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 ...

Clinical Evaluation:

What do Directives 93/42/EEC and 90/385/EEC say

(after Revision 2007/47/EC)?

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

Draft

Draft

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:

HTA

FDA/CDRH - Guidance

Thank You!Thank You!

3rd National Conference for Medical Devices, 13/14 April 2010, Rome