FprEN ISO 14155
(Main)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/FDIS 14155:2020)
Dieses Dokument legt die gute klinische Praxis für die Gestaltung, die Durchführung, Aufzeichnung und Dokumentation klinischer Prüfungen fest, die an menschlichen Versuchspersonen durchgeführt werden, um die klinische Leistungsfähigkeit oder die medizinische Wirksamkeit und Sicherheit von Medizinprodukten zu bewerten.
Bei klinischen Prüfungen nach dem Inverkehrbringen können die in diesem Dokument dargelegten Grundsätze befolgt werden, soweit sie, unter Berücksichtigung der Art der klinischen Prüfung, relevant sind (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 Versuchspersonen;
- die Sicherstellung der wissenschaftlich korrekten Durchführung der klinischen Prüfung und der Glaubwürdigkeit der Ergebnisse der klinischen Prüfung;
- die Festlegung der Verantwortlichkeiten des Sponsors und Prüfungsleiters;
- die Unterstützung der Arbeit von Sponsoren, Prüfern, Ethikkommissionen, Aufsichtsbehörden und anderen am Konformitätsbewertungsverfahren für Medizinprodukte beteiligten Institutionen.
ANMERKUNG 1 Anwender dieses Dokuments haben zu überlegen, 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 Ausgabe der SaMD ist für eine vorgegebene Eingabe genau) und gegebenenfalls auch der wissenschaftlichen Validität (die Ausgabe der SaMD ist mit dem klinischen Zustand/der physiologischen Verfassung assoziiert) sowie der klinischen Leistungsfähigkeit (die Ausgabe der SaMD steht in einen klinisch sinnvollen Zusammenhang mit der beabsichtigten Anwendung) der SaMD die Anforderungen dieses Dokuments, soweit sie relevant sind (siehe Verweisung [5]). Als Rechtfertigung für eine Befreiung von den Anforderungen dieses Dokuments kann die Einzigartigkeit des indirekten Kontakts zwischen den Versuchspersonen und der SaMD in Erwägung gezogen werden.
Dieses Dokument gilt nicht für Medizinprodukte für die In-vitro-Diagnostik. Es kann jedoch, abhängig vom Produkt und nationalen oder regionalen Anforderungen, Situationen geben, in denen Anwender dieses Dokuments in Erwägung ziehen möchten, ob bestimmte Abschnitte und/oder Anforderungen dieses Dokuments anwendbar sein könnten.
Investigation clinique des dispositifs médicaux pour sujets humains - Bonnes pratiques cliniques (ISO/FDIS 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/FDIS 14155:2020)
General Information
RELATIONS
Standards Content (sample)
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
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: 11.100.20THIS 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
Reference number
NATIONAL REGULATIONS.
ISO/DIS 14155:2018(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
PROVIDE SUPPORTING DOCUMENTATION. ISO 2018
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oSIST prEN ISO 14155:2018
ISO/DIS 14155:2018(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Published in Switzerland
ii © ISO 2018 – All rights reserved
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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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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 becovered ......... ................................................................................................................................................................................................................86
Bibliography .............................................................................................................................................................................................................................90
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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 devices3 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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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
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 deviceNote 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 requirements3.4
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, i
...
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