1. Classification of Medical Devices –
Clinical Evaluation and Conformity Assessment
Committee for Advance Therapies (CAT) Presidency meeting
Dr. Juliet M. Doran
Pre-market Evaluation Assessor
Human Products Authorisation & Registration
28th February 2013

2. Presentation Content Definition of a Device Scope of MD legislation
Medical device life-cycle
Classification
Clinical Evaluation
Conformity Assessment

3. Medical Device Legislation Definition of a Medical Device (Article 1 93/42/EEC)
any instrument, apparatus, appliance, software, material or other article…
intended …for…
— diagnosis, prevention, monitoring, treatment or
alleviation of disease…or handicap,
— investigation, replacement or modification of
the anatomy or of a physiological process,
— control of conception,
and which does not achieve its principal intended action in or on
the human body by pharmacological, immunological or metabolic
means, but which may be assisted in its function by such means;”

4. Medical Device Legislation- Definition of an Active Implantable Device (Article 1 90/385/EEC)
‘‘active implantable medical device’ …
any device …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;”

5. Medical Device Legislation- Definition of an In-Vitro Diagnostic Device (Article 1 98/79/EC
“‘in vitro diagnostic medical device’
…any medical device which is a reagent… instrument,
or system… intended …to be
used in vitro for the examination of specimens,
…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.”

6. Scope of MD legislation (Directive 93/42/EC)
Does not apply to…
IVDs, active implantable medical device
MPs covered by 2001/83/EC
Cosmetic products
Human blood, blood products, plasma or blood cells of human origin
Transplants or tissues or cells of human origin
Viable transplants or tissues or cells of animal origin.

7. Scope of MD legislation
Does apply to devices incorporating…
a medicinal product, with an ancillary action
a medicinal product derived from human blood or plasma, with an ancillary action
non-viable tissues of animal origin

8. Lifecycle of Medical Device
Prototype
1. Classification
3. Conformity Assessment
by Notified Body
2. Clinical Evaluation
4. CE marking &
certificate issued
XXXX
Pre-market
Class I
& Custom-made devices
Class IIa, Class IIb, Class III & Class I sterile or measuring
3. Registration
with Competent Authority
4. CE-marking
5. Post Market Surveillance
Post-market
5. Post-market Clinical Follow-up

9. 1. Classification
To qualify as a medical device- must have medical purpose & primary physical mode of action.
4 device classes, based on risk:
Device class determined by 18 rules:
Rules 1-4- Non invasive devices
Rules 5-8- Invasive devices
Rules Active devices
Rules Special rules
These consider:
Duration contact (e.g. 1second15years?)
Degree invasiveness (e.g. intact  surgery?)
Anatomy affected (e.g. oral cavity  CNS?)
Active (i.e. uses a power source)
Re-usable?
Device Class determines the route to CE marking.
Class
Risk
Examples I
Low
Wheelchairs, simple wound dressings, Stethoscopes, ECG electrodes, syringes
IIa
Medium
Contact lenses, ECG machines, electronic BP monitors
IIb
Medium – High
Peripheral Bare Metal Stents (BMS), External Defibrillator
III
High
Joint replacements, Drug-Eluting Stents (DES), Pacemakers,

10. 1. Classification Rule 13** Drug-Device Combinations (Class III)
If MD contains MP:
Device aspect assessed under device legislation but general principles of other MP legislation must apply
Notified body must verify the ‘usefulness’ of the MP
‘Drug consultation’ required with a Competent Authority/EMA must give opinion on the ‘quality, safety and benefit/risk profile’.
**Rule 13 also covers human blood derivatives.
Primary mode of action physical=> Medical Device (MD)
e.g. Drug-Eluting Stent → MD
e.g. Bone cement containing antibiotic → MD
Primary mode of action pharmacological, immunological / metabolic => Medicinal Product (MP)
e.g. Asthma inhaler → MP
e.g. Patches for trans-dermal drug delivery → MP

11. 1. Classification
Rule 17 Devices Containing Tissues of Animal Origin (Class III)
If MD contains Tissue of animal origin (relevant):
(In addition to MDD) Manufacturer subject to Directive 2003/32/EC (Regulation 722/2012 from 28th August 2013).
If starting material has an EDQM CEP- considered by notified body in its overall assessment.
If starting material has no EDQM CEP, the notified body prepares a Summary Evaluation Report (SER) (conduct risk assessment, review alternative materials, evaluate source of tissue)
SER circulated to all CAs for comments, considered by notified body.

12. 1. Classification
The exception to the 18 medical device classification rules is….
‘Medical devices’ containing Advanced Therapy Medicinal Products (ATMPs)- combined ATMPs under ATMP Regulation No 1394/2007).
Doesn’t matter if primary mode of action is physical (i.e. by a medical device)

13. 1. Scientific literature route 2. Clinical Investigation route
2. Clinical Evaluation
All medical devices require clinical evaluation: Class I, IIa, IIb, III & AIMD
Must be based on clinical data- 3 different routes:
Clinical investigation
Clinical investigations “shall be performed unless it is duly justified” to rely on existing clinical data for (high risk devices):
Implantable devices
Class III devices
Active implantable medical devices.
1. Scientific literature route
2. Clinical Investigation route
3. Combination route
Critical evaluation of the relevant scientific literature
demonstration of equivalence between devices
data adequately demonstrate compliance with Essential Requirements
Critical evaluation of the results of clinical investigation(s)
Combination of
Scientific literature route +
Clinical Investigation route

14. 3. Conformity Assessment (by a Notified Body)
Notified bodies assess medium and high risk devices for conformity:
Notified bodies are-
Designated by their national Designating Authority as competent for particular device types &
Notified to the European Commission as NANDO scope expressions.
Monitored routinely by Designating Authority.
Currently 77 notified bodies for medical devices in Europe (
Medical Devices
Class I with a measuring or sterile function Class IIa, Class IIb & Class III
Active Implantable Medical Device
All

15. 3. Conformity Assessment (by a Notified Body)
The number of (the 77) notified bodies designated to assess selected device types/technologies:
(Ref.
Medical Device Scope Expression
No. of NBs
MD Non-active functional implants 39
MD Non-active soft tissue implants 38
MD Devices for wound care 48
MDS Medical devices incorporating medicinal substances, according to Directive 2001/83/EC 37
MDS Medical devices utilising tissues of animal origin, according to Directive 2003/32/EC 26
MDS 7003-Medical devices incorporating derivatives of human blood, according to Directive 2000/70/EC, amended 16
MDS 7008-Medical devices utilising nano-materials 22

16. 3. Conformity Assessment (by a Notified Body)
Class III devices (assessed by a notified body under e.g. Annex II) would require…
ANNEX I Essential Requirements review of device including…
General
Risk : benefit assessment (clinical & safety) and reduction (Risk EN ISO 14971)
State-of-the-art design & construction
Lifetime device performance
Transport& storage impact
Clinical evaluation (Clinical Investigation EN ISO 14155)
Side effects
Residual risk information
Chemical, physical & biological properties
Materials of construction: toxicity, flammability
Compatibility of materials of construction
Biocompatibility (EN ISO 10993) & Compatibility with other contact materials
Device <-> MP compatibility
Pre-clinical testing- animal, bench, computer
Drug & blood consultation
Residual material contamination, leaking & ingress

17. 3. Conformity Assessment (by a Notified Body)
Infection & microbial contamination
Animal tissues- SER/EDQM (TSE EN ISO )
Sterility & packaging validation and stability (Sterilisation EN ISO 11135, 556)
Construction & environmental properties
Combination safety & performance testing
Device ergonomics, usability & interference (Usability EN ISO 62366)
Measurement
Accuracy & stability (Thermometers ISO EN 1060)
Radiation
Energy sources (Medical electrical equipment EN 60601)
Labelling/IFU (Labelling EN ISO 980, IFU EN ISO1041)
Full Quality System (ISO13485) plus…
Clinical data SOPs
Design Control & Verification SOPs
Post-market surveillance system
In-process and Final QC release tests & SOPs
Sterilisation, Purchasing, labelling SOPS

18. 3. Conformity Assessment (by a Notified Body)
Design dossier review of device
Product description & Intended use
Design Verification & Validation
Risk assessment
Standards applied
Sterilisation, Biocompatibility, Risk etc.
Solution to Essential Requirements
Pre-Clinical Testing
Bench Testing / simulation
Animal Model
Clinical Evaluation
Literature review
Clinical Investigation (Human Model)
First In Man
Acute In-Vivo Device Performance
Device labelling & IFU
Stability Testing
Significant changes
Performance / Complaint Analysis

19. 3. Conformity Assessment (by a Notified Body)
Declaration of Conformity by the manufacturer
CE certificate issued
Notified body assessment of all Substantial Changes
Annual surveillance, recertification- 3-5 years.