EN ISO 14155:2011

SLOVENSKI STANDARD
SIST EN ISO 14155:2012
01-januar-2012
1DGRPHãþD
SIST EN ISO 14155:2011
SIST EN ISO 14155:2011/AC:2011
.OLQLþQHUD]LVNDYHPHGLFLQVNLKSULSRPRþNRY]DOMXGL'REUHNOLQLþQHSUDNVH,62

Clinical investigation of medical devices for human subjects - Good clinical practice (ISO
14155:2011)
Klinische Prüfung von Medizinprodukten an Menschen - Gute klinische Praxis (ISO
14155:2011)
Investigation clinique des dispositifs médicaux pour sujets humains - Bonnes pratiques
cliniques (ISO 14155:2011)
Ta slovenski standard je istoveten z: EN ISO 14155:2011
ICS:
11.040.01 Medicinska oprema na Medical equipment in general
splošno
SIST EN ISO 14155:2012 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 14155:2012

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SIST EN ISO 14155:2012


EUROPEAN STANDARD
EN ISO 14155

NORME EUROPÉENNE

EUROPÄISCHE NORM
October 2011
ICS 11.100.20 Supersedes EN ISO 14155:2011
English Version
Clinical investigation of medical devices for human subjects -
Good clinical practice (ISO 14155:2011)
Investigation clinique des dispositifs médicaux pour sujets Klinische Prüfung von Medizinprodukten an Menschen -
humains - Bonnes pratiques cliniques (ISO 14155:2011) Gute klinische Praxis (ISO 14155:2011)
This European Standard was approved by CEN on 20 September 2011.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same
status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,
Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.





EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2011 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 14155:2011: E
worldwide for CEN national Members.

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices .4
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .6

2

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Foreword
This document (EN ISO 14155:2011) has been prepared by Technical Committee ISO/TC 194 "Biological
evaluation of medical devices" in collaboration with Technical Committee CEN/TC 258 “Clinical investigation
of medical devices” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by April 2012, and conflicting national standards shall be withdrawn at the
latest by April 2012.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 14155:2011.
This new edition contains revised Annexes ZA and ZB.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directives, see informative Annexes ZA and ZB, which are an integral part of this
document.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 14155:2011 has been approved by CEN as EN ISO 14155:2011 without any modification.
3

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Annex ZA
(informative)

Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC on medical
devices
For all requirements related to clinical investigations contained in the directive and referred to in the following
chart: Obligations attributed to the "sponsor" under ISO 14155 shall be incumbent, under the MDD to the
manufacturer, if located in the EU/EEA/Turkey/Switzerland, and incumbent to the Authorized Representative
otherwise͘ Both may refer to external service providers in order to fulfil their obligations.
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
EN of Directive 93/42/EEC
Partial fulfilment of the ER, as
regards
1) the documentation of
clinical investigations of
medical devices used in the
Entire standard Annex I. 6a
clinical evaluation process
as referred to in Annex
1
X.1.1 and
2) parts of Annex X.2 listed
below.

ISO 14155 does not refer to a

particular version of the declaration

of Helsinki. The latest available

version of the declaration of Helsinki

must be taken into account.
4.1, 5.2 and 5.3
Annex X:
National/regional requirements for
2.2.
ethics in clinical research and for
protecting the safety, wellbeing,
health and rights of subjects must
be observed.
Annex X:

5,3, 5.4, A.7
2.3.1
Annex X
5.3, A.3 and A.6
2.3.2.

1
See MEDDEV 2.7/1, Section 6.3.
4

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
EN of Directive 93/42/EEC
Annex X:

5.3, A.3 and A.6
2.3.3.
Annex X:

5.3, A.5 and 8.2.5
2.3.4.
Annex X: Partial compliance: covers internal
2.3.5. procedures of sponsor to address
6.4.1, 8.2.5 d) and 9.8
2
SAE -reporting requirements of the
Directive.
Annex X:

5.5, 5.8, 6, 9.2, 9.3 and Annex B
2.3.6.
Annex X:
7.3
2.3.7.
National/regional requirements for
Annex VIII, 2.2., structure/content of ethics in clinical research and for
nd
5.4, Annex A; 5.5, Annex B; 4.7 ,
the documents required in the 2 protecting the safety, wellbeing,
rd th
3 and 5 indent. health and rights of subjects must
be observed.

WARNING — Other requirements and other EU Directives may be applicable to the product(s)/clinical
investigations falling within the scope of this standard.


2
SAE = Serious Adverse Event.
5

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Annex ZB
(informative)

Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical
Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 90/385/EEC on active implantable medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in Table ZB.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
Table ZB.1 — Correspondence between this European Standard and Directive 90/385/EEC on active
implantable medical devices
For all requirements related to clinical investigations contained in the directive and referred to in the following
chart: Obligations attributed to the "sponsor" under ISO 14155 shall be incumbent, under the MDD to the
manufacturer, if located in the EU/EEA/Turkey/Switzerland, and incumbent to the Authorized Representative
otherwise͘ Both may refer to external service providers in order to fulfil their obligations.
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
EN of Directive 90/385/EEC
Partial fulfilment of the ER, as
regards
1) the documentation of
clinical investigations of
medical devices used in the
Entire standard 6a
clinical evaluation process
as referred to in Annex
3
VII.1.1 and
2) parts of Annex VII.2 listed
below.

ISO 14155 does not refer to a

particular version of the declaration

of Helsinki. The latest available

version of the declaration of Helsinki
Annex 7:
must be taken into account.
4.1, 5.2 and 5.3
2.2.
National/regional requirements for
ethics in clinical research and for
protecting the safety, wellbeing,
health and rights of subjects must
be observed.
Annex 7:

5,3, 5.4, A.7
2.3.1.

3
See MEDDEV 2.7/1, Section 6.3.
6

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SIST EN ISO 14155:2012
EN ISO 14155:2011 (E)
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
EN of Directive 90/385/EEC
Annex 7:

5.3, A.3 and A.6
2.3.2.
Annex 7:

5.3, A.3 and A.6
2.3.3.
Annex 7:

5.3, A.5 and 8.2.5
2.3.4.

Partial compliance: covers internal
Annex 7:
procedures of sponsor to address
6.4.1, 8.2.5 d) and 9.8
2.3.5.
4
SAE -reporting requirements of the
Directive.
Annex 7:

5.5, 5.8, 6, 9.2, 9.3 and Annex B
2.3.6.
Annex 7:

7.3
2.3.7.
National/regional requirements for
Annex 7, 2.2., structure/content of ethics in clinical research and for
nd
5.4, Annex A; 5.5, Annex B; 4.7 the documents required in the 2 , protecting the safety, wellbeing,
rd th
3 and 5 indent. health and rights of subjects must
be observed.

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.

4
SAE = Serious Adverse Event.
7

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SIST EN ISO 14155:2012

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SIST EN ISO 14155:2012

INTERNATIONAL ISO
STANDARD 14155
Second edition
2011-02-01


Clinical investigation of medical devices
for human subjects — Good clinical
practice
Investigation clinique des dispositifs médicaux pour sujets humains —
Bonnes pratiques cliniques




Reference number
ISO 14155:2011(E)
©
ISO 2011

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SIST EN ISO 14155:2012
ISO 14155:2011(E)
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ii © ISO 2011 – All rights reserved

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SIST EN ISO 14155:2012
ISO 14155:2011(E)
Contents Page
Foreword .v
1 Scope.1
2 Normative references.1
3 Terms and definitions .2
4 Ethical considerations .7
4.1 General .7
4.2 Improper influence or inducement .8
4.3 Compensation and additional health care.8
4.4 Responsibilities.8
4.5 Communication with the ethics committee (EC).8
4.5.1 General .8
4.5.2 Initial EC submission .8
4.5.3 Information to be obtained from the EC.9
4.5.4 Continuing communication with the EC .9
4.5.5 Continuing information to be obtained from the EC .9
4.6 Vulnerable populations.9
4.7 Informed consent .10
4.7.1 General .10
4.7.2 Process of obtaining informed consent.10
4.7.3 Special circumstances for informed consent .10
4.7.4 Information to be provided to the subject .11
4.7.5 Informed consent signature .13
4.7.6 New information .13
5 Clinical investigation planning .14
5.1 General .14
5.2 Risk evaluation .14
5.3 Justification for the design of the clinical investigation.14
5.4 Clinical investigation plan (CIP).14
5.5 Investigator's brochure (IB).15
5.6 Case report forms (CRFs).15
5.7 Monitoring plan.15
5.8 Investigation site selection .15
5.9 Agreement(s) .15
5.10 Labelling.15
5.11 Data monitoring committee (DMC) .16
6 Clinical investigation conduct .16
6.1 General .16
6.2 Investigation site initiation .16
6.3 Investigation site monitoring .16
6.4 Adverse events and device deficiencies.16
6.4.1 Adverse events.16
6.4.2 Device deficiencies .16
6.5 Clinical investigation documents and documentation.17
6.5.1 Amendments.17
6.5.2 Subject identification log.17
6.5.3 Source documents .17
6.6 Additional members of the investigation site team.17
6.7 Subject privacy and confidentiality of data .17
6.8 Document and data control.18
© ISO 2011 – All rights reserved iii

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SIST EN ISO 14155:2012
ISO 14155:2011(E)
6.8.1 Traceability of documents and data . 18
6.8.2 Recording of data . 18
6.8.3 Electronic clinical data systems . 18
6.9 Investigational device accountability . 19
6.10 Accounting for subjects. 19
6.11 Auditing . 19
7 Suspension, termination and close-out of the clinical investigation. 20
7.1 Suspension or premature termination of the clinical investigation. 20
7.1.1 Procedure for suspension or premature termination . 20
7.1.2 Procedure for resuming the clinical investigation after temporary suspension . 21
7.2 Routine close-out. 21
7.3 Clinical investigation report . 21
7.4 Document retention. 22
8 Responsibilities of the sponsor . 22
8.1 Clinical quality assurance and quality control . 22
8.2 Clinical investigation planning and conduct . 23
8.2.1 Selection of clinical personnel. 23
8.2.2 Preparation of documents and materials. 23
8.2.3 Conduct of clinical investigation . 24
8.2.4 Monitoring . 24
8.2.5 Safety evaluation and reporting. 27
8.2.6 Clinical investigation close-out. 27
8.3 Outsourcing of duties and functions. 28
8.4 Communication with regulatory authorities . 28
9 Responsibilities of the principal investigator. 28
9.1 General. 28
9.2 Qualification of the principal investigator. 28
9.3 Qualification of investigation site . 29
9.4 Communication with the EC . 29
9.5 Informed consent process. 29
9.6 Compliance with the CIP. 29
9.7 Medical care of subjects . 30
9.8 Safety reporting . 31
Annex A (normative) Clinical investigation plan (CIP). 32
Annex B (normative) Investigator's brochure (IB). 39
Annex C (informative) Case report forms (CRFs) . 41
Annex D (informative) Clinical investigation report. 43
Annex E (informative) Essential clinical investigation documents. 48
Annex F (informative) Adverse event categorization . 55
Bibliography. 58


iv © ISO 2011 – All rights reserved

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SIST EN ISO 14155:2012
ISO 14155:2011(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 14155 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This second edition cancels and replaces the first edition of ISO 14155-1:2003 and the first edition of
ISO 14155-2:2003, which have been technically revised.
© ISO 2011 – All rights reserved v

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SIST EN ISO 14155:2012

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SIST EN ISO 14155:2012
INTERNATIONAL STANDARD ISO 14155:2011(E)

Clinical investigation of medical devices for human subjects —
Good clinical practice
1 Scope
This International Standard addresses good clinical practice for the design, conduct, recording and reporting
of clinical investigations carried out in human subjects to assess the safety or performance of medical devices
for regulatory purposes.
The principles set forth in this Internat
...