SIST EN ISO 14155:2020
(Main)Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2020)
Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2020)
This document addresses good clinical practice for the design, conduct, recording and reporting of
clinical investigations carried out in human subjects to assess the clinical performance or effectiveness
and safety of medical devices.
For post-market clinical investigations, the principles set forth in this document are intended to be
followed as far as relevant, considering the nature of the clinical investigation (see Annex I).
This document specifies general requirements intended to
— protect the rights, safety and well-being of human subjects,
— ensure the scientific conduct of the clinical investigation and the credibility of the clinical
investigation results,
— define the responsibilities of the sponsor and principal investigator, and
— assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved
in the conformity assessment of medical devices.
NOTE 1 Users of this document need to consider whether other standards and/or national requirements
also apply to the investigational device(s) under consideration or the clinical investigation. If differences in
requirements exist, the most stringent apply.
NOTE 2 For Software as a Medical Device (SaMD) demonstration of the analytical validity (the SaMD’s output
is accurate for a given input), and where appropriate, the scientific validity (the SaMD’s output is associated to the
intended clinical condition/physiological state), and clinical performance (the SaMD’s output yields a clinically
meaningful association to the target use) of the SaMD, the requirements of this document apply as far as relevant
(see Reference [4]). Justifications for exemptions from this document can consider the uniqueness of indirect
contact between subjects and the SaMD.
This document does not apply to in vitro diagnostic medical devices. However, there can be situations,
dependent on the device and national or regional requirements, where users of this document might
consider whether specific sections and/or requirements of this document could be applicable.
Klinische Prüfung von Medizinprodukten an Menschen - Gute klinische Praxis (ISO 14155:2020)
Dieses Dokument legt die Gute Klinische Praxis für das Design, die Durchführung, Aufzeichnung und Berichterstattung klinischer Prüfungen von Medizinprodukten an menschlichen Prüfungsteilnehmern fest, um die klinische Leistungsfähigkeit oder Wirksamkeit und Sicherheit zu bewerten.
Für klinische Untersuchungen nach dem Inverkehrbringen sollen die in diesem Dokument dargelegten Grundsätze unter Berücksichtigung der Art der klinischen Prüfung, soweit relevant, befolgt werden (siehe Anhang I).
Dieses Dokument legt allgemeine Anforderungen fest, mit denen Folgendes erreicht werden soll:
- der Schutz der Rechte, Sicherheit und des Wohlbefindens der beteiligten Prüfungsteilnehmer;
- die Sicherstellung der wissenschaftlich korrekten Durchführung der klinischen Prüfung und der Glaubwürdigkeit der Ergebnisse der klinischen Prüfung;
- die Festlegung der Verantwortlichkeiten des Sponsors und Hauptprüfers;
- die Unterstützung der Arbeit von Sponsoren, Prüfern, Ethik-Kommissionen, Aufsichtsbehörden und anderen am Konformitätsbewertungsverfahren für Medizinprodukte beteiligten Institutionen.
ANMERKUNG 1 Anwender dieses Dokuments haben zu berücksichtigen, ob noch weitere Normen und/oder nationale Anforderungen auf das jeweils zu beurteilende Prüfprodukt oder die klinische Prüfung anwendbar sind. Liegen Unterschiede zwischen den Anforderungen vor, gelten die strengsten.
ANMERKUNG 2 Bei Software als Medizinprodukt (SaMD) gelten für die Demonstration der analytischen Validität (die Ausgabewerte der SaMD sind für vorgegebene Eingabewerte korrekt) und falls angemessen, die wissenschaftlichen Validität (die Ausgabewerte der SaMD sind mit dem beabsichtigten klinischen Zustand/des beabsichtigten physiologischen Zustands assoziiert) sowie die klinische Leistungsfähigkeit (die Ausgabewerte der SaMD stehen in einem klinisch sinnvollen Zusammenhang mit der zweckbestimmten Nutzung) der SaMD die Anforderungen dieses Dokuments, soweit sie relevant sind (siehe Literaturhinweis [4]). Als Rechtfertigung für eine Befreiung von den Anforderungen dieses Dokuments kann die Einzigartigkeit des indirekten Kontakts zwischen den Prüfungsteilnehmern und der SaMD in Erwägung gezogen werden.
Dieses Dokument gilt nicht für Medizinprodukte für die In-vitro-Diagnostik. Es kann jedoch, in Abhängigkeit vom Produkt und nationalen oder regionalen Anforderungen, Situationen geben, in denen Anwender dieses Dokuments in Erwägung ziehen könnten, ob bestimmte Abschnitte und/oder Anforderungen dieses Dokuments anwendbar sein könnten.
Investigation clinique des dispositifs médicaux pour sujets humains - Bonne pratique clinique (ISO 14155:2020)
Le présent document traite des bonnes pratiques cliniques pour la conception, la conduite, l'enregistrement et l'établissement des rapports relatifs aux investigations cliniques menées sur des sujets humains en vue d'évaluer la performance clinique, l'efficacité ou la sécurité des dispositifs médicaux.
Dans le cadre des investigations cliniques après mise sur le marché, les principes définis dans le présent document sont destinés à être appliqués, le cas échéant, en prenant en compte la nature de l'investigation clinique (voir Annexe I).
Le présent document spécifie les exigences générales pour:
— protéger les droits, la sécurité et le bien-être des sujets humains;
— assurer la conduite scientifique de l'investigation clinique et la crédibilité des résultats de l'investigation;
— définir les responsabilités du promoteur et de l'investigateur principal; et
— aider les promoteurs, les investigateurs, les comités d'éthique, les autorités réglementaires et les autres organismes impliqués dans l'évaluation de la conformité des dispositifs médicaux.
NOTE 1 Les utilisateurs du présent document doivent estimer si d'autres normes et/ou exigences nationales peuvent également s'appliquer au(x) dispositif(s) sous investigation ou à l'investigation clinique. Si différentes exigences existent, la plus stricte s'applique.
NOTE 2 Pour les logiciels constituant des dispositifs médicaux (Software as a Medical Device ou SaMD), la démonstration de la validité analytique (le SaMD donne un résultat exact pour une entrée donnée), de la validité scientifique quand elle s'applique (le résultat du SaMD est associé à l'état clinique/physiologique attendu) et de la performances clinique (le résultat du SaMD a un lien cliniquement significatif avec l'utilisation cible) sont couvertes par les exigences du présent document le cas échéant (voir Référence [4]). Des dérogations au présent document peuvent être justifiées par la spécificité du contact indirect entre les sujets et le SaMD.
Le présent document ne s'applique pas aux dispositifs médicaux de diagnostic in vitro. Toutefois, dans certaines situations, en fonction du dispositif et des exigences nationales ou régionales, les utilisateurs du présent document peuvent déterminer si des sections et/ou exigences spécifiques du présent document sont applicables ou non.
Klinične raziskave medicinskih pripomočkov za ljudi - Dobre klinične prakse (ISO 14155:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 14155:2020
01-oktober-2020
Nadomešča:
SIST EN ISO 14155:2011/AC:2011
SIST EN ISO 14155:2012
Klinične raziskave medicinskih pripomočkov za ljudi - Dobre klinične prakse (ISO
14155:2020)
Clinical investigation of medical devices for human subjects - Good clinical practice (ISO
14155:2020)
Klinische Prüfung von Medizinprodukten an Menschen - Gute klinische Praxis (ISO
14155:2020)
Investigation clinique des dispositifs médicaux pour sujets humains - Bonne pratique
clinique (ISO 14155:2020)
Ta slovenski standard je istoveten z: EN ISO 14155:2020
ICS:
11.040.01 Medicinska oprema na Medical equipment in general
splošno
SIST EN ISO 14155:2020 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 14155:2020
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SIST EN ISO 14155:2020
EN ISO 14155
EUROPEAN STANDARD
NORME EUROPÉENNE
August 2020
EUROPÄISCHE NORM
ICS 11.100.20 Supersedes EN ISO 14155:2011
English Version
Clinical investigation of medical devices for human
subjects - Good clinical practice (ISO 14155:2020)
Investigation clinique des dispositifs médicaux pour Klinische Prüfung von Medizinprodukten an Menschen
sujets humains - Bonne pratique clinique (ISO - Gute klinische Praxis (ISO 14155:2020)
14155:2020)
This European Standard was approved by CEN on 2 May 2020.
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, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 14155:2020 E
worldwide for CEN national Members.
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the essential
requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered . 5
Annex ZB (informative) Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered . 7
2
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
European foreword
This document (EN ISO 14155:2020) has been prepared by Technical Committee ISO/TC 194
"Biological and clinical evaluation of medical devices" in collaboration with Technical Committee
CEN/TC 206 “Biological and clinical evaluation 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 February 2021, and conflicting national standards
shall be withdrawn at the latest by February 2021.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 14155:2011.
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 the relationship with EU Directive(s) see informative Annex ZA and ZB, which is an integral part of
this document.
The following referenced documents are indispensable for the application of this document. For
undated references, the latest edition of the referenced document (including any amendments) applies.
For dated references, only the edition cited applies. However, for any use of this document ‘within the
meaning of Annex ZA’, the user should always check that any referenced document has not been
superseded and that its relevant contents can still be considered the generally acknowledged state-of-
art.
When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version
of the ISO or IEC standard, as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
Table — Correlations between undated normative references and dated EN and ISO standards
Equivalent dated standard
Normative references as listed
in Clause 2 of the ISO standard
EN ISO or IEC
ISO 14971 EN ISO 14971:2020 ISO 14971:2019
3
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
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, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 14155:2020 has been approved by CEN as EN ISO 14155:2020 without any modification.
4
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
Annex ZA
(informative)
Relationship between this European Standard and the essential
requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered
This European Standard has been prepared under a Commission’s standardization request [M/295
concerning the development of European Standards related to medical devices] to provide one
voluntary means of conforming to essential requirements of Council Directive 93/42/EEC of 14 June
1993 concerning medical devices [OJ L 169].
Once this standard is cited in the Official Journal of the European Union under that Directive,
compliance with the normative 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.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Directive 93/42/EEC as amended by 2007/47/EC. This
means that risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’
or ‘removed’, according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with Essential
Requirements 1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
For all requirements related to clinical investigations contained in the regulation and referred to in the
following table: obligations attributed to the "sponsor" under ISO 14155 shall be incumbent under the
Directive 93/42/EEC to the manufacturer if located in the EU/EEA/Turkey/Switzerland, and incumbent
to the Authorized Representative otherwise. Both may refer to external service providers in order to
fulfil their obligations.
Table ZA.1 — Correspondence between this European Standard and
Annex I of Directive 93/42/EEC [OJ L 169]
Essential Requirements of Clause(s)/sub-clause(s) of
Remarks/Notes
Directive 93/42/EEC this EN
Partial fulfilment of the ER, as
regards
1) the documentation of clinical
investigations of medical
Annex I, 6a Entire standard
devices used in the clinical
evaluation process as referred
a
to in Annex X.1.1 and
parts of Annex X.2 listed below.
5
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
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.
Annex X, 2.2 4, 5, 6.2, 6.3 and 8.4
National/regional requirements for
ethics in clinical research and for
protecting the safety, wellbeing,
health and rights of subjects must
be observed.
Annex X, 2.3.1 6.2, 6,3, 6.4, A.4, A.5, A.6 and A.7
Annex X, 2.3.2 6.3, 6.4, A.2 i), A.3, A.4, A.5 and A.6
Covered provided that the
investigation site’s facilities are
Annex X, 2.3.3 6.3, 6.8, 7.3, 10.2, 10.3and A.6 similar to the facilities required for
the intended use of the
investigational device.
6.2, 6.3, 7.4, 9.2.5, 10.8, A.3, A.4, A.5,
Annex X, 2.3.4
A.6 and A.7
Annex X, 2.3.5 7.4, 9.2.5 and 10.8
6.5, 6.8, 9.2.1, 10.2, 10.3 and
Annex X, 2.3.6
Annex B
Annex X, 2.3.7 8.4, 9.2.6, 10.6 r) and Annex D
a
See MEDDEV 2.7/1, Section 6.3.
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
Standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the products falling within the scope of
this standard.
6
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
Annex ZB
(informative)
Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered
This European Standard has been prepared under a Commission’s standardization request [M/295
concerning the development of European Standards related to medical devices] to provide one
voluntary means of conforming to essential requirements of Council Directive 90/385/EEC of 20 June
1990 on the approximation of the laws of the Member States relating to active implantable medical
devices [OJ L 189].
Once this standard is cited in the Official Journal of the European Union under that Directive,
compliance with the normative 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.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Directive 90/385/EEC as amended by 2007/47/EC. This
means that risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’
or ‘removed’, according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with Essential
Requirements 1, 4, 5, 8, 9 and 10 of the Directive.
NOTE 3 This Annex ZB is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZB.1, it means that it is not addressed by this
European Standard.
For all requirements related to clinical investigations contained in the regulation and referred to in the
following table: obligations attributed to the "sponsor" under ISO 14155 shall be incumbent under the
Directive 90/385/EEC to the manufacturer if located in the EU/EEA/Turkey/Switzerland, and
incumbent to the Authorized Representative otherwise. Both may refer to external service providers in
order to fulfil their obligations.
Table ZB.1 — Correspondence between this European Standard and
Annex I of Directive 90/385/EEC [OJ L 189]
Essential Requirements of Clause(s)/sub-clause(s) of
Remarks/Notes
Directive 90/385/EEC this EN
Partial fulfilment of the ER, as
regards
1) the documentation of clinical
investigations of medical
5 a Entire standard
devices used in the clinical
evaluation process as referred
a
to in Annex VII.1.1 and
parts of Annex VII.2 listed below.
7
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SIST EN ISO 14155:2020
EN ISO 14155:2020 (E)
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.
Annex 7, 2.2 4, 5, 6.2, 6.3 and 8.4
National/regional requirements for
ethics in clinical research and for
protecting the safety, wellbeing,
health and rights of subjects must
be observed.
Annex 7, 2.3.1 6.2, 6,3, 6.4 and Annex A
Annex 7, 2.3.2 6.3, 6.4, A.2 i)and A.3 to A.6
Covered provided that the
investigation site’s facilities are
Annex 7, 2.3.3 6.3, 6.8, 7.3, 10.2, 10.3 and A.6 similar to the facilities required for
the intended use of the
investigational device.
6.2, 6.3, 7.4, 9.2.5, 10.8 and A.3 to
Annex 7, 2.3.4
A.7
Annex 7, 2.3.5 7.4, 9.2.5 and 10.8
6.5, 6.8, 9.2.1, 10.2, 10.3 and
Annex 7, 2.3.6
Annex B
Annex 7, 2.3.7 8.4, 9.2.6, 10.6 r) and Annex D
a
See MEDDEV 2.7/1, Section 6.3.
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
Standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the products falling within the scope of
this standard.
8
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SIST EN ISO 14155:2020
INTERNATIONAL ISO
STANDARD 14155
Third edition
2020-07
Clinical investigation of medical
devices for human subjects — Good
clinical practice
Investigation clinique des dispositifs médicaux pour sujets humains —
Bonne pratique clinique
Reference number
ISO 14155:2020(E)
©
ISO 2020
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SIST EN ISO 14155:2020
ISO 14155:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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SIST EN ISO 14155:2020
ISO 14155:2020(E)
Contents Page
Foreword .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Summary of good clinical practice (GCP) principles . 9
5 Ethical considerations .10
5.1 General .10
5.2 Improper influence or inducement .10
5.3 Compensation and additional health care.10
5.4 Registration in publicly accessible database .11
5.5 Responsibilities .11
5.6 Communication with the ethics committee (EC) .11
5.6.1 General.11
5.6.2 Initial EC submission .11
5.6.3 Information to be obtained from the EC.12
5.6.4 Continuing communication with the EC .12
5.6.5 Continuing information to be obtained from the EC .12
5.7 Vulnerable populations .12
5.8 Informed consent .13
5.8.1 General.13
5.8.2 Process of obtaining informed consent .13
5.8.3 Special circumstances for informed consent .14
5.8.4 Information to be provided to the subject .15
5.8.5 Informed consent signature .17
5.8.6 New information .17
6 Clinical investigation planning .17
6.1 General .17
6.2 Risk management .18
6.2.1 General.18
6.2.2 Investigational device including clinical procedure risks and their disclosure .18
6.2.3 Clinical investigation process .18
6.3 Justification for the design of the clinical investigation .19
6.4 Clinical investigation plan (CIP) .19
6.5 Investigator's brochure (IB) .19
6.6 Case report forms (CRFs) .20
6.7 Monit oring plan .20
6.8 Investigation site selection .21
6.9 Agreement(s).21
6.10 Labelling .21
6.11 Data monitoring committee (DMC) .21
7 Clinical investigation conduct .22
7.1 General .22
7.2 Investigation site initiation .22
7.3 Investigation site monitoring .22
7.4 Adverse events and device deficiencies .22
7.4.1 Signals requiring immediate action .22
7.4.2 Adverse events .23
7.4.3 Device deficiencies .23
7.4.4 Risk assessment process for potentially unacceptable risks .23
7.5 Clinical investigation documents and documentation .24
7.5.1 Amendments .24
7.5.2 Subject identification log .24
© ISO 2020 – All rights reserved iii
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SIST EN ISO 14155:2020
ISO 14155:2020(E)
7.5.3 Source documents .25
7.6 Additional members of the investigation site team .25
7.7 Subject privacy and confidentiality of data .25
7.8 Document and data control.25
7.8.1 Traceability of documents and data .25
7.8.2 Recording of data . . .25
7.8.3 Electronic clinical data systems .26
7.9 Investigational device accountability .27
7.10 Accounting for subjects .27
7.11 Auditing .27
8 Suspension, termination, and close-out of the clinical investigation .28
8.1 Completion of the clinical investigation .28
8.2 Suspension or premature termination of the clinical investigation .28
8.2.1 Procedure for suspension or premature termination .28
8.2.2 Procedure for resuming the clinical investigation after temporary suspension .29
8.3 Routine close-out .29
8.4 Clinical investigation report .30
8.5 Risk assessment and conclusions .30
8.6 Document retention.31
9 Responsibilities of the sponsor .31
9.1 Clinical quality management .31
9.2 Clinical investigation planning and conduct .31
9.2.1 Selection and training of clinical personnel .31
9.2.2 Preparation of documents and materials .32
9.2.3 Conduct of clinical investigation .33
9.2.4 Monitoring
...
SLOVENSKI STANDARD
oSIST prEN ISO 14155:2018
01-september-2018
.OLQLþQHUD]LVNDYHPHGLFLQVNLKSULSRPRþNRY]DOMXGL'REUHNOLQLþQHSUDNVH
,62',6
Clinical investigation of medical devices for human subjects - Good clinical practice
(ISO/DIS 14155:2018)
Klinische Prüfung von Medizinprodukten an Menschen - Gute klinische Praxis (ISO/DIS
14155:2018)
Investigation clinique des dispositifs médicaux pour sujets humains - Bonnes pratiques
cliniques (ISO/DIS 14155:2018)
Ta slovenski standard je istoveten z: prEN ISO 14155
ICS:
11.040.01 Medicinska oprema na Medical equipment in general
splošno
oSIST prEN ISO 14155:2018 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 14155:2018
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oSIST prEN ISO 14155:2018
DRAFT INTERNATIONAL STANDARD
ISO/DIS 14155
ISO/TC 194 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-06-19 2018-09-11
Clinical investigation of medical devices for human
subjects — Good clinical practice
Investigation clinique des dispositifs médicaux pour sujets humains — Bonnes pratiques cliniques
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
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NATIONAL REGULATIONS.
ISO/DIS 14155:2018(E)
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PROVIDE SUPPORTING DOCUMENTATION. ISO 2018
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oSIST prEN ISO 14155:2018
ISO/DIS 14155:2018(E)
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oSIST prEN ISO 14155:2018
ISO/DIS 14155:2018(E)
Contents Page
Foreword .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Summary of Good Clinical Practices (GCP) principles . 9
5 Ethical considerations .10
5.1 General .10
5.2 Improper influence or inducement .10
5.3 Compensation and additional health care.10
5.4 Registration in publicly accessible database .10
5.5 Responsibilities .10
5.6 Communication with the ethics committee (EC) .10
5.6.1 General.10
5.6.2 Initial EC submission .11
5.6.3 Information to be obtained from the EC.11
5.6.4 Continuing communication with the EC .11
5.6.5 Continuing information to be obtained from the EC .12
5.7 Vulnerable populations .12
5.8 Informed consent .12
5.8.1 General.12
5.8.2 Process of obtaining informed consent .12
5.8.3 Special circumstances for informed consent .13
5.8.4 Information to be provided to the subject .14
5.8.5 Informed consent signature .16
5.8.6 New information .16
6 Clinical investigation planning .16
6.1 General .16
6.2 Risk management .17
6.2.1 General.17
6.2.2 Investigational device .17
6.2.3 Clinical investigation process .17
6.3 Justification for the design of the clinical investigation .17
6.4 Clinical investigation plan (CIP) .18
6.5 Investigator's brochure (IB) .18
6.6 Case report forms (CRFs) .18
6.7 Monitoring plan .19
6.8 Investigation site selection .19
6.9 Agreement(s).20
6.10 Labelling .20
6.11 Data monitoring committee (DMC) .20
7 Clinical investigation conduct .20
7.1 General .20
7.2 Investigation site initiation .20
7.3 Investigation site monitoring .20
7.4 Adverse events and device deficiencies .21
7.4.1 General.21
7.4.2 Adverse events .21
7.4.3 Device deficiencies .21
7.4.4 Escalation process for assessing unanticipated serious adverse device effects .22
7.5 Clinical investigation documents and documentation .22
7.5.1 Amendments .22
7.5.2 Subject identification log .23
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oSIST prEN ISO 14155:2018
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7.5.3 Source documents .23
7.6 Additional members of the investigation site team .23
7.7 Subject privacy and confidentiality of data .23
7.8 Document and data control.23
7.8.1 Traceability of documents and data .23
7.8.2 Recording of data . . .24
7.8.3 Electronic clinical data systems .24
7.9 Investigational device accountability .25
7.10 Accounting for subjects .25
7.11 Auditing .25
8 Suspension, termination and close-out of the clinical investigation .26
8.1 Completion of the clinical investigation .26
8.2 Suspension or premature termination of the clinical investigation .26
8.2.1 Procedure for suspension or premature termination .26
8.2.2 Procedure for resuming the clinical investigation after temporary suspension .27
8.3 Routine close-out .27
8.4 Clinical investigation report .28
8.5 Feeding results into risk management .28
8.6 Document retention.28
9 Responsibilities of the sponsor .29
9.1 Clinical quality management .29
9.2 Clinical investigation planning and conduct .29
9.2.1 Selection and training of clinical personnel .29
9.2.2 Preparation of documents and materials .30
9.2.3 Conduct of clinical investigation .31
9.2.4 Monitoring .31
9.2.5 Safety evaluation and reporting .34
9.2.6 Clinical investigation close-out .34
9.3 Outsourcing of duties and functions .35
9.4 Communication with regulatory authorities .35
10 Responsibilities of the principal investigator .35
10.1 General .35
10.2 Qualification of the principal investigator . .36
10.3 Qualification of investigation site .36
10.4 Communication with the EC .36
10.5 Informed consent process .36
10.6 Compliance with the CIP .37
10.7 Medical care of subjects .37
10.8 Safety reporting .38
Annex A (normative) Clinical investigation plan (CIP) .39
Annex B (normative) Investigator's brochure (IB) .47
Annex C (informative) Case report forms (CRFs).50
Annex D (normative) Clinical investigation report .52
Annex E (informative) Essential clinical investigation documents.57
Annex F (informative) Adverse event categorisation .65
Annex G (informative) Ethics Committee (EC) responsibilities .67
Annex H (informative) Application of ISO 14971 to clinical investigations .71
Annex I (informative) Clinical development stages .73
Annex J (informative) Clinical investigation audits .78
Annex ZA (informative) Relationship between this European Standard and the essential
requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered .82
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Annex ZB (informative) Relationship between this European Standard and the essential
requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered .84
Annex ZC (informative) Relationship between this European standard and the general
safety and performance requirements of Regulation (EU) 2017/745 aimed to be
covered . .86
Bibliography .90
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oSIST prEN ISO 14155:2018
ISO/DIS 14155:2018(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.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/directives).
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. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: www .iso .org/iso/foreword .html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
This third edition cancels and replaces the second edition (see ISO 14155:2011), which has been
technically revised.
The main changes compared to the previous edition are as follows:
— inclusion of a summary section of GCP principles (see Clause 4);
— reference to registration of the clinical investigation in a publicly accessible data base (see 5.4);
— inclusion of guidance with regards to clinical quality management (see 9.1);
— inclusion of risk-based monitoring (see 6.7);
— inclusion of guidance statistical considerations (see Annex A);
— inclusion of guidance for ethics committees (see Annex G);
— reinforcement of risk management throughout the process of a clinical investigation (planning to
consideration of results) including Annex H;
— clarification of applicability of the requirements of this standard to the different clinical development
stages (see Annex I);
— inclusion of guidance on clinical investigation audits (see Annex J).
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oSIST prEN ISO 14155:2018
DRAFT INTERNATIONAL STANDARD ISO/DIS 14155:2018(E)
Clinical investigation of medical devices for human
subjects — Good clinical practice
1 Scope
This document addresses good clinical practice for the design, conduct, recording and reporting of
pre-market clinical investigations carried out in human subjects to assess the clinical performance or
effectiveness and safety of medical devices.
The principles set forth in this document also apply to post-market clinical investigations and should be
followed as far as relevant, considering the nature of the clinical investigation and the requirements of
national regulations (see Annex I).
This document specifies general requirements intended to
— protect the rights, safety and well-being of human subjects,
— ensure the scientific conduct of the clinical investigation and the credibility of the clinical
investigation results,
— define the responsibilities of the sponsor and principal investigator, and
— assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved
in the conformity assessment of medical devices.
NOTE 1 This standard can be used for regulatory purposes.
NOTE 2 Users of this International Standard will need to consider whether other standards and/or
requirements also apply to the investigational device(s) under consideration.
NOTE 3 For Software as a Medical Device (SaMD), justifications for exemptions of this standard can consider
the uniqueness of indirect contact between subjects and the SaMD. However it is required to demonstrate the
analytical validity (the SaMD’s output is accurate for a given input), and where appropriate, the scientific validity
(the SaMD’s output is associated to the intended clinical condition/physiological state), and clinical performance
(the SaMD’s output yields a clinically meaningful association to the target use) of the SaMD (see Reference [5]).
This document does not apply to in vitro diagnostic medical devices.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardisation at the following addresses:
— IEC Electropedia: available at http: //www .electropedia .org/
— ISO Online browsing platform: available at http: //www .iso .org/obp
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oSIST prEN ISO 14155:2018
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3.1
adverse device effect
ADE
adverse event related to the use of an investigational medical device
Note 1 to entry: This definition includes adverse events resulting from insufficient or inadequate instructions for
use, deployment, implantation, installation, or operation, or any malfunction of the investigational medical device.
Note 2 to entry: This definition includes any event resulting from use error or from intentional misuse of the
investigational medical device.
3.2
adverse event
AE
untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the
investigational medical device
Note 1 to entry: This definition includes events related to the investigational medical device or the comparator.
Note 2 to entry: This definition includes events related to the procedures involved.
Note 3 to entry: For users or other persons, this definition is restricted to events related to the use of
investigational medical devices.
3.3
audit
systematic independent examination of activities and documents related to clinical investigation to
determine whether these activities were conducted, and the data recorded, analysed and accurately
reported, according to the CIP, standard operating procedures, this International Standard and
applicable regulatory requirements
3.4
audit trail
documentation that allows reconstruction of the course of events
3.5
blinding/masking
procedure in which one or more parties to the clinical investigation are kept unaware of the treatment
assignment(s)
Note 1 to entry: Single blinding usually refers to the subject(s) being unaware of the treatment assignment(s).
Double blinding usually refers to the subject(s), investigator(s), monitor and, in some cases, cent
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