1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS EN ISO 14155:2011Clinical investigation ofmedical devices for humansubjects Good clinicalpractice (ISO 14155:2011)BS EN ISO 14155:2011 BRITISH STANDARDNational forewordThis Br
2、itish Standard is the UK implementation of EN ISO14155:2011. It supersedes BS EN ISO 14155-1:2009 and BS EN ISO14155-2:2009, which are withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/194, Biological evaluation of medical devices. A list of organizations repre
3、sented on this committee can beobtained on request to its secretary.This publication does not purport to include all the necessaryprovisions of a contract. Users are responsible for its correctapplication. BSI 2011 ISBN 978 0 580 54473 6 ICS 11.100.20 Compliance with a British Standard cannot confer
4、 immunity fromlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee on 28 February 2011. Amendments issued since publicationDate T e x t a f f e c t e dEUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN ISO 14155 February 2011 ICS 1
5、1.100.20 Supersedes EN ISO 14155-1:2009, EN ISO 14155-2:2009English Version Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2011) Investigation clinique des dispositifs mdicaux pour sujets humains - Bonnes pratiques cliniques (ISO 14155:2011) Klinisch
6、e Prfung von Medizinprodukten an Menschen - 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
7、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).
8、 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, Cy
9、prus, 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
10、COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2011 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 14155:2011: EBS EN ISO 14155:2011 BS EN ISO 14155:2011EN IS
11、O 14155:2011 (E) 4 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 t
12、o 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
13、 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 getti
14、ng 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 sc
15、ope of this standard. BS EN ISO 14155:2011BS EN ISO 14155:2011EN ISO 14155:2011 (E) 5 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 ma
16、ndate 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 a
17、nd 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 EFT
18、A 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 require
19、ments and other EU Directives may be applicable to the product(s) falling within the scope of this standard. BS EN ISO 14155:2011ISO 14155:2011(E) ISO 2011 All rights reserved iiiContents Page Foreword .v 1 Scope1 2 Normative references1 3 Terms and definitions .2 4 Ethical considerations 7 4.1 Gene
20、ral .7 4.2 Improper influence or inducement 8 4.3 Compensation and additional health care8 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 EC9 4.5.4 Continuing communication with the EC
21、.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 consent10 4.7.3 Special circumstances for informed consent 10 4.7.4 Information to be provided to the subject 11 4.7.5 Informed con
22、sent 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 Investigators brochure (IB)15 5.6 Case report forms (CRFs).15 5.7 Mon
23、itoring plan15 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 deficiencie
24、s.16 6.4.1 Adverse events16 6.4.2 Device deficiencies .16 6.5 Clinical investigation documents and documentation17 6.5.1 Amendments17 6.5.2 Subject identification log17 6.5.3 Source documents 17 6.6 Additional members of the investigation site team.17 6.7 Subject privacy and confidentiality of data
25、17 6.8 Document and data control18 BS EN ISO 14155:2011ISO 14155:2011(E) iv ISO 2011 All rights reserved6.8.1 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.
26、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
27、 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 Prep
28、aration 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 o
29、f 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 Ann
30、ex A (normative) Clinical investigation plan (CIP). 32 Annex B (normative) Investigators 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 (informati
31、ve) Adverse event categorization . 55 Bibliography. 58 BS EN ISO 14155:2011ISO 14155:2011(E) ISO 2011 All rights reserved vForeword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International
32、 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, a
33、lso 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 commit
34、tees 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 pos
35、sibility 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 an
36、d replaces the first edition of ISO 14155-1:2003 and the first edition of ISO 14155-2:2003, which have been technically revised. BS EN ISO 14155:2011BS EN ISO 14155:2011INTERNATIONAL STANDARD ISO 14155:2011(E) ISO 2011 All rights reserved 1Clinical investigation of medical devices for human subjects
37、 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 fo
38、rth 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 prot
39、ect 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
40、, 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 consid
41、er 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 referenc
42、es, the latest edition of the referenced document (including any amendments) applies. ISO 14971:2007, Medical devices Application of risk management to medical devices BS EN ISO 14155:2011ISO 14155:2011(E) 2 ISO 2011 All rights reserved3 Terms and definitions For the purposes of this document, the f
43、ollowing 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 operatio
44、n, 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 s
45、igns (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 th
46、e 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 conducte
47、d, 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 treatm
48、ent 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 for
49、ms 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”. BS EN ISO 14155:2011ISO 14155:2011(E) ISO 2011 All rights reserved 33.7 clinical investigation plan CIP document that state(s) the rationale, obje
