood group testing
HIV 1&2, HTLV I&II
& hepatitis B, C & D
Recommended
Manufacturers choice
Annex IV IVDD Annex V IVDD

Design dossier Annex VII IVDD

examination production quality audit
IVD Conformity Assessment Procedure

Note that batch testing required as
agreed with the notified body.

Annex II List B
Reagents & related:

- not in List A but on List B
- self-diagnosis of blood sugar
Recommended

Annex VI IVDD Annex VII IVDD

Self-Test Devices
Self-test for lay user at home;

not covered by Annex II;
not for performance evaluation
Recommended
Annex IV IVDD Annex III IVDD Annex V IVDD

full quality audit Declaration of type-examination
by notified body conformity by notified body
Annex III IVDD Para 6 Annex VI IVDD Annex VII IVDD

design examination product verification production quality audit
All Other Devices
IVDs not listed on either

Annex II List A or B
Not self-test device
Yes No
Performance evaluation?
Annex VIII IVDD statement &

Annex III IVDD
procedures concerning devices
for performance evaluation Declaration of conformity
Make statement Affix CE marking
IVDs on Annex II List A or B or

self-test devices can be subject
to a performance evaluation

Recommended Active Implantable Device
Annex 2 AIMDD Annex 3 AIMDD

Design dossier
examination
by notified body Manufacturers choice between Annexes IV & V
Annex 4 AIMDD Annex 5 AIMDD

AIMDD Conformity Assessment Procedure
Very similar to Class III CAP.
Annex II Full Quality Assurance System
Important to be based on the globally

recognised standard:
EN ISO 13485: 2016 Medical

devices Quality management
systems Requirements for
regulatory purposes
191
Annex II Design Dossier
Achieving full quality assurance requires

Full quality system assessment
(ISO 13485 + MDD)
For all devices in Classes IIa, IIb & III
Technical file system review by Notified Body.
Cannot be Class I (Sterile) or I (Measuring).
For Class III devices
Design dossier submission.
EC design dossier examination certificate.
192

Annex II Full Quality Assurance System
Under Annex II, Section 3

The manufacturer must submit an application to
the NB.
The manufacturers quality system must meet
Annex II and should include adequate design
controls, to ensure safety, performance and
reliability are addressed.
Generation and control of technical
documentation.
Post-market surveillance including vigilance.
Output is a QMS certificate from the Notified Body.
193
Annex II Design Dossier for Class III
Under Annex II, Section 4, the manufacturer:

Applies to the NB for examination of the design
dossier.
Provides conclusions of the risk analysis.
Must ensure applicable essential requirements
are addressed.
Provides conclusions from clinical data (applies
to all products).
The Notified Body:
Reviews solutions adopted by the manufacturer.
Ensures relevant standards are applied.
Output is a design examination certificate.
194
Annex III Type-Examination
Device and technical documentation

submitted for examination.
Notified body examines device and
documentation.
EC type examination certificate issued.
195

Annex IV Verification
by examination and testing of every
product or batch
Notified body examines every individual

device, or samples from every batch.
Devices verified against technical
documentation and EC type examination
certificate if applicable.
Notified body approves affixing its
identification number.
196

no design
Manufacturing quality system assessment

(ISO 13485, without design + MDD).
Technical documentation system review.
Device manufactured in compliance with
technical documentation and EC type
examination certificate if applicable.
Post-market surveillance including vigilance.
197
Annex VI Production quality assurance

primarily by inspection, NB audit excludes design
and manufacture
Application of the quality system must

ensure that products conform to the type
described in the EC type examination
certificate
or
conformity with technical documentation
(Class IIa).
198

Annex VII Declaration of Conformity
A Declaration of Conformity
must contain:
Manufacturers name and
address
Details of the products
Conformity assessment route
Statement that the devices
comply
A current date
Authorisation (if already CE
marked)
Guidance is given in
consensus Statement
S01/99
199
MDR Conformity Assessment

Based a number of annexes that are based on the
previous approach with more details prescriptively
spelt out, more rigour demanded, with more checks
and verification/validation.
Annex I General Safety and Performance
Requirements
Annex II Technical Documentation
Annex IIa Post-Market Surveillance
Annex III EU Declaration of Conformity
Annex IV CE Marking of Conformity
Annex V Registration, UDI & RFID Requirements
Annex VI Requirements to be met by Notified Bodies

Annex VII Classification Criteria
Annex VIII Conformity Assessment based on a Quality
Management System and on Assessment of the
Technical Documentation.
Annex IX Conformity Assessment based on Type
Examination.
Annex X Conformity Assessment based on Product
Conformity Verification. Part A: Product Quality
Assurance and Part B: Product Verification.
Annex XI Procedure for Custom-Made Devices.
Annex XII Certificates Issued by a Notified Body.

Annex XIII Part A Clinical Evaluations and Part B Post-

Market Clinical Follow-Up.
Annex XIV Clinical Investigations.
Annex XV List of Groups of Products without an
Intended Medical Purpose Referred to Article 1.
This includes a lot of cosmetic products and brain stimulation
products using electrical current or magnetic or electromagnetic
fields.
Annex XVI Correlation Table for MDD, AIMDD & MDR.
Time for a break.
Lunch!
203
What was (is) the New Approach?
A concept to facilitate the the free movement of

goods in the Internal Market whilst ensuring a
high level of protection for consumers.
The elimination of barriers to trade through

technical harmonisation.
The New Approach aims for technical harmonisation within

the European Union (EU the Internal Market) by only
harmonising the essential requirements of products and by
applying the "general reference to standards" formula and
the principle of mutual recognition in order to eliminate
technical obstacles to the free movement of goods.


The New Approach is based on four fundamental
principles:
legislative harmonisation is limited to essential
safety requirements (or other requirements in the
general interest) with which products put on the
market must conform and can therefore enjoy free
movement throughout the European Union;
the task of drawing up technical production
specifications is entrusted to organisations competent
in industrial standardisation, which take into account
the current stage of technology;

The New Approach is based on four fundamental
principles:
these technical specifications are not mandatory
and maintain their status of voluntary standards;
the authorities are obliged to recognise that
products manufactured in conformity with harmonised
standards are presumed to conform to the essential
requirements established by the Directive. If the
producer does not manufacture in conformity with
these standards, he has an obligation to prove that his
products conform to the essential requirements.
Two conditions have to be met in order that this

system may operate:
the standards must guarantee the quality of the

product;
the public authorities must ensure the protection of

safety (or other requirements envisaged) on their
territory. This is a necessary condition to establish
mutual trust between Member States.




operate.

26th July 2016.
Blue Guide Framework &

Regulator Expectations
The Blue Guide is not law but does reflect the current
state of the art which may/will change over time.
A historical perspective is provided that is useful to
know, especially for those new to the subject.
A summary is included concerning the New Legislative
Framework that was developed from around 2002 until
2008 and is still modifying current regulations.
It discusses the General Product Safety Directive
(GPSD) and legislation on Product Liability.
It provides insights onto general issues concerning the
application and implementation of the directives, such
as the need for a risk based approach when more than
one directive applies to a particular product.
209
What are New Approach Directives
Community legislation which sets out :

Essential safety requirements for products
common levels of protection.
Conformity assessment procedures level of
intervention dependent upon safety risk.
Harmonised product standards.
Requirements for CE Marking.

What are New Approach Directives
Community legislation which is :

Is produced by the European Commission.
Is reviewed and published in the Official Journal
(OJ) after due process through the European
Parliament.
Transposed into National Law in each Member State.
Relies upon compliance by the manufacturer and
strong post-market surveillance by all those involved.
The amount of pre-market intervention by
accredited Notified Bodies (NBs) and Competent
Authorities (CAs) is driven by the devices classification
and intended use.
What is the New Legislative Framework?

Review of the New Approach
The New Legislative Framework
The New Approach was reviewed but changes relatively little
for medical device manufacturers. This is because other
product areas are moving towards the market surveillance,
accreditation and controls already well established in the
medical device directives.
Changes were applicable from 1 January 2010.
Economic operators defined to include manufacturer,
authorised representative, the importer and distributor.
Economic operators should take appropriate measures to
ensure they only make available products in regulatory
compliance. These changes have to be in the MDR/IVDR.
What did the 2007 Revision (2007/47/EC)

try to do?
Resolve issues arising from technical progress,

multiple interpretations and misunderstandings.
Attempted to force industry to take clinical

evaluation more seriously.
However it inevitably created further issues to keep

everyone engaged in dialogue for the foreseeable
future.

Current Revision
The Current Revision is nearing the final stages of
process through the EU system. It will reinforce the
previous revision with additional new processes and
requirements.
The transition to these regulations is likely to take

from early 2017 until the end of 2021, although
they are already affecting the interpretation of
current regulations.
Please note the MDR is 355 pages long and the IVDR
is 306 pages long. Clearly only some initial comments
can be currently made for this course.
The EU comitology procedure is lengthy but is now
nearing its end for the MDR & IVDR. So you are now
encouraged to start looking more closely into it.
What else needs to be considered by

manufacturers?
Validation of Product Design, especially safety and for

electronic products EMC (Electromagnetic Compatibility) &
software.
Risk Management for product, processes, Quality Management

System (QMS) and Clinical Evaluation.
Pre-Clinical Testing, including laboratory and animal work - if

required.
Validation of Clinical Evidence, i.e. Clinical Literature Review

and Clinical Investigation for devices.
For IVDs analytical laboratory testing, Performance Evaluation

and Clinical Validation.
What else needs to be considered by

manufacturers?
Human Factors Engineering more than usability part of the

design.
Translation of all labelling in languages to both meet regulatory
requirements and maximum commercial success in the market!
Rigorous Post Market Surveillance (PMS)
Selection of Notified Body, they need to select one they can
work with and that has an excellent reputation.
Reimbursement and Health Technology Assessment (HTA)
Evidence-based decision making and purchasing is fast
becoming the norm all around the world.
Optimum pricing and correct market positioning are always
crucial to commercial success.

Some useful / important tips for

manufacturers
Do not rely on Regulators / Notified Bodies, Consultants,
Lawyers, the Public, Doctors, Patients or anyone else to ensure
you comply as the legal manufacturer you are
responsible for everything.
You need to ensure you have the time to keep up-to-date
and understand the ever changing state-of-the-art of medical
device regulation.
You need to read, to learn, to lead, to motivate, review and
do all the routine things well, that we all do everyday, to make
progress in our regulatory lives. Nearly all medical device
businesses require teams of specialists and partners to make
things happen and ensure compliance. So we all need to be,
especially Top Management, good listeners and be open to
learn from our teams and others.
Regulatory Compliance
- is it really useful?
Regulatory activities reflect the expectations and standards
that customers demand and effectively set the current state-
of-the-art.
With ever increasing regulatory requirements and clinical

proof demanded, only the determined and well funded are
likely to succeed over the long term. Regulatory compliance
is a prerequisite for market access but it is also vital for
staying on the market without adverse events becoming fatal
to the business.
With high risk and complex products that require a global

market to secure adequate ROIs regulatory can certainly be
a barrier to entry and an opportunity for excellence.
Regulatory activities can feedback critical useful information

to inform where the direction of new product development
(NPD) should be going, i.e. the upstream process of
introducing new products that customers really want.
Matthew Theobald, Quality Factors Director

Three Circles
219

Science Based
Regulation
throughout the
TPLC
220
Will true global regulatory harmonisation

ever be achieved?
Global Harmonisation Task Force (GHTF)
and the
International Medical Device

Regulators Forum (IMDRF)
of which the
Asian Harmonization Working Party
(AHWP) including India is an
Affiliate Organization
Mature regulations in well established highly

regulated markets
EU / EFTA
USA
Japan GHTF FOUNDING MEMBERS
Canada
Australia

Markets with developing regulations and an

interest in global convergence
India
Peoples Republic
of China Members of Asian
Hong Kong Harmonization Working
Party (AHWP) which is
Saudi Arabia
established as a
Singapore non-profit organization.
South Africa
and 20 others.
GHTF Organisation
Conceived in September 1992.

Purpose: to encourage convergence of existing
medical device regulations, and publish regulatory
guidance documents for use by new-entrants.
A self-funding organisation with equal
participation from regulators and industry of the
Founding Member jurisdictions (eventually
included AHWP).
Five Study Groups to undertake the work under
the direction of a Steering Committee. Study
Groups (SGs) met face-to-face about 3 times per
annum.
GHTF Objectives
Improve public health, globally.

Remove unnecessary regulatory differences and
duplicative controls to simplify trade and reduce
regulatory costs.
Encourage the introduction of beneficial new
technology.
Encourage RAs to exchange information on
adverse events / incidents.
continued ..

GHTF Objectives
Share the experience of GHTF Founding

Members with other countries introducing or
modifying regulations.
Secure the universal recognition of regulatory
decisions, certificates and inspections.
Rotating Secretariat with an informative
website www.ghtf.org.
GHTF Overarching Documents
GHTF Medical Device Regulatory Model.

Definition and Glossary of Terms Used in GHTF
Documents.
Unique Device Identification (UDI) System for
Medical Devices.
GHTF Retrospective Assessment - Key Findings
and Recommendations (Jan. 08).
GHTF Study Group Themes
SG1: premarket procedures.

SG2: reporting adverse incidents and post-
market surveillance.
SG3: quality systems for manufacturers and
inspectors of medical devices.
SG4: quality system auditing practices.
SG5: clinical safety and performance.

GHTF So why was it replaced?
GHTF wound up at the end of 2012.

Major items of work are completed.
Remaining issues are difficult to harmonize e.g.
combination products / devices incorporating
viable animal or human tissues / nanomaterials.
Pressure on regulatory affairs budgets. Why should
a government devote resource to global rather
than national priorities?
continued ..
GHTF reasons for change
To accelerate international medical device

regulatory harmonization and convergence.
Public / media / political criticisms of the
effectiveness of Founding Members regulations
(e.g. breast implants / orthopaedic implants etc.).
Regulators seen as being too close to industry.
While the legal manufacturer is located in
Founding Member jurisdictions, most medical
devices are made in China, Mexico, Brazil and the
developing World. This affects the regulatory task.
The GHTF is dead long live the IMDRF
International Medical Device Regulators Forum first

met in May 2011 (Australian Chair).
The forum is for Regulators only
- Industry is not a member.
Industry invited to participate in some Working
Groups but otherwise are limited to providing
comments on draft documents.
China, Brazil, India, Russia were invited to join.

GHTF documents were transfered over to

IMDRF
All GHTF documents available on IMDRF website.

http://www.imdrf.org/
It is intended these documents will be maintained.
Anyone can suggest changes if they believe a
document needs to be updated.
The IMDRF management team will review and
decide if work is required or not. If it does, the
produced document will become an IMDRF
document.
First Five IMDRF Work Items
Improvement of GHTF National Competent Authority

Reporting (NCAR) system and exchange of PMS
information. RA only WG - I. Isabelle Demade of the
European Commission led.
Roadmap for implementation of UDI system. Joint
WG - Laurent Sells European Commission led.
Report by Dec. 2012.
Single QMS audit programme accreditation
requirements. Closed WG Kimberley Trautmann of
US FDA to led. Initial focus on guidance on
qualifications / certification / accreditation of
auditors for regulatory purposes. Report 12-18
months.
continued ..
First Five IMDRF Work Items
List of standards recognised by IMDRF regulators

as basis for demonstrating conformity. RA only
WG - M. Neumann (Germany BfArM). Report end-
2013.
Regulated Product Submission (RPS) in electronic
format standard. Part open / part closed WG - M.
Ward (Health Canada). Pre- and post-marketing
submissions; assess fitness for purpose for medical
devices; start with table of contents based on
GHTF STED.

Sample of Closed IMDRF Discussions
Post Market Surveillance.

Medical Device Single Audit Program
(MDSAP).
Software as a medical device, including
standalone.
In-Vitro Diagnostics Market
Authorisation.
Auditor Competence.
UDI for medical devices.
Closed IMDRF Work Items
IMDRF recognized standards.

Roadmap for implementation of UDI system.
Numerous discussion items.
Current IMDRF Work Items
Quality of Standards.
Patient Registries.
Good Regulatory Practice for Pre-Market
Reviewers.
A review of the NCAR system, i.e. the
exchange of confidential information
concerning serious Adverse Events (AEs) with
global distribution, including terminology.
Medical Device Single Audit Program
(MDSAP).
Regulated Product Submission.

Current IMDRF Consultations
Regulatory Product Submission

Table of Contents Pilot.
Time for a break.
Lunch!
239
Specific In Vitro Diagnostic

(IVD
IVD) ) Considerations
240

In Vitro Diagnostic Directive 98/79/EC

(IVDD) Classification
Current classification is from checking the IVDD List
A and List B to determine the conformity
assessment procedure (CAP).
List A
Reagents and reagent products, including related
calibrators and control materials, for determining the
following blood groups: ABO system, rhesus (C, c, D, E,
e) anti-Kell,
reagents and reagent products, including related
calibrators and control materials, for the detection,
confirmation and quantification in human specimens of
markers of HIV infection (HIV 1 and 2), HTLV I and II,
and hepatitis B, C and D,
variant Creutzfeldt-Jakob disease (vCJD) assays for
blood screening, diagnosis and confirmation.

List B
Reagents and reagent products, including related
following blood groups: anti-Duffy and anti-Kidd,
calibrators and control materials, for determining
irregular anti-erythrocytic antibodies,
calibrators and control materials, for the detection and
quantification in human samples of the following
congenital infections: rubella, toxoplasmosis,
calibrators and control materials, for diagnosing the
following hereditary disease: phenylketonuria,

List B
following human infections: cytomegalovirus, chlamydia,
following HLA tissue groups: DR, A, B,
following tumoral marker: PSA,
calibrators, control materials and software, designed
specifically for evaluating the risk of trisomy 21,
the following device for self-diagnosis, including its
related calibrators and control materials: device for the
measurement of blood sugar.

Annex II List A
Reagents & related for

blood group testing
HIV 1&2, HTLV I&II
& hepatitis B, C & D
Recommended

Design dossier Annex VII IVDD

examination production quality audit

Note that batch testing required as
agreed with the notified body.
Annex II List B
Reagents & related:

- not in List A but on List B
- self-diagnosis of blood sugar
Recommended

Annex VI IVDD Annex VII IVDD

Self-Test Devices
Self-test for lay user at home;

not covered by Annex II;
not for performance evaluation
Recommended
Annex IV IVDD Annex III IVDD Annex V IVDD

full quality audit Declaration of type-examination
by notified body conformity by notified body
Annex III IVDD Para 6 Annex VI IVDD Annex VII IVDD

design examination product verification production quality audit

All Other Devices
IVDs not listed on either

Annex II List A or B
Not self-test device
Yes No
Performance evaluation?
Annex VIII IVDD statement &

Annex III IVDD
procedures concerning devices
for performance evaluation Declaration of conformity
Make statement Affix CE marking
IVDs on Annex II List A or B or

self-test devices can be subject
to a performance evaluation

Important Essential Requirements
Basic new approach very similar to MDD but

there specific IVD issues to note:
analytical sensitivity, diagnostic sensitivity,
analytical specificity, diagnostic specificity,
accuracy, repeatability, reproducibility, including
control of known relevant interference, and limits of
detection, stated by the manufacturer.
The traceability of values assigned to calibrators
and/or control materials must be assured through
available reference measurement procedures
and/or available reference materials of a higher
order.

Performance Evaluation
Annex VIII Statement and Procedures

concerning Devices for Performance
Evaluation provides insights into the
requirements.
A Performance Evaluation typically compares the
diagnostic under study to a recognised gold
standard and the diagnostic under study does
not play any part in informing the clinical pathway.
Some companion diagnostics are co-developed
and tested with specific drugs. This is a complex
and expensive process.


The diagnostic sensitivity and specificity are

the two key parameters in determining
performance from which we can also derive
Positive Predictive Value (PPV) and Negative
Predictive Value (NPV). insights into the
requirements. Please see next slide for a
summary.
It is important to understand that as a disease
prevalence in a population increase, the PPV also
increase.
A discussion of these points can be found in the
Indian Journal of Ophthalmology. Please see:
Indian J Ophthalmol. 2008 Jan-Feb; 56(1): 4550.

A discussion of these points can be found in the

Indian Journal of Ophthalmology.
Understanding and using sensitivity,
specificity and predictive values by Rajul
Parikh, Annie Mathai, Shefali Parikh, G. Chandra
Sekher and Ravi Thomas.
These are likely to be useful people to discuss this
further with in India, if required. Dr. Rajul Parikh is
based in Mumbai and some of his colleagues are
based in Hyderabad.
Indian J Ophthalmol. 2008 Jan-Feb; 56(1): 4550.

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(09)70043-X/fulltext?version=printerFriendly


MEDDEVs
MEDDEV 2.14/1 GUIDELINES ON MEDICAL DEVICES IVD
Medical Device Borderline and Classification issues A GUIDE
FOR MANUFACTURERS AND NOTIFIED BODIES revision 2
January 2012
MEDDEV 2.14/4 January 2012 Guideline for the CE

marking of blood based in vitro diagnostic medical devices for
vCJD based on detection of abnormal PrP. Guidelines relating
to the application of: Decision 2002/364/EC on common
technical specifications for in vitro diagnostic medical
devices.
MEDDEV. 2.14/3 rev.1 January 2007 IVD GUIDANCES:

Supply of Instructions For Use (IFU) and other information
for In-vitro Diagnostic (IVD) Medical Devices
MEDDEV. 2.14/2 rev.1 February 2004IVD GUIDANCE :

Research UseInitiative
Capacity Building Only for
products
Trade Development in India (CITD) Lot 1 SPS/TBT/Customs

MEDDEVs
MEDDEV 2.14/1 GUIDELINES ON MEDICAL DEVICES IVD
Medical Device Borderline and Classification issues A GUIDE
FOR MANUFACTURERS AND NOTIFIED BODIES revision 2
January 2012
MEDDEV 2.14/4 January 2012 Guideline for the CE

marking of blood based in vitro diagnostic medical devices for
vCJD based on detection of abnormal PrP. Guidelines relating
to the application of: Decision 2002/364/EC on common
technical specifications for in vitro diagnostic medical
devices.
MEDDEV. 2.14/3 rev.1 January 2007 IVD GUIDANCES:

Supply of Instructions For Use (IFU) and other information
for In-vitro Diagnostic (IVD) Medical Devices
MEDDEV. 2.14/2 rev.1 February 2004IVD GUIDANCE :

Research UseInitiative
Capacity Building Only for
products
Trade Development in India (CITD) Lot 1 SPS/TBT/Customs

Harmonised Standards
Some Important Examples
EN 13532:2002 General requirements for in vitro

diagnostic medical devices for self-testing.
EN 13612:2002 Performance evaluation of in vitro
diagnostic medical devices.
EN 14136:2004 Use of external quality assessment
schemes in the assessment of the performance of in vitro
diagnostic examination procedures.
EN ISO 14971:2012 Medical devices - Application of risk
management to medical devices.
EN ISO 15197:2015 In vitro diagnostic test systems -
Requirements for blood-glucose monitoring systems for
self-testing in managing diabetes mellitus.
https://ec.europa.eu/growth/single-market/european-standards/harmonised-standards/iv-diagnostic-medical-devices_en


EN ISO 18113-1:2011 In vitro diagnostic medical devices -

Information supplied by the manufacturer (labelling) - Part
1: Terms, definitions and general requirements.
2: In vitro diagnostic reagents for professional use.
3: In vitro diagnostic instruments for professional use.
4: In vitro diagnostic reagents for self-testing.

5: In vitro diagnostic instruments for self-testing.
EN ISO 23640:2015 In vitro diagnostic medical devices -
Evaluation of stability of in vitro diagnostic reagents.
EN 61010-2-101:2002 Safety requirements for electrical
equipment for measurement, control, and laboratory use -
Part 2-101: Particular requirements for in vitro diagnostic
(IVD) medical equipment.
EN 62304:2006 Medical device software - Software life-
cycle processes.
EN 62366:2008 Medical devices - Application of usability
engineering to medical devices.
Current Revision some highlights

IVDR transitional period is essentially life of current
certificate or 2 years after application of the IVDR.
This means until around 2022 for IVDs certified to
IVDD or at the latest around early 2024.
MDR transitional period is essentially life of current
certificate or 2 years after application of the MDR.
This means until around 2022 for devices certified
devices to current MDD but some AIMDD will be
sooner, perhaps as early as 2019.
There are some variations and each product group
needs to be checked carefully for the detailed
requirements for the IVDR and MDR.

In Vitro Diagnostic Regulation (IVDR)

Classification
No more list A & B, although some elements

are evident.
Now risk based following on from the GHTF /
IMDRF model.
Annex VII Classification Criteria provides
implementing rules. Driven by intended use of
the manufacturer.
2.1 Rule 1 for high risk transmissible or
infectious diseases are class D.
2.2 Rule 2 for blood grouping or tissue typing
or cell administration are class C, except those
listed as higher risk class D.
IVDR Classification
2.3 Rule 3 devices in class C if they are intended:
(a) for detecting the presence of, or exposure to, a sexually transmitted agent;
(b) for detecting the presence in cerebrospinal fluid or blood of an infectious agent without
a high or suspected high risk of propagation;
(c) for 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, foetus or
embryo being tested, or to the individual's offspring;
(d) for pre-natal screening of women in order to determine their immune status towards
transmissible agents;
(e) for 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 a life-
threatening situation for the patient or for the patient's offspring;
(f) to be used as companion diagnostics;
(fa) to be used for disease staging, if there is a risk that an erroneous result would
lead to a patient management decision resulting in a life-threatening situation
for the patient or for the patient's offspring;
(fb) to be used in screening, diagnosis, or staging of cancer;
(g) for human genetic testing;
(h) for 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 life-threatening situation for the patient or for the patient's offspring;
(i) for management of patients suffering from a life-threatening disease or condition;
(j) for screening for congenital disorders in the embryo or foetus.
(k) for screening for congenital disorders in new-born where failure to detect and
treat such disorders could lead to life-threatening situations or severe
disabilities.
IVDR Classification
2.4 Rule 4
(a) Devices intended for self-testing are classified as
class C, except for devices for the detection of
pregnancy, for fertility testing and for
determining cholesterol level, and devices for
the detection of glucose, erythrocytes,
leucocytes and bacteria in urine, which are
Class B.
(b) Devices intended for near-patient testing are

classified in their own right.

IVDR Classification
2.5. Rule 5
The following devices are classified as class A:
(a) products for general laboratory use, accessories
which possess no critical characteristics, buffer
solutions, and washing solutions, and general culture
media and histological stains, 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.
IVDR Classification - Consequences
It should be clear that there will be a truly large quantum leap

of IVD manufacturers who will the intervention of a Notified
Body (NB) to achieve CE marking certification that did not
previously require it.
With the new
IVDR 80% to
90% of
manufacturers
will require a
With the NB.
current IVDD
only 10% to
20% of
manufacturers
require a NB.
How to prepare for and implement the

upcoming IVDR Dos and donts
The BSI White Paper How to prepare for and

implement the upcoming IVDR Dos and
donts by Erik Vollebregt and Gert Bos is
useful reading for IVD manufacturers to
understand the IVDR better.
Please remember to always check for the latest

copy of the IVDR (or MDR) and check even for
small changes applicable to you. These
changes will almost certainly reflect the
inevitable evolving interpretation of the new
regulations as they become truly finalised and
then amended over time.

Recommended CAP Full QMS
For companies placing innovative, high risk and

implantable devices, especially those subject to
the Active Implantable Medical Devices (AIMDD),
it is strongly recommended that the full quality
Conformity Assessment Procedure (CAP) be
used. This should be based on the globally
recognized quality assurance standard:
EN ISO 13485 Medical devices

Quality management systems
Requirements for regulatory purposes.
ISO 13485: 2016 Medical

devices Quality management
systems Requirements for
regulatory purposes
Risk Management
266
Global Quality System
ISO 13485: 2016 Medical devices - Quality

management systems - Requirements for
regulatory purposes has become the world
ISO 13485: 2003 became a harmonized
standard for all the Medical Device Directives on
the April 2, 2004.
It was originally based on ISO 9001/2 with the
elements on customer satisfaction and continual
improvement modified.
267

Access the relevant ISO standards

that effect audits / inspections
ISO 9001: 2015 Quality management

systems Requirements
is important to the medtech supply chain!!!
268
ISO 9001: 2008 and ISO 13485: 2003

ISO 9001 ISO 13485
Quality Management
System Standards
9 sections
5 main clauses
Section 7 justified
exclusion possible
Customer satisfaction Maintain
Continual improvement Effectiveness
ISO 9001: 2008 and ISO 13485: 2003
ISO 9001 ISO 13485

Concept of risk
management
Product realization
Business environment &
organisation
Regulatory requirements
applicable to product
Traceability required
throughout product
realization
270

ISO 9001: 2008 and ISO 13485: 2003
ISO 9001 ISO 13485

Expectations for
outsourcing of processes
similar, now more notes in
9001
Documentation required by
national or regional
regulations
Specific medical device
requirements in the standard
such as for implantable and
sterile devices
271
BSI web site comments on ISO 9001

http://www.bsigroup.com/en-GB/about-bsi/media-centre/press-releases/2015/august/BSI-obtains-first-global-
accreditation-for-the-new-Quality-Management-standard-ISO-90012015-from-ANAB/#.VffbgyCFOie
Greater emphasis on building a management

system suited to each organizations particular
needs.
A requirement that those at the top of an

organization be involved and accountable,
aligning quality with wider business strategy.
Alignment with other key management system

standards through the use of a common
structure and core text.
BSI web site comments on ISO 9001

http://www.bsigroup.com/en-GB/about-bsi/media-centre/press-releases/2015/august/BSI-obtains-first-global-
accreditation-for-the-new-Quality-Management-standard-ISO-90012015-from-ANAB/#.VffbgyCFOie
Risk-based thinking throughout the standard

makes the whole management system a
preventive tool and encourages continuous
improvement.
Less prescriptive requirements for

documentation: the organization can now decide
what documented information it needs and what
format it should be in.

Quality Management Principles
Customer focus Leadership

Involvement of Process approach
people
System approach to Continual
management improvement
Factual approach to Mutually beneficial
decision making supplier relationships
274
Process Model ISO 9001

Quality Management System
Continual Improvement
Management S
responsibility a
R t
C e i C
u q Measurement, s u
u Resource analysis, f
s i a s
t r management improvement c t
o e t o
m i
m e o
m
e n n e
r t r
s Input Product Output Product
(and/or service)
/Service
realisation
Fig 1. - Quality management system

Process Model ISO 13485
276

Key Difference between ISO and EN 13485

ISO 13485 and some US versions such as AAMI do not
include the informative Annexes ZA for AIMD, ZB for
MDD or ZC for IVDD. For full EU compliance applying
the guidance in these is vital. This is most apparent in
Note 1 of each Annex:
NOTE 1 Where a reference from a clause of this European

Standard to the risk management process is made, the risk
management process needs to be in compliance with Directive
93/42/EEC, as amended by 2007/47/EC. This means that risks
have to be reduced as far as possible, to a minimum, to the
lowest possible level, minimized or removed, according to
the wording of the corresponding essential requirement.
Risk Management
and
Product Development
278
279

Product Evaluation
Design outputs define the product

concept.
Outputs provide core material for the

design reviews that need to be
successfully completed before product
verification / validation can be
undertaken.
Verification and validation activities

often include independent third party
testing for electrical safety,
electromagnetic compatibility (EMC),
biocompatibility, usability, etc., etc.
280
Product Evaluation
Outputs are established and maintained within

the Quality Management System (QMS).
These outputs provide the manufacturer and the
regulators with the definitive reference of the
medical devices intended performance.
Changes to the design will result in changes to
design outputs (and is considered part of
maintaining effectiveness). These changes need
to be validated ultimately in normal use and
monitored via the Post Market Surveillance
(PMS) system.
281
Technical Documentation
Specifically Required for Annexes II VII

product description and variants
drawings, methods of manufacture
formulations, etc + necessary explanations
results of risk analysis + list of standards or
alternative solutions used
method of sterilization
results of design calculations &
inspections/checks on connectability with other
devices
test reports & clinical data
label & instructions for use

Design Dossier Documentation

The structure of a design dossier or technical file
can be broken down into 12 sections as below:
1. Introduction
2. Essential Requirements Checklist
3. Risk Analysis
4. Drawings, Design, Product Specifications
5. Chemical, physical and biological tests
including In Vitro Testing - Preclinical Studies,
Biocompatibility Tests, Biostability Tests,
Microbiological Safety, Animal origin tissue,
Coated Medical Devices
Design Dossier Documentation
6. Clinical Data
7. Package Qualification and Shelf life
8. Labels - Instructions for use: including
patient information and advertising materials
9. Manufacturing
10. Sterilization
11. Conclusion
12. Declaration of Conformity (Draft)
European Risk Management
What? Why? When?

Tips
285

Risk Management What is it?
See EN ISO 14971: 2012 Medical devices

Application of risk management to medical
devices.
Do obtain and read latest version.
The aim of the Directives is to determine that
any risks which may be associated with their

[device] intended 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.
286
Risk What is it? Some Definitions
Harm physical injury or damage to the health

of people, or damage to property or the
environment.
Hazard potential source of harm.
Risk combination of the probability of
occurrence of harm and the severity of that
harm.
Residual Risk risk remaining after risk control
measures have been taken.
287
Risk Management Process

Risk Assessment
Risk Analysis
Risk Management
Risk Evaluation
Risk Control
Post-production
Information
288

Risk Management and Analysis

Risk Management is an iterative planned process
that is documented and controlled.
Risk Analysis has both quantitative and qualitative
elements.
It does cover the intended use and reasonably
foreseeable misuse.
There is a need to identify known and foreseeable
hazards.
Risks are estimated for each hazard based on:
Probability of occurrence
Severity of harm
289
Note some well used risk tools include:

Preliminary Hazard Analysis (PHA). Useful
during early stage design and development.
Please see IEC 60300-3-9 Ed2.
Fault Tree Analysis (FTA). A top down analysis
that starts with a series of top level events and
deduces what could have caused them. It is a
systematic approach but can be become large
and complex for sophisticated systems but
there are software tools available.
290
Hazard and Operability Study (HAZOP). Please

see IEC International Standard 61882, Hazard and
Operability Studies (HAZOP) Application Guide for
more about this qualitative method often used in
the pharmaceutical industry.
Hazard Analysis and Critical Control Point

(HACCP) used a lot in the food industry and
has some similarities with HAZOP.
291


Failure Mode & Effects Analysis (FMEA). Please
see IEC 60812: 2006 Analysis techniques for
system reliability, Procedure for failure mode and
effects analysis. A bottom up single fault
condition is analysed to determine the
subsequent effects. Often used by engineers in
detailed design and development work.
Uses R = S X P for risk analysis where S =
Severity of the risk and P = Probability of
occurrence.
Tables of risk estimation can be created.
292
293
Risk Evaluation
Follow EN ISO 14971 and use recognized techniques
where appropriate.
Evaluate the risk for each hazard for acceptability
based on pre-approved criteria, both qualitative and
quantitative.
Historically the aim was to reach the As Low As
Reasonably Practical level ALARP. Please see:
http://www.hse.gov.uk/risk/theory/alarpglance.htm
and
http://www.hse.gov.uk/foi/internalops/hid_circs/permissioning/spc_perm_37/
Risk Evaluation is a never ending process.
294

Risk ALARP Concept
http://www.hse.gov.uk/foi/internalops/hid_circs/permissioning/spc_perm_37/
Risk As Far As Possible Vs ALARP

Evaluation of Risk / Benefit (EN ISO 14971:2012)
Please see Annex ZA (MDD) / Annex ZB (AIMD)

Deviations 1 to 7, here is 3:
a) Annex D.8 to ISO 14971, referred to in 3.4, contains

the concept of reducing risks "as low as reasonably
practicable" (ALARP concept). The ALARP concept
contains an element of economic consideration.
b) However, the first indent of Section 2 of Annex I to
Directive 93/42/EEC and various particular Essential
Requirements require risks to be reduced "as far as
possible" without there being room for economic
considerations.
c) Accordingly, manufacturers and Notified Bodies may
not apply the ALARP concept with regard to economic
considerations.
296
Risk Control
If risk reduction / mitigation is required:

Identify appropriate risk reduction measures
such validation, specification changes, training,
labelling, etc.
Implement risk reduction measures.
Evaluate residual risks for acceptability.
Are other hazards generated from risk
reduction measures?
Complete and document overall residual risk
process.
297

Post Market Information

Review information gained from Post Market
Surveillance (PMS), consider and review:
Manufacturing or Proposed Design Changes;
Complaints; and of course
CAPA (corrective actions & preventive actions).
Evaluate the above information for the following:
If previously unrecognized hazards are
present;
If estimated risks are no longer acceptable;
and
If the original assessment is invalidated.
298
Risk Management &

Product Development Cycle
Risk Management should be applied throughout

the product development cycle.
Risk Management should be an integral part of

Design Controls and Design Reviews.
Risk Management is an iterative process.
299
Risk eliminate by design?
The MDD ERs demands that risk be reduced as

far as possible by adopting an inherently safe
design and construction.
Inherently safe design is the first means to
eliminate risk wherever possible and reduce it to
at the very least as low as is practical. This
requires judgement and is an imprecise activity
that changes with the state-of-the-art.
Alarms or warnings in the information supplied by
the manufacturer are NOT a substitute for good
design practice.
300

Risk Management &

User Needs
Design
Traditional Waterfall
Input
Model
Design
Process
Design Design
Verification Output
Design Medical
Validation Device
301
Risk Management &

User Needs
Applying Risk
Design
Input Management
Design
Process
Design Design Design

Verification Output Transfer
Design Medical
Validation Device
Changes
Complaints
302
The Design Process
Clinical
Design Plan
Validation
Design Clinical
Validation Evaluation
Design Risk
Verification Management
Design User
Outputs Requirements
Design Inputs
303

Why do Risk Management?

Design Input
Identify risks before they can ever happen.
Design Output
Even if design input is assessed and mitigated,
there are many ways to design a product.
Each design could produce different hazards or
risks.
Design Transfer
A perfect design without risks could be unsafe
if manufactured incorrectly.
Post Production
What really counts is what really happens.
Measures the effectiveness and is part of
maintaining a devices fitness for purpose.
Some Useful Tips

Do Risk Management as a team.
Do include and involve relevant clinical users,
service engineers, production, and others with no
design or production involvement.
Always keep risk management issues in mind in
all activities, it is a way of thinking.
Do use EN ISO 14971; use relevant standards for
other techniques to maximise consistency.
Remember Risk Management requires judgement
and most of all experience. Ensure a balanced
approach is taken and undue time is not spent on
the highly improbable.
Two Important Standards

- for all manufacturers to consider
1. Quality Systems and Global Harmonisation EN 13485:

2016 Medical devices Quality management systems
Requirements for regulatory purposes.
2. EN ISO 14971:2012 Medical devices - Application
of risk management to medical devices.
No device should be placed on the market without a risk
management process being completed.
These two standards can help manufacturers produce
medical devices that are in compliance.
Please, please do obtain and read the latest versions of
these very important standards.

Risk Management Concept Diagram
Risk Assessment
methodical, mostly science Risk Management policy
based but experience, and procedure based
judgement and teamwork experience and teamwork
are all important. essential.
The customer the patient is the ultimate beneficiary,

subjected only to devices with benefits that outweigh
the acceptable residual risks.
Risk Communication
is essential to teamwork, compliance and overall effectiveness
of the risk management process.
307
A Holistic Approach to Risk Management

Annex ZA (MDD) / Annex ZB (AIMD) Deviation 4
The manufacturer must undertake the risk-benefit analysis for the individual risk
and the overall risk-benefit analysis (weighing all risks combined against the
benefit) in all cases.
Annex D
Those involved in making risk/benefit judgments have a responsibility to

understand and take into account the technical, clinical, regulatory, economic,
sociological and political context of their risk management decisions.
The decision as to whether risks are

outweighed by benefits is essentially a matter
of judgment by experienced and
knowledgeable individuals.
An important consideration in the acceptability of a residual risk is whether an
anticipated clinical benefit can be achieved through the use of alternative design
solutions or therapeutic options that avoid exposure to that risk or reduce the
overall risk.
308
Design Process and Technical Documentation
The design process is one of the most

crucial activities to ensure medical devices
are fit for purpose.
The audit of the design process is a very
complex activity requiring the management
of many competencies and personnel.
Auditor/notified body focus/competencies
are generally split between several areas
and aspects, some covering specific design,
design validation, quality management
system activities and any third party
activities and certifications.
309

Types of Personnel used in the Audit of

Design and Technical Documentation
Device Type Clinical Biological Manufacturing Microbiological & Product Testing
Sterilisation
Wound Dressing Tissue Toxicologist Polymer Microbiologist Analytical Chemist

Antimicrobial Viability Engineering / Packaging Engineer Mechanical Engineer
specialist Chemist Materials Engineer
Drug Device Anatomy & Toxicologist Polymer Microbiologist Analytical Chemist

Implant Pathology Pharmacist Engineering / Packaging Engineer Chemist
specific BioChemist Coatings Pharmacist
Engineering Qualified Person
Mechanical Mechanical Engineer
Engineering Materials Engineer
Orthopaedic Orthopaedic Toxicologist Mechanical Microbiologist Materials Engineer

Joint Surgeon Engineer Packaging Engineer Mechanical Engineer
Replacement BioEngineer Metallurgist Chemist (Coatings)
Linear Oncologist NA Software Microbiologist Electrical Engineer

Accelerator Dosimetrist Engineer Packaging Engineer Software Engineer
Physicist Electromechanic Safety Engineer
al Engineer
Physicist
The Design Process
Clinical
Design Plan
Validation
Design Clinical
Validation Evaluation
Design Risk
Verification Management
Design User
Outputs Requirements
Design Inputs
311
The Design Process

Defining the Acceptance
Developing the Design, Criteria &
New Clinical Purpose New Product Proposal Feasibility Clinical and Risk Risk Acceptability
New Function(s) Management Plans
New Market
New Technology
New Standards
New Regulations
Milestone Reviews
New Essential Reqs
DESIGN MASTER
Design Control Audits
RECORD
Clinical & Regulatory
TECHNICAL FILE
Evaluation
Customer and
Regulatory Essential Requirement
Inputs Outputs Test Deviations
RISK MGT REPORT
Requirements Risk Analysis CLINICAL SUMMARY

Risk Evaluation
& Risk Control DESIGN VALIDATION
Current clinical SUMMARY
outcomes
Design Requirements DESIGN DOSSIER
Statements
& Clinical Validation PRODUCT
Design Inputs
Risk Management Plan

Verification Product Validation
Product Characteristics
User Requirements
Regulatory Requirements Process Validation
Market Requirements
Company Requirements Packaging
Sterilisation
Animal Tissue Viability
Medicinal Delivery
DESIGN HISTORY FILE


The Design Process
Do Inputs
reflect Have Inputs Create Does the
Develop Test & Verify
Obtain Inputs Our been Requirements Spec reflect
Solutions Solutions
Design approved Specification the inputs
Plan
Create Is it in
Did it Is the Risk Design Output Is it in
Meet our control Approved
Validation line with Undertake
Strategy line with Validation
Criteria strong our
Stds.
Reqs.
Risk Benefit
Validation
Summaries
DESIGN
Deviation Actions
REVIEWS
CAPA
CLINICAL
SUMMARIES
Did it
Meet our
Risk
Accept
Criteria
Please do use an
Essential Requirements Checklist!
Every applicable ER must have documented

proof associated with it!
Must be easy to navigate and provide clear

summaries of conformance.
314
Please do use all the applicable

MEDDEVs, Standards,
Guidance Documents
and
other recognised documents that assist
in the correct, state-of-the-art, interpretation
of requirements.
Update it regularly!
315

How it works in one slide

European Commission and
Member States
Surveillance
Competent Notified
Designation
Enforcement
316
Practical Session
Please consider the major stages in the
development of a combination product,
including risk management issues.
317
Device Labelling
318

Information supplied by the manufacturer

Please see Annex I ERs section 13 Information supplied by the
manufacturer in Directive 93/42/EC (MDD); Annex 1 ERs sections
11 to 15 Directive 90/385/EC (AIMDD); and Annex I section 8 of
Directive 98/79/EC (IVDD). These all require basic information to
be provided such as, but not limited to:
Information to use the device safely.
Name and address of the manufacturer and authorised
representative where the manufacturer does not have a
registered place of business in the EU.
Where appropriate indication of sterility, lot, expiry date
and any relevant storage information.
Degree of accuracy of any measuring function.
Warnings or precautions.
Labelled exclusively for clinical investigations if so.
Date of issue or latest revision of the instructions for use.
Information supplied by the manufacturer

Continued:
Active devices year of manufacture.
Intended purpose if not obvious to user.
Devices and detachable components identified in
terms of batches where reasonable and practical.
Appropriate statement where the device contains a
human blood derivative.
A warning where the device contains pathalates for
certain uses.
Labelled custom-made device if so.
Instructions For Use (IFU) Comments
IFU must accompany or be included with packaging

of one or more devices.
By way of exception, no such instructions for
use are needed for devices in Class I or IIa if they
can be used safely without any such instructions.
Justification needs to consider it the device can be
used properly and safely without IFU. So a risk
analysis of knowledge and experience of users,
complexity of operation, preparation required before
use and any special disposal instructions do need to be
considered.

Instructions For Use (IFU) Content
All information from label except LOT & Expiry.

Performances and side effects.
Safe combinations of use.
Verification of correct installation & use.
Avoidance of risks connected to implantation.
Action if sterile packaging is damaged or open.
Method to reuse including sterilisation, if applicable.
Preparation before use.
Emitted radiation.
Instructions For Use (IFU) Content
The instructions for use must also include details

allowing the medical staff to brief the patient on any
contra-indications and any precautions to be taken.
These details should cover in particular:
Change in device performance.
Exposure to environmental conditions.
Details of medicines intended to be delivered.
Medicinal substances incorporated.
Disposal and associated risks.
Accuracy of measuring functions.
Issue date or revision number.
Labelling Practical Considerations

Needs to take into account the training, technical
knowledge, experience, education and status of users
especially if they are lay, professional, disabled or
other users.
Device characteristics are important including size
and available space for labelling on the device. Or if
the device is implantable!
The human factors of label text / font size and level
of comprehension and where they are to be used can
affect how the labelling is finally implemented.
Choice of medium(s), i.e. paper, screen, CD/DVD,
web site, phone or other device.

Symbols they can help and

do transcend language
Manufacturers should according to the MDD: Where
appropriate, this information should take the form of
symbols. Any symbol or identification colour used must
conform to the harmonized standards. In areas for which no
standard exist, the symbols and colours used must be
described in the documentation supplied with the device.
EN ISO 15223-1: 2012 Medical devices Symbols

to be used with medical device labels, labelling
and information to be supplied Part 1: General
requirements.
This standard has been published and adopted it will replace

EN980 globally and become a harmonized standard for the
medical device directives in the near future.
Symbols they can help and

do transcend language
Some examples:
Can you spot the odd symbol out??
Transposition of Directives always raises

the need for National Language use
Icelandic:
Iceland* Swedish:
Norwegian:
Sweden
Norway*
English:
UK
Ireland Danish: Finnish: Finland
Denmark Estonian: Estonia
Dutch:
Netherlands Latvian: Latvia
Belgium Lithuanian: Lithuania
German:
French: Belgium Germany,
France Liechtenstein*,
Luxembourg Luxembourg
Austria
Czech: Czech Republic Polish: Poland
Letzeburgish:Luxembourg
Hungarian: Hungary
Portuguese: Portugal
Spanish: Italian:
Slovene: Slovenia Spain Italy
English/(Maltese): Malta
Non-EEA countries that recognise CE-marking: SwitzerlandSlovak: Slovakia
(German, French, Italian) Greek: Greece - Cyprus

Lots of Languages
The Publications Office of the European Union (EU)

publishes the daily Official Journal of the European
Union in 24 languages and produces (or co-produces)
publicity for EU initiatives and activities. (Compare this
to 2,000 written languages worldwide! 116 official!)
However for over-the-counter (OTC) and products

used in the home it is important to consider other
languages beyond the basic 24, i.e. Asian and Welsh
languages in the UK or Turkish in Germany.
The first thing Member States do when

transposing Directives into National Law is to
demand use of their National Languages!
Lots of Languages
- you need a translation procedure
MEDDEV 2.5/5 Rev.3 (February 1998) Translation

Procedure states:
As part of the quality system or of the documents

defining the manufacturing process, the manufacturer
should have procedures for ensuring accurate
translation of e.g. labelling, instructions for use and
product claims in marketing material.
These are especially important for user instructions

where the safety and claimed performance of the
device may be compromised through inadequate
translation.
Lots of Languages
- eIFU for IVDs possible
MEDDEV 2.14/3 rev.1 (January 2007) IVD Guidance: Supply of

Instructions For Use (IFU) and other information for In-Vitro
Diagnostic (IVD) Medical Devices. A Guide for Manufacturers and
Notified Bodies.
This IVD eIFU MEDDEV is very helpful for laboratory based IVDs
where there is a lot of relevant scientific support and professionals
often speak more than one language.
This MEDDEV states that IVDs for lay use such as pregnancy tests
must be supplied with an IFU in paper format.
The rationale for eIFU must be based in a thorough risk analysis.
Note that software graphical user interfaces (GUI) are a form of
labelling.

Lots of Languages
- eIFU for medical devices possible
There is an equivalent to MEDDEV 2.14/3 rev.1 IVD eIFU
provided by Commission Regulation (EU) No 207/2012
of 9 March 2012 on electronic instructions for use of
medical devices.
This does cover Active Implantable Medical Devices (AIMD);
Implantable Medical Devices; fixed medical device
installations; medical devices and accessories covered by
Directive 93/42/EEC (MDD) and stand alone software.
The rationale for eIFU must be based in a thorough risk
analysis.
Note that software graphical user interfaces (GUI) are a
form of labelling.
Lots of Languages
- eIFU for medical devices possible
Manufacturers may provide instructions for use in electronic
form instead of paper provided:
The devices and accessories are intended for exclusive
use by professional users.
The use by other persons is not reasonably foreseeable.
Updates and clear revision dates on the eIFU are required
and it is noted that they are required to be available 2 years
after the end of the expiry date of the last produced device.
For implantable devices this is rightly extended to 15 years
after the last device has been manufactured.
As with the IVD eIFU this does not really help where devices
are used by lay persons.
Labelling More Standards

EN 1041:2008 Information supplied by the
manufacturer of medical devices.
EN ISO 3826-2:2008 Plastics collapsible containers for
human blood and blood components - Part 2: Graphical
symbols for use on labels and instruction leaflets.
EN 15986:2011 Symbol for use in the labelling of
medical devices - Requirements for labelling of medical
devices containing phthalates.
IEC/TR 60878 ed2.0 Graphical symbols for electrical
equipment in medical practice EN 18113 (1 to 5) IVD
Information to be supplied for professional and self
testing.
EN 45502-1:2015 Implants for surgery. Active implantable
medical devices. General requirements for safety, marking and
for information to be provided by the manufacturer.

Labelling More IVD Standards
EN ISO 18113-1:2011 In vitro diagnostic medical

devices - Information supplied by the manufacturer
(labelling) - Part 1: Terms, definitions and general
requirements (ISO 18113-1:2009).
(labelling) - Part 2: In vitro diagnostic reagents for
professional use (ISO 18113-2:2009).
EN ISO 18113-3:2011 In vitro diagnostic
medical devices - Information supplied by the
manufacturer (labelling) - Part 3: In vitro diagnostic
instruments for professional use (ISO 18113-
3:2009).
Labelling More IVD Standards

(labelling) - Part 4: In vitro diagnostic reagents for
self-testing (ISO 18113-4:2009).
(labelling) - Part 5: In vitro diagnostic instruments
for self-testing (ISO 18113-5:2009).
Please remember:
Unique Device Identification

(UDI
UDI))
Commission Recommendation 2013/172/EU
and
Global Medical Device Nomenclature

(GMDN
GMDN) )
336

Key Labelling Point from

The Revision of Medical Device Directives
The need for a product to have a Unique Device

Identification (UDI) will be finalised as part of the
implementing Act after the Council/Parliament
position is agreed. Should prove helpful provided
only one system is used globally
http://ec.europa.eu/growth/sectors/medical-devices/specific-
areas-development/udi/index_en.htm
UDI in the United States
Already required by United States (US) Food and

Drug Administration (FDA) for Class III devices.
Class II devices start by 24Sep16 & Class I by
24Sep18. For more please see
http://www.fda.gov/medicaldevices/deviceregulationandguidance/
uniquedeviceidentification/default.htm
UDI
Device identifier should contain fixed information

specific to a manufacturer and a device model. It is
used as an access key to information stored in a
UDI database.
Production identifier should contain information

that changes. Identifying data related to the unit of
device production and required traceability. This
varies with manufacturing/expiration dates,
lot/batch number of serial number.

UDI labelling and records
UDI allows labelling of products with a printed UDI

label on the device, product packaging and other
levels of packaging if required.
Manufacturers need to keep an electronic record of
both device identifier and production identifier.
Manufacturers should keep an electronic record of
the economic operator, health institution, or
professional users they have supplied.
Advantages of UDI
Assists with traceability and recalls.

Helps with managing Adverse Event Reporting (AER)
and Post-Market Surveillance (PMS).
Assists in procurement, especially inventory
management and accounting.
Helps to reduce the possibility of counterfeiting.
European Databank and

Global Medical Device Nomenclature (GMDN)
Please see:
www.gmdn.org
for much more background;
the following quotes used here are taken
from this site.
342

Purpose of an international Medical Device

Nomenclature :
To facilitate cooperation and exchange of

regulatory data on an international level
between interested parties such as
regulatory authorities, manufacturers,
suppliers, healthcare providers, and end
users (scope, EN ISO 15225)
343
Its intended use :
Notification and certificates
Warning, advising users concerning a

device generic group
Scope of Notified Bodies
Facilitate electronic communication
344
European Databank and

This is evidence of the global convergence of

medical device regulation and is a system for
providing common descriptions of medical
devices. It is currently being implemented across
Europe but each countrys implementation
timetable is different.
The GMDN nomenclature will probably be used
for registering medical devices and exchanging
information about them around the world,
especially for vigilance issues.
345

The Global Medical Device Nomenclature

(GMDN) is a collection of internationally
recognized terms used to accurately describe and
catalogue medical devices.
It contains nearly 7,000 terms plus more than
10,000 synonyms to make the GMDN easier to
use.
The GMDN is a classification system developed to
allow for the classification of all Medical Devices
put onto the market as defined in the three
European Directives.
346
Competent Authorities (CAs) in the EU do ask

manufacturers to register using the GMDN codes.
The licence fee for using the GMDN database is in

Euros varies with company turnover, starting at
Euro 200 and going up to Euro 4000.
347
GMDN and UDI
Assists with traceability and recalls.

Helps with managing Adverse Event Reporting (AER)
and Post-Market Surveillance (PMS).
Assists in procurement, especially inventory
management and accounting.
Helps to reduce the possibility of counterfeiting.

Labelling More Specialist Standards

EN 60601 series; IEC 416, 417 & 878 many
symbols for electrical equipment.
ISO/IEC 15417-2007 information technology -
automatic identification and data capture
techniques - code 128 bar code symbology
specification.
EN 1556 Bar Coding Terminology.
EN 1571 Bar Coding Data Identifiers.
EN/IEC 80416 Basic principles for the creation of
graphical symbols.
ISO 9186-1 Graphical symbols. Method for
testing.
ISO 9186-2 Graphical symbols, Method for
testing perceptual quality.
Note on European Database

EUDAMED
Ashley Yeo wrote an article for Scrip Regulatory Affairs on
the 17th March 2014 entitled Looking for signals and
joining up reporting: UK MHRA takes a new
approach to medical device incidents and the
following extract makes for interesting reading concerning
the ever ongoing EUDAMED implementation (bold emphasis
added):
The development of the major EU device data

transparency electronic system, Eudamed III, has been
held up due to the slow progress in the EUs processing of
the proposed Medical Device Regulation. With a delay of a
year or more now expected in the implementation of the
MDR, the improved Eudamed database is
unlikely to be in place until 2018, at the
earliest. 350
Practical Session Labelling
make your own label!
351

Practical Session Labelling
Please create a label for an

Over The Counter (OTC) Device
Please try ONE of the following:

A simple box of sticky plasters.
Heated pad for pain relief.
A combination product one you
are familiar with or have used.
352
Time for a break.
Time for some light

refreshment!
353
Clinical Evaluation
354

If in doubt please ask a question?

and always work as a team!
Please make your questions

short, helpful and of a general
nature wherever you can.
355
Clinical Evaluation and Clinical Investigation
What is a Clinical Evaluation?
356
What is a Clinical Evaluation
Clinical evaluation is the assessment

and analysis of clinical data pertaining to
a medical device in order to verify the
clinical safety and performance of the
device.
Demonstrate that the device complies with

the relevant Essential Requirements from
the Medical Device Directive 93/42/EEC and
amendment 2007/47/EEC covering safety
and performance.
357

Scope of a Clinical Evaluation
Analysis of available pre- and post market clinical

data regarding clinical performance and safety
relevant to the intended use of the device in question
or substantially equivalent devices.
Address clinical claims of device.
Adequacy of product labelling and product
information
Claims
Contraindications
Precautions/warnings
Suitability of Instructions for Use (IFU).
Risks acceptable when weighed against benefits the
device provides.
358
Clinical Data
The hierarchy for clinical evidence in the

scientific literature is as follows:
Systematic reviews and meta-analysis.
Randomised controlled trials (RCTs).
Cohort studies.
Case-control studies.
Cross-sectional surveys.
Case reports.
359
Clinical Data
Other sources of clinical data/documentation:

Pre- and post market investigation reports
(manufacturer sponsored)
Adverse event reports:
Manufacturers database.
Competent Authority database e.g.
MHRA, FDA including the Total Product
Life Cycle (TPLC) database and US
National Institutes of Health
ClinicalTrails.gov database.
360

Essential Requirements that require support

from Clinical Data
See: Annex I and Annex X of the MDD

-Annex I of the AIMDD.
ER 1. The devices must be designed and

manufactured in such a way that, when used
under the conditions and for the purposes
intended, they will not compromise the clinical
condition or the safety of patients, or the safety
and health of users
361
Essential Requirements that require support

from Clinical Data
ER 3. The devices must achieve the

performances intended by the manufacturer..
ER 6. Any undesirable side-effect must
constitute an acceptable risk when weighed
against the performances intended.
ER 6a. Demonstration of conformity with the
essential requirements must include a clinical
evaluation in accordance with Annex X.
362
Clinical Evaluation Process
Identify the Essential Requirements that require

support from relevant clinical data.
Identify available clinical data relevant to the device
and its intended use (clinical literature search).
Evaluate data in terms of its suitability for
establishing the safety and performance of the
device (clinical literature review).
Identify any clinical data needed to address
outstanding issues.
Document all the clinical data used to reach
conclusions about the clinical safety & performance
of the device in a Clinical Evaluation Report (CER).

Summary
Identify all relevant clinical data / literature from all

possible sources.
Review and assess, scientifically and methodically,
the scientific clinical literature.
Establish the evidence for performance and safety
of the medical device including the manufacturers
claims, IFU and risk management process.
If the scientific literature is incomplete, i.e. some
evidence is not available, then a Clinical
Investigation will be required to establish this
required evidence.
Produce Clinical Evaluation Report as independently
and as professionally as possible, do include the
good, the bad and the ugly. 364
Who is involved in the regulatory process?
Manufacturer - Performs the clinical

evaluation in order to verify the clinical
safety and performance of the device.
Notified Body Assesses the clinical

evaluation to verify that conformity is
demonstrated.
365
Who should conduct the clinical evaluation?
- A suitably qualified individual or individuals.

- Should possess knowledge of the following:
the device technology and its application.
research methodology (clinical investigation
design and biostatistics).
diagnosis and management of the conditions
intended to be treated or diagnosed by the
device.
366

Clinical staff
Conduct literature review, collect additional
data, write report
Regulatory staff
Ensure all regulations complied with
Quality Assurance
Review and sign off
367
Sponsor or Medical Expert

Can be independent assessor
Review and sign off
Can be performed by Manufacturer or contracted

out CRO
CV of author appended to report
368
What does the Notified Body do?
The assessment and verification of clinical

evaluations provided by medical device
manufacturers to support demonstration of
conformity of a device with the essential
requirements of the relevant directive.
When
Examination of Technical File or Design
Dossier pre CE mark.
As part of a quality system approval
audit.
During scheduled surveillance audits and
especially when the Clinical Evaluation is
updated.
369

What is involved in a clinical evaluation?
Define the scope of the clinical evaluation.
Identify available clinical data relevant to the device
Evaluate the suitability of data for establishing the

safety and performance of the device.
Generate any clinical data needed to address

outstanding issues.
Compile the clinical evaluation report (CER).
370
Scope of the Clinical Evaluation
Before a clinical evaluation is undertaken the

manufacturer should define its scope, based on:
the Essential Requirements that require support
from relevant clinical data.
any performance and safety claims made about
the device.
any design features that pose special performance
or safety concerns.
any residual risks that remain in the Technical File
or Design Dossier. Please remember this needs to be
as low as possible by inherent design.
371
Scope of the Clinical Evaluation
Determine whether data from equivalent devices

can be used to support safety and/or performance
Same intended use / technical and biological
characteristics.
Identify the data sources and types of data to be
used in the clinical evaluation:
Established use? New technology? High risk?
372

Identify Available Clinical Data
Data generated through a scientific literature search

published clinical data that is not in the
possession of the manufacturer.
may relate to the device or equivalent devices.
use a search protocol or plan that is creditable
and professional.
Data generated through clinical experience
post market surveillance reports, registries.
adverse events databases (in-house or
regulatory, e.g. MHRA, FDA, etc).
relevant field corrective actions
373
Evaluate the Clinical Data
Identified data should be appraised to

determine:
if it contains sufficient information to allow a

rational and objective assessment
the relevance to the performance and/or

safety of the device
the quality of the data and its contribution to

establishing the safety and performance of
the device
Data accepted or rejected.

374
Appraised data should be analysed to

determine that it demonstrates the clinical
performance and safety of the device in
relation to its intended use
the device performs as intended by the
manufacturer;
the device does not pose any undue
safety concerns to either the recipient or
end-user;
any risks associated with the use of the
device are acceptable when weighed
against the benefits to the patient.
375

Clinical data is sufficient to demonstrate the

clinical performance and safety of the device?
Yes write the clinical evaluation report
No generate clinical data
376
Compile the Clinical Evaluation Report
Background information
scope and context of the evaluation
technology on which the medical device is
based
intended use
performance & safety claims
Clinical data
identification
appraisal and analysis
demonstration of safety & performance
Conclusions 377
Clinical Evaluation for the MDD

What? Why? When?
Guidance, Standards and Tips
+How it relates to
Post Market Surveillance
More insights are covered but yes, there

is a significant amount of repeat in this
section to ensure this vital subject is
given due consideration.
378

What is it? See MDD Annex X!
Proof of compliance with essential requirements.

Verification of performance under normal
conditions of use.
Determination of side effects and assessment of
whether they constitute an acceptable risk or not
when weighed against the intended performance
of the device.
Do note there is increased emphasis and

strengthening of clinical evaluation and
clinical investigations (Chapter VI) in the
proposed MDD Revision (MDR).
379
Why Do Clinical Evaluations?
The root cause of serious market problems is

often related to inadequate clinical data.
Post Market Surveillance alone is not sufficient.
Often needed to gain reimbursement.
Helps in liability defence cases.
Enhances reputation and improves the prospects
of sales to scientifically sceptic customers.
Leads to better and safer medical devices being
placed on the market and put into service.
380
Why Do Clinical Evaluations?
Evidence Based Medicine.

Prove it when it goes right!
Strict Liability.
Consumer Protection.
Prove it when it goes wrong!
381

Legal Requirements / Expectations

Clinical trials need to be well planned, ethical
and undertaken in accordance with the
Declaration of Helsinki.
Notified to the Competent Authority before
proceeding. CA has a 60 day assessment
window.
Are expected to be preceded by appropriate
literature search, and possibly laboratory and/or
animal studies.
Monitored and controlled to ensure participant
safety at all times.
Manufacturers undertaking clinical trials need to
provide insurance cover for both the patients
and themselves.
382
When are Clinical Investigations Required?

To provide proof of regulatory compliance, especially
with the essential requirements, unless this can be
adequately done in other ways or is considered
unethical and/or unnecessary experimentation on
humans.
The reasons for undertaking clinical investigations or
not should be documented and justified.
For novel devices where no market experience or
literature is available.
For a new material, function, feature or modification
where no market experience or literature is available
and laboratory tests cannot adequately simulate the
clinical situation.
Possibly when the device is made by a new
manufacturer.
Research Ethics Committee (REC)

Research ethics committee
means an independent and properly constituted body of

medical professionals and non-medical members whose
responsibility is to ensure that the health, safety and human
rights of the patients participating in a particular clinical
investigation are protected.
Such RECs only meet once a month and sometimes once
every other month. So an early approach is clearly
recommended.
Clearly the consideration of ethics and the approval of a
Local Research Ethics Committee (LREC) is a very important
part of medical device regulation in regard to clinical
investigations. It is typically an individual focused, bottom-
up view of the world where the need of the individual trumps
the needs of the many.

An excellent and very detailed document of the

process in the United Kingdom is provided in the
National Health Service (NHS), National Patient
Safety Agency, National Research Ethics Service
guidance for researchers, manufacturers, research
ethics committees and NHS R&D offices (2008)
document entitled: Approval for medical
devices research. Available from:
http://www.hra.nhs.uk/documents/2013/09/approval-of-
medical-devices-research-version-2-april-2008.pdf
385
Important Note on model Clinical Investigation

Agreement (mCIA)
The model Clinical Investigation Agreement
(mCIA) is available with other useful information
at:
http://www.nihr.ac.uk/industry/Pages/model_clinica
l_trials_agreement.aspx
This is the recommended form of agreement
between a medical technology company and a
National Health Service (NHS) hospital in the United
Kingdom (UK). Whilst this is UK specific, with a little
adaption it could be used more internationally.
386
Required Documentation Summary
Investigator Brochure
Clinical Investigation Plan
Sample Labelling
CVs for Principal Investigator and other members of
clinical site and project, plus a review of relevant
qualifications
Log of investigators and sites
Signed agreement between sponsor and investigation
sites and Clinical Research Organisation (CRO) if used.
Informed Consent Form.
Monitoring Plan.
Case Report Forms (CRFs).
Post Market Surveillance Plan.
387

Some Useful Tips for Manufacturers

Do enter into a dialogue with all stakeholders as
soon as possible, especially Competent Authorities
(CAs) and Notified Bodies (NBs).
Follow guidance in MEDDEVs & NB-MEDs.
Use EN ISO 14155: 2011 Clinical investigation of
medical devices for human subjects. Good clinical
practice.
This supersedes the old 2009 two part standard:
EN ISO 14155-1: 2009 Clinical investigation of
medical devices for human subjects Part 1:
General requirements; and
Use EN ISO 14155-2: 2009 Clinical
investigation of medical devices for human
subjects Part 2: Clinical investigation plans.
EN ISO 14155
Manufacturers are expected to use this standard.

It covers justification, ethical considerations,
compensation of participants, consent,
information to be supplied concerning informed
consent, documentation and its control,
responsibilities of investigation monitors, and
suggested procedure for the literature review.
It covers all aspects of the clinical investigation
plan.
To be used in conjunction with the MEDDEVs,
directives and MDR.
389
More Useful Tips for Manufacturers
Always do a thorough literature review using

appropriately qualified persons using a
structured, highly professional and scientific
methodology.
Do as much as you can in the pre-clinical
environment.
Remember all the essential requirements must be
complied with, except that for the purpose of the
investigation.
390

Some Useful Tips for Manufacturers

A thorough risk analysis to EN 14971 is vital. Have
clear relevant clinical end points and be clear what
the purpose of the investigation is.
In the study background do cover any current
clinical experience, adverse incident analysis and
relevant experience with substantially equivalent
devices.
Do make sure the biocompatibility, biological and
microbiological safety have been satisfactorily dealt
with. Use EN ISO 10993 series of standards for the
biological evaluation of medical devices.
Be scientific about everything concerned with the
clinical investigation.
391
Clinical Evaluation Final Report
Must be professional and scientific.

Must be written by a medical practitioner or
other authorised person and must contain a
critical evaluation of all the data collected.
The report and author both need to be
creditable and objective.
Sometimes the report can be split into pre-
clinical technical/laboratory and clinical
investigation parts where appropriate.
392
Final Report &

Post Market Surveillance
Should be written in accordance with the

MEDDEV 2.7.1 revision 4 (June 2016) Clinical
Evaluation: A Guide for Manufacturers and
Notified Bodies.
Should also consider and link to requirements
outlined in MEDDEV 2.12/2 rev.2 (January
2012) Post Market Clinical Follow-up studies.
Now must start reading and using the MDR and
especially all those pertaining to clinical evaluation
and post-market procedures.
393

MDR some sections to examine

and consider using now
Annex IIa Post-Market Surveillance

Annex XIII Part A Clinical Evaluations and Part B Post-
Market Clinical Follow-Up.
Annex XIV Clinical Investigations.
Annex XV List of Groups of Products without an
Intended Medical Purpose Referred to Article 1.
This includes a lot of cosmetic products and brain stimulation
products using electrical current or magnetic or electromagnetic
fields.
Annex XVI Correlation Table for MDD, AIMDD & MDR.
What makes for a good Clinical Evaluation

for all stakeholders?
This includes
Pre- and Post-Clinical Requirements,

including
recent proposed changes and

future direction.
395
Clinical Evaluation
Clinical Practice of Medicine
Key Opinion Leaders (KOLs)
Publications, Posters,
Papers and Patents
396

Clinical Evaluation an Essential Requirement

for all medical devices
Directive 90/385/EEC Annex 1 5a. :
Demonstration of conformity with the essential requirements

must include a clinical evaluation in accordance with Annex 7.
Directive 93/42/EEC Annex I 6a. :
Demonstration of conformity with the essential requirements

must include a clinical evaluation in accordance with Annex X.
397
Clinical Evaluation
Directive 93/42/EEC Annex X Clinical Evaluation:
1.1.1. Either a critical evaluation of the relevant scientific
literature currently available relating to the safety,
performance, design characteristics and intended purpose of
the device, where:
there is demonstration of equivalence of the device to the
device to which the data relates, and
the data adequately demonstrate compliance with the
relevant essential requirements.
1.1.2. Or a critical evaluation of the results of all clinical
investigations made.
1.1.3. Or a critical evaluation of the combined clinical data
provided in 1.1.1 and 1.1.2.
This is central to clinical proof your medical device does what

you say it does! It must be evidence-based and be appropriate
to the risk presented by the device.
398
Clinical Evaluation
Directive 90/385/EEC Annex 7 Clinical Evaluation:
1.1.1. Either a critical evaluation of the relevant scientific
literature currently available relating to the safety,
performance, design characteristics and intended purpose of
the device, where:
there is demonstration of equivalence of the device to the
device to which the data relates, and
the data adequately demonstrate compliance with the
relevant essential requirements.
1.1.2. Or a critical evaluation of the results of all clinical
investigations made.
1.1.3. Or a critical evaluation of the combined clinical data
provided in 1.1.1 and 1.1.2.
This is central to clinical proof your medical device does what

you say it does! It must be evidence-based and be appropriate
to the risk presented by the device.
399

Clinical Evaluation

1.2. Clinical investigations shall be performed unless
it is duly justified to rely on existing clinical data.
1.3. The clinical evaluation and its outcome shall be
documented. This documentation shall be included
and/or fully referenced in the technical
documentation of the device.
1.4. The clinical evaluation and its documentation
must be actively updated with data obtained from
the post-market surveillance. Where post-market
clinical follow-up as part of the post-market
surveillance plan for the device is not deemed
necessary, this must be duly justified and
documented.
400
Clinical Evaluation

1.5. Where demonstration of conformity with
essential requirements based on clinical data is not
deemed appropriate, adequate justification for any
such exclusion has to be given based on risk
management output and under consideration of the
specifics of the device/body interaction, the clinical
performances intended and the claims of the
manufacturer. Adequacy of demonstration of
conformity with the essential requirements by
performance evaluation, bench testing and pre-
clinical evaluation alone has to be duly
substantiated.
1.6. All data must remain confidential unless it is
deemed essential that they be divulged.
401
Clinical Evaluation
1.1a In the case of implantable devices and devices

in Class III clinical investigations shall be
performed unless it is duly justified to rely on
existing clinical data.
1.1b The clinical evaluation and its outcome shall be

documented. This documentation shall be included
and/or fully referenced in the technical
documentation of the device.
402

Clinical Evaluation
1.1c The clinical evaluation and its documentation

must be actively updated with data obtained from
the post-market surveillance. Where post-market
clinical follow-up as part of the post-market
surveillance plan for the device is not deemed
necessary, this must be duly justified and
documented.
403
Clinical Evaluation
1.1d Where demonstration of conformity with

essential requirements based on clinical data is
not deemed appropriate, adequate justification for
any such exclusion has to be given based on risk
management output and under consideration of
the specifics of the device/body interaction, the
clinical performances intended and the claims of
the manufacturer. Adequacy of demonstration of
conformity with the essential requirements by
performance evaluation, bench testing and pre-
clinical evaluation alone has to be duly
substantiated.
404
Clinical Practice of Medicine

Medicine is what professionally trained and qualified clinicians
practice. (As well as something you take when ill!). According
to the British Medical Journal (BMJ / John Saunders):
The practice of clinical medicine as an art and as a

science
The practice of modern medicine is the application of science,

the ideal of which has the objective of value-neutral truth. The
reality is different: practice varies widely between and within
national medical communities. Neither evidence from
randomised controlled trials nor observational methods can
dictate action in particular circumstances. Their conclusions are
applied by value judgments that may be impossible to specify
in focal particulars. Herein lies the art which is integral to the
practice of medicine as applied science.
Med Humanities 2000;26:18-22 doi:10.1136/mh.26.1.18

http://mh.bmj.com/content/26/1/18.long
405

Clinical Evaluation
Vs
Clinical Practice of Medicine?
Clinical Evaluation does not equal to Global Clinical Practice
Clinical Evaluation is to prove your device meets all applicable

Essential Requirements in the intended environment when used
by the intended end users.
Clinical Practice by definition is led by
Key Opinion Leaders (KOLs)
Clinical Evaluation is led by manufacturers who will always

display inadvertent bias (as we all do!).
Understanding how Global Clinical Practice varies from country

to country and which KOLs are important to your products will
help you to sell product and learn how discover needs that are:
met; unmet; known and unknown! But it is not enough!
406
Remember the Silicon Valey Nurse Story!
The Quiet Touch (QT) Air-Shields Vickers

baby incubator combines proven technology
with innovative features to minimize
excessive stimulation to the infant while, at
the same time, reducing stress to parents
and attending staff. Following its launch
every incubator has been designed and
made with these principles.
The key was following up a salesman that

said:
you just got to meet this nurse!
407
Who else might have a god idea?

and do you talk to them??
The answer is almost anyone! Although the
most likely are those lots of customer and /
or product contact such as:
Customers (includes healthcare providers)
Doctors and Nurses (not just KOLs)
Patients
Sales
Service and Maintenance
Customer Service
Manufacturing
R&D
For the QT all these stakeholders and more

were sought out and the salesman
introduction was NOT luck or chance!!!
408

The Four Clinical Ps
Publications. Academics are often very

concerned with publish or perish. This is great if
they provide competitive insights but can be a
negative if the idea discussed has not been
intellectually protected, i.e. patented. Many new
product ideas are to be found by studying
publications -including old ones as it usually takes
two or more goes to make something really
innovative!
Posters. Often neglected and not always available
on the web but a great source of ideas and usually
you can get a private conversation with the
authors! Actively seek them out and when doing
so try to spot the future KOL!!
409
The Four Clinical Ps
Papers. A subset of publications generally meant

to refer to peer reviewed publication in
respected, quality journals. Clearly the clinical
evaluation should help you find them!
Patents. The main form of Intellectual Property
(IP) protection and source of detailed competitive
information in the sector but not the only one!
In general get any original idea of value
patented (or IP protected) before you or
anyone else publishes it!!!
410
Clinical Evaluation in Europe
The European Union (EU) has regulated medical device

clinical evaluation since January 1990-1995 for Active
Implantable Medical Devices (AIMD) and since June 1998
for most medical devices. Since then numerous guidance
documents have been provided and adherence to
international best practices documents such as with GHTF
guidance (now the International Medical Device
Regulators Forum IMDRF) and / or ISO 14155 Clinical
investigation of medical devices for human subjects
Good clinical practice have been an important part of
the process. However it is the specific directives for
medical devices, namely Directive 90/385/EEC for AIMD
(AIMDD) and Directive 93/42/EEC for Medical Devices
(MDD) that provide the key legislation guidance that is
transposed into each Member States National Law.
411

Clinical Evaluation in Europe
Future medical device legislation in the EU is

likely to be introduced via Regulations that should
provide a more uniform application and
interpretation across all Member States.
New regulations are being formulated in the EU

as already discussed and these are likely to
reinforce the importance of clinical evaluation to
regulatory compliance, especially for higher risk
devices.
412
A Good Clinical Evaluation for All Stakeholders

It is highly desirable to have the IMDRF working towards an
internationally agreed GCP standard / guidance that is as
consistent as possible throughout the world is highly desirable
so that clinical evaluations and investigations are:
Ethical, well controlled and uniform in quality of process;
Always preceded by as much bench-work, technical analysis

and clinical literature review as possible to avoid any
unnecessary experimentation on animals or humans;
Only as demanding as required consistent with the risk

presented by the product and intended use; and
Sufficiently large in the number of enrolled patients to ensure

that results are statistically significant and provide confidence
that the medical device is both safe and efficacious for its
intended purpose in normal use.
413
Clinical Evaluation in Europe & beyond

will it harmonise??
ISO 14155 Clinical investigation of medical

devices for human subjects Good clinical
practice now being put forward as the globally
recognized standard in the way that ISO 13485
has for quality and ISO 14971 has for risk
management...
414

Clinical Evaluation MEDDEVs
Clinical Evaluation: A Guide for Manufacturers and

Notified Bodies (MEDDEV 2.7/1 revision 4 June 2016).
Guidelines for Competent Authorities for making a
Validation / Assessment of a Clinical Investigation
Application (MEDDEV 2.7/2 revision 2 September 2015).
Guidelines on Clinical Investigation: A Guide for
Manufacturers and Notified Bodies (MEDDEV 2.7/4
December 2010).
Clinical Investigations: Serous Adverse Event Reporting
under Directive 90/285/EEC and 93/42/EC (MEDDEV 2.7/3
rev.3 May 2015).
Post Market Clinical Follow-Up Studies A Guide for
Manufacturers and Notified Bodies (MEDDEV 2.12/2 rev.2
January 2012). 415
Clinical Evaluation MEDDEVs

Evaluation of Clinical Data A Guide for Manufacturers
and Notified Bodies Appendix 1 : Clinical Evaluation of
Coronary Stents (MEDDEV 2.7.1 Appendix 1 - December
2008)
Plus device specific vigilance guidance for cardiac
ablation devices and coronary stents.
MEDDEVs are not mandatory but are expected to be

followed by regulators and anything used as an alternative
has to be at least as comprehensive and effective.
These MEDDEVs need to be read in conjunction
Annex X Clinical Evaluation of Directive 93/42//EEC
(MDD) and Annex 7 Clinical Evaluation of Directive
90/385/EEC (AIMDD). And now of course in
416
conjunction with MDR requirements.
Clinical Data Evaluation

- A Holistic Approach to Risk Management
UK NB BSIs Laurel Macomber, Product Expert,

General Devices and David Francis, Global Head
Active Implantable Devices provided insights to the
title of this slide at the BSI Annual Consultants Day
2014.
The full presentation can be provided on request.
Here some important extracts are provided.
417


Clinical evaluation is an ongoing process and is to

be conducted throughout the life cycle of a medical
device.
It is first performed as part of the Conformity
Assessment Procedure (CAP) and then repeated
periodically as new clinical safety and performance
information about the device is obtained during its
normal use.
This information is then fed back into the ongoing
risk analysis and may result in changes to device,
labelling or instructions for use.
418

NBs are told to check that manufacturers can

demonstrate the device achieves its intended
performance during normal conditions of use and
that the known and foreseeable risks, and any
adverse events, are minimized and acceptable
when weighed against the benefits of the
intended performance and safety are
supported by suitable evidence.
419

The Clinical Evaluation Report (CER) must be

thorough & objective. It has to consider both the
favourable and unfavourable pre- and post-market
clinical data relevant to the intended use.
Needs to be informed by and cross-referenced to the

risk management documents. These documents
should identify all known risks associated with
device and how such risks have been addressed.
420


It is often possible to draw on experience from

equivalent devices.
May be possible to use compliance with recognized

standards to assist in the clinical evaluation.
The depth of evaluation must be commensurate with

classification, intended use, claims, and risk of
device in question.
421

The CER must be actively updated with data from

Post-Market Surveillance (PMS). The next slide
provides a few suggestions of possible sources
there are many others.
Where post-market clinical follow-up (PMCF) as part

of the post-market surveillance (PMS) plan for the
device is not deemed necessary, this must be duly
justified and documented.
422
Post-Market Surveillance
- some suggested inputs
Post-market surveillance
Inputs
TECHNICAL REVIEWS
DESIGN AUDITS
RISK ANALYSIS TREND ANALYSIS
STABILITY STUDIES
POST LAUNCH
EXPERIENCE WITH PMS REVIEWS
SIMILAR TECHNOLOGY
USER GROUPS
INCIDENT REPORTS
SURVEYS
CUSTOMER COMPLAINTS LITERATURE REVIEWS
CUSTOMER FEEDBACK


Where demonstration of conformity with ERs based

on clinical data is not deemed appropriate:
Adequate justification for any such exclusion has
to be given based on risk management output and
under consideration of the specifics of the
device/body interaction, the clinical performances
intended, and the claims of the manufacturer.
Adequacy of demonstration of conformity with the
essential requirements by performance evaluation,
bench testing and pre-clinical evaluation alone has
to be duly substantiated.
424
Risk As Far As Possible Vs ALARP

Please see Annex ZA (MDD) / Annex ZB (AIMD)

Deviations 1 to 7, here is 3:
a) Annex D.8 to ISO 14971, referred to in 3.4, contains

the concept of reducing risks "as low as reasonably
practicable" (ALARP concept). The ALARP concept
contains an element of economic consideration.
b) However, the first indent of Section 2 of Annex I to
Directive 93/42/EEC and various particular Essential
Requirements require risks to be reduced "as far as
possible" without there being room for economic
considerations.
c) Accordingly, manufacturers and Notified Bodies may
not apply the ALARP concept with regard to economic
considerations.
425

Annex ZA (MDD) / Annex ZB (AIMD) Deviation 4
The manufacturer must undertake the risk-benefit analysis for the individual risk
and the overall risk-benefit analysis (weighing all risks combined against the
benefit) in all cases.
Annex D
Those involved in making risk/benefit judgments have a responsibility to

understand and take into account the technical, clinical, regulatory, economic,
sociological and political context of their risk management decisions.
The decision as to whether risks are

outweighed by benefits is essentially a matter
of judgment by experienced and
knowledgeable individuals.
An important consideration in the acceptability of a residual risk is whether an
anticipated clinical benefit can be achieved through the use of alternative design
426
solutions or therapeutic options that avoid exposure to that risk or reduce the
overall risk.


- Do Use US FDA Resources
FDA Pre-Market Notification Databases for

510(k)s and especially PMAs provide excellent
insights and often a lot of data.
FDA databases exist for Consensus Standards,
Medical Device Reporting, Post-Approval Studies and
Postmarket Surveillance Studies.
FDA Total Product Life Cycle database provides
information on substantially equivalent devices
(your competitors) by Product Code!
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTPLC/tplc.cfm
427
A final comment:
All product claims made must ultimately be based on
well controlled and well managed clinical evaluations
and always be evidence based.
Regulators want to see key compliance documents
based on sound scientific knowledge and good practice,
that is as independent from the manufacturer as
practically possible.
Clinical literature searches must be scientifically
based, well structured and be weighted for the quality
of journal and statistical significance of each paper or
report provided.
Presentation of the
Indian Certification of
Medical Devices Scheme
(ICMED
ICMED))
429

Capacity Building Initiative for

Trade Development in India (CITD)
Questions?
&
Answers
Thank you for your kind attention.

Trevor Lewis, lewlink@btclick.com and
Shrihari Dharmadhikari, shrihari_d@rediffmail.com


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Capacity building Initiative for Trade

Development (CITD) in India

Capacity Building Initiative for

Two Days Training on

National Accreditation Board for

Honourable Invited Speakers.

Capacity Building Initiative for Trade

Two Days Training on EU Medical Device Directives and

Two Days Training on EU Medical Device Directives and

If in doubt please ask a question?

Please make your questions

What is a medical device and

Two Days Training on EU Medical Device Directives and

Common view of medical devices

but also includes the less obvious:

Medical devices are diverse, from contact lenses to condoms, from

Two Days Training on EU Medical Device Directives and

Examples of medical devices

Examples of medical devices

Examples of medical devices

Two Days Training on EU Medical Device Directives and

Examples of medical devices

What are NOT medical devices

Medicines Directive 2001/83/EC and

Examples of High Risk

Two Days Training on EU Medical Device Directives and

Examples of High Risk

Examples of High Risk

List A blood grouping tests

Examples of Low to Moderate Risk

Most tests not List A or List B

Two Days Training on EU Medical Device Directives and

Medical Device Definition

means an article which whilst not being a device

Please note that accessories are treated exactly the

Definition of Pharmaceutical, i.e. Drug

Primary intended purpose is achieved by

Expensive and lengthy regulatory process, generally

Note a medical syringe intended for use in humans

Two Days Training on EU Medical Device Directives and

CE Marking is an indication that a

CE Marking is not a voluntary mark of

CE marked products can be sold throughout

European Union (EU) Member States

EFTA: Norway, Iceland, Switzerland, Liechtenstein

Two Days Training on EU Medical Device Directives and

How it works in one slide

Competent Authorities and Notified Bodies

Role of Competent Authorities (CAs) and

Two Days Training on EU Medical Device Directives and

The Role of Competent Authorities

The Competent Authority is the body authorised to act on

The Role of Competent Authorities

Operation of a vigilance system for the reporting of

The Role of Notified Bodies

Two Days Training on EU Medical Device Directives and

The Role of Notified Bodies

Notified Bodies Operation Group - NBOG

NBOG set up in 2000 by Member States & EC to

Notified Bodies Operation Group - NBOG

CAs & NBs / NBOG

Two Days Training on EU Medical Device Directives and

European Commission MEDDEV

MEDDEV 2.10/2 Designation and