SIST EN ISO 14155-1:2003
(Main)Clinical investigation of medical devices for human subjects - Part 1: General requirements (ISO 14155-1:2003)
Clinical investigation of medical devices for human subjects - Part 1: General requirements (ISO 14155-1:2003)
Migrated from Progress Sheet (TC Comment) (2000-07-10): Revision of EN 540:1993 (TC Res 112/1998) (CC/990121) ++ Contact Mr Vyze ext 850 when processing this project through each stage++TC forecasts updated (TC forecasts updating exercise.sj 00-10-03)++
Klinische Prüfung von Medizinprodukten an Menschen - Teil 1: Allgemeine Anforderungen (ISO 14155-1:2003)
Diese Internationale Norm legt Verfahren für die Durchführung klinischer Prüfungen von Medizinprodukten fest. Sie legt allgemeine Anforderungen fest, mit denen folgendes erreicht werden soll
der Schutz der beteiligten Versuchspersonen
die Sicherstellung der wissenschaftlich korrekten Durchführung der klinischen Prüfung
die Unterstützung von Sponsoren, Monitoren, Prüfern, Ethikkommissionen, Behörden und der am Konformitätsbewertungsverfahren für Medizinprodukte beteiligten Institutionen.
Dieser Teil von ISO 14155
a) gilt für alle klinischen Prüfungen von Medizinprodukten, deren klinische Leistungsfähigkeit und Sicherheit an menschlichen Versuchspersonen bewertet wird.
b) legt Anforderungen für die Durchführung einer klinischen Prüfung fest, so dass die Leistung des Medizinprodukts während der klinischen Prüfung, die die normale klinische Anwendung nachahmen soll, nachgewiesen wird, deckt unerwünschte Ereignisse unter normalen klinischen Anwendungsbedingungen auf, und ermöglicht eine Bewertung der vertretbaren Risiken, die mit der vorgesehenen Leistung des Medizinprodukts verbunden sind.,
c) legt Anforderungen für die Organisation, die Durchführung, Überwachung, Datenerfassung und die Dokumentation der klinischen Prüfung eines Medizinprodukts fest,
Dieser Teil von ISO 14155 gilt nicht für Medizinprodukte für die in vitro Diagnostik.
Investigation clinique des dispositifs médicaux pour sujets humains - Partie 1: Exigences générales (ISO 14155-1:2003)
Klinične raziskave medicinskih pripomočkov za ljudi – 1. del: Splošne zahteve (ISO 14155-1:2003)
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Standards Content (Sample)
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.Clinical investigation of medical devices for human subjects - Part 1: General requirements (ISO 14155-1:2003)Investigation clinique des dispositifs médicaux pour sujets humains - Partie 1: Exigences générales (ISO 14155-1:2003)Klinische Prüfung von Medizinprodukten an Menschen - Teil 1: Allgemeine Anforderungen (ISO 14155-1:2003)Ta slovenski standard je istoveten z:EN ISO 14155-1:2003SIST EN ISO 14155-1:2003en11.040.01Medicinska oprema na splošnoMedical equipment in generalICS:SIST EN 540:20001DGRPHãþDSLOVENSKI
STANDARDSIST EN ISO 14155-1:200301-september-2003
EUROPEAN STANDARDNORME EUROPÉENNEEUROPÄISCHE NORMEN ISO 14155-1February 2003ICS 11.100Supersedes EN 540:1993English versionClinical investigation of medical devices for human subjects -Part 1: General requirements (ISO 14155-1:2003)Investigation clinique des dispositifs médicaux pour sujetshumains - Partie 1: Exigences générales (ISO 14155-1:2003)Klinische Prüfung von Medizinprodukten an Menschen -Teil 1: Allgemeine Anforderungen (ISO 14155-1:2003)This European Standard was approved by CEN on 7 February 2003.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nationalstandards may be obtained on application to the 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 translationunder the responsibility of a CEN member into its own language and notified to the Management Centre has the same status as the officialversions.CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,Hungary, Iceland, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Portugal, Slovak Republic, Spain, Sweden, Switzerland andUnited Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMITÉ EUROPÉEN DE NORMALISATIONEUROPÄISCHES KOMITEE FÜR NORMUNGManagement Centre: rue de Stassart, 36
B-1050 Brussels© 2003 CENAll rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 14155-1:2003 E
EN ISO 14155-1:2003 (E)2CORRECTED
2003-04-30ForewordThis document (EN ISO 14155-1:2003) has been prepared by Technical Committee ISO/TC 194"Biological evaluation of medical devices" in collaboration with Technical Committee CEN/TC258 "Clinical investigation of medical devices", the secretariat of which is held by AFNOR.This European Standard shall be given the status of a national standard, either by publication ofan identical text or by endorsement, at the latest by August 2003, and conflicting nationalstandards shall be withdrawn at the latest by August 2003.This document supersedes EN 540:1993.This document has been prepared under a mandate given to CEN by the European Commissionand the European Free Trade Association, and supports essential requirements of EUDirective(s).For relationship with EU Directive(s), see informative annex ZA, which is an integral part of thisdocument.According to the CEN/CENELEC Internal Regulations, the national standards organizations ofthe following countries are bound to implement this European Standard: Austria, Belgium, CzechRepublic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy,Luxembourg, Malta, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, Switzerland andthe United Kingdom.Endorsement noticeThe text of ISO 14155-1:2003 has been approved by CEN as EN ISO 14155-1:2003 without anymodifications.
EN ISO 14155-1:2003 (E)3Annex ZA(informative)Clauses of this European Standard addressing essential requirements orother provisions of EU DirectivesThis European standard has been prepared under a mandate given to CEN/CENELEC by theEuropean Commission and the European Free Trade Association and supports essentialrequirements of EU Directives 90/385/EEC and 93/42/EEC.WARNING : Other requirements and other EU Directives may be applicable to the product(s)falling within the scope of this standard.The clauses of this standard are likely in support of annex X of Directive 90/385/EEC and annexVII of Directive 93/42/EEC.Compliance with these clauses of this standard provides one means of conforming with thespecific provisions of the Directives concerned and associated EFTA regulations.
Reference numberISO 14155-1:2003(E)© ISO 2003
INTERNATIONAL STANDARD ISO14155-1First edition2003-02-15Clinical investigation of medical devices for human subjects —
Part 1: General requirements Investigation clinique des dispositifs médicaux pour sujets humains —
Partie 1: Exigences générales
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ii © ISO 2003 — All rights reserved
ISO 14155-1:2003(E) © ISO 2003 — All rights reserved iii Contents Page Foreword.v Introduction.vi 1 Scope.1 2 Normative references.1 3 Terms and definitions.2 4 Justification for a clinical investigation.5 5 Ethical considerations.5 5.1 Declaration of Helsinki.5 5.2 Improper influence or inducement.5 5.3 Compensation and additional health care.5 5.4 Responsibilities.5 6 General requirements.5 6.1 Formal agreement(s).5 6.2 Qualifications.5 6.3 Clinical investigation plan.6 6.4 Design of the clinical investigation.6 6.5 Confidentiality.6 6.6 Start of clinical investigation.6 6.7 Informed consent.6 6.8 Suspension or early termination of the clinical investigation.8 6.9 Document and data control.8 6.10 Accounting for subjects.9 6.11 Access to preclinical and clinical information.9 6.12 Auditing.9 7 Documentation.9 7.1 General.9 7.2 Clinical investigator's brochure.9 7.3 Other documents.10 8 Sponsor.10 8.1 General.10 8.2 Responsibilities of sponsor.10 9 Monitor.11 9.1 Responsibilities of monitor.11 10 Clinical investigator.12 10.1 General.12 10.2 Qualification of clinical investigator.12 10.3 Responsibilities of clinical investigator.12 11 Final report.14 11.1 Presentation of results.14 11.2 Contents of the final report.14
ISO 14155-1:2003(E) iv © ISO 2003 — All rights reserved Annex A (informative)
Suggested procedure for literature review.15 Annex B (informative)
Information for the ethics committees.17 Annex C (informative)
Final reports of clinical investigations with medical devices.18 Bibliography.21
ISO 14155-1:2003(E) © ISO 2003 — All rights reserved v 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 14155-1 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices. This first edition of ISO 14155-1, together with ISO 14155-2, cancels and replace ISO 14155:1996, which has been technically revised. ISO 14155 consists of the following parts, under the general title Clinical investigation of medical devices for human subjects: Part 1: General requirements Part 2: Clinical investigation plans
ISO 14155-1:2003(E) vi © ISO 2003 — All rights reserved Introduction This part of ISO 14155 is intended to be applied worldwide to clinical investigations of medical devices in order to fulfil the technical aspects of the various national, regional and international regulatory requirements. As the legal regulatory requirements presently differ throughout the world, regulatory specifics have been excluded from the scope of this part of ISO 14155. They are part of national or regional legislative texts and can be referenced in the national or regional forewords, as appropriate.
INTERNATIONAL STANDARD ISO 14155-1:2003(E) © ISO 2003 — All rights reserved 1 Clinical investigation of medical devices for human subjects — Part 1: General requirements 1 Scope This part of ISO 14155 defines procedures for the conduct and performance of clinical investigations of medical devices. It specifies general requirements intended to protect human subjects, ensure the scientific conduct of the clinical investigation, assist sponsors, monitors, investigators, ethics committees, regulatory authorities and bodies involved in the conformity assessment of medical devices. This part of ISO 14155 a) specifies requirements for the conduct of a clinical investigation such that it establishes the performance of the medical device during the clinical investigation intended to mimic normal clinical use, reveals adverse events under normal conditions of use, and permits assessment of the acceptable risks having regard to the intended performance of the medical device, b) specifies requirements for the organization, conduct, monitoring, data collection and documentation of the clinical investigation of a medical device, c) is applicable to all clinical investigation(s) of medical devices whose clinical performance and safety is being assessed in human subjects. This part of ISO 14155 is not applicable to in vitro diagnostic medical devices. 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 14155-2, Clinical investigation of medical devices for human subjects — Part 2: Clinical investigation plans
ISO 14155-1:2003(E) 2 © ISO 2003 — All rights reserved 3 Terms and definitions For the purposes of this document, the following terms and definitions apply. 3.1 adverse device effect any untoward and unintended response to a medical device NOTE 1 This definition includes any event resulting from insufficiencies or inadequacies in the instructions for use or the deployment of the device. NOTE 2 This definition includes any event that is a result of a user error. 3.2 adverse event any untoward medical occurrence in a subject NOTE This definition does not imply that there is a relationship between the adverse event and the device under investigation. 3.3 case report form document designed to record all information to be reported to the sponsor on each subject as required by the clinical investigation plan 3.4 clinical investigation any designed and planned systematic study in human subjects undertaken to verify the safety and/or performance of a specific device 3.5 clinical investigation plan CIP document that states the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct and record-keeping of the clinical investigation NOTE The word “protocol” is often used synonymously with the term “clinical investigation plan”. However, it has many different meanings, some not related to clinical investigations, and these may differ from country to country. Therefore, it is not used in this part of ISO 14155. 3.6 clinical investigator individual and/or institution responsible for the conduct of a clinical investigation who and/or which takes the clinical responsibility for the well-being of the subjects involved NOTE Whether this is an individual or an institutional responsibility may depend on national legislation. 3.7 clinical investigator's brochure compilation of the clinical and non-clinical information on the device(s) under investigation, that is relevant to the investigation in human subjects 3.8 clinical performance behaviour of a specific medical device and/or its performance in relation to its intended use when correctly applied to appropriate subjects 3.9 coordinating clinical investigator clinical investigator who is appointed by the sponsor to coordinate work in a multicentre clinical investigation
ISO 14155-1:2003(E) © ISO 2003 — All rights reserved 3 3.10 ethics committee independent and properly constituted competent body whose responsibility is to ensure that the safety, well-being and human rights of the subjects participating in a clinical investigation are protected NOTE For the purposes of this part of ISO 14155, “ethics committee” is synonymous with “research ethics committee” or “institutional review board”. The regulatory requirements pertaining to ethics committees or similar institutions may differ from country to country. 3.11 final report description, results and evaluation of the clinical investigation after its completion 3.12 informed consent legally effective, documented confirmation of a subject's (or his/her legal guardian or representative) voluntary agreement to participate in a particular clinical investigation after information has been given to the subject on all aspects of the clinical investigation that are relevant to the subject's decision to participate 3.13 investigation centre investigation site institution or site where the clinical investigation is carried out 3.14 medical device any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application, intended by the manufacturer to be used on human beings for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease, diagnosis, monitoring, treatment, alleviation or compensation for an injury or handicap, investigation, replacement or modification of the anatomy or of a physiological process, control of conception, and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means. NOTE The term “medical device” is usually defined by national law. In order to inform the user of this part of ISO 14155, the definition from reference [1] is listed (see Bibliography). More information is given in reference [3]. 3.15 monitor individual appointed by the sponsor responsible for assessing the investigator's compliance with the clinical investigation plan and for performing source-data verification NOTE The monitor is also responsible for reporting to the sponsor on the progress of the clinical investigation, including the compliance of the investigators. 3.16 multicentre investigation clinical investigation which is conducted according to a single clinical investigation plan and which takes place at two or more sites 3.17 principal clinical investigator clinical investigator responsible for the organization of the clinical investigation at one site
ISO 14155-1:2003(E) 4 © ISO 2003 — All rights reserved 3.18 serious adverse device effect adverse device effect that has resulted in any of the consequences characteristic of a serious adverse event or that might have led to any of these consequences if suitable action had not been taken or intervention had not been made or if circumstances had been less opportune 3.19 serious adverse event adverse event that a) led to a death, b) led to a serious deterioration in the health of the subject that 1) resulted in a life-threatening illness or injury, 2) resulted in a permanent impairment of a body structure or a body function, 3) required in-patient hospitalization or prolongation of existing hospitalization, 4) resulted in medical or surgical intervention to prevent permanent impairment to body structure or a body function. c) led to foetal distress, foetal death or a congenital abnormality or birth defect. 3.20 source data all information in original and identified records and certified copies of original records of clinical findings, observations, or other activities in a clinical investigation, necessary for the reconstruction and evaluation of the clinical investigation 3.21 source documents original documents, data and records NOTE This may be for example, hospital records, laboratory notes, pharmacy dispensing records, copies or transcriptions certified after verification as being accurate copies, photographic negatives, radiographs, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical investigation. 3.22 sponsor individual or organization who or which takes responsibility for the initiation and/or implementation of a clinical investigation NOTE 1 For the purposes of this part of ISO 14155 the word “sponsor” is synonymous with the word “promoter”. NOTE 2 When a clinical investigator independently initiates, implements and takes full responsibility for the clinical investigation, the clinical investigator also assumes the role of the sponsor. 3.23 subject individual who participates in a clinical investigation, either as a recipient of the device under investigation or as a control
ISO 14155-1:2003(E) © ISO 2003 — All rights reserved 5 4 Justification for a clinical investigation In order to determine the justification and optimal design for a clinical investigation, an objective review of published and available unpublished medical and scientific data and information shall be conducted and documented. NOTE 1 Guidance for such a literature review is given in Annex A. The decision to embark upon a clinical investigation of a medical device requires inter alia the residual risks to be balanced against the anticipated benefits of the clinical investigation. NOTE 2 For further information, see ISO 14971[6]. 5 Ethical considerations 5.1 Declaration of Helsinki
The rights, safety and wellbeing of clinical investigation subjects shall be protected consistent with the ethical principles laid down in the Declaration of Helsinki. This shall be understood, observed and applied at every step in the clinical investigation. 5.2 Improper influence or inducement The sponsor and the clinical investigator(s) shall avoid improper influence or inducement of the subject, monitor, the clinical investigator(s) or other parties participating in or contributing to the clinical investigation. 5.3 Compensation and additional health care The sponsor shall state what provision will be made for compensation of subjects in the event of injury arising from participation in the clinical investigation and this shall be documented. Arrangements for additional health care for subjects required as a result of an adverse device effect shall be made and documented. NOTE This may be the subject of national legislation. 5.4 Responsibilities All parties involved in the conduct of the clinical investigation shall share the responsibility for its ethical conduct in accordance with their respective roles in the investigation. 6 General requirements 6.1 Formal agreement(s) There shall be agreement(s) between the sponsor, the clinical investigator(s) and other relevant parties which define(s) their responsibilities. All formal agreements shall be recorded in writing and signed by all parties involved. 6.2 Qualifications All parties participating in the conduct of the clinical investigation shall be appropriately qualified by education and/or experience to perform their tasks.
ISO 14155-1:2003(E) 6 © ISO 2003 — All rights reserved 6.3 Clinical investigation plan A clinical investigation plan shall be compiled in accordance with ISO 14155-2. 6.4 Design of the clinical investigation The clinical investigation shall be designed to evaluate whether the device is suitable for the purpose(s) and the population(s) for which it is intended. It shall be designed in such a way as to ensure that the results obtained have clinical relevance and scientific validity and will support the clinical investigation objectives. 6.5 Confidentiality At all times throughout the clinical investigation confidentiality shall be observed by all parties involved. All data shall be secured against unauthorized access. Privacy and confidentiality of information about each subject shall be preserved in the reports and any publication of the clinical investigation data. Lists of subjects' names and identifying information should, wherever possible, be maintained separately from case report forms. 6.6 Start of clinical investigation No clinical investigation shall start until a) a clinical investigation plan has been written and signed, b) the opinion and/or approval of the ethic(s) committee(s) has been obtained, c) regulatory clearance or approval, if applicable, has been obtained. 6.7 Informed consent 6.7.1 General Informed consent shall be obtained in writing and documented before a subject is enrolled into the clinical investigation. NOTE The consent form usually consists of an information part and an approval/signature part. These two parts can either be combined in one document (patient information and consent form) or separated into a patient information sheet and a patient consent form. 6.7.2 Process of obtaining informed consent The process of obtaining informed consent shall a) avoid any coercion of or undue influence of subjects to participate, b) not waive or appear to waive subject’s legal rights, c) use language that is non-technical and understandable to the subject or his/her legal representative, d) provide ample time for the subject to consider participation, e) include dated signatures of the subject or the subject's legal representative and of the clinical investigator,
ISO 14155-1:2003(E) © ISO 2003 — All rights reserved 7 f) show how informed consent will be obtained and recorded in circumstances in which the subject is unable to give it, NOTE A subject intended for the participation in a clinical investigation may be unable to make the necessary decisions (foetus, infant, child and juvenile, the seriously ill or unconscious, mentally ill, mentally handicapped). In such circumstances, informed consent can only be given by the legal guardian or representative. g) be documented in the clinical investigation plan. 6.7.3 Information to be provided to the subject for the purpose of obtaining informed consent At least the following information shall be provided in writing and in non-technical language that is understandable to the subject (or the subject's legal representative): a) description/purpose: 1) the investigation involves research; 2) the objective of the investigation; 3) the anticipated duration and involvement of subject participation in the investigation; 4) description of the device under investigation ; 5) description of procedures, emphasising any that are experimental. b) foreseeable risks: 1) description of any foreseeable risks an
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