Current EU and Global
Activities in the „Clinicals“
Dr. Wolfgang Ecker
Federal Ministry of Health, Austria
Chairman of EU WG CIE
3rd National Conference for Medical Devices, 13/14 April 2010, Rome
EU Working Group on
Clinical Investigation and Evaluation
COM + Member States + NB + Industry
CIE
EU WG on
Clinical Investigation and Evaluation
(incl. PMCF)
GHTF SG 5
Clinical Safety and Performance
ISO/CEN/CLC
Request for high quality
clinical trials will raise!
!Upgrade of Clinical Evaluation in the
Revision of the Medical Device Directives
2007/47/EC
!HTA/EBM use by health care financers
Acceptance in Health Care/Remuneration
HTA Health Technology Assessment
Medico-(Economical) Analysis
Market
PMCF
Conformity Assessment/CE
Premarket Approval
Pre-Market
Medical Evaluation
Clinical Evaluation/Performance Evaluation
Technical/Preclinical/Analytical Evaluation
Medical Devices/IVD‘s
Important documents for medical devices
EU – Legal System
New Approach
Global Approach
Medical Device Directives
MEDDEV‘s + other
Interpretative doc‘s
COM-legislation
Harmonised Standards
GHTF-Guidelines
Nat. Medical Device Act
Decrees, Ordinancies
EU Medical Device Directives
Directive 90/385/EEC
Active Implantable
Medical Devices
Directive 93/42/EEC
Medical Devices
Directive 98/79/EC
In-vitro-DiagnosticMedical Devices
Pacemakers; ICD‘s
Implantable Infusion pumps
Artificial hearts ...
+ software and accessories
NMR, US, X-ray,
Hip-implants, ECG, EEG,
Intravascular catheters, Stents,
syringes, IOL, RR, med. lasers,
med. software
HIV-tests, Hepatitis-tests,
Pregnancy-tests,
Lab-Automats, Reagents,
Calibrators, Control materials
Prim. specimen receptacles ...
Clinical Evaluation:
What do Directives 93/42/EEC
and 90/385/EEC say
(after Revision 2007/47/EC)?
Revision of 93/42/EEC and 90/385/EEC
CLINICAL EVALUATION = Core Element of 2007/47/EC!!
3.Layer
Conformity Assessment
2.Layer
Documentation
1. Layer
Clinical Data/Evaluation Flow Model
3 layer model of clinical evaluation
in EU medical device regulation
Design
Modules
(+)
Techn Doc/STED/Design dossier
incl. clinical data and
Clin. Evaluation Report
+ preclinical data
+ Risk management output
3.Layer
Conformity
assessment
QM
Modules
Documentation of
Clinical Evaluation Process
+ Preclinical Evaluation
+ Risk management
2.Layer
Documentation
Conformity
with ER
Clin Invest Route
Literature Route
Clin Exper. Route
Clinical
Data
Combin Route
Updates of clin eval; ev. PMCF
Clinical
Evaluation
Demonstration
of conformity
with
clinical ER
1.Layer
Clinical Model
Manuf. Claims; risk mgt output
State of the art
EN's,
Techn+other Eval
Clinical Investigation:
What do Directives 93/42/EEC
and 90/385/EEC say
(after Revision 2007/47/EC)?
Clinical Investigation
Table of correspondence of Directives
Aspect
Dir 93/42/EEC
Dir 90/385/EEC
Definition of device
for CI; clinical data
Art. 1.2. (e) + (k)
Art. 1.2. (e)+(k)
Free movement
if Art. 15+Ann. VIII
if Art. 10+Ann. 6
Administrative
Procedures for CI
Art. 15
Art. 10
Statement for CA
+ Documentation
Ann. VIII
Ann. 6
Clinical Evaluation
Clinical
Investigation
Ann I.I.6a+Ann X.1 Ann I.I.5a+ Ann 7.1.
Ann. X.2
Ann. 7.2.
Revision Directive 2007/47/EC
 Clinical Investigation
(Art. 15/10; Ann VIII/6, X/7)
Manufacturer/Sponsor:
Notification of SAE to all MS concerned
Notification of finalisation to MS concerned;
in case of early termination with justification!
If for safety reasons > all MS + COM!
Declaration/Documentation
accompanying notification of a Clin. Investigation
(Ann. VIII/Ann. 6)
Draw EUDAMED-Code for Clinical Investigation
(from May 2011; optional from 2010)
Draft
Draft
Revision Directive 2007/47/EC
MS:
MS Info-Exchange (refusal, halt, sign.
modification, temp. interruption of CI)
Inclusion of CI-module in EUDAMED
Ethics Committee has to evaluate
Clinical Investigation Plan
CIE
Clinical Investigation and Evaluation
•
Preparation of EUDAMED Clinical Investigation Module
Stage 1: administrative data > identifier
1a: general administrative data > identifier
1b: Art.15-6/7 procedures (refusal, halt, sign. modification, temp.
interruption of CI; early termination on safety reasons)
Stage 2: SAE-Reporting
 Stage 3: (full dossiers)?
Informed
Consent
General Safety/Ethical
and
Procedural Aspects
EN ISO
14155-1
Investigator‘s
Brochure
Documents
Final
Report
Clinical
Investigation
Plan
Clinical
Investigator
Roles
Literature
Review
Sponsor
Monitor
EN ISO
14155-2
CRF
Clinical Investigation of Medical Devices
Essential
Requirements
Safety
Performance
Preclinical and
Clinical
Experiences
Risk Analysis
Training
Science
Clinical
Investigation
Plan
CRF‘s
Investigator‘s
Brochure
Literature
Review
EN ISO 14155
Harmonized
Standards
EN ISO 14155
Directives
Ethics
Organisation
Finances
Informed
Consent;
Insurance;
Special
Target Groups;
Roles;
Documentation;
Decl. of Helsinki
EN ISO 14155
Model of
Financiation of MD
Administrative
Administrative
Procedures
Procedures
Ethics Committee
Ethics Committee
Notification to CA
60-Day Procedure
Notification
to CA
CE marked MD
60-Day Procedure
Communication
Decisions
CE marked MD
EUDAMED
DIRECTIVES
DIRECTIVES
(Inspections)
(Inspections; Fees)
SAE/Changes/(early) Termination Directive MEDDEV EN ISO 14155
Final Report EN ISO 14155
MF/Sponsor
Art. 10/15
Administrative Procedures
for Clinical Investigations
Dir. 90/385/EEC and 93/42/EEC
Ethics Committee(s)
Notification Art. 10/15
Statement Ann. 6/VIII.2.2
(Documentation) Ann. 6/VIII.3.2
Competent Authority
AIMD;
MD: Class III,
Class IIa+IIb-Implantable or long-term invasive
(TACIT) APPROVAL
(<) 60 d
Start of Clinical Investigation
Statement accompanying notification of a
clinical investigation
(Ann. 6 of 90/385/EEC and Ann. VIII of 93/42/EEC)
•(Notification form)
•Clinical Investigation Plan (CIP) incl. CRFs
•Investigator‘s Brochure
•Votum of Ethics Committee(s)
•Material for informed consent
•Confirmation of insurance of subjects
•Declaration to Essential Requirements
•Statement/Declaration concerning components
of human/animal origin
Directive 93/42/EEC
Directive 90/385/EEC
Clinical Investigations:
Where can you find
helpful documents?
Documents
• Directives
• National Legislation/Administration and Guidance
• Declaration of Helsinki
•
Harmonized Standards
– EN ISO 14155-1 and 2; forthcoming: FDIS (GCP for Medical Devices)
– 14971; 10993; 60601; 14630; 10555; …
•
Horizontal Guidance (MEDDEVs: Clinical Evaluation; PMCF; …)
•
Vertical Guidelines (Coronary stents; …)
•
•
•
FDA:
– IDE/PMA-Guidelines
– summaries of safety and effectiveness
HTA-Reports, Cochrane-Reports
Clinical/Scientific Societies
CIE
Clinical Investigation and Evaluation
•
•
New/updated Guidance
 Guidance on SAE-Reporting/Forms
 Guidance on Clinical Investigations (> GHTF)
 Update of PMCF-Guidance (> GHTF)
Strategic Development
 Recast Clinicals
 Build up Cooperation with
• Clinical Societies
• (Implant) Registries
• EUnetHTA (Joint Action HTA of DG SANCO)
 Rapid Clinical Task Force(s)/Device Panels?
 Regulator‘s Forum for (specific) multinational CI‘s
EN DIS ISO 14155
Clinical investigation of medical devices for human subjects —
Good clinical practices
1.
2.
3.
4.
5.
6.
7.
8.
9.
Scope
Normative References
Terms and Definitions
Ethical Considerations
Clinical Investigation Planning
Clinical Investigation Conduct
Suspension, Termination and Close-out
Responsibilities of the Sponsor
Responsibilities of the Principal Investigator
EN DIS ISO 14155
Clinical investigation of medical devices for human subjects — Good
clinical practices
Annexes
a. Clinical Investigation Plan (CIP) n
b. Investigators Brochure (IB) n
c. Case Report Forms (CRF) i
d. Clinical Investigation Report i
e. Essential clinical investigation documents i
f. Adverse event classification decision tree i
ZA Relationship between this European standard
and the Essential requirements of EU Directive
93/42/EEC i
Bibliography
Tables
n ... normative; i ... informative
GHTF SG5 Guidelines:
SG5/N2R8:2007
SG5/N1R8:2007
SG5 …..
SG5 …..
SG2/5 ….
SG1/5 ….
Clinical Evaluation
Clinical Evidence – Key Definitions and Concepts
Post Market Clinical Follow Up Studies
Clinical Investigations
SAE-Reporting
Clinical Evaluation of IVDs
HTA
FDA/CDRH - Guidance
Thank You!
3rd National Conference for Medical Devices, 13/14 April 2010, Rome