SIST EN ISO 14155:2011
(Main)Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2011)
Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2011)
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 erformance of medical devices for regulatory purposes.
The principles set forth in this International Standard also apply to all other clinical investigations and should be followed as far as possible, considering the nature of the clinical investigation and the requirements of national regulations.
This International Standard 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.
It does not apply to in vitro diagnostic medical devices.
NOTE Standards developed by ISO/TC 194 are intended to be applied to medical devices. Users of this International Standard will need to consider whether other standards and/or requirements also apply to the investigational device(s) under consideration.
Klinische Prüfung von Medizinprodukten an Menschen - Gute klinische Praxis (ISO 14155:2011)
ISO 14155 bezieht sich auf technische Fragen klinischer Prüfungen an menschlichen Versuchspersonen, die durchgeführt werden, um die Sicherheit und Leistungsfähigkeit von Medizinprodukten gemäß Rechts- und Verwaltungs¬vorschriften zu bewerten, indem die Gute Klinische Praxis für die Gestaltung, die Durchführung, Aufzeichnung und Dokumentation klinischer Prüfungen festgelegt wird.
Die Norm legt allgemeine Anforderungen fest, mit denen Folgendes erreicht werden soll
der Schutz der Rechte, Sicherheit und des Wohlergehens der beteiligten Versuchspersonen,
die Sicherstellung der wissenschaftlich korrekten Durchführung der klinischen Prüfung und der Glaubwürdigkeit der Prüfungsergebnisse,
die Unterstützung der Arbeit von Sponsoren, Monitoren, Prüfern, Ethikkommissionen, gesetzlich zuständigen Behörden und der am Konformitätsbewertungsverfahren für Medizinprodukte beteiligten Institutionen.
ISO 14155 gilt nicht für Medizinprodukte für die In-vitro-Diagnostik.
ANMERKUNG Von ISO/TC 194 erarbeitete Normen sind in erster Linie für die Anwendung auf Medizinprodukte vorgesehen. In Anbetracht der zunehmenden Anzahl von Kombinationsprodukten werden Anwender dieser Norm berücksichtigen müssen, ob weitere Normen auf das zu prüfende Produkt ebenfalls angewendet werden können.
Die in der vorliegenden Norm dargestellten Grundsätze können auf klinische Prüfungen, die für nicht regulative Zwecke durchgeführt werden, angewendet werden. In diesem Fall sollten die Anforderungen der vorliegenden Norm so weit wie möglich unter Berücksichtigung der Art der Prüfung und der Anforderungen der nationalen Bestimmungen eingehalten werden. Signifikante Ausnahmen von den Grundsätzen sollten in dem klinischen Prüfplan oder in anderen Ausführungsunterlagen des Sponsors vermerkt werden.
Investigation clinique des dispositifs médicaux pour sujets humains - Bonnes pratiques cliniques (ISO 14155:2011)
L'ISO 14155:2011 traite les bonnes pratiques cliniques pour la conception, la conduite, l'enregistrement et l'établissement des rapports des investigations cliniques menées sur des sujets humains en vue d'évaluer la sécurité ou les performances des dispositifs médicaux à des fins réglementaires.
Les principes définis dans l'ISO 14155:2011 s'appliquent également aux autres investigations cliniques et il convient de les suivre dans la mesure du possible, en prenant en compte la nature de l'investigation et les exigences imposées par les réglementations nationales.
L'ISO 14155:2011 fixe 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.
L'ISO 14155:2011 ne s'applique pas aux dispositifs médicaux de diagnostic in vitro.
Klinične raziskave medicinskih pripomočkov za ljudi - Dobre klinične prakse (ISO 14155:2011)
Ta mednarodni standard naslavlja dobro klinično prakso za načrtovanje, izvajanje, beleženje in poročanje o kliničnih preiskavah, izvedenih na ljudeh, za ocenjevanje varnosti ali delovanja medicinskih pripomočkov za potrebe regulacije.
Načela, določena v tem mednarodnem standardu, prav tako veljajo za vse preostale klinične raziskave in jim je treba slediti, kolikor je mogoče, upoštevajoč naravo kliničnih raziskav in zahteve državnih predpisov.
Ta mednarodni standard določa splošne zahteve za:
– zaščito pravic, varnost in dobro počutje ljudi,
– zagotavljanje znanstvenega izvajanja klinične raziskave in verodostojnost rezultatov klinične raziskave,
– opredelitev odgovornosti sponzorja in vodilnega raziskovalca ter
– pomoč sponzorjem, preiskovalcem, etičnim odborom, regulativnim organom in drugim organom, ki so vključeni v ugotavljanje skladnosti medicinskih pripomočkov.
Ne velja za diagnostične medicinske pripomočke in vitro.
OPOMBA Standardi, ki jih je razvil ISO/TC, so namenjeni uporabi pri medicinskih pripomočkih. Uporabniki tega mednarodnega standarda bodo morali upoštevati, ali drugi standardi in/ali zahteve prav tako veljajo za raziskovalne naprave, ki jih obravnavajo.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 14155:2011
01-april-2011
1DGRPHãþD
SIST EN ISO 14155-1:2009
SIST EN ISO 14155-2:2009
.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 14155:2011 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 14155:2011
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SIST EN ISO 14155:2011
EUROPEAN STANDARD
EN ISO 14155
NORME EUROPÉENNE
EUROPÄISCHE NORM
February 2011
ICS 11.100.20 Supersedes EN ISO 14155-1:2009, EN ISO 14155-2:2009
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 10 December 2010.
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 14155:2011
EN ISO 14155:2011 (E)
Contents Page
Foreword .3
Annex ZA .4
Annex ZB .5
2
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SIST EN ISO 14155:2011
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 August 2011, and conflicting national standards shall be withdrawn at
the latest by August 2011.
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 14155-1:2009 and EN ISO 14155-2:2009.
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 a EN ISO 14155:2011 without any modification.
3
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SIST EN ISO 14155:2011
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 normative clauses of
this standard 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 This standard is specifically intended to provide a means for getting presumption of conformity to the part of
Essential Requirement 6a that refers to clinical investigations, as developed in Annex X, 2nd part (2.1 to 2.3.7) of the
above-mentioned directive.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
4
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SIST EN ISO 14155:2011
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 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 normative clauses of
this standard 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 This standard is specifically intended to provide a means for getting presumption of conformity to the part of
Essential Requirement 5. that refers to clinical investigations, as developed in Annex 7, 2nd part (2.1 to 2.3.7) of the above
mentioned directive.
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
5
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SIST EN ISO 14155:2011
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SIST EN ISO 14155:2011
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 14155:2011
ISO 14155:2011(E)
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ii © ISO 2011 – All rights reserved
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SIST EN ISO 14155:2011
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 14155:2011
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 14155:2011
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 14155:2011
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SIST EN ISO 14155:2011
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 International Standard also apply to all other clinical investigations and should
be followed as far as possible, considering the nature of the clinical investigation and the requirements of
national regulations.
This International Standard 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.
It does not apply to in vitro diagnostic medical devices.
NOTE Standards developed by ISO/TC 194 are intended to be applied to medical devices. Users of this International
Standard will need to consider whether other standards and/or requirements also apply to the investigational device(s)
under consideration.
2 Normative references
The following referenced documents are indispensable for the application 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 14971:2007, Medical devices — Application of risk management to medical devices
© ISO 2011 – All rights reserved 1
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SIST EN ISO 14155:2011
ISO 14155:2011(E)
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
adverse device effect
ADE
adverse event related to the use of an investigational medical device
NOTE 1 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 This definition includes any event resulting from use error or from intentional misuse of the investigational
medical device.
3.2
adverse event
AE
any 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 This definition includes events related to the investigational medical device or the comparator.
NOTE 2 This definition includes events related to the procedures involved.
NOTE 3 For users or other persons, this definition is restricted to events related to 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
blinding/masking
procedure in which one or more parties to the clinical investigation are kept unaware of the treatment
assignment(s)
NOTE 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, centralized assessors being unaware of the
treatment assignment(s).
3.5
case report forms
CRFs
set of printed, optical or electronic documents for each subject on which information to be reported to the
sponsor is recorded, as required by the CIP
3.6
clinical investigation
systematic investigation in one or more human subjects, undertaken to assess the safety or performance of a
medical device
NOTE “Clinical trial” or “clinical study” are synonymous with “clinical investigation”.
2 © ISO 2011 – All rights reserved
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SIST EN ISO 14155:2011
ISO 14155:2011(E)
3.7
clinical investigation plan
CIP
document that state(s) the rationale, objectives, design and proposed analysis, methodology, monitoring,
conduct and record-keeping of the clinical investigation
NOTE The term “protocol” is synonymous with “CIP”. However, protocol has many different meanings, some not
related to clinical investigation, and these can differ from country to country. Ther
...
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