current eu and global activities in the „clinicals“ dr. wolfgang ecker federal ministry of...
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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 onClinical Investigation and Evaluation
CIE
GHTF SG 5
EU WG onClinical Investigation and Evaluation(incl. PMCF)
Clinical Safety and Performance
COM + Member States + NB + Industry
ISO/CEN/CLC
!Upgrade of Clinical Evaluation in the Upgrade of Clinical Evaluation in the Revision of the Medical Device Directives Revision of the Medical Device Directives 2007/47/EC2007/47/EC
!HTA/EBM use by health care financersHTA/EBM use by health care financers
Request for high quality Request for high quality clinical trials will raise!clinical trials will raise!
Acceptance in Health Care/Remuneration
HTA Health Technology AssessmentMedico-(Economical) Analysis
Conformity Assessment/CEPremarket Approval
Medical Devices/IVD‘s
Medical EvaluationClinical Evaluation/Performance Evaluation
Technical/Preclinical/Analytical Evaluation
Market
Pre-Market
PMCF Market
Important documents for medical devices
EU – Legal System
New ApproachGlobal Approach
Medical Device Directives
Decrees, Ordinancies
Nat. Medical Device Act
Harmonised Standards
MEDDEV‘s + otherInterpretative doc‘s
GHTF-Guidelines
COM-legislation
EU Medical Device - Directives
Directive 90/385/EECActive Implantable
Medical Devices
Directive 93/42/EECMedical Devices
Directive 98/79/ECIn-vitro-Diagnostic-
Medical Devices
Pacemakers; ICD‘sImplantable 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 materialsPrim. specimen receptacles ...
1. LayerClinical Data/Evaluation Flow Model
2.LayerDocumentation
3.LayerConformity Assessment
Revision of 93/42/EEC and 90/385/EEC CLINICAL EVALUATION = Core Element of 2007/47/EC!!
(+)
Clin Invest Route
Literature Route
Combin Route
ClinicalData
ClinicalEvaluation
Demonstrationof conformity
withclinical ER
Conformitywith ER
Documentation ofClinical Evaluation Process
+ Preclinical Evaluation+ Risk management
Techn Doc/STED/Design dossierincl. clinical data and
Clin. Evaluation Report+ preclinical data
+ Risk management output
QMModules
DesignModules
1.LayerClinical Model
2.LayerDocumentation
3.LayerConformityassessment
3 layer model of clinical evaluationin EU medical device regulation
Updates of clin eval; ev. PMCF Manuf. Claims; risk mgt outputState of the art
EN's,Techn+other Eval
Clin Exper. Route
Clinical Investigation:
What do Directives 93/42/EEC and 90/385/EEC say
(after Revision 2007/47/EC)?
Clinical InvestigationTable of correspondence of Directives
Art. 10Art. 15Administrative
Procedures for CI
Ann. 6Ann. VIIIStatement for CA
+ Documentation
Ann I.I.5a+ Ann 7.1.Ann I.I.6a+Ann X.1Clinical Evaluation
Ann. 7.2.Ann. X.2Clinical
Investigation
if Art. 10+Ann. 6if Art. 15+Ann. VIIIFree movement
Art. 1.2. (e)+(k)Art. 1.2. (e) + (k)Definition of device for CI; clinical data
Dir 90/385/EECDir 93/42/EECAspect
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/Documentationaccompanying notification of a Clin. Investigation (Ann. VIII/Ann. 6)
Draw EUDAMED-Code for Clinical Investigation(from May 2011; optional from 2010)
Revision Directive 2007/47/EC
MS:MS Info-Exchange (refusal, halt, sign. (refusal, halt, sign.
modification, temp. interruption of CI)modification, temp. interruption of CI)
Inclusion of CI-module in EUDAMED
Ethics Committee has to evaluateClinical Investigation Plan
Revision Directive 2007/47/EC
• Preparation of Preparation of EUDAMED Clinical Investigation ModuleEUDAMED Clinical Investigation ModuleStage 1: administrative data > identifierStage 1: administrative data > identifier
1a: general administrative data > identifier1a: general administrative data > identifier1b: Art.15-6/7 procedures 1b: Art.15-6/7 procedures (refusal, halt, sign. modification, temp. (refusal, halt, sign. modification, temp.
interruption of CI; early termination on safety reasons)interruption of CI; early termination on safety reasons)
Stage 2: SAE-ReportingStage 2: SAE-Reporting Stage 3: (full dossiers)?Stage 3: (full dossiers)?
CIECIEClinical Investigation and EvaluationClinical Investigation and Evaluation
EN ISO14155-1
General Safety/Ethicaland
Procedural Aspects
ClinicalInvestigation
Plan
InformedConsent
Documents
EN ISO14155-2
FinalReport
Investigator‘sBrochure
LiteratureReview
CRFRoles
Monitor
Sponsor
ClinicalInvestigator
Clinical Investigation of Medical DevicesClinical Investigation of Medical Devices
EssentialRequirements
SafetyPerformance
Preclinical andClinical
ExperiencesRisk Analysis
Training
Investigator‘sBrochure
EN ISO 14155HarmonizedStandards
Science
ClinicalInvestigation
Plan
CRF‘s
LiteratureReview
EN ISO 14155Directives
EthicsOrganisation
Finances
InformedConsent;
Insurance;Special
Target Groups;Roles;
Documentation;
Decl. of HelsinkiEN ISO 14155
Model ofFinanciation of MD
AdministrativeAdministrativeProceduresProcedures
Ethics Committee
Notification to CA
60-Day Procedure
CE marked MD
DIRECTIVES(Inspections)
Final Report EN ISO 14155
AdministrativeProcedures
Ethics CommitteeNotification to CA60-Day Procedure
CE marked MD
CommunicationDecisionsEUDAMED
DIRECTIVES(Inspections; Fees)
SAE/Changes/(early) Termination Directive MEDDEV EN ISO 14155
Art. 10/15Administrative Proceduresfor Clinical Investigations
Dir. 90/385/EEC and 93/42/EECMF/Sponsor
Ethics Committee(s)
Notification Art. 10/15Statement 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/EECDirective 90/385/EEC
Clinical Investigations:
Where can you findhelpful 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
Documents
• New/updated GuidanceNew/updated Guidance Guidance on SAE-Reporting/FormsGuidance on SAE-Reporting/Forms Guidance on Clinical InvestigationsGuidance on Clinical Investigations (> GHTF)(> GHTF)
Update of PMCF-Guidance Update of PMCF-Guidance (> GHTF)(> GHTF)
• Strategic DevelopmentStrategic DevelopmentRecast ClinicalsRecast Clinicals Build up Cooperation withBuild up Cooperation with
• Clinical SocietiesClinical Societies
• (Implant) Registries(Implant) Registries
• EUnetHTA (Joint Action HTA of DG SANCO)EUnetHTA (Joint Action HTA of DG SANCO)
Rapid Clinical Task Force(s)/Device Panels?Rapid Clinical Task Force(s)/Device Panels? Regulator‘s Forum for (specific) multinational CI‘sRegulator‘s Forum for (specific) multinational CI‘s
CIECIEClinical Investigation and EvaluationClinical Investigation and Evaluation
EN DIS ISO 14155 Clinical investigation of medical devices for human subjects —
Good clinical practices
1. Scope2. Normative References3. Terms and Definitions4. Ethical Considerations5. Clinical Investigation Planning6. Clinical Investigation Conduct7. Suspension, Termination and Close-out8. Responsibilities of the Sponsor9. Responsibilities of the Principal Investigator
EN DIS ISO 14155 Clinical investigation of medical devices for human subjects — Good
clinical practices
Annexesa. Clinical Investigation Plan (CIP) nb. Investigators Brochure (IB) nc. Case Report Forms (CRF) id. Clinical Investigation Report ie. Essential clinical investigation documents if. Adverse event classification decision tree iZA Relationship between this European standard
and the Essential requirements of EU Directive 93/42/EEC i
BibliographyTablesn ... normative; i ... informative
SG5/N2R8:2007 Clinical EvaluationSG5/N1R8:2007 Clinical Evidence – Key Definitions and ConceptsSG5 ….. Post Market Clinical Follow Up StudiesSG5 ….. Clinical InvestigationsSG2/5 …. SAE-ReportingSG1/5 …. Clinical Evaluation of IVDs
GHTF SG5 Guidelines: