MassMEDIC: The European Medical
Device Market – Re-Examined
June 13, 2012
Securing the CE Mark for Your Medical
Device
Peter Rose – Managing Director
High Edge Consulting Ltd
www.highedge.co.uk
© High Edge Consulting 2012
High Edge Consulting
Quality Systems
Sterilization
Worldwide Regulatory
Affairs
Auditing
Services
Contamination Control
& Microbiology
Training
Services
www.highedge.co.uk
© High Edge Consulting 2012
High Edge Authorized Rep
European Union Authorized Representative
www.highedge.co.uk
© High Edge Consulting 2012
CE Marking
• ‘Passport’ to legally place medical
devices on the market in the EFTA
& European Union (EU) (total 31
countries)
• CE Marking on a product ensures
the free movement of the product
• CE Marking on a product permits
the withdrawal of the nonconforming products by customs
and enforcement/vigilance
authorities
www.highedge.co.uk
© High Edge Consulting 2012
Countries of Europe
www.highedge.co.uk
© High Edge Consulting 2012
Why CE Mark
Population
• USA
• Europe
• UK
312 million
857 million
62 million
(September 2011 – US census bureau)
(2010, includes Russia & Turkey)
(June 2011)
Medical Device Market Size
• USA
US $ 105.8 billion (2010), world’s largest
• Europe US $ 51.2 billion (2010)
• Germany US $ 19.5 billion (2011), Europe’s largest
• UK
US $ 9.0 billion (2011), Europe’s #2 (rising to US $ 10.8bn by 2016)
• France
US $ 8.8 billion (2011), Europe’s #3
Source: Espicom
www.highedge.co.uk
© High Edge Consulting 2012
Route Map to CE Marking
Determine that
your product is a
Medical Device
Classify your
product according
to risk category
Chose your
conformity
assessment route
Document ISO
13485 Quality
Management
System
Construct a Product
Technical File
Appoint a Notified
Body (If applicable)
Undergo Regulatory
Audit and Approval
www.highedge.co.uk
© High Edge Consulting 2012
What is and is not a Medical
Device
In Vitro
Diagnostic
Medical
Device
Directive
(IVDs)
90/385/EEC
Medical
Device
Directive
98/79/EC
93/42/EEC
3 Medical Device Directives that define what is a Medical Device
Active
Implantable
Medical
Devices
Directive
(AIMDs)
www.highedge.co.uk
© High Edge Consulting 2012
Definitions - MDD
Definition MDD: “any instrument, apparatus, appliance, software,
material or other article, whether used alone or in combination,
including the software intended by its manufacturer to be used
specifically for diagnostic and/or therapeutic purposes and necessary
for its proper application, intended by the manufacturer to be used
for human beings. Devices are to be used for the purpose of:
• Diagnosis, prevention, monitoring, treatment or 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”
www.highedge.co.uk
© High Edge Consulting 2012
FDA Definition of Medical Device
A medical device is "an instrument, apparatus, implement, machine,
contrivance, implant, in vitro reagent, or other similar or related article,
including a component part, or accessory which is:
• recognized in the official National Formulary, or the United States
Pharmacopoeia, or any supplement to them,
• intended for use in the diagnosis of disease or other conditions, or in the
cure, mitigation, treatment, or prevention of disease, in man or other
animals, or
• intended to affect the structure or any function of the body of man or
other animals, and which does not achieve any of it's primary intended
purposes through chemical action within or on the body of man or other
animals and which is not dependent upon being metabolized
for the achievement of any of its primary intended purposes."
www.highedge.co.uk
© High Edge Consulting 2012
Definition - Accessories
‘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;
www.highedge.co.uk
© High Edge Consulting 2012
Definitions – MDD Example
Example: Hip replacement (Femoral Head & Cup)
“any instrument, apparatus, appliance, software, material or other article, whether
used alone or in combination, including the software intended by its manufacturer
to be used specifically for diagnostic and/or therapeutic purposes and necessary
for its proper application, intended by the manufacturer to be used for human
beings. Devices are to be used for the purpose of:
• Diagnosis, prevention, monitoring, treatment or 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”
www.highedge.co.uk
© High Edge Consulting 2012
Definitions – MDD Example
Example: Condom
“any instrument, apparatus, appliance, software, material or other article, whether
used alone or in combination, including the software intended by its manufacturer
to be used specifically for diagnostic and/or therapeutic purposes and necessary
for its proper application, intended by the manufacturer to be used for human
beings. Devices are to be used for the purpose of:
• Diagnosis, prevention, monitoring, treatment or 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”
www.highedge.co.uk
© High Edge Consulting 2012
Definitions - IVDs
• Definition IVD: “any medical device which is a reagent, reagent
product, calibrator, control material, kit, instrument, apparatus,
equipment, or system, whether used alone or in combination,
intended by the manufacturer to be used in vitro for the
examination of specimens, including blood and tissue donations,
derived from the human body, solely or principally for the
purpose of providing information:
–
–
–
–
concerning a physiological or pathological state, or
concerning a congenital abnormality, or
to determine the safety and compatibility with potential recipients, or
to monitor therapeutic measures”
www.highedge.co.uk
© High Edge Consulting 2012
Definitions - IVDs
• Specimen receptacles are considered to be in vitro diagnostic
medical devices – “‘Specimen receptacles’ are those devices,
whether vacuum-type or not, specifically intended by their
manufacturers for the primary containment and preservation of
specimens derived from the human body for the purpose of in
vitro diagnostic examination.
Products for general laboratory use are not in vitro diagnostic
medical devices unless such products, in view of their
characteristics, are specifically intended by their manufacturer to
be used for in vitro diagnostic examination”
www.highedge.co.uk
© High Edge Consulting 2012
Definitions – IVDs Example
Example: Blood Glucose Tests
“any medical device which is a reagent, reagent product, calibrator, control
material, kit, instrument, apparatus, equipment, or system, whether used alone or
in combination, intended by the manufacturer to be used in vitro for the
examination of specimens, including blood and tissue donations, derived from the
human body, solely or principally for the purpose of providing information:
– concerning a physiological or pathological state, or
– concerning a congenital abnormality, or
– to determine the safety and compatibility with potential recipients, or
– to monitor therapeutic measures”
www.highedge.co.uk
© High Edge Consulting 2012
Definitions – IVDs Example
Example: Chorionic villus sampling (CVS)
“any medical device which is a reagent, reagent product, calibrator, control
material, kit, instrument, apparatus, equipment, or system, whether used alone or
in combination, intended by the manufacturer to be used in vitro for the
examination of specimens, including blood and tissue donations, derived from the
human body, solely or principally for the purpose of providing information:
– concerning a physiological or pathological state, or
– concerning a congenital abnormality, or
– to determine the safety and compatibility with potential recipients, or
– to monitor therapeutic measures”
www.highedge.co.uk
© High Edge Consulting 2012
Definition - AIMDs
• Definition AIMD: “Any medical device which is intended to be
totally or partially introduced, surgically or medically, into the
human body or by medical intervention into a natural orifice, and
which is intended to remain after the procedure”
A device is ‘active’ if it relies for its functioning on a source of
electrical energy or any source of power other than that directly
generated by the human body or gravity.
www.highedge.co.uk
© High Edge Consulting 2012
Definition – AIMDs Example
Example: implantable cardiac pacemakers
“Any medical device which is intended to be totally or partially
introduced, surgically or medically, into the human body or by
medical intervention into a natural orifice, and which is intended to
remain after the procedure”
A device is ‘active’ if it relies for its functioning on a source of
electrical energy or any source of power other than that directly
generated by the human body or gravity.
www.highedge.co.uk
© High Edge Consulting 2012
Definition – AIMDs Example
Example: cochlear implants
“Any medical device which is intended to be totally or partially
introduced, surgically or medically, into the human body or by
medical intervention into a natural orifice, and which is intended to
remain after the procedure”
A device is ‘active’ if it relies for its functioning on a source of
electrical energy or any source of power other than that directly
generated by the human body or gravity.
www.highedge.co.uk
© High Edge Consulting 2012
What is and is not a Medical
Device
• If it does not meet any of the European Directives then it can
be CE Mark Exempt
• Check Intended Use !
www.highedge.co.uk
© High Edge Consulting 2012
Intended Use
• The intended use statement is the manufacturers stated
intentions for the device and all claims and regulations hinge
on that
• Important to be consistent with the statement in marketing
and literature including salespersons behaviour and website
Cotton Buds:
Intended to apply make up or medicine ?
Walking Stick:
Intended to compensate for an injury or
handicap or just for a hill walker ?
Surface Wipes: Intended to disinfect an endoscope or work
surfaces?
www.highedge.co.uk
© High Edge Consulting 2012
Device Classification
• Annex IX of the MDD sets out the classification rules to
determine which class a device falls into according to its
properties, function and intended purpose
• Devices are assigned to one of three risk categories:
– Class I for low-risk devices,
– Classes IIa and IIb for medium-risk devices and
– Class III for high-risk devices
www.highedge.co.uk
© High Edge Consulting 2012
Device Classification
Example 1: Plasters & Wound Dressings
• Section 1 - Non invasive
• Rule 4
All non-invasive devices which come into contact with
injured skin:
–
–
–
Normal plasters for superficial wounds. Class I
Fly Larvae system for chronic or necrotic wounds. Class IIa
Absorbent dressing for major trauma. Class IIb
www.highedge.co.uk
© High Edge Consulting 2012
Device Classification
Example 2: Contact Lens
• Section 2 – Invasive
• 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:
–
–
Short term use. Class IIa
Long Term use. Class IIb
www.highedge.co.uk
© High Edge Consulting 2012
Device Classification
Example 3: Heart Defibrillation Catheter
• Section 2 – 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,
Note: Section 3 “Additional rules applicable to active devices” do
not apply in this case
www.highedge.co.uk
© High Edge Consulting 2012
Device Classification
Example 4: Breast Implant
• Section 2 – Invasive
• Rule 8
All implantable devices and long-term surgically invasive
devices are in Class IIb unless they are intended….
www.highedge.co.uk
© High Edge Consulting 2012
Classification
IVDs
• IVDs
– Annex II List A – which includes test kits for HIV, HTLV and
Hepatitis and some blood grouping products, including those
used to test donated blood
– Annex II List B – which amongst others includes test kits for
rubella, toxoplasmosis and phenylketonuria test kits as well as
self test kits for blood glucose
– Self Testing
– All others
www.highedge.co.uk
© High Edge Consulting 2012
Classification
AIMDs
• Active Implantable Medical Devices are considered
unique and have no classification except for their
designation as an AIMD
www.highedge.co.uk
© High Edge Consulting 2012
Conformity Assessment –Medical Devices
Class I
Class I
Non sterile &
Non measuring
Sterile and/or
measuring
Comply with
Essential
Requirements
Comply with
Essential
Requirements
Document Product
Technical File
Document Product
Technical File
ECDC
ECDC
Self Declaration
Self Declaration
Notified Body
certificate for
sterility and/or
metrology
Class IIa
Comply with Essential Requirements
Annex VII with
Annex IV
EC verification
Examination &
testing of each
product or
homogenous batch
by Notified Body
Submit RG2 to MHRA
CE Mark
CE Mark
Annex VII with
Annex V
Annex VII with
Annex VI
Annex II
Audit of the
production quality
assurance system
ISO 13485:2003
(excluding design) by
Notified Body
Audit of final
inspection and
testing ISO
13485:2003
(excluding design &
Manufacture) by
Notified Body
Audit of the full
quality assurance
system ISO
13485:2003 by
Notified Body
Declaration of Conformity
CE Mark
CE Mark
CE Mark
CE Mark
www.highedge.co.uk
© High Edge Consulting 2012
Conformity Assessment –Medical Devices
Annex III
Type examination by
Notified Body
With Annex IV
Every Device/batch
verified by NB (non
sterile only)
Class IIb
Class III
Comply with Essential Requirements
Comply with Essential
Requirements
Annex III
Type examination by
Notified Body
With Annex V
Production QA
ISO13485: 2003 (excl
design) by NB
Annex III
Type examination by
Notified Body
With Annex VI
Inspection QA (non
sterile only)
ISO13485:2003 (exl
design & manufacture)
Annex II
Audit of the full quality
assurance system ISO
13485:2003 by Notified
Body
Submit Design Dossier
to Notified Body
Annex II
Audit of the full quality
assurance system ISO
13485:2003 by Notified
Body
Declaration of Conformity
CE Mark
CE Mark
CE Mark
CE Mark
CE Mark
www.highedge.co.uk
© High Edge Consulting 2012
Conformity Assessment – IVDs
Self-testing
General
List B Products
List A products
Annex III
Excluding Section 6
Annex III
Including Section 6
Annex IV
Self Certification
Design examination
by Notified Body
Full Quality system
audited by Notified
Body
CE Mark
CE Mark
CE Mark
Annex V
EC type examination
by Notified Body
Annex V
EC type examination
by Notified Body
Annex VII
Annex VI Section 5
Production quality
system audit by
Notified Body
Batch verification by
Notified Body
CE Mark
CE Mark
www.highedge.co.uk
© High Edge Consulting 2012
Conformity Assessment - AIMDs
Active Implantable Medical Devices
• There are no
classifications for
AIMDs, either devices
fall into this definition
or they do not
Comply with Essential Requirements
Annex 3
EC Type Examination
by Notified Body
with
Annex 4
EC verification
Annex 3
EC Type Examination
by Notified Body
with
Annex 5
EC Declaration of
conformity
(Production Quality)
Annex 2
EC Declaration of
Conformity
Audit of the
complete quality
assurance system
ISO 13485:2003 by
Notified Body
Declaration of Conformity
CE Mark
CE Mark
CE Mark
www.highedge.co.uk
© High Edge Consulting 2012
The Regulators
• Competent Authorities
– Government Organisations
– 1 per country
– 32 Competent Authorities
– http://ec.europa.eu/health/medical-devices/files/list-of-contactpoints-within-the-national_en.pdf
• Notified Bodies
– Commercial Organisations
– Currently 77 NBs
– http://ec.europa.eu/enterprise/newapproach/nando/index.cfm?fusea
ction=directive.notifiedbody&sort=name
www.highedge.co.uk
© High Edge Consulting 2012
Role of Competent Authority
• The organisation appointed by each national government to
enforce compliance with the directive in that country
www.highedge.co.uk
© High Edge Consulting 2012
Role of the Notified Body
• Agents of Competent Authority
• Independent but commercial organisations
• Provide services for conformity assessment as
required by the MDDs for CE marking
• Conformity assessment may include inspection,
quality assurance, type examination or design
examination, or a combination of the above
www.highedge.co.uk
© High Edge Consulting 2012
Typical Technical File
Section 1
Section 2
Section 3
Section 4
Section 5
Section 6
Device Description
Labelling
Design & Manufacturing
Essential Requirements
Risk Analysis & Control
Product Verification & Validation
www.highedge.co.uk
© High Edge Consulting 2012
Device Description
• General description
• Product variants and configurations
• Accessories, other medical devices and other products that to be
used with
• Intended use statement:
– Medical condition is to be treated
– Intended patient population
– Contraindications
• Description of how the device works including unique features
and performance claims
www.highedge.co.uk
© High Edge Consulting 2012
Device Description
• Product specification
• List of components and their materials
– Materials of Animal Origin statement
– Human cells/tissue products/derivatives statement
• Previous generations or similar competitor devices
• Device classification
• Conformity assessment route
www.highedge.co.uk
© High Edge Consulting 2012
Labelling
• All labelling associated with the device
– labels on the device itself
– labels on the primary pack
– labels on the packaging, etc
• IFU (Instructions for Use)
• Sales / Promotional Literature
• A list of countries where the
device will be marketed, and corresponding official languages
www.highedge.co.uk
© High Edge Consulting 2012
Design & Manufacturing
• Description of the design stages applied to the device
• Technical drawings
• Further detail on product design
• General overview of the manufacturing process
• Manufacture, assembly, in process and final product testing,
device packaging
– Documentation comprising the Device Master Record
– Critical suppliers including sub-contracted manufacturing
processes
• Product Release process
www.highedge.co.uk
© High Edge Consulting 2012
Essential Requirements
• EC Declaration of Conformity
• Full details for product Classification
• Completed Essential Requirements Checklist
• List of Applied Standards
www.highedge.co.uk
© High Edge Consulting 2012
Risk Management
• Risk Management according to
EN ISO 14971:2009
– Risk Management Plan
– dFMEA
– pFMEA
– uFMEA
Risk Analysis
Risk Evaluation
Risk Control
Evaluation of overall
residual risk acceptability
Risk Management Report
Production & Post Production
Info
www.highedge.co.uk
© High Edge Consulting 2012
Product Verification & Validation
• Summary of the results of verification and validation activities
typically:
– Engineering tests
– Laboratory tests
– Pre-clinical test data
– Published literature inc. relevant competitor products
• Biocompatibility data
• Medicinal substances
• Animal or human cells, tissues or their derivatives
• Sterilization
www.highedge.co.uk
© High Edge Consulting 2012
Product Verification & Validation
• Software verification and validation
• Pre-clinical data related to clinical safety and performance of the
device.
• Clinical Evaluation
• Shelf Life with supporting data
• Other relevant data
www.highedge.co.uk
© High Edge Consulting 2012
ISO 13485
• 21 CFR 820 is a great starting point
• ISO 13485 is based on the ISO 9001 format but with additional
requirements for medical devices relating to:
– Design
– Special Processes
– Environmental Control
– Traceability
– Documentation records
– Regulatory actions
www.highedge.co.uk
© High Edge Consulting 2012
ISO 13485
EN ISO 13485:2012
• Medical Devices Quality Management Systems- Requirements
for Regulatory Purposes
• Requirements section identical to ISO 13485:2012
ISO/TR 14969:2005
• Medical Devices Quality Management Systems Guidance on
the Application of ISO 13485: 2003
www.highedge.co.uk
© High Edge Consulting 2012
ISO 13485 Overview
0
1
2
3
4
5
6
7
8
Introduction
Scope
Normative References
Terms & Definitions
Quality Management System
Management Responsibility
Resource Management
Product Realization
Measurement Analysis & Improvement
www.highedge.co.uk
© High Edge Consulting 2012
Questions
www.highedge.co.uk
© High Edge Consulting 2012
Thank You
High Edge Consulting Ltd
BioCity Nottingham
Pennyfoot Street
Nottingham
NG1 1GF
United Kingdom
www.highedge.co.uk
info@highedge.co.uk
Office: +44 115 921 6200
@HighEdgeConsult
www.highedge.co.uk
© High Edge Consulting 2012