Notified Body

Report
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
Slide 1
Presentation Content
• Definition of a Device
• Scope of MD legislation
• Medical device life-cycle
• Classification
• Clinical Evaluation
• Conformity Assessment
Slide 2
Medical Device Legislation
Definition of a Medical Device (Article 1 93/42/EEC)
“‘medical device’
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;”
Slide 3
Medical Device LegislationDefinition 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;”
Slide 4
Medical Device LegislationDefinition 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.”
Slide 5
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.
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
Lifecycle of Medical Device
Prototype
1. Classification
Pre-market
2. Clinical Evaluation
Class I
& Custom-made devices
Class IIa, Class IIb, Class III &
Class I sterile or measuring
3. Registration
with Competent Authority
4. CE-marking
Post-market
3. Conformity Assessment
by Notified Body
4. CE marking &
certificate issued XXXX
5. Post Market Surveillance
5. Post-market Clinical Follow-up
1. Classification
To qualify as a medical device- must have
medical purpose & primary physical mode
of action.
4 device classes, based on risk:
Class
I
Risk
Examples
Low
Wheelchairs,
simple wound
dressings,
Stethoscopes,
ECG electrodes,
syringes
Medium
Contact
lenses, ECG
machines,
electronic BP
monitors
Medium
– High
Peripheral Bare
Metal Stents
(BMS), External
Defibrillator
High
Joint
replacements,
Drug-Eluting
Stents (DES),
Pacemakers,
Device class determined by 18 rules:
• Rules 1-4- Non invasive devices
• Rules 5-8- Invasive devices
• Rules 9-12- Active devices
• Rules 13-18- 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.
IIa
IIb
III
1. Classification
Rule 13** Drug-Device Combinations (Class III)
–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
If MD contains MP:
1. Device aspect assessed under device legislation but general principles of other
MP legislation must apply
2. Notified body must verify the ‘usefulness’ of the MP
3. ‘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.
1. Classification
Rule 17 Devices Containing Tissues of Animal Origin (Class III)
If MD contains Tissue of animal origin (relevant):
1. (In addition to MDD) Manufacturer subject to Directive 2003/32/EC
(Regulation 722/2012 from 28th August 2013).
2. If starting material has an EDQM CEP- considered by notified body in its
overall assessment.
3. 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)
4. SER circulated to all CAs for comments, considered by notified body.
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)
2. Clinical Evaluation
•
•
All medical devices require clinical evaluation: Class I, IIa, IIb, III & AIMD
Must be based on clinical data- 3 different routes:
1. Scientific literature route
2. Clinical Investigation
route
3. Combination route
Critical evaluation of the relevant
scientific literature
Critical evaluation of the results
of clinical investigation(s)
Combination of
Scientific literature route
+
Clinical Investigation
route
•demonstration of equivalence
between devices
•data adequately demonstrate
compliance with Essential
Requirements
•
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.
3. Conformity Assessment (by a Notified Body)
• Notified bodies assess medium and high risk devices for conformity:
Medical Devices
Active Implantable
Medical Device
Class I with a measuring or sterile function Class IIa, Class IIb & Class III
All
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
(http://ec.europa.eu/enterprise/newapproach/nando/).
0050
0123
0086
0124
3. Conformity Assessment (by a Notified Body)
The number of (the 77) notified bodies designated to assess selected device
types/technologies:
Medical Device Scope Expression
No. of NBs
MD 0204- Non-active functional implants
39
MD 0204- Non-active soft tissue implants
38
MD 0300- Devices for wound care
48
MDS 7001- Medical devices incorporating medicinal substances,
according to Directive 2001/83/EC
37
MDS 7002- 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
(Ref. http://ec.europa.eu/enterprise/newapproach/nando)
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
3. Conformity Assessment (by a Notified Body)
Infection & microbial contamination
Animal tissues- SER/EDQM (TSE EN ISO 22442 )
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
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
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.

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